Digital imaging colposcopy: corrected area measurements using shape-from-shading.
The quantitative measurement of areas on the cervix is of interest to researchers studying the natural history of human papilloma viral lesions. Measurement of areas from images obtained through a colposcope are, however, inherently in error due to the image being a two-dimensional projection of a three-dimensional object. The ability to correct for these errors through use of digital imaging colposcopy and a practical application of a shape from shading algorithm was developed in this study. The shape from shading technique requires empirical measurement of the relationship between observed light intensity and the viewing angle (referred to as a reflection map). It was found that a population mean reflection map provided a correction that was about as accurate as using an individual's own reflection map (making it unnecessary to measure a map for each exam). Digital red filtering of the images increased accuracy and precision of measurement.


Purification of the regulatory protein AlgR1 and its binding in the far upstream region of the algD promoter in Pseudomonas aeruginosa.
A regulatory protein AlgR1, previously suggested to be a member of a two-component sensory transduction system because of its homology to OmpR and NtrC and its ability to allow activation of the algD promoter under conditions of high osmolarity, has been hyperproduced in Escherichia coli after deletion of the upstream region including part of the Shine-Dalgarno sequence of the algR1 gene and its subsequent cloning under the tac promoter. The AlgR1 protein is purified as a monomer, and the sequence of the nine N-terminal amino acids of the monomer matches with that predicted from the DNA sequence of the algR1 gene. The purified AlgR1 protein binds to two separate DNA fragments of the algD upstream region. DNase protection experiments identify these two DNA segments as 14-mer sequences centered at -382 and -458 regions, which contain a common CCGT-TCGTC sequence in them. While the presence of at least one AlgR1 binding site is important for the activation of the algD promoter, the presence of both of the binding sites in the upstream region leads to a higher level of activation.


Oxidative metabolism in muscle.
Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantages and problems of near-infrared spectroscopy measurements, in resting and exercising skeletal muscles studies, are discussed through some representative examples.


Novel extracellular vesicles mediate an ABCG2-dependent anticancer drug sequestration and resistance.
Overexpression of the multidrug efflux transporter ABCG2 in the plasma membrane of cancer cells confers resistance to various anticancer drugs, including mitoxantrone. Here, we explored the mechanism underlying drug resistance in the MCF-7 breast cancer sublines MCF-7/MR and MCF-7/FLV1000 cells in which wild-type (R482) ABCG2 overexpression is highly confined to cell-cell attachment zones. The latter comprised the membrane of novel extracellular vesicles in which mitoxantrone was rapidly and dramatically sequestered. After 12 hours of incubation with mitoxantrone, the estimated intravesicular drug concentration was approximately 1,000-fold higher than in the culture medium. This drug compartmentalization was prevented by the specific and potent ABCG2 transport inhibitors Ko143 and fumitremorgin C, thereby resulting in restoration of drug sensitivity. Consistently, this intravesicular drug concentration was abrogated by energy deprivation and was restored upon provision of energy substrates. Fine-structure studies corroborated the presence of numerous large extracellular vesicles that were highly confined to cell-cell attachment zones between neighbor cells. Furthermore, high-resolution electron microscopy revealed that the membrane of these extracellular vesicles contained microvilli-like invaginations protruding into the intravesicular lumen. It is likely that these microvilli-like projections increase the vesicular membrane surface, thereby allowing for a more efficient ABCG2-dependent intravesicular anticancer drug concentration. Hence, these novel extracellular vesicles mediate the ABCG2-dependent extraction of intracellular drug, thereby serving as cytotoxic drug disposal chambers shared by multiple neighbor cancer cells. This constitutes a novel modality of anticancer drug resistance.


Self-efficacy as a mediator between maternal depression and child hospitalizations in low-income urban families.
The objective of this study is to examine the role of maternal self-efficacy as a potential mediator between maternal depression and child hospitalizations in low-income families. We analyzed data from 432 mother-child pairs who were part of the control-group for the Nurse-Family Partnership trial in Memphis, TN. Low-income urban, mostly minority women were interviewed 12 and 24 months after their first child's birth and their child's medical records were collected from birth to 24 months. We fit linear and ordered logistic regression models to test for mediation. We also tested non-linear relationships between the dependent variable (child hospitalization) and covariates (depressive symptoms and self-efficacy). Elevated depressive symptoms (OR: 1.70; 90% CI: 1.05, 2.74) and lower maternal self-efficacy (OR: 0.674; 90% CI: 0.469, 0.970) were each associated with increased child hospitalizations. When both maternal self-efficacy and depressive symptoms were included in a single model, the depressive symptoms coefficient decreased significantly (OR decreased by 0.13, P = 0.069), supporting the hypothesis that self-efficacy serves as a mediator. A non-linear, inverse-U shaped relationship between maternal self-efficacy and child hospitalizations was supported: lower compared to higher self-efficacy was associated with more child hospitalizations (P = 0.039), but very low self-efficacy was associated with fewer hospitalizations than low self-efficacy (P = 0.028). In this study, maternal self-efficacy appears to be a mediator between maternal depression and child hospitalizations. Further research is needed to determine if interventions specifically targeting self-efficacy in depressed mothers might decrease child hospitalizations.


[Radiation exposure of cultured tissue cells and animals (mice) within 10-kilometers zone of accident at Chernobyl nuclear plant. Effect on radiosensitivity to future radiation].
The effect of chronic low-level radiation exposure on radiosensitivity to posterior acute irradiation at high doses has been studied. Cells and mice were exposed within the ten-kilometer zone of Chernobyl disaster during various spaces of time (1-12 days), then over one or more days were additionally irradiated by doses of 1-4 Gy. It was shown that no adaptive response was developed under chronic exposure of cells and mice within the zone of disaster. On the contrary increased sensitivity to posterior irradiation was revealed. The number of cytogenetic damages of cultured tissue cells and marrow cells (chromosome aberrations and micronuclei) increases, the spectrum of aberrations being shifted to chromosome type, cells with multiaberration appearing. The decay of chromatine increases indicating an interphase death; the number of leucocytes in peripheral blood decreases.


Nickel(III) oxidation of its glycylglycylhistamine complex.
The doubly-deprotonated Ni(III) complex of Gly(2)Ha (where Ha is histamine) undergoes base-assisted oxidative self-decomposition of the peptide. At </= p[H(+)] 7.0, a major pathway is a two-electron oxidation at the alpha-carbon of the N-terminal glycyl residue. Major products (up to 73%) of this two-electron oxidation are glyoxylglycylhistamine and ammonia. Glyoxylglycylhistamine will decay to give isocyanatoacetylhistamine and formaldehyde. Two-electron oxidations of the second glycyl and histamine residues occur as minor pathways (12% of the total possible reaction). Above p[H(+)] 8.5, two Ni(III)-peptide complexes form an oxo bridge in the axial positions to give a reactive dimer species. This proximity allows the resulting Ni(II)-peptide radical intermediates to undergo peptide-peptide cross-linking at the N-terminal glycyl residues. The products found below p[H(+)] 7.0 are observed above p[H(+)] 8.5 as well, although in lower yields. In contrast to this work, Ni(III)(H(-2)Gly(2)HisGly) undergoes a four-electron oxidation at the N-terminal glycyl residue. Oxidation at the internal glycyl and histidyl residues are not observed. The reactivity of Ni(III)(H(-2)Gly(2)Ha)(+) is also different than Cu(III)(H(-2)Gly(2)Ha)(+), which undergoes a two-electron oxidation at the histamine group with no peptide-peptide cross-linking in basic solution.


Risk factors of nutritional blindness and determinants of a successful vitamin A prophylaxis programme.
Data on 7668 children (0-72 months) and their 4621 mothers and 81 Anganwadi Workers (AWWs) collected for the USAID Assisted ICDS Evaluation Surveys were analysed. The results indicated that the major risk factors of nutritional blindness were lack of nutrition and health knowledge among mothers; presence of iron deficiency anemia in the children; and history of the child having had measles in the past one year. Mother's health and nutrition, knowledge and maternal literacy status were the determinants of the success of a vitamin A prophylaxis programme. Factors that determined AWW's performance in vitamin A supplementation were her nutrition and health knowledge, her literacy status and the amount of supervisory assistance she received from Auxillary Nurse Midwife (ANM).


Recombinantly engineered human proteins: transforming the treatment of psoriasis.
Psoriasis is a chronic, inflammatory disease with lesions that produce considerable physical discomfort and often lead to substantial disruption in patients' daily activities. The use of currently available, nonspecific, systemic immunosuppressive therapies for patients with moderate to severe psoriasis is limited by an inability to maintain disease remission safely. Advances in recombinant DNA technology paralleled with increased understanding of the immunopathology of psoriasis have led to the development of numerous biologic agents for the treatment of this disease. These new biologic therapies target specific steps in psoriasis pathology, including direct effects on T cells, T cell activation, T cell migration, and cellular production and secretion of cytokines. By selectively targeting the activities of T cells that are directly involved in psoriasis pathogenesis, these novel agents offer improved safety profiles and enhanced efficacy. In this article, the mechanisms of T cell pathogenicity that guided the development of these new biologic therapies are reviewed along with clinical data on the progress of these agents.


Effect of Elevated Ambient Temperature on Simulator-Derived Oscillometric Blood Pressure Measurement.
Oscillometric blood pressure (BP) devices are typically labeled for use up to 40 °C. Many geographic regions have ambient temperatures exceeding 40 °C. We assessed the effect of increased ambient temperature (40-55 °C) on simulator-derived oscillometric BP measurement. Three Omron BP769CAN devices, 3 A&D Medical UA-651BLE devices, and accompanying cuffs were used. A custom heat chamber heated each device to the specified temperature. A noninvasive BP simulator was used to take 3 measurements with each device at differing temperatures (22, 40, 45, 50, and 55 °C) and BP thresholds: 80/50, 100/60, 120/80, 140/90, 160/110, and 180/130 mm Hg. Using each device as its own control (22 °C), we determined the relative differences in mean BP for each device at each temperature and BP setting, assessed graphical trends with increasing temperature, and examined variability. Graphical trends of mean simulator-subtracted BP differences from room temperature showed no discernable pattern, with differences clustered around zero. Overall mean difference in BP (combined elevated temperatures minus room temperature) was -0.8 ± 2.1 (systolic ± SD)/1.2 ± 3.5 (diastolic ± SD) mm Hg for the A&D device and 0.2 ± 0.4 (systolic ± SD)/-0.1 ± 0.1 (diastolic ± SD) mm Hg for the Omron. All individual elevated temperature differences (elevated temperature minus room temperature) except A&D diastolic BP at 50 °C were within 5 mm Hg. In this simulator-based study assessing within-device differences, higher ambient temperatures resulted in oscillometric BP measurements that were comparable to those performed at room temperature.


