Upper gastrointestinal bleeding.
Bleeding in the upper gastrointestinal tract is a problem that confronts all physicians involved in primary patient care. It continues as one of the most common acute medical management problems, leads to substantial morbidity and mortality, and presents both diagnostic and therapeutic challenges to the physician. The purpose of this paper is to provide an overview of the common causes of upper gastrointestinal bleeding and to discuss initial assessment, diagnosis, management, and, where possible, prevention.


Collagen biosynthesis in bleomycin-induced pulmonary fibrosis in hamsters.
Bleomycin results in pulmonary interstitial fibrosis characterized by accumulation of collagen. We studied the mechanisms of this accumulation in hamsters 4 to 24 days after intratracheal injection of 1 U of bleomycin. Lung collagen was significantly increased within 11 days. Collagen synthesis was increased 10-fold in explant cultures obtained 8 days after injection. Prolyl hydroxylase activity and the degradation of newly synthesized collagen were also increased proportionally to collagen synthesis. Total protein synthesis also increased but not as much as collagen synthesis. We conclude that the accumulation of collagen in the lung following proceeds from an increased rate of collagen synthesis that is maximal early after injection and persists for at least 24 days after exposure.


The in vitro effect of ivermectin on the activity of trehalose synthesis pathway enzymes and their mRNA expression in the muscle of adult female Ascaris suum (Nematoda).
The in vitro effect of ivermectin lethal dose on the activity of trehalose-6-phosphate synthase (TPS) and phosphatase (TPP) and the expression of their mRNA (tps1, tps2, and tpp genes) in the muscle of adult female Ascaris suum was investigated. The presence of ivermectin in the medium caused a decrease in TPS and TPP activities during the experiment compared with the start and control groups. The exception was the group of worms grown for 8 hours in a IVM solution, in which there was a little higher TPS activity than in the control. Real-time qPCR analysis showed reduced expression of tps1 and tps2, and unchanged tpp expression after 20 hours of incubation relative to the expression at time zero. Relative to the appropriate control groups, the expression of tps2 gene was slight increased but the other two genes were reduced after 8-hours of IVM-treatment. Then the expression of all three genes was lower at the end of cultivation. The level of gene expression was positively correlated with the activity of specific enzymes. In the case of tpp gene there was only a weak correlation. Prolonged exposure to ivermectin was effective in lowering TPS and TPP activity and their mRNA expression. However, the drug did not block the pathway.


Impaired interaction of platelets with endothelial progenitor cells in patients with cardiovascular risk factors.
Recent studies indicate that platelets influence endothelial progenitor cell (EPC) recruitment to sites of vascular injury and promote their differentiation to an endothelial phenotype. Patients with cardiovascular risk factors (CVRF) demonstrate a reduced number and impaired function of EPC, as well as platelet hyper-reactivity. Therefore, we investigated the interaction of platelets and EPC from patients with CVRF. Co-incubation of platelets and peripheral blood mononuclear cells, both from healthy volunteers, dose-dependently increased the number of adherent EPC. In contrast, patient-derived platelets failed to augment the number of adherent and migrating healthy and patient-derived EPC. However, co-incubation of platelets from healthy donors with mononuclear cells from patients with CVRF significantly enhanced the number of EPC, indicating that platelets from healthy volunteers are able to partially rescue the impairment of patient-derived EPC formation. Likewise, healthy donor-derived platelets augmented the impaired migration and clonal capacity of patient-derived EPC. Analysis of individual CVRF of platelet donors revealed that only diabetes mellitus inversely correlated with EPC number, colony formation and migration. The platelet supernatants from healthy volunteers that significantly increased EPC number contained IL-6, SDF-1, sCD40L and PDGF. While sCD40L and PDGF levels were comparable in platelet supernatants from healthy volunteers and patients with CVRF, the release of IL-6 and SDF-1 by patient-derived platelets was rather increased, thus, indicating that these soluble factors are not mediating the effect of platelet supernatants. Healthy volunteer-derived platelets provide a source of soluble factors to improve the number and function of EPC from patients with cardiovascular risk factors, particularly diabetes mellitus.


Insulin signaling in development.
Nutrient intake is obligatory for animal growth and development, but nutrients alone are not sufficient. Indeed, insulin and homologous hormones are required for normal growth even in the presence of nutrients. These hormones communicate nutrient status between organs, allowing animals to coordinate growth and metabolism with nutrient supply. Insulin and related hormones, such as insulin-like growth factors and insulin-like peptides, play important roles in development and metabolism, with defects in insulin production and signaling leading to hyperglycemia and diabetes. Here, we describe the insulin hormone family and the signal transduction pathways activated by these hormones. We highlight the roles of insulin signaling in coordinating maternal and fetal metabolism and growth during pregnancy, and we describe how secretion of insulin is regulated at different life stages. Additionally, we discuss the roles of insulin signaling in cell growth, stem cell proliferation and cell differentiation. We provide examples of the role of insulin in development across multiple model organisms: Caenorhabditis elegans, Drosophila, zebrafish, mouse and human.


[Transcutaneous oxygen tension measurement in pediatrics (author's transl)].
The development of a new electrode by A. Huch, R. Huch, and D. Lübbers to measure the arterial oxygen tension transcutaneously (tcPo2) has provided the opportunity for continuous monitoring in critically ill children. For the first time it is possible to monitor oxygen therapy and to minimize considerably the risk of oxygen therapy. With this technique respirator therapy can be managed much more critically and effectively. Changes in PaO2 are recognized within seconds and dangerous hyper- and hypoxias can be corrected immediately. We demonstrated that there exist different heart rate patterns with hypoxemia; these changes normally are not recognized with convential methods. The significance of the silent heart rate pattern has not yet been established. As there are no problems now with the manufacturing of the electrodes, we hope that this excellent method will be used wherever critically ill children are treated.


Integrative study reveals the prognostic and immunotherapeutic value of CD274 and PDCD1LG2 in pan-cancer.
Background: Disorders of CD274 and PDCD1LG2 contribute to immune escape in human cancers, and treatment with anti-programmed death receptor 1 (PD-1) has been widely used in recurrent or metastatic tumors. However, integrated studies considering CD274 and PDCD1LG2 across cancers remain limited. Materials and Methods: Differences in expression levels of CD274 and PDCD1LG2 were analyzed in diverse cancer types using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The clinical information and matched expression profiles of TCGA patients were obtained to determine the prognostic value of CD274 and PDCD1LG2. Moreover, correlations between CD274 and PDCD1LG2 and the immune signature were analyzed by exploring the TIMER2 and TISIDB databases. We also investigated correlations between CD274 and PDCD1LG2 and immunotherapeutic biomarkers, including mismatch repair (MMR), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA methylation. Results: Expression levels of CD274 and PDCD1LG2 varied across multiple cancer types. CD274 and PDCD1LG2 not only impacted the prognosis of patients with cancer but were associated with clinical characteristics (lymph node metastasis, tumor stage, and sex) in kidney renal papillary cell carcinoma, thyroid carcinoma, and some other cancer types. Typically, CD274 and PDCD1LG2 could be strongly correlated with macrophages, dendritic cells, neutrophils, and CD8+ T-cells. Furthermore, CD274 and PDCD1LG2 expression were associated with various immunosuppressive biomarkers, such as CTLA4, TIGIT, and LAG3. In addition, CD274 and PDCD1LG2 were significantly associated with MMR, TMB, MSI, and DNA methylation. Finally, enrichment analysis confirmed that CD274 and PDCD1LG2 were associated with numerous biological pathways, such as: "Activation of Immune Reactions" and "Epithelial-Mesenchymal Transition," suggesting that CD274 and PDCD1LG2 play crucial roles in cancer immunity and tumor metastasis. Conclusion: CD274 and PDCD1LG2 play critical roles in cancer progression and immune response and could serve as effective biomarkers to predict the prognosis and immune signature of cancer.


Molecular characterization of SUT Gene Family in Solanaceae with emphasis on expression analysis of pepper genes during development and stresses.
Sucrose, an essential carbohydrate, is transported from source to sink organs in the phloem and is involved in a variety of physiological and metabolic processes in plants. Sucrose transporter proteins (SUTs) may play significant parts in the phloem loading and unloading of sucrose. In our study, the SUT gene family was identified in four Solanaceae species (Capsicum annuum, Solanum lycopersicum, S. melongena, and S. tuberosum) and other 14 plant species ranged from lower and high plants. The comprehensive analysis was performed by integration of chromosomal distribution, gene structure, conserved motifs, evolutionary relationship and expression profiles during pepper growth under stresses. Chromosome mapping revealed that SUT genes in Solanaceae were distributed on chromosomes 4, 10 and 11. Gene structure analysis showed that the subgroup 1 members have the same number of introns and exons. All the SUTs had 12 transmembrane structural domains exception from CaSUT2 and SmSUT2, indicating that a structure variation might occurred among the Solanaceae SUT proteins. We also found a total of 20 conserved motifs, with over half of them shared by all SUT proteins, and the SUT proteins from the same subgroup shared common motifs. Phylogenetic analysis divided a total of 72 SUT genes in the plant species tested into three groups, and subgroup 1 might have diverged from a single common ancestor prior to the mono-dicot split. Finally, expression levels of CaSUTs were induced significantly under heat, cold, and salt treatments, indicating diverse functions of the CaSUTs to adapt to adverse environments.