Cytokine expression in feline osteoclastic resorptive lesions.
Feline osteoclastic resorptive lesions (FORL) of the teeth are common in cats, and lead to pain, destruction of the periodontal ligament, and tooth loss. The expression of interleukin (IL)-1 beta and IL-6 mRNA was higher in teeth with FORL than in normal teeth (P<0.01 and P<0.001, respectively), but no such differences were found between pathological and normal gingival tissue samples. There were no differences between teeth affected with FORL and normal teeth in respect of the expression of receptor activator of NF kappa B ligand (RANKL) mRNA or osteoprotegerin (OPG) mRNA. However, OPG mRNA expression was higher in gingival tissue associated with teeth affected with FORL than in normal gingival tissue (P<0.05), whereas the reverse was true of RANKL mRNA expression (P<0.05). OPG mRNA expression was significantly higher in teeth than in femoral and alveolar bone (P<0.001). RANKL and OPG mRNAs were detected in all tissues examined. The data suggest that the elevated expression of IL-l beta and IL-6 mRNA plays a role in the mediation of osteoclast activity in advanced FORL. In contrast, OPG and RANKL do not appear to regulate osteoclasts in advanced disease. The results also suggest that OPG and RANKL mRNA play a role in mediating inflammatory responses in gingival cells, and that OPG has an inhibiting effect on tooth resorption.


Unsaturated Zone Flow Processes and Aquifer Response Time in the Chalk Aquifer, Brighton, South East England.
The Chalk aquifer is one of the main sources of water in South East England. The unsaturated zone in the aquifer plays an important role controlling the time and magnitude of recharge and is major pathway for contaminant transport to the water table. A range of previous work has addressed flow processes in the Chalk unsaturated zone, but physical understanding is still incomplete. Here we present the results of a study on flow mechanism in the Chalk unsaturated zone using a combination of statistical analysis and novel laboratory methods. The study was undertaken at three sites (North Heath Barn [NHB], Pyecombe East [PE], and Preston Park [PP]) on the Chalk of the Brighton block, South East England. Daily and hourly time series data of groundwater level and rainfall were correlated. The results show that a slower groundwater level response to rainfall occurs during dry seasons (summer and autumn) when the amount of effective rainfall is less than 4 mm/day, with a thicker and drier unsaturated zone. A faster response occurs during wet seasons (winter and spring) when the daily effective rainfall exceeds 4 mm/day with a thinner and wetter unsaturated zone. Periods of very rapid response (within 15 h) were observed during wet seasons at NHB and PE sites, with unsaturated hydraulic conductivity (Ku ) inferred to reach 839 mm/day. A slower response was observed at an urbanized site (PP) as a result of reduction in direct recharge due to reduced infiltration, due to presences of impermeable infrastructure covering the area around PP borehole. Laboratory measurements of Ku of the Chalk matrix using a geotechnical centrifuge show variation from 4.27 to 0.07 mm/day, according to the level of saturation. Thus, the rapid responses cannot be linked to matrix flow only but indicate the contribution of fracture and karstic flow processes in conducting water.


Fusion-Learning of Bayesian Network Models for Fault Diagnostics.
Bayesian Network (BN) models are being successfully applied to improve fault diagnosis, which in turn can improve equipment uptime and customer service. Most of these BN models are essentially trained using quantitative data obtained from sensors. However, sensors may not be able to cover all faults and therefore such BN models would be incomplete. Furthermore, many systems have maintenance logs that can serve as qualitative data, potentially containing historic causation information in unstructured natural language replete with technical terms. The motivation of this paper is to leverage all of the data available to improve BN learning. Specifically, we propose a method for fusion-learning of BNs: for quantitative data obtained from sensors, metrology data and qualitative data from maintenance logs, corrective and preventive action reports, and then follow by fusing these two BNs. Furthermore, we propose a human-in-the-loop approach for expert knowledge elicitation of the BN structure aided by logged natural language data instead of relying exclusively on their anecdotal memory. The resulting fused BN model can be expected to provide improved diagnostics as it has a wider fault coverage than the individual BNs. We demonstrate the efficacy of our proposed method using real world data from uninterruptible power supply (UPS) fault diagnostics.


Making the most of evaluation: a mixed methods study in the English NHS.
To increase understanding about how evaluations of health policy initiatives are commissioned, conducted and used. A mapping exercise was conducted to identify evaluation of initiatives promoted by the White Paper 'Our health, our care, our say' in the English NHS. All evaluations were subjected to critical appraisal and 21 were purposively selected as case studies, involving documentary analysis and 60 interviews with those commissioning, conducting and affected by the evaluation. Variation in the types of evaluation being undertaken did not reflect the importance of the initiatives being evaluated. Most evaluations collected evidence about uptake, processes of care and users' perceptions. While some provided useful information about how initiatives could be improved, few provided robust evidence about the benefits or costs of the initiatives. Those who commissioned evaluations had similar concerns to those who conducted them. There was a commitment to the concept of evaluation but little clarity about how findings would be used. Evaluation was often commissioned too late to influence decisions about implementation. Compromises over research design and difficulties collecting data limited the potential to provide robust evidence about benefits. There were tensions between the desire of evaluators for methodological rigour and the needs of service providers for swift, contextually relevant findings. There were concerns about the transparency of methods and results. Considerable public resources are committed to evaluation, but this investment is less productive than it could be. This article specifies several ways in which the use of evaluation of initiatives in health and social care could be improved.


BMFPs, a versatile therapeutic tool for redirecting a preexisting Epstein-Barr virus antibody response toward defined target cells.
Industrial production of therapeutic monoclonal antibodies is mostly performed in eukaryotic-based systems, allowing posttranslational modifications mandatory for their functional activity. The resulting elevated product cost limits therapy access to some patients. To address this limitation, we conceptualized a novel immunotherapeutic approach to redirect a preexisting polyclonal antibody response against Epstein-Barr virus (EBV) toward defined target cells. We engineered and expressed in bacteria bimodular fusion proteins (BMFPs) comprising an Fc-deficient binding moiety targeting an antigen expressed at the surface of a target cell, fused to the EBV-P18 antigen, which recruits circulating endogenous anti-P18 IgG in EBV+ individuals. Opsonization of BMFP-coated targets efficiently triggered antibody-mediated clearing effector mechanisms. When assessed in a P18-primed mouse tumor model, therapy performed with an anti-huCD20 BMFP significantly led to increased survival and total cancer remission in some animals. These results indicate that BMFPs could represent potent and useful therapeutic molecules to treat a number of diseases.


The cohesion stabilizer sororin favors DNA repair and chromosome segregation during mouse oocyte meiosis.
Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program. Sororin is constantly expressed throughout meiosis and accumulates on chromatins at germinal vesicle (GV) stage/G2 phase. It localizes onto centromeres from germinal vesicle breakdown (GVBD) to metaphase II stage. Inactivation of Sororin compromises the GVBD and first polar body extrusion (PBE). Furthermore, Sororin inactivation induces DNA damage indicated by positive γH2AX foci in GV oocytes and precocious chromatin segregation in MII oocytes. Finally, our data indicate that PlK1 and MPF dissociate Sororin from chromosome arms without affecting its centromeric localization. Our results define Sororin as a determinant during mouse oocyte meiotic maturation by favoring DNA damage repair and chromosome separation, and thereby, maintaining the genome stability and generating haploid gametes.


Size-dependent assembly of ligated gold nanocrystals in two dimensions.
Brownian dynamics (BD) simulation based on a coarse-grained model is performed to study the assembly of dodecanethiol-ligated Au nanocrystals (NCs) at a toluene-air interface. With increasing diameter from 3 nm to 9 nm, the NCs are found to form three different phases-a dispersed phase without aggregation, a mixture of dispersed NCs and rounded clusters, and a compactly packed solid phase of the fractal structure. Such size dependence of the assembled phase is attributed to the variation in the well depth [Formula: see text] of the interaction potential between NCs, and the value of [Formula: see text] for 6 nm NCs turns out to be most suitable to form monolayers with hexagonal packing. The result is of universal importance for assembling complete monolayers, because the valley of the interaction potential can be well tailored by properly choosing the NC size, ligand length and solvent.


Distinct roles of two ceramide synthases, CaLag1p and CaLac1p, in the morphogenesis of Candida albicans.
Lag1p and Lac1p catalyse ceramide synthesis in Saccharomyces cerevisiae. This study shows that Lag1 family proteins are generally required for polarized growth in hemiascomycetous yeast. However, in contrast to S. cerevisiae where these proteins are functionally redundant, C. albicans Lag1p (CaLag1p) and Lac1p (CaLac1p) are functionally distinct. Lack of CaLag1p, but not CaLac1p, caused severe defects in the growth and hyphal morphogenesis of C. albicans. Deletion of CaLAG1 decreased expression of the hypha-specific HWP1 and ECE1 genes. Moreover, overexpression of CaLAG1 induced pseudohyphal growth in this organism under non-hypha-inducing conditions, suggesting that CaLag1p is necessary for relaying signals to induce hypha-specific gene expression. Analysis of ceramide and sphingolipid composition revealed that CaLag1p predominantly synthesizes ceramides with C24:0/C26:0 fatty acid moieties, which are involved in generating inositol-containing sphingolipids, whereas CaLac1p produces ceramides with C18:0 fatty acid moieties, which are precursors for glucosylsphingolipids. Thus, our study demonstrates that CaLag1p and CaLac1p have distinct substrate specificities and physiological roles in C. albicans.