Hazardous substances in separately collected grey- and blackwater from ordinary Swedish households.
The objective of this paper is to present the mass flows of a number of selected hazardous substances in raw, separate grey- and blackwater from ordinary Swedish households. The Vibyasen housing area was selected for the investigation since its wastewater system has separate flows for grey- and blackwater. Due to the high analytical costs, a limited number of hazardous substances had to be selected and the number of samples restricted. The greywater flow was manually measured and the samples were collected at set time intervals. The blackwater samples were randomly collected from a blackwater tank. A total of 105 selected hazardous substances were measured in both fractions. Of the 24 elements (Ca, Fe, K, Mg, Na, S, Al, Ag, As, Ba, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Pt, Sb, Sn, Te, Zn) measured in both fractions, 22 were detected in the greywater and 23 in the blackwater. 81 organic substances were selected and measured in both fractions (nonylphenol- and octylphenol ethoxylates, brominated flame-retardants, organotin compounds, PAH, PCB, phthalates, monocyclic aromatics, and triclosan). 46 organic substances were found in greywater and 26 in blackwater. PCB was the only group found in neither grey- nor blackwater. The greywater flow fluctuated, with a specific average flow of 66 L per person and day. The composition of blackwater also fluctuated, with shifting proportions of urine, faeces, and flush water. The specific average blackwater flow was 28.5 L per person and day. The mixture of substances in separate wastewater fractions from Swedish households was too complex to exactly distinguish their specific sources.


Point of care testing: randomised controlled trial of clinical outcome.
To describe the proportion of patients attending an accident and emergency department for whom blood analysis at the point of care brought about a change in management; to measure the extent to which point of care testing resulted in differences in clinical outcome for these patients when compared with patients whose samples were tested by the hospital laboratory. Open, single centre, randomised controlled trial. Blood samples were randomly allocated to point of care testing or testing by the hospital's central laboratory. The accident and emergency department of the Bristol Royal Infirmary, a large teaching hospital which cares for an inner city population. Representative sample of patients who attended the department between April 1996 and April 1997 and who required blood tests. Data collection was structured in 8 hour blocks so that all hours of the day and all days of the week were equally represented. The proportion of patients for whom point of care testing brought about a change in treatment in which timing was considered to be critical to clinical outcome. Mortality, the length of stay in hospital, admission rate, the amount of time spent waiting for results of blood tests, the amount of time taken to decide on management plans, and the amount of time patients spent in the department were compared between patients whose samples were tested at the point of care and those whose samples were sent to the laboratory. Samples were obtained from 1728 patients. Changes in management in which timing was considered to be critical occurred in 59 out of 859 (6.9%, 95% confidence interval 5.3% to 8.8%) patients in the point of care arm of the trial. Decisions were made 74 minutes earlier (68 min to 80 min, P < 0.0001) when point of care testing was used for haematological tests as compared to central laboratory testing, 86 minutes earlier (80 min to 92 min, P < 0.0001) for biochemical tests, and 21 minutes earlier (-3 min to 44 min, P = 0.09) for analyses of arterial blood gases. There were no differences between the groups in the amount of time spent in the department, length of stay in hospital, admission rates, or mortality. Point of care testing reduced the time taken to make decisions on patient management that were dependent on the results of blood tests. It also brought about faster changes in treatment for which timing was considered to be critical in about 7% of patients. These changes did not affect clinical outcome or the amount of time patients spent in the department.


Undergraduates' understanding of cardiovascular phenomena.
Undergraduates students in 12 courses at 8 different institutions were surveyed to determine the prevalence of 13 different misconceptions (conceptual difficulties) about cardiovascular function. The prevalence of these misconceptions ranged from 20 to 81% and, for each misconception, was consistent across the different student populations. We also obtained explanations for the students' answers either as free responses or with follow-up multiple-choice questions. These results suggest that students have a number of underlying conceptual difficulties about cardiovascular phenomena. One possible source of some misconceptions is the students' inability to apply simple general models to specific cardiovascular phenomena. Some implications of these results for teachers of physiology are discussed.