Long-term mortality and incidence of renal dialysis and transplantation in type 1 diabetes mellitus.
We investigated long-term mortality and requirement of renal replacement therapy (RRT) in type 1 diabetes mellitus (T1DM) to study risk factors and late complication incidence of T1DM in a prospective cohort study at Lainz Hospital, Vienna, Austria. In 1983-1984, T1DM patients [n = 648; 47% females, 53% males; age, 30 +/- 11 yr; T1DM duration, 15 +/- 9 yr; body mass index, 24 +/- 4 kg/m(2); glycated hemoglobin (HbA1c), 7.6 +/- 1.6%] were stratified into HbA1c quartiles [1st, 5.9 +/- 0.5% (range, 4.2-6.5%); 2nd, 6.9 +/- 0.3% (6.6-7.4%); 3rd, 7.9 +/- 0.3% (7.5-8.4%); and 4th, 9.6 +/- 1.3% (8.5-14.8%)]. Twenty years later, both endpoints (death and RRT) were investigated by record linkage with national registries. At baseline, creatinine clearance, blood pressure, and body mass index were comparable among the HbA1c quartiles, whereas albuminuria was more frequent in the 4th quartile (+15%; P < 0.03). After the 20-yr follow-up, 13.0% of the patients had died [rate, 708 per 100,000 person-years (95% confidence interval, 557-859)], and 5.6% had received RRT [311 per 100,000 person-years (95% confidence interval, 210-412)]. Patients with the highest HbA1c values (4th quartile) had a higher mortality rate and a greater incidence of RRT (P < 0.04). In the Cox proportional hazards analysis, age, male gender, increased HbA1c, albuminuria, and reduced creatinine clearance were predictors of mortality (P < 0.05). Predictors of RRT were albuminuria (P < 0.001), reduced creatinine clearance (P < 0.001), and belonging to the 4th HbA1c quartile (P = 0.06). In Kaplan-Meier analysis, mortality was linearly associated with poor glycemia, whereas RRT incidence appeared to rise at a HbA1c threshold of approximately 8.5%. In the Lainz T1DM cohort, 13.0% mortality and 5.6% RRT were directly associated with and more frequently found in poor glycemia, showing that good glycemic control is essential for the longevity and quality of life in T1DM.


[Malignant glaucoma following combined Ahmed valve implant and phacoemulsification surgery for chronic angle-closure glaucoma].
Simultaneous Ahmed valve implant, combined with phacoemulsification cataract surgery, is a useful therapeutic option for patients with chronic angle-closure glaucoma, when conventional filtering surgery fails. This combined approach permits both control of intraocular pressure and early recovery of visual function. We report the results in five patients successfully treated with this combined procedure, two of whom developed early postoperative malignant glaucoma. Predisposing anatomic features in patients with chronic angle-closure glaucoma, associated with sudden anterior chamber decompression and increased postoperative inflammation, may facilitate the development of malignant glaucoma following combined glaucoma implant and phacoemulsification surgery.


[The effect of nedocromil sodium on levels of IL-4 and IgE in serum of children with bronchial asthma].
Levels of pro-allergic cytokine IL-4 are increased in asthmatic airways, contributing to allergic inflammation. IL-4 and IL-13 are the most important factors in production of class E immunoglobulin, playing major role in childhood atopic asthma. The mechanism of effect of nedocromil, often prescribed in children, has been discussed. Our previous study on the effect of nedocromil on different inflammatory markers, showed decreased levels of IL-4 and IgE after monotherapy in 15 asthmatic children. The purpose of this study was to define the effect of treatment with nedocromil on serum level of IL-4 and IgE, clinical symptoms and bronchial hyperreactivity (BHR) in children with moderate atopic asthma. It was 8 week, placebo-controlled and randomized, double blind trial of 81 children with moderate atopic asthma allergic to dust mite. Patients were randomly allocated to receive nedocromil sodium two puffs four times daily (0.002 g/puff) (n = 34) or placebo (n = 47). 69 children completed the study. After treatment with nedocromil the levels of IL-4 and IgE in blood serum in study group significantly decreased, and all clinical parameters improved. Mean levels of IL-4 in serum before and after treatment with nedocromil were 0.13 pg/ml +/- 0.01 and 0.12 pg/ml +/- 0.02 respectively (p < 0.01). Mean serum levels of IgE before and after treatment with nedocromil were 556.83 IU/ml +/- 201.3 and 485 IU/ml +/- 200.5 respectively (p < 0.02). This study demonstrate that one possible way by which nedocromil contribute to inhibition of allergic inflammation is by decreasing IL-4 and IgE levels.


Use of critically important antimicrobial classes early in life may adversely impact bacterial resistance profiles during adult years: potential co-selection for plasmid-borne fluoroquinolone and macrolide resistance via extended-spectrum beta-lactam use in dairy cattle.
The transfer of antimicrobial resistance genes commonly occurs via vertical and horizontal gene transfer, as such genes are often found on the same mobile genetic element. This occurrence can lead to the co-selection of resistance to antimicrobials without their application. Dairy cattle located in the south-western United States were enrolled in a matched-pair longitudinal study to evaluate the effects of a two-dose ceftiofur treatment for metritis on levels of third-generation cephalosporin resistance among faecal Escherichia coli temporally. Escherichia coli chosen for further investigation were isolated on selective media, harboured extended-spectrum beta-lactam, fluoroquinolone and macrolide resistance genes. This combination has previously been unreported; importantly, it included genes encoding for resistance to antibiotics that can only be used in dairy cattle less than 20 months of age. Fluoroquinolones, macrolides and third and higher generation cephalosporins are considered critically important and highest priority for human medicine by the World Health Organization.


Unsedated transnasal endoscopy: a new technique for accurately detecting and grading esophageal varices in cirrhotic patients.
Endoscopic screening of cirrhotics for large esophageal varices (EV) is advocated before initiation of prophylactic therapy for variceal bleeding. Conscious sedation for conventional endoscopy is problematic in cirrhotic patients because of risk of prolonged encephalopathy. Unsedated transnasal endoscopy (T-EGD) is a new technique, which allows for unsedated examination because it is well tolerated. The aims of this study were to determine whether T-EGD is feasible for screening of cirrhotic patients for presence of EV and to compare the diagnostic yield of T-EGD with conventional endoscopy for detecting and grading of EV. Fifteen cirrhotics with no history of variceal bleeding, known EV, severe thrombocytopenia, or recurrent epistaxis were evaluated by unsedated T-EGD using a 5.3-mm outer diameter endoscope. Immediately afterward, a different endoscopist, blinded to T-EGD findings, performed sedated conventional endoscopy in standard fashion. The presence and size of EV, gastric varices, and other findings were recorded. Patient tolerance was also evaluated. Both modalities detected EV in the same 10 and gastric varices in the same two patients and completely agreed on size of EV. No stigmata of recent variceal bleeding were noted. Average time for unsedated T-EGD was 5 min 6 s. All patients found both procedures acceptable overall, with no significant difference in choking, discomfort, and sore throat. One patient developed self-limited epistaxis after T-EGD. 1) EV are accurately detected and graded by T-EGD in cirrhotic patients. 2) T-EGD is a safe and less costly screening alternative for EV in cirrhotic patients.


Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships.
Antagonists of 5HT3 receptors are clinically effective in treating nausea and emesis associated with certain oncolytic drugs, including cisplatin. Moreover, these agents may be useful in pharmacological management of several central nervous system disorders, including anxiety, schizophrenia, dementia, and substance abuse. Our studies on aroyltropanamides led to the discovery that dihydrobenzofuranyl esters and amides are potent 5HT3 receptor antagonists. Simple benzoyl derivatives of tropine and 3 alpha-aminotropane possessed weak 5HT3 receptor antagonist activity, as judged by blockade of bradycardia produced by iv injection of serotonin (5HT) to anesthetized rats. Within this series, use of benzofuran-7-carboxamide as the aroyl moiety led to a substantial increase of 5HT3 receptor affinity. The optimal 5HT3 receptor antagonist identified via extensive SAR studies was endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oc t- 3-yl)-7-benzofurancarboxamide (Z)-2-butenedioate (zatosetron maleate). The 7-carbamyl regiochemistry, dimethyl substitution, chloro substituent, and endo stereochemistry were all crucial elements of the SAR. Zatosetron maleate was a potent antagonist of 5HT-induced bradycardia in rats (ED50 = 0.86 micrograms/kg i.v.). Low oral doses of zatosetron (30 micrograms/kg) produced long-lasting antagonism of 5HT3 receptors, as evidenced by blockade of 5HT-induced bradycardia for longer than 6 h in rats. Moreover, this compound did not produce hemodynamic effects after i.v. administration to rats, nor did it block carbamylcholine-induced bradycardia in doses that markedly blocked 5HT3 receptors. Thus, zatosetron is a potent, selective, orally effective 5HT3 receptor antagonist with a long duration of action in rats.


Environmental characteristics of the cemeteries of Buenos Aires City (Argentina) and infestation levels of Aedes aegypti (Diptera: Culicidae).
Cemeteries with many water-filled containers, flowers, sources of human blood, and shade are favorable urban habitats for the proliferation of Aedes aegypti, a vector of yellow fever and dengue. A total of 22,956 containers was examined in the five cemeteries of the city of Buenos Aires, Argentina. The vector was found in four cemeteries that showed an average infestation level of 5.5% (617 positive out of 11,196 water-filled containers). The four cemeteries positive for Ae. aegypti showed significantly different (p<0.01) infestation levels. Vegetation cover and percentage of infestation were significantly correlated (p<0.01), but neither cemetery area nor number of available containers were significantly related to the proportion of positive vases. Our results suggest that the cemeteries of Buenos Aires represent a gradient of habitat favorableness for this vector species, some of which may act as foci for its proliferation and dispersal.


[Analysis of the regulation of IgG production to Cryptomeria japonica pollen antigen].
Genetic control of the immune response to Cryptomeria japonica pollen antigen (CPAg) in humans was analyzed using 72 unrelated healthy adults. The 72 were classified into a low responder group and a high responder group by using purified CPAg. Significant associations were found between IgG low responsiveness to purified CPAg and possession of HLA-DQw3. Relative risks for the two groups were 4.80. Peripheral blood lymphocytes from low responders revealed a specific IgG response to CPAg when the CD8+ T cell fraction was depleted. Thereby, low response due to the presence of CPAg-specific CD8+ suppressor T cells was suggested.