Can compassion be taught.
Compassion is a vital part of good nursing care, but many commentators say that it is increasingly lacking. Martin Johnson examines the concept and whether it can be taught.


A simplified quantification method of complex-release activity using peroxidase as immune complex antigen.
The complement-mediated solubilization of precipitable immune complexes (complex-release activity) in serum specimens was determined by a simplified method using peroxidase as an immune complex antigen. The results correlated well with the hemolytic activity via the classical complement pathway and that via the alternative complement pathway. This simplified method proved to be reliable and useful.


The compatibility of swine BMDC-derived bile duct endothelial cells with a nanostructured electrospun PLGA material.
To investigate the production of bile duct endothelial cells via directed differentiation of porcine bone marrow mesenchymal stem cells (BMSCs) down the hepatic lineage in vitro and the biocompatibility of differentiated bile duct endothelial cells with electrospun nanofibers. Porcine BMSCs were differentiated in vitro into bile duct endothelial cells, which were identified by morphology and RT-PCR. PLGA nanofiber membranes were prepared by electrospinning. The morphology was detected by scanning electron microscopy and the short-term (two weeks) in vitro degradation rate was determined. Adhesion and proliferation of the bile duct endothelial cells on the nanofiber surface were analyzed by calculating the cell adhesion rate and MTT assay, respectively. Cell growth, morphology and distribution on the material surface were observed by fluorescence staining and scanning electron microscopy, respectively. After four weeks of directed differentiation of BMSCs in vitro, cells showed the typical morphology of dendritic bile duct endothelial cells and had the expression of CK19. Scanning electron micrographs showed that electrospun materials were continuous nanofibers with diameters between 200 and 500 nm. No significant degradation of the PLGA nanofibers was observed within two weeks. Based on the measured cell adhesion rate, MTT assay, fluorescence staining, and scanning electron microscopy, the differentiated cells possess a good proliferative capacity on PLGA nanofibers. BMSCs can be differentiated into the bile duct endothelial cells in vitro. Materials prepared by the electrospinning method have a nanofiber structure, which does not significantly degrade within two weeks. Differentiated cells exhibit good biocompatibility with the nanofibers.


Cardiotocographic features in COVID-19 infected pregnant women.
We aimed to evaluate the cardiotocograph (CTG) traces of 224 women infected with novel coronavirus 2019 (COVID-19) and analyze whether changes in the CTG traces are related to the severity of COVID-19. We designed a prospective cohort study. Two-hundred and twenty-four women who had a single pregnancy of 32 weeks or more, and tested positive for SARS-CoV-2 were included. Clinical diagnosis and classifications were made according to the Chinese management guideline for COVID-19 (version 6.0). Patients were classified into categories as mild, moderate, severe and the CTG traces were observed comparing the hospital admission with the third day of positivity. There was no statistically significant relationship between COVID-19 severity and CTG category, variability, tachycardia, bradycardia, acceleration, deceleration, and uterine contractility, Apgar 1st and 5th min. Maternal COVID-19 infection can cause changes that can be observed in CTG. Regardless of the severity of the disease, COVID-19 infection is associated with changes in CTG. The increase in the baseline is the most obvious change.


Marked increase in serum levels of liver enzymes in patients receiving chenic acid and phenobarbital for gallstone dissolution.
In a group of 16 patients, receiving chenic acid (20 mg/kg/day) and phenobarbital (60 mg/day) for gallstone dissolution, three patients were observed to develop a marked increase in serum levels of SGOT-SGPT and alkaline phosphatase without associated symptoms. Liver biopsy in one patient showed cellular infiltration with neutrophils and eosinophils, suggestive of a hypersensitivity reaction. Enzyme levels returned to normal, following cessation of chenotherapy, and a second biopsy 3 months later was normal. In that patient a challenge with chenic acid, at 250 mg/day, was again followed by a marked elevation in levels of SGOT-SGPT and alkaline phosphatase. These patients are the first to show marked elevation in liver enzyme levels during chenotherapy; the mechanism and significance are unclear.