Comparison of the Mayo Endoscopy Score and the Ulcerative Colitis Endoscopy Index of Severity and the Ulcerative Colitis Colonoscopy Index of Severity.
Background and study aims: Endoscopy plays an essential role in managing patients with ulcerative colitis (UC), as it allows us to visualize and assess the severity of the disease. As such assessments are not always objective, different scores have been devised to standardize the findings. The main aim of this study was to assess the interobserver variability between the Mayo Endoscopy Score (MES), Ulcerative Colitis Endoscopy Index of Severity (UCEIS) and Ulcerative Colitis Colonoscopy Index of Severity (UCCIS) analyzing the severity of the endoscopic lesions in patients with ulcerative colitis. Patients and methods: This was a single-cohort observational study in which a colonoscopy was carried out on patients with UC, as normal clinical practice, and a video was recorded. The results from the video were classified according to the MES, UCEIS and UCCIS by three endoscopic specialists independently, and they were compared to each other. The Mayo Endoscopy Score (MES) was used to assess the clinical situation of the patient. The therapeutic impact was analyzed after colonoscopy was carried out. Results: Sixty-seven patients were included in the study. The average age was 51 (SD ± 16.7) and the average MES was 3.07 (SD ± 2.54). The weighted Kappa index between endoscopists A and B for the MES was 0.8; between A and C 0.52; and between B and C 0.49. The intraclass correlation coefficient for UCEIS was 0.92 among the three endoscopists (CI 95 %: 0.83-0.96) and 0.96 for UCCIS among the three endoscopists (CI 95 % 0.94-0.97). A change in treatment for 34.3 % of the patients was implemented on seeing the results of the colonoscopy. Conclusions: There was an adequate, but not perfect, correlation between the different endoscopists for MES, UCEIS, UCCIS. This was higher with the last two scores. Thus, there is still some subjectivity to be minimized through special training, on assessing the seriousness of the endoscopic lesions in patients with UC.


Muscle Twitch Kinetics Are Dependent on Muscle Group, Disease State, and Age in Duchenne Muscular Dystrophy Mouse Models.
Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by the lack of functional dystrophin protein. In muscular dystrophy preclinical research, it is pertinent to analyze the force of the muscles affected by the disease to assess pathology and potential effectiveness of therapeutic interventions. Although muscles function at sub-maximal levels in vivo, maximal tetanic contractions are most commonly used to assess and report muscle function in muscular dystrophy studies. At submaximal activation, the kinetics of contraction and relaxation are heavily impacted by the kinetics of the single twitch. However, maximal tetanic force is often the main, if not sole, outcome measured in most studies, while contractile kinetics are rarely reported. To investigate the effect of muscle disease on twitch contraction kinetics, isolated diaphragm and extensor digitorum longus (EDL) muscles of 10-, 20-week, "het" (dystrophin deficient and utrophin haplo-insufficient), and 52-week mdx (dystrophin deficient) mice were analyzed and compared to wild-type controls. We observed that twitch contractile kinetics are dependent on muscle type, age, and disease state. Specific findings include that diaphragm from wildtype mice has a greater time to 50% relaxation (RT50) than time to peak tension (TTP) compared to the het and mdx dystrophic models, where there is a similar TTP compared to RT50. Diaphragm twitch kinetics remain virtually unchanged with age, while the EDL from het and mdx mice initially has a greater RT50 than TTP, but the TTP increases with age. The difference between EDL contractile kinetics of dystrophic and wildtype mice is more prominent at young age. Differences in kinetics yielded greater statistical significance compared to previously published force measurements, thus, using kinetics as an outcome parameter could potentially allow for use of smaller experimental groups in future study designs. Although this study focused on DMD models, our findings may be applicable to other skeletal muscle conditions and diseases.


VCAM-1 and VLA-4 modulate dendritic cell IL-12p40 production in experimental visceral leishmaniasis.
Vascular cell adhesion molecule-1 (VCAM-1) interacts with its major ligand very late antigen-4 (VLA-4) to mediate cell adhesion and transendothelial migration of leukocytes. We report an important role for VCAM-1/VLA-4 interactions in the generation of immune responses during experimental visceral leishmaniasis caused by Leishmania donovani. Our studies demonstrate that these molecules play no direct role in the recruitment of leukocytes to the infected liver, but instead contribute to IL-12p40-production by splenic CD8(+) dendritic cells (DC). Blockade of VCAM-1/VLA-4 interactions using whole antibody or anti-VCAM-1 Fab' fragments reduced IL-12p40 mRNA accumulation by splenic DC 5 hours after L. donovani infection. This was associated with reduced anti-parasitic CD4(+) T cell activation in the spleen and lowered hepatic IFNgamma, TNF and nitric oxide production by 14 days post infection. Importantly, these effects were associated with enhanced parasite growth in the liver in studies with either anti-VCAM-1 or anti-VLA-4 antibodies. These data indicate a role for VCAM-1 and VLA-4 in DC activation during infectious disease.


Five-year incidence of age-related maculopathy lesions: the Blue Mountains Eye Study.
To describe the 5-year incidence and progression of early and late age-related maculopathy (ARM) lesions. Population-based cohort study. Three thousand six hundred fifty-four noninstitutionalized residents, aged 49 years or older, living in the Blue Mountains area west of Sydney, Australia, participated in the study during 1992 to 1994. The cohort was reexamined after 5 years (1997-1999). Excluding 543 participants who died since the baseline, 2335 (75%) survivors attended 5-year follow-up examinations. Retinal photographs from both examinations were graded using the Wisconsin ARM Grading System. Photographs of participants with any ARM lesions at either examination were regraded in detail using a modification of the side-by-side method developed for the Beaver Dam Eye Study. Incidence and progression of ARM lesions were defined in a similar manner to that used in the Beaver Dam Eye Study. Incidence rates for all ARM lesions increased significantly with age. For late ARM lesions (geographic atrophy and neovascular ARM), the overall 5-year incidence was 1.1%. The combined late ARM incidence was 0.0%, 0.6%, 2.4%, and 5.4% for participants aged 60 years and younger, 60 to 69 years, 70 to 79 years, and 80 years and older at baseline, respectively. After excluding participants with either early or late ARM in either eye at baseline, the overall 5-year incidence of early ARM was 8.7%, including 3.2%, 7.4%, 18.3%, and 14.8% for the corresponding age groups. The incidence of neovascular ARM in women was double that for men (P = 0.1). This study has documented the incidence of ARM lesions in an older Australian population. The slightly higher incidence of hyperpigmentation found in our population compared with the Beaver Dam Eye Study may be due to sample variability, or this could reflect real differences between the two populations. Our lower incidence of soft drusen could have resulted from our non-inclusion of intermediate soft drusen in the soft distinct and indistinct drusen categories.


Progenitor cell therapy for traumatic brain injury: effect of serum osmolarity on cell viability and cytokine production.
The potential translation of mesenchymal stem cell (MSC) therapy into a multimodal protocol for traumatic brain injury requires evaluation of viability and cytokine production in a hyperosmolar environment. Optimization of MSC therapy requires delivery to the target area without significant loss of cellular function or viability. No model evaluating the potential efficacy of MSC therapy at varying osmolarities currently exists. Rat MSCs were characterized with flow cytometric immunophenotyping. MSCs (passage 3) were placed in culture with multipotent adult progenitor cell media at varying osmolarities (250, 270, 290, 310, 330, 350 and 370 mOsm) potentially found with hypertonic saline infusion. After culture for 24 h, cellular viability was measured using flow cytometry (n = 6). Next, brain tissue supernatant was harvested from both normal rat brains and injured brains 6 h after cortical injury. Subsequently, MSCs were placed in culture with multipotent adult progenitor cell media +/- 20% normal brain or injured brain supernatant (at the aforementioned osmolarities) and allowed to remain in culture for 24 h (n = 11). At this point, media supernatant cytokine levels were measured using a multiplex cytokine assay system. MSCs showed no clinically significant difference in viability at 24 h. MSCs cultured with 20% injured brain supernatant showed an decrease in proinflammatory cytokine production (IL-1alpha and IL-1beta) with increasing osmolarity. No difference in anti-inflammatory cytokine production (IL-4 and IL-10) was observed. Progenitor cell therapy for traumatic brain injury may require survival and activity in a hyperosmolar environment. Culture of MSCs in such conditions shows no clinically significant effect on cell viability. In addition, MSC efficacy could potentially be enhanced via a decrease in proinflammatory cytokine production. Overall, a multimodal traumatic brain injury treatment protocol based upon MSC infusion and hypertonic saline therapy would not negatively affect progenitor cell efficacy and could be considered for multicenter clinical trials.


Blood-induced joint damage: a human in vitro study.
To investigate mechanisms underlying cartilage damage caused by brief exposure of cartilage to blood, such as that occurring during intraarticular bleeding. Human articular cartilage was cultured for 4 days in the presence of blood (components; 7.5-50% volume/volume). The synthesis of cartilage matrix, as determined by proteoglycan synthesis (incorporation of 35SO4(2-)), was measured directly after exposure and after a recovery period of 20 days, during which the cartilage was cultured in the absence of blood or blood components. The production of the cytokines interleukin-1 (IL-1) and tumor necrosis factor a (TNFalpha), which have a destructive effect on cartilage, was determined by enzyme-linked immunosorbent assay, and the viability of chondrocytes was determined by measuring lactate dehydrogenase release and with electron microscopy. The involvement of oxygen metabolites was evaluated by using N-acetylcysteine. Brief exposure to blood resulted in dose-dependent inhibition of proteoglycan synthesis. The combination of mononuclear cells and red blood cells was responsible for this effect. The effect was irreversible, independent of IL-1 and TNFalpha production, and was accompanied by chondrocyte death. These effects were partially prevented by N-acetylcysteine. Brief exposure of cartilage to blood, as occurs after a single episode or a limited number of bleeding episodes, results in lasting cartilage damage in vitro, in which cytotoxic oxygen metabolites play a role.


An advanced strategy for efficient recycling of bovine bone: Preparing high-valued bone powder via instant catapult steam-explosion.
As the major byproduct of meat processing, bovine bone are produced in large amounts annually. However, the inefficient utilization with low-added value resulted in serious resource waste. The study aims to prepare high-value bovine bone power (BBP) via instant catapult steam-explosion (ICSE) treatment, taking ball milling (BM) method as control. Results showed that ICSE treatment deconstructed bovine bone with more holes emerging, and effectively promoted mineral dissolution and protein degradation while reduced energy consumption. Compared with BM-BBP, ICSE-BBP possessed more protein and essential minerals, presenting in regular elliptical shapes with narrow distribution of particle size (0.1 ∼ 40 μm), and owned better solution stability and protein solubility. ICSE-BBP also exhibited higher mineral release and protein digestibility during GI digestion while revealed no obvious cytotoxicity, indicating the potential applicability in nutrition-fortified foods. Taken together, ICSE technology holds promise in reusing bovine bone, providing an efficient and eco-friendly process for BBP industrial production.


Predicting RNA 5-Methylcytosine Sites by Using Essential Sequence Features and Distributions.
Methylation is one of the most common and considerable modifications in biological systems mediated by multiple enzymes. Recent studies have shown that methylation has been widely identified in different RNA molecules. RNA methylation modifications have various kinds, such as 5-methylcytosine (m5C). However, for individual methylation sites, their functions still remain to be elucidated. Testing of all methylation sites relies heavily on high-throughput sequencing technology, which is expensive and labor consuming. Thus, computational prediction approaches could serve as a substitute. In this study, multiple machine learning models were used to predict possible RNA m5C sites on the basis of mRNA sequences in human and mouse. Each site was represented by several features derived from k-mers of an RNA subsequence containing such site as center. The powerful max-relevance and min-redundancy (mRMR) feature selection method was employed to analyse these features. The outcome feature list was fed into incremental feature selection method, incorporating four classification algorithms, to build efficient models. Furthermore, the sites related to features used in the models were also investigated.


Historical Perspectives on the Removal of Intraradicular Posts Prior to the Availability of Ultrasonic Applications.
For decades the dismantling of previous dental work to correct inferior root canal procedures or to address recurrent dental caries has provided a significant amount of work for the restorative dentist. When coupled with teeth that have been root treated and also have an intraradicular post or dowel, the clinician was often presented with the challenge of post removal, without fracturing the root, and revision (retreatment) of the root canal procedures. While today's contemporary dentistry has the wherewithal to use ultrasonic devices to loosen and remove the post, this was not always the case historically, and creativity in this process was the hallmark of many of our predecessors.


Investigation of Phenolic Content in Five Different Pine Barks Species Grown in Turkey by HPLC-UV and LC-MS.
Investigation of phenolic content from different pine bark species grown in Turkey was performed using a reversed-phase high pressure liquid chromatography with ultraviolet (RP-HPLC-UV) method. All phenolic constituents were separated in <26 min on reversed-phase C18 column with gradient mobile phase that consists of orthophosphoric acid, methanol and acetonitrile. Detections were made on an UV detector at 280 nm and at a flow rate of 1 mL/min. Samples were prepared according to Masqueller's conventional sample preparation method with slight modifications. To avoid the reduction in extraction efficiency the sample preparation step was carried out under argon atmosphere. The linearity of the method was between 0.9994 and 0.9999. The detection limits for the five phenolic constituents ranged from 0122 to 0.324 mg/L. Catechin and taxifolin were found in all pine barks at a concentration of 0.065 ± 0.002-1.454 ± 0.004 and 0.015 ± 0.001-23.164 ± 0.322 mg/g, respectively. Epicatechin was determined in four pine barks between 0.027 ± 0.001 and 0.076 ± 0.002 mg/g, ferulic acid in two pine barks between 0.010 ± 0.001 and 0.022 ± 0.001 mg/g and epicatechin gallate in only one of the pine barks at 0.025 ± 0.001 mg/g. Finally, the total amount of phenolic compounds and antioxidant capacities of the pine barks were found to be very high.


Identification of Key Genes and Molecular Pathways in Keratoconus: Integrating Text Mining and Bioinformatics Analysis.
To identify the potential key genes and molecular pathways associated with keratoconus and allergic disease. The pubmed2ensembl database was used to identify the text mining genes (TMGs) collectively involved in keratoconus and allergic disease. The GeneCodis program was used to perform the Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of TMGs. The protein-protein interaction (PPI) network of the TMGs was established by STRING; the significant gene modules and hub genes of PPI were further performed using the Cytoscape software. The DAVID database was used to perform the GO and KEGG analyses of the significant module. In total, 98 TMGs collectively involved in keratoconus and allergic disease were identified. 19 enriched biological processes including 71 genes and 25 enriched KEGG pathways including 59 genes were obtained. A TMG PPI network was constructed, and 51 genes/nodes were identified with 110 edges; 3 most significant modules and 12 hub genes were chosen from the PPIs. GO enrichment analysis showed that the TMGs were primarily associated with collagen catabolic process, extracellular matrix organization and disassembly, cell adhesion and migration, collagen-containing extracellular matrix, extracellular matrix, and structure organization. KEGG pathway analysis showed that these DEGs were mainly involved in the IL-17 signaling pathway, inflammatory bowel disease, rheumatoid arthritis, allograft rejection, T cell receptor signaling pathway, cytokine-cytokine receptor interaction, and TNF signaling pathway. The results revealed that IL10, IL6, MMP9, MMP1, HGF, VEGFA, MMP3, MMP2, TGFB1, IL4, IL2, and IFNG were potential key genes involved in keratoconus. IL-17 signaling pathway was the potential pathways accounting for pathogenesis and development of keratoconus.


The effectiveness of popular, non-prescription weight loss supplements.
To review the evidence for the effectiveness of popular, non-prescription weight loss supplements. A detailed literature search including all relevant medical and supplementary medicine databases and evidence submitted from manufacturers. The theoretical basis and rationale for the use of each substance is considered along with available research in the published literature on effectiveness and potential risks. We classified the level of evidence represented by the main research studies on each substance. There is no good evidence for any weight loss benefits from most of the substances reviewed here. There is some support for mild effects of capsaicin, caffeine and fibre, but only in whole foods. In some cases (e.g., chitosan), there is a plausible theoretical basis for the product, but no supporting proof of effect in humans in the absence of a calorie-controlled diet. Possible synergistic effects of different ingredients cannot be dismissed, but cannot be assessed from current data. There is an absence of good quality research on many substances, which means that advertising claims may be misleading.


[Present status and research train of thoughts in integrative medicine on unstable plaque].
The changing of atherosclerosis (AS) plaque from stable to unstable is closely related to the incidence of cardio-cerebrovascular events. So, to stabilize AS plaque become the hot point of the modern study on prevention and treatment of cardio-cerebrovascular diseases. The formation of AS plaque is a very long and complicated process with the participation of many factors. However, inflammation reaction plays an important role in the formation and rupture of unstable plaque. Traditional Chinese medicine (TCM) shows latent therapeutic advantages in stabilizing AS plaque with its characteristics of multi-way, multi-link, and multi-target point and all-sided treatment as well as its rather milder adverse reactions. The paper gives a comparatively systematic retrospection of study on unstable plaque treated by integrated Chinese and Western medicine conducted in recent years. Combined with the related topics conducted by the authors, they raise the theory of "unstable plaque is induced by toxinduced by toxin and stagnation", and introduce the study on the intervention of unstable plaque by removing toxic substances and activating blood flow. They believe that the explorative study can provide objective experimental and clinical basis for TCM therapeutic method in stabilizing AS plaque.


Twin plane re-entrant mechanism for catalytic nanowire growth.
A twin-plane based nanowire growth mechanism is established using Au catalyzed Ge nanowire growth as a model system. Video-rate lattice-resolved environmental transmission electron microscopy shows a convex, V-shaped liquid catalyst-nanowire growth interface for a ⟨112⟩ growth direction that is composed of two Ge {111} planes that meet at a twin boundary. Unlike bulk crystals, the nanowire geometry allows steady-state growth with a single twin boundary at the nanowire center. We suggest that the nucleation barrier at the twin-plane re-entrant groove is effectively reduced by the line energy, and hence the twin acts as a preferential nucleation site that dictates the lateral step flow cycle which constitutes nanowire growth.


C19orf48 encodes a minor histocompatibility antigen recognized by CD8+ cytotoxic T cells from renal cell carcinoma patients.
Tumor regression has been observed in some patients with metastatic renal cell carcinoma (RCC) after nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). Cellular and molecular characterization of antigens recognized by tumor-reactive T cells isolated from responding patients could potentially provide insight into the mechanisms of tumor regression. CD8+ CTL clones that recognized a novel RCC-associated minor histocompatibility (H) antigen presented by HLA-A*0201 were isolated from two patients with metastatic RCC who experienced tumor regression or stable disease following nonmyeloablative allogeneic HCT. These clones were used to screen a cDNA library and isolate the unique cDNA encoding the antigen. An alternative open reading frame in the C19orf48 gene located on chromosome 19q13 encodes the HLA-A*0201-restricted minor H antigen recognized by the RCC-reactive T cells. The differential T-cell recognition of donor- and recipient-derived target cells is attributable to a nonsynonymous single-nucleotide polymorphism within the nucleotide interval that encodes the antigenic peptide. Assays for gene expression and CTL recognition showed that the C19orf48-encoded peptide is widely expressed in renal tumors and solid tumors of other histologies. The antigenic peptide can be processed for CTL recognition via both TAP-dependent and TAP-independent pathways. Donor T-cell responses against the HLA-A*0201-restricted minor H antigen encoded by C19orf48 may contribute to RCC regression after MHC-matched allogeneic HCT.


A fluorometric and colorimetric dual-signal nanoplatform for ultrasensitive visual monitoring of the activity of alkaline phosphatase.
Considering the limited sensitivity and accuracy of single-signal assay strategies, the multi-signal assay strategy has sparked significant excitement in recent years. In this study, for the first time, we reported a one-pot method in situ synthesis of carbon-containing nanoparticles (CNPs) via p-aminophenol (AP) and diethylenetriamine (DETA). The CNP solution exhibits yellow and light blue fluorescence under UV-light. Moreover, the CNPs exhibited excellent photoluminescence stability even under extreme conditions. Inspired by the alkaline phosphatase (ALP)-triggered specific catalytic reaction, we constructed an ultrasensitive fluorescence and colorimetric two-channel strategy for monitoring the ALP activity. By optimizing the detection parameters, the detection limits for both fluorometric and colorimetric were 0.05 mU mL-1. Moreover, the strategy showed high specificity and was successfully applied to monitor the ALP activity level in human serum samples. The analytical strategy opened a new window for the detection of the ALP activity, screening of the ALP inhibitor, and disease diagnosis.