Amplified fragment length polymorphism of Streptococcus suis strains correlates with their profile of virulence-associated genes and clinical background.
Amplified fragment length polymorphism (AFLP) typing was applied to 116 Streptococcus suis isolates with different clinical backgrounds (invasive/pneumonia/carrier/human) and with known profiles of virulence-associated genes (cps1, -2, -7 and -9, as well as mrp, epf and sly). A dendrogram was generated that allowed identification of two clusters (A and C) with different subclusters (A1, A2, C1 and C2) and two heterogeneous groups of strains (B and D). For comparison, three strains from each AFLP subcluster and group were subjected to multilocus sequence typing (MLST) analysis. The closest relationship and lowest diversity were found for patterns clustering within AFLP subcluster A1, which corresponded with sequence type (ST) complex 1. Strains within subcluster A1 were mainly invasive cps1 and mrp+ epf+ (or epf*) sly+ cps2+ strains of porcine or human origin. A new finding of this study was the clustering of invasive mrp* cps9 isolates within subcluster A2. MLST analysis suggested that A2 correlates with a single ST complex (ST87). In contrast to A1 and A2, subclusters C1 and C2 contained mainly pneumonia isolates of genotype cps7 or cps2 and epf- sly-. In conclusion, this study demonstrates that AFLP allows identification of clusters of S. suis strains with clinical relevance.


Incorporating the pedigree information in multi-environment trial analyses for improving common vetch.
Common vetch is one of the most profitable forage legumes due to its versatility in end-use which includes grain, hay, green manure, and silage. Furthermore, common vetch is one of the best crops to rotate with cereals as it can increase soil fertility which results in higher yield in cereal crops. The National Vetch Breeding Program located in South Australia is focused on developing new vetch varieties with higher grain and dry matter yields, better resistance to major diseases, and wider adaptability to Australian cropping environments. As part of this program, a study was conducted with 35 field trials from 2015 to 2021 in South Australia, Western Australia, Victoria, and New South Wales with the objective of determining the best parents for future crosses and the vetch lines with highest commercial value in terms of grain yield production. A total of 392 varieties were evaluated. The individual field trials were combined in a multi-environment trial data, where each trial is identified as an environment. Multiplicative mixed models were used to analyze the data and a factor analytic approach to model the genetic by environment interaction effects. The pedigree of the lines was then assembled and incorporated into the analysis. This approach allowed to partition the total effects into additive and non-additive components. The total and additive genetic effects were inspected across and within environments for broad and specific selections of the lines with the best commercial value and the best parents. Summary measures of overall performance and stability were used to aid with selection of parents. To the best of our knowledge, this is the first study which used the pedigree information to breed common vetch. In this paper, the application of this statistical methodology has been successfully implemented with the inclusion of the pedigree improving the fit of the models to the data with most of the total genetic variation explained by the additive heritable component. The results of this study have shown the importance of including the pedigree information for common vetch breeding programs and have improved the ability of breeders to select superior commercial lines and parents.


Molecular determinants of steroid inhibition for the mouse constitutive androstane receptor.
The constitutive androstane receptor (CAR) regulates drug and steroid metabolism through binding to cytochrome P450 2B, 2C, and 3A gene enhancers. Uniquely among nuclear receptors, mouse CAR (mCAR) can be suppressed by androstenol and activated by structurally diverse drugs, pesticides, and environmental pollutants. To gain insight into presently ill-defined structural requirements of mCAR ligands, we employed a mCAR inhibition assay in mammalian HEK293 cells to create a QSAR model that could well predict the inhibition by three unknown steroids. Two novel mCAR inhibitors were thus identified. Yeast two-hybrid assays indicated that steroids inhibit mCAR primarily by promoting association of mCAR with the corepressor NCoR, with only minor contribution from other mechanisms. Analysis of chimeric and mutant mCAR constructs suggested that androstenol sensitivity is controlled by residues between amino acids 201-263 (helices 5-7) and it does not depend on the residue 350 within helix 12, as previously suggested.