Chronic dietary toxicity and oncogenicity evaluation of MCPA (4-chloro-2-methylphenoxyacetic acid) in rodents.
The chronic toxicity and oncogenicity of 4-chloro-2-methylphenoxyacetic acid (MCPA) were evaluated in Wistar rats at target doses of 20, 80, and 320 ppm for 2 years. Chronic effects were noted in male and/or female rats in the 80- and 320-ppm dose groups, namely elevations in triglycerides and serum glutamic transaminase levels. Nephrotoxicity was confined to male rats in the 320-ppm dose group. The systemic NOEL was determined to be 20 ppm for male and female rats. No oncogenic potential was observed. Doses in the 2-year oncogenicity study in mice were 20, 100, and 500 ppm. Kidney weight changes with corresponding minor histopathological findings in the kidney were evident in females in the 500-ppm dose group. MCPA was determined to have no oncogenic potential in B6C3F1 mice. In summary, there is no evidence of any oncogenic potential after dietary exposure of MCPA in rats or mice even at doses where limited chronic toxicity is seen.


An Adult with Polyneuropathy and Hypogonadism due to Poems Syndrome.
POEMS (acronym for polyneuropathy, organomegaly, endocrinopathy, M protein myeloma and skin changes), is a rare disease which occurs in the setting of plasma cell dyscrasias. We describe a case of an adult lady who presented with gradual onset weakness of all four limbs and multisystem involvement characterized by pedal edema, ascites, hyperpigmentation and hypogonadism. Nerve conduction study showed severe sensorimotor polyneuropathy. Serum immunofixation showed lambda light chain restricted monoclonal gammopathy. Bone marrow biopsy consistent with plasma cell dyscrasia. Hormonal assay showed decreased FSH, LH and estradiol levels which led us to diagnosis of hypogonadotrophic hypogonadism. The patient responded well to combination therapy of thalidomide, melphalan and dexamethasone. Eight months after the therapy, she noted decreased paresthesias and increased strength. She had reduced edema and ascites.


Comparative effects of cyclosporine A and FK-506 on endothelin secretion by a cultured renal cell line, LLC-PK1.
Cyclosporine A (CSA) stimulated endothelin secretion by a cultured renal epithelial cell line, LLC-PK1. A less nephrotoxic immunosuppressant (FK-506) did not affect endothelin secretion. Putative endothelin converting enzyme inhibitors or specific receptor antagonists may therefore prevent CSA nephrotoxicity.


Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics.
The nervous system is one of the most complex physiological systems, and central nervous system diseases (CNSDs) are serious diseases that affect human health. Ginseng (Panax L.), the root of Panax species, are famous Chinese herbs that have been used for various diseases in China, Japan, and Korea since ancient times, and remain a popular natural medicine used worldwide in modern times. Ginsenosides are the main active components of ginseng, and increasing evidence has demonstrated that ginsenosides can prevent CNSDs, including neurodegenerative diseases, memory and cognitive impairment, cerebral ischemia injury, depression, brain glioma, multiple sclerosis, which has been confirmed in numerous studies. Therefore, this review summarizes the potential pathways by which ginsenosides affect the pathogenesis of CNSDs mainly including antioxidant effects, anti-inflammatory effects, anti-apoptotic effects, and nerve protection, which provides novel ideas for the treatment of CNSDs.


A program to interest medical students in Changhua, Taiwan in the incorporation of visual arts in medicine.
Visual arts have been used to facilitate the teaching of the United States Accreditation Council for Graduate Medical Education (ACGME) competencies used in some countries. Some medical students may not appreciate the usefulness of incorporating arts in medical education. Therefore, arts programs that can interest medical students are necessary. We initiated and evaluated a visual arts program at the Changhua Christian Hospital in Changhua, Taiwan, with an aim to give the students a short review of visual arts and to interest them in the incorporation of arts in medicine. A total of 110 students in clerkship or internship participated in a visual arts program with emphasis on medicine-related visual arts. Content analysis of the data from the notes made by the instructor from direct observation of students; descriptions during discussions and the written feedback from students at the end of the program was used to evaluate the effect of the program. Anonymous questionnaires were also used for self-assessment of students. Qualitative analysis of the data revealed that the course was interesting to students. Themes emerged including its helpfulness to students in interpreting paintings, enhanced empathy, increased cultural awareness, enhanced observational skills, better team work, listening and communication skills and reduced stress. Ratings on the questionnaire showed similar results. Moreover, students had an increase in their confidence and desire to interpret paintings. The structured visual arts program, with emphasis on medicine-related visual arts and other humanities subjects, was able to attract the attention of medical students. It might be helpful to improve the required skills of ACGME competencies, but further studies are needed to support these conclusions.


A 66-Year-Old Female with Apical Hypertrophic Cardiomyopathy Presenting with Hypertensive Crises and Type 2 Myocardial Infarction and a Normal Coronary Angiogram.
A 66-year-old female presented to the emergency room with an episode of chest pain that lasted for a few minutes before resolving spontaneously. Electrocardiogram showed a left bundle branch block, left ventricular hypertrophy, and T wave inversions in the lateral leads. Initial cardiac troponin level was 0.15 ng/ml, with levels of 4 ng/ml and 9 ng/ml obtained 6 and 12 hours later, respectively. The peak blood pressure recorded was 195/43 mmHg. Echocardiogram with DEFINITY showed a small left ventricular cavity with apical hypertrophy, and coronary angiogram showed no stenotic or occluding lesions in the coronary arteries. The patient was admitted for a type 2 myocardial infarction with hypertensive crises. She was diagnosed with having apical hypertrophic cardiomyopathy, which is a variant of hypertrophic cardiomyopathy (HCM) in which the hypertrophy predominantly involves the apex of the left ventricle resulting in midventricular obstruction, as opposed to the left ventricular outflow tract obstruction seen in HCM. Patients with apical HCM may present with angina, heart failure, myocardial infarction, syncope, or arrhythmias and are typically managed with medications like verapamil and beta-blockers for those who have symptoms and antiarrhythmic agents like amiodarone and procainamide for treatment of atrial fibrillation and ventricular arrhythmias. An implantable cardioverter defibrillator (ICD) is recommended for high-risk HCM patients with a history of previous cardiac arrest or sustained episodes of ventricular tachycardia, syncope, and a family history of sudden death.


Crushing or splitting medications: unrecognized hazards.
Given the high use and the cost of medications in the current economy, one way older adults may save money on prescription costs is to split some of their medications in half. However, not all oral medications can be split. Splitting inappropriate medications such as extended-release tablets can be harmful and in some instances very dangerous. In addition to splitting medications, older adults who have difficulty swallowing pills may resort to crushing the medication for ease of administration. This option is also problematic and potentially harmful if the medication is not intended to be crushed. Clinicians managing the care of older adults need to discuss medication administration, clarify the dosing schedule, and clearly indicate the route of administration. Patients should be cautioned not to split or crush a medication without checking with the health care provider or pharmacist.


A simple micellar electrokinetic capillary chromatographic method for the quantitative analysis of organic expectorants.
A simple and rapid micellar electrokinetic capillary chromatographic method is described for the separation and quantification of five expectorant drugs, including ambroxol (AMB), bromhexine (BRM), carbocysteine, guaiacol and guaifenesin. The drugs were separated in a mixed solution of phosphate buffer (35 mM; pH 3.90) and acetonitrile (75:25, v/v) with sodium dodecylsulfate (120 mM) as the micellar source, and the separated drugs were directly monitored with UV detector (200 nm). Several key parameters affecting the separation and analysis of the drugs were studied and optimized. Based on the corrected peak-area ratios of the drugs to an internal standard (7-hydroxy-4-methyl-coumarin) versus the concentration of the drugs, the established method is applicable to quantify AMB and BRM each over 20-150 microM, carbocysteine over 100-1500 microM, guaiacol and guaifenesin each over 10-150 microM. The detection limits (S/N=3; 0.5 psi, 5 s injection) of the method for the analytes are in the range of 3.0-5.0 microM (except that of carbocysteine at 30 microM). The precision (relative standard deviation) and accuracy (relative error) of the method for the intra-day (n=3) and inter-day (n=5) analyses of the analytes at three levels are all below 4%. The method is speedy with a run time of about 6 min for the analysis of the five analytes. Application of this method to the analysis of AMB and BRM in pharmaceutical preparations or AMB in the urine of a dosed subject proved simple and effective.


Shared aperture for two beams of different wavelength using reflective phase gratings and the Talbot effect.
A shared aperture system for two laser beams with different wavelengths and composed entirely of reflective phase gratings is described. Beams that share an aperture are collinear, and they have the same transverse phase profile across the aperture as their respective sources. Using the Talbot effect that is observed in Fresnel diffraction from periodic objects, we preserve the phase of the beams, and we maximize the efficiency of the system. An experimental Talbot shared aperture system using He-Ne and He-Cd beams has an efficiency of 88.1% for the He-Ne beam and 70.3% for the He-Cd beam. These measured efficiencies agree well with theoretical predictions and computer simulations.


Structural differences of ovalbumin and S-ovalbumin revealed by denaturing conditions.
We found, by circular dichroism and Raman spectroscopy measurements, that the secondary structure of the native ovalbumin and of its heat-stable form, called S-ovalbumin, is a probe of the structural differences between the two proteins. Small angle X-ray scattering and circular dichroism measurements performed on the two proteins under denaturing conditions, with different concentrations of guanidine hydrochloride, show the changes of the tertiary and secondary structure and a different pathway in the unfolding process. These experimental data confirm that the conversion of native ovalbumin into S-ovalbumin is irreversible and reveal that the response of the two proteins to the same chemical environment is different.


Reduction in surgical innovation, 1988 to 2006.
We hypothesize that increasing regulation of human subject research has reduced the number of published reports of surgical innovation in otolaryngology. A systematic review of a predetermined subset of otolaryngology literature. We randomly selected half of the articles published in 1988 and 2006 in three prominent journals. After identifying information was concealed, abstracts were classified independently by two authors into three groups: innovation, modification, or neither. Disagreements were resolved by a third author who read the entire article. Proportions were compared with chi(2) analysis. The proportion of articles classified as innovation or modification decreased significantly from 67 of 367 (18.3%) in 1988 to 59 of 548 (10.8%) in 2006 (P = 0.001). The elimination of radiology and pathology quiz cases yielded similar results: 11.1 percent vs 18.9 percent, P = 0.001. Innovation or modification in animal model research also decreased (0.9% vs 3.8%, P = 0.003). Overall, only 4 articles were actually classified as true innovation. The frequency of true innovation was low in both years, but articles that described surgical modifications decreased significantly over this 18-year period. One reason may be increased administrative barriers for clinical research approval. Although our analysis cannot determine cause and effect, it is an important finding that deserves further study.


Seasonal changes in plasma concentrations of immunoreactive inhibin and testicular activity in male Japanese monkeys.
Seasonal changes in plasma immunoreactive (ir-) inhibin, testosterone, LH, and FSH concentrations were examined in five sexually mature male Japanese monkeys (Macaca fuscata fuscata) housed indoors individually, to explore the reproductive cyclicity in the male. Blood samples were collected monthly throughout one year, and testicular size, semen volume, and number of sperm in the semen were ascertained at the same time in the same animals. Semen samples were obtained by penile electrostimulation. The results showed a clear seasonal increase in all parameters: plasma ir-inhibin, testosterone, testicular size, semen volume, and total number of sperm in the liquid portion of the semen during the autumn and winter months in synchrony with the natural breeding season. In contrast, plasma LH and FSH remained unchanged throughout the year, although plasma FSH tended to increase during the breeding season concomitant with an increase in plasma ir-inhibin. A significant positive correlation between FSH and ir-inhibin was observed in two of five monkeys. The positive correlations between plasma ir-inhibin and testicular activities during both the developing and regressing phases of the testicular cycle indicate that plasma ir-inhibin is a useful indicator of testicular activity as well as an indicator of Sertoli cell function in the Japanese monkey.


Clinical Utility of the Prenatal BACs-on-Beads™ Assay in Invasive Prenatal Diagnosis.
Background: The prenatal BACs-on-Beads™ (PNBoBs™) assay has been applied worldwide for prenatal diagnosis. However, there are neither guidelines nor consensus on choosing patients, sample types, or clinical pathways for using this technique. Moreover, different perspectives have emerged regarding its clinical value. This study aimed to evaluate its clinical utility in the context of clinical practice located in a prenatal diagnostic center in Xiamen, a city in southeast China. Methods: We tested 2,368 prenatal samples with multiple referral indications using both conventional karyotyping and PNBoBs™. Positive results from PNBoBs™ were verified using current gold-standard approaches. Results: The overall rates for the detection of pathogenic copy number variation (pCNV) by karyotyping and PNBoBs™ were 1.9% (46/2,368) and 2.0% (48/2,368), respectively. The overall detection rate of karyotyping combined with PNBoBs™ for pCNV was 2.3% (54/2,368). A total of 13 cases of copy number variation (CNV)with a normal karyotype were detected by PNBoBs™. Another case with a normal karyotype that was detected as a CNV of sex chromosomes by PNBoBs™ was validated to be maternal cell contamination by short tandem repeat analysis. Conclusion: Karyotyping combined with PNBoBs™ can improve both the yield and efficiency of prenatal diagnosis and is appropriate in the second trimester in all patients without fetal ultrasound anomalies who undergo invasive prenatal diagnosis.


Impaired glutathione-conjugating capacity by cryopreserved human and rat hepatocytes.
The activity of glutathione transferase was measured in sonicates of fresh rat hepatocytes and of cryopreserved rat, human and dog hepatocytes in the presence of added glutathione and by using 1-chloro-2,4-dinitrobenzene (CDNB) as non-selective substrate. The glutathione-conjugating capacity was also investigated in the presence of CDNB alone (without glutathione) with intact fresh rat hepatocytes and cryopreserved rat and human hepatocytes. Finally, the intracellular level of glutathione was measured in these hepatocytes. The specific activity of glutathione transferase in sonicates of fresh rat hepatocytes (in the presence of added GSH and CDNB) was about 415 nmol/min/10(6) cells. The corresponding activities in cryopreserved rat, human and dog hepatocytes were approximately 320, 440 and 540 nmol/min/10(6) cells, respectively. In contrast, glutathione conjugation by the intact cryopreserved human and rat hepatocytes in the presence of CDNB alone was less than 10% of the corresponding conjugation by fresh rat hepatocytes, indicating that glutathione was depleted in these cryopreserved hepatocytes. Glutathione depletion was confirmed after analytical measurement of the glutathione levels in fresh and cryopreserved hepatocytes. In fresh rat hepatocytes the level of glutathione was 44 nmol/10(6) cells, whereas it was 2.5 and 4.4 nmol/10(6) cells in cryopreserved rat and human hepatocytes, respectively. In summary, glutathione transferase was active in these cryopreserved hepatocytes but the cryopreservation procedure likely causes depletion in the intracellular level of glutathione, resulting in an overall reduced glutathione conjugating capacity.


Ribavirin effect on experimental Junin virus-induced encephalitis.
Junin virus, the etiological agent of Argentine hemorrhagic fever, produces in man a disease mainly characterized by hemorrhagic alterations, commonly accompanied by neurological symptoms, and leading to 10% mortality. Intracerebral inoculation in 10-day-old rats or intraperitoneal inoculation in 2-day-old rats leads to high mortality due to severe encephalitis. Here, the effect of Ribavirin on these experimental models was tested in order to evaluate the degree of protection achieved against neuropathological manifestations. In intracerebrally infected 10-day-old rats the drug was administered 2 hr before virus inoculation. Doses ranged from 30 to 90 mg/kg body weight. Protection reached 40% for the 60 and 90 mg doses. Intraperitoneally infected 2-day-old rats received the drug in five 30-mg daily doses, starting the same day as virus inoculation. Survival was 73%. Viral replication within peritoneal macrophages dropped markedly, leading to much lower CNS viral titres. Together with results reported in primates, our findings support further studies on Ribavirin, with a view to eventual trials in humans.


Solution and gas-phase acidities of all-trans (all-E) retinoic acid: an experimental and computational study.
Retinoic acid is of fundamental biological importance. Its acidity was determined in the gas phase and in acetonitrile solution by means of mass spectrometry and UV/Vis spectrophotometry, respectively. The intrinsic acidity is slightly higher than that of benzoic acid. In solution, the situation is opposite. The experimental systems were described theoretically applying quantum chemical methods (wave function theory and density functional theory). This allowed the determination of the molecular structure of the acid and its conjugate base, both in vacuo and in solution, and for computational estimates of its acidity in both phases.


[Acne infantum as presenting symptom of congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency].
Infantile acne is a rare condition which usually begins after the third month of life and appears mainly on the cheeks. Spontaneous healing typically occurs within 2 years. A 2-year-old boy developed acne infantum during the first days after birth; it failed to respond to topical treatment. Detailed physical examination and endocrinologic evaluation confirmed the presumed diagnosis of congenital adrenal hyperplasia (CAH), and showed it was caused by 11-beta-hydroxylase deficiency. CAH comprises a group of autosomal-recessively inherited disorders. These hereditary enzyme defects in steroid biosynthesis cause glucocorticoid deficiency and an overproduction of biosynthetic precursor steroids. Adrenal androgen biosynthesis is not impaired but shows a massive reactive overproduction due to the increased ACTH secretion within the up-regulated hypothalamo-pituitary-adrenal system. The characteristic features of CAH in male infants are demonstrated on the basis of this case report.


The extremely high diversity of Collembola in relict forests of Primorskii Krai of Russia.
The diversity of soil animals of relict forest ecosystems in East Asia continues to be insufficiently studied and almost not represented in international databases, including GBIF. This article is based on 7550 records of 175 species which were collected in Ussuriiskii, Sikhote-Alinskii and Kedrovaya Pad' natural reserves of Russian Far East in 2016-2017. A multi-scale sampling design allowed us to estimate population densities and local species richness of Collembola at areas of different sizes. The work continues the digitization of the collections of the Moscow Pedagogical State University (MPSU) and their publication through GBIF.org, which began in 2019. This article is based on original data including 2377 specimens of springtails from eight forests and 648 soil cores. Within the framework of modern taxonomy, this work represents the first publication of lists of Collembola species of forests of Primorsky Krai. The work focused on the relict protected cedar-deciduous forests. Nine species new to science were described and data on the fauna of the region were significantly revised. Considerable contribution was made to the biogeography of Collembola of East Asia. The design of the sampling allowed us to draw conclusions about the species saturation of springtails at various spatial scales within the habitat: from a few square cm to 100 sq. m. Number of species reached record high values reflecting the benchmark state of Collembola communities of undisturbed old temperate forest ecosystems.


Economic and workload impact of therapeutic interchange of inhaler medications and nebulizer solutions.
To examine the financial impact of automatic formulary substitution of nebulization solutions for pressurized metered dose inhalers and dry powder inhalers and the effect of the automatic substitution initiative on respiratory care practitioner (RCP) workload at a community hospital. A retrospective observational study was conducted in a 326-bed nonacademic community hospital. Adult patients who received respiratory medications and had an inpatient stay, were admitted for observation, or had an emergency room visit from December 2016 through February 2017 (the control group) or from December 2017 through February 2018 (the study group) were included in the analysis. The primary outcomes were the cost of respiratory medications per hospital stay and the number of RCP visits per hospital stay. The secondary outcome was the cost of wasted doses per hospital stay. A total of 3,766 patients were included in the study: 2,030 in the study group and 1,736 in the control group. The mean cost of respiratory medications per hospital stay was significantly lower in the study group vs the control group ($13.29 vs $36.48, P < 0.001). The mean number of RCP visits per hospital stay was also statistically lower in the study group vs the control group (11.6 vs 12.9, P = 0.04). The mean cost of wasted doses was significantly lower in study group vs the control group ($0.25 vs $22.91, P < 0.001). Automatic formulary substitution of nebulization solutions for inhaler medications significantly decreased medication costs without increasing the average number of RCP visits per hospital stay.


Endocrine tumors associated with neurofibromatosis type 1, Peutz-Jeghers syndrome and other familial neoplasia syndromes.
Endocrine tumors are a less common but important component of the clinical spectrum of a number of hereditary tumor syndromes such as neurofibromatosis type 1, Peutz-Jeghers syndrome, Beckwith-Wiedemann syndrome, the tuberous sclerosis complex, Li-Fraumeni syndrome, PTEN hamartoma tumor syndrome, and APC-associated polyposis. It is important to recognize the often unique clinical presentations of these tumors and possible strategies for presymptomatic screening and early diagnosis.


Distinct role of Pyk2 in mediating thromboxane generation downstream of both G12/13 and integrin αIIbβ3 in platelets.
Proline-rich tyrosine kinase 2 (Pyk2) is activated by various agonists in platelets. We evaluated the signaling mechanism and the functional role of Pyk2 in platelets by using pharmacological inhibitors and Pyk2-deficient platelets. We found that platelet aggregation and secretion in response to 2-methylthio-ADP (2-MeSADP) and AYPGKF were diminished in the presence of Pyk2 inhibitors or in Pyk2-deficient platelets, suggesting that Pyk2 plays a positive regulatory role in platelet functional responses. It has been shown that ADP-, but not thrombin-induced thromboxane (TxA2) generation depends on integrin signaling. Unlike ADP, thrombin activates G12/13 pathways, and G12/13 pathways can substitute for integrin signaling for TxA2 generation. We found that Pyk2 was activated downstream of both G12/13 and integrin-mediated pathways, and both 2-MeSADP- and AYPGKF-induced TxA2 generation was significantly diminished in Pyk2-deficient platelets. In addition, TxA2 generation induced by co-stimulation of Gi and Gz pathways, which is dependent on integrin signaling, was inhibited by blocking Pyk2. Furthermore, inhibition of 2-MeSADP-induced TxA2 generation by fibrinogen receptor antagonist was not rescued by co-stimulation of G12/13 pathways in the presence of Pyk2 inhibitor. We conclude that Pyk2 is a common signaling effector downstream of both G12/13 and integrin αIIbβ3 signaling, which contributes to thromboxane generation.


A six-minute walk test for assessing exercise tolerance in severely ill children.
The primary objective of this study was to compare exercise tolerance, heart rate, and oxyhemoglobin saturation (Sao2) between a traditional progressive maximal exercise test and a self-paced, 6-minute walk test in severely ill children. Seventeen patients (9 to 19 years of age) performed a progressive maximal exercise test on a cycle ergometer and a self-paced, 6-minute walk test as part of the evaluation for possible heart, lung, or combined heart and lung transplantation. Physical work capacity and peak oxygen uptake were measured during the progressive cycle test. The walk test was performed in a hospital corridor, with patients trying to cover as much distance as possible in 6 minutes at their own pace. Oxyhemoglobin saturation and heart rate were monitored continuously by pulse oximetry and compared between the two tests. The distance walked in 6 minutes correlated with peak oxygen uptake (r = 0.70, p < 0.01) and physical work capacity (r = 0.64, p < 0.005). The minimum (Min) Sao2 on the bike test correlated significantly with Min Sao2 on the walk test (r = 0.82, p < 0.001), with 11 of 17 patients having a lower Min Sao2 on the walk test than the bike test (mean Min Sao2, 84% and 86%, respectively). The peak heart rate did not correlate significantly between the bike and walk tests (r = 0.25), although significantly lower (p < 0.01) values were observed on the walk (148 beats/min) than bike (169 beats/min) test. The results suggest that the 6-minute self-paced walk test may provide an alternative method for assessing functional capacity in severely ill children, and that Sao2 measured during progressive exercise testing on a cycle ergometer may not reflect the degree of oxyhemoglobin desaturation during self-paced walking in some patients with severe cardiopulmonary disease.


[Electrocochleographic analysis of the suppression of tinnitus by electrical promontory stimulation and changes in compound action potentials].
We performed Electrical Promontory Stimulation (EPS) for the suppression of tinnitus in 52 patients and measured Compound Action Potentials (CAP) using electrocochleography before and after EPS. We examined the relation between residual inhibition and CAP. The purpose of this study was to investigate the origin and mechanism of suppression of tinnitus. Tinnitus was suppressed in 27 patients (52%) after EPS. In the group of patients in which we suppressed tinnitus, the CAP amplitudes increased from 3.0 +/- 1.5 microV to 3.2 +/- 1.6 microV (p < 0.05), the loudness of tinnitus was reduced from 7.3 +/- 4.7 dBSL to 5.6 +/- 5.1 dBSL (p < 0.05) and the CAP latencies did not exhibit remarkable change. In the group of patients in which we did not suppress tinnitus, the CAP amplitudes, latencies and the loudness of tinnitus did not change remarkably. These data indicate that EPS affects auditory nerve fibers directly. It was reported that EPS is effective for tinnitus of peripheral origin and not for that of central origin and, that in tinnitus of peripheral origin, the spontaneous discharges of the auditory nerve increase in number. It is hypothesized that EPS affects auditory nerve fibers and suppresses tinnitus by synchronizing these spontaneous discharges. Side effects of EPS were cough and discomfort of the throat, nose, lips and oral cavity. These effects were observed only during electrical stimulation and there were no permanent side effects. In conclusion, EPS affects auditory nerve fibers directly, is effective for tinnitus of peripheral origin and is not associated with serious complications.


Prevalence, Antibiogram, and Multidrug-Resistant Profile of E. coli O157: H7 in Retail Raw Beef in Addis Ababa, Ethiopia.
Escherichia coli O157:H7 is an emerging foodborne pathogen of public health importance. The objectives of this study were to estimate the prevalence and evaluate the antimicrobial susceptibility pattern and multidrug-resistant profile of E. coli O157:H7 isolated from raw beef sold in butcher shops in Addis Ababa, Ethiopia. A total of 384 raw beef samples were collected from randomly selected butcher shops across the 10 sub-cities of Addis Ababa. E. coli O157:H7 was isolated following ISO-16654:2001 standard, and isolates were tested for resistance to 13 antimicrobial agents using the Kirby-Bauer disk diffusion method. Out of the 384 retail raw beef samples examined, 14 (3.64%) (95% CI = 1.77-5.51%) carried E. coli O157:H7 serotype. Of the 14 E. coli O157:H7 isolates, 8 (57.14%) were found to be resistant to three or more antimicrobial categories. The frequency of resistant phenotype was more common for ampicillin (92.8%), nitrofurantoin (92.8%), and tetracycline (50%). Multidrug-resistant E. coli O157:H7 were present in raw beef sold in butcher shops in Addis Ababa. Thus, more stringent monitoring of antimicrobial use in both human and animal populations should be implemented. In addition, further studies should be conducted to understand the E. coli O157:H7 points of contamination and define appropriate risk mitigation strategies.


The role of achievement goal orientations and perceived ability upon somatic and cognitive indices of sport competition trait anxiety. A study of young athletes.
Goal orientation theory and competence motivation theory were used to examine the relationships between young athletes' achievement goals and indices of somatic and cognitive trait sport competition anxiety. Included in these analyses were also the potential mediating and moderating role of the athletes' perceived competence in sport. We examined 136 young athletes aged 13 to 18 years involved in organized sport within a community in northern Norway. Whereas no association was found between an ego oriented achievement goal and indices of anxiety, multiple regression analyses revealed that both a high task goal orientation and high perceived sport competence predicted a reduced tendency to report cognitive anxiety when competing in sport. In addition, athletes who perceived their competence in sport as high were found to be less predisposed to experiencing somatic anxiety in the form of elevated physiological arousal when competing than those who doubt their competence. The results further showed that perceived competence did not mediate or moderate the relationships between achievement goal orientations and somatic and cognitive indices of trait sport competition anxiety. The findings suggest that being task oriented in sport as well as having a sense of being competent are important in order to prevent sport competitions giving rise to elevated cognitive anxiety in young athletes.


Aortic valve replacement: better myocardial protection by cold or warm retrograde blood cardioplegia?
To determine whether warm blood cardioplegia (BCP) is superior to cold BCP in terms of myocardial protection, we compared warm (37 degrees C) and cold (4 degrees C) continuous retrograde administration of BCP in 40 patients undergoing aortic valve replacement (AVR) in a prospective, randomized study. The main subjects of investigation were the myocardial oxygen consumption and the maintenance of the ultrastructure of the tissue. In addition, we looked at intraoperative recordings of time, heart rhythm disturbances, CK/MB serum levels, and inotropic support. We found, that oxygen consumption is significantly higher during warm BCP (7.95-10.38 ml/min) than during cold BCP (2.11-3.47 ml/min). Mild, reversible myocardial damage occurs during cold and warm BCP. The intraoperative serum potassium level was significantly higher after warm (7.25 mmol/l) than after cold (6.55 mmol/l) BCP. There was no statistically significant difference in the duration of extracorporeal circulation and of cardiac arrest, the CK/MB serum level or the recorded right and left ventricular performance data in the two groups. We conclude that continuous retrograde warm BCP is not superior to continuous retrograde cold BCP as far as myocardial protection is concerned. The administration of cold BCP prolongs the tolerated ischemic time of the myocardium and provides a higher safety margin.


The emotional and psychological impact of mass casualty incidents on forensic odontologists.
Motivated by the findings of a previous research project, 38 forensic odontologists with known occupational experience of mass casualty incidents completed a questionnaire designed to elicit both quantitative and qualitative data. The questionnaire sought to provide an insight into the psychological and emotional impact of conducting work of this nature. Two psychometric scales were included in the questionnaire, The Positive and Negative Affect scale (PANAS) and the Impact of Events Scale (IOE). In addition, a number of open-ended questions relating to the personal experiences of the respondent during the mass casualty incident were also included. Quantitative findings indicate that on the whole mass casualty incidents resulted in a positive experience for the respondents, although over a third reported being distressed, upset or irritable at some time during the event. Sense of achievement and camaraderie were among the qualitative themes elicited that help explain the positive reactions. Working conditions, politics and the ictims were cited as sources of negativity.


Liquid-liquid extraction of alkali metal ions with photochromic crowned spirobenzopyrans.
On the liquid-liquid extraction using 1,2-dichloroethane as an organic solvent, the crowned spirobenzopyrans exhibited textractability in the following order: Li+ >> Na+ > K+ > or = tetramethylammonium ion (TMA+), Li+ > Na+ >> K+ > TMA+, and Na+ > K+ >> Li+ > TMA+ for spirobenzopyran derivatives bearing monoaza-12-crown-4, 1; monoaza-15-crown-5, 2; and monoaza-18-crown-6, 3; respectively, under dark conditions. The ion selectivity of 1 depends on the metal-ion complexing ability of monoaza-12-crown-4. Even 2, which carries a 15-crown-5 moiety, showed Li+ selectivity because of the much stronger interaction of Li+ with the phenolate ion of the merocyanine form of 2 than that of Na+. The Na+ selectivity of 3 is also attributed to the ionic interaction with the phenolate ion of the merocyanine form, since the ionic interaction prefers Na+ to K+ regardless of the higher affinity of the 18-crown-6 ring itself to the latter ion. The Li+ extraction into the organic phase with 1 was enhanced by UV irradiation (300-400 nm), while some depression in the extraction was found by visible irradiation (>500 nm). The effect of visible irradiation on the Li+ complexing ability of 1 was also examined with electrospray ionization mass spectrometry.