National Vulnerability to Pandemics: The Role of Macroenvironmental Factors in COVID-19 Evolution.
The aim of this research is to show that vulnerability to pandemics is unequal across nations, and that culture besides other national factors helps unleash some of the disparities. A nation's vulnerability to pandemics is defined as a state of fragility and dereliction at the national level perceptible at the early stage of the emergence of a pathogen when no definite information is available about it and no clear response is in place, creating a dependence on national factors as well as contextual factors. That is, vulnerability reflects the evolution or spread of a nascent pandemic in a given nation. A set of hypotheses that prescribe how a nation's factors would contribute to its vulnerability is developed. Data reflecting the national factors of a sample of countries that reported early COVID-19 cases were collected from secondary sources to test the hypotheses. The results show that, whereas factors such as economy and healthcare had a modest effect, two cultural factors were salient in shaping a nation's vulnerability to COVID-19. Furthermore, poverty prevalence associated with a nation's vulnerability. Delineating how a nation's culture and macroenvironmental factors shape its vulnerability at early stages of pandemic evolution, the results encourage policymakers to extend timely support to nations high on uncertainty avoidance and low on indulgence, as well as where poverty is prevalent. Such nations require proactive measures such as behavioral interventions and communications that are culturally sensitive and inclusive.


Evaluation of a proposed mixture model to specify the distributions of nuchal translucency measurements in antenatal screening for Down's syndrome.
A mixture model of crown-rump length (CRL)-dependent and CRL-independent nuchal translucency (NT) measurements has been proposed for antenatal screening for Down's syndrome. We here compare the efficacy of the mixture model method with the standard method, which uses NT multiple of the median (MoM) values in a single distribution. Settings A routine antenatal screening programme for Down's syndrome comprising 104 affected and 22,284 unaffected pregnancies. The ability of NT to distinguish between affected and unaffected pregnancies was compared using the mixture model method and the standard MoM method by using published distribution parameters for the mixture model of NT and parameters derived from these for the standard MoM method. The accuracy of the two methods was compared for NT and maternal age by comparing the median estimated risk with the prevalence of Down's syndrome in different categories of estimated risk. Using NT alone observed estimates of discrimination using the two methods are similar; at a 70% detection rate the false-positive rates were 12% using the mixture model method and 10% using the MoM method. Risk estimation was marginally (but not statistically significantly) more accurate using the standard MoM method. The mixture model method offers no advantage over the standard MoM method in antenatal screening for Down's syndrome, is more complicated and less generalizable to other data-sets. The standard MoM method remains the method of choice.


The genomic sequence analysis of the left and right species-specific terminal region of a cowpox virus strain reveals unique sequences and a cluster of intact ORFs for immunomodulatory and host range proteins.
Sequencing and computer analysis of the left (52,283 bp) and right (49,649 bp) variable DNA regions of the cowpox virus strain GRI-90 (CPV-GRI) has revealed 51 and 37 potential open reading frames (ORFs), respectively. Comparison of the structure-function organization of these DNA regions of CPV-GRI with those previously published for corresponding regions of genomes of vaccinia virus, strains Copenhagen (VAC-COP) and Western Reserve (VAC-WR); and variola major virus, strains India-1967 (VAR-IND), Bangladesh-1975 (VAR-BSH); and alastrim variola minor virus, strain Garcia-1966 (VAR-GAR), was performed. Within the left terminal region under study, an extended DNA sequence (14,171 bp), unique to CPV, has been found. Within the right region of the CPV-GRI genome two segments, which are unique to CPV DNA (1579 and 3585 bp) have been found. Numerous differences have been revealed in the genetic structure of CPV-GRI DNA regions, homologous to fragments of the genomes of the above-mentioned orthopoxvirus strains. A cluster of ORFs with structural similarity ot immunomodulatory and host range function of other poxviruses have also been detected. A comparison of the sequences of ORF B, crmA, crmB, crmC, IMP, and CHO hr genes of CPV Brighton strain (CPV-BRI) with the corresponding genes in strain GRI-90 have revealed an identity at the amino acid level ranging from 82 to 96% between the two strains. The findings are significant in light of the recent demonstration of CPV as an important poxvirus model system to probe the precise in vivo role(s) of the unique virally encoded immunomodulatory proteins. Also, the presence of a complete and intact repertoire of immunomodulatory proteins, ring canal proteins family, and host range genes indicates that CPV may have been the most ancient of all studied orthopoxviruses.


C-terminal unfolding of an amyloidogenic β2-microglobulin fragment: ΔN6β2-microglobulin.
A β2-microglobulin (β2m) fragment that lacks the first six amino acids, i.e., ΔN6β2-microglobulin (ΔN6β2m), is an endogenous, proteolytically derived, amyloidogenic fragment of β2m, the precursor protein in Aβ2M amyloidosis (dialysis-related amyloidosis). As reports suggest the importance of C-terminal unfolding for the amyloidogenicity of β2m, in this study we aimed to investigate conformational characteristics of ΔN6β2m related to amyloidogenicity. We also measured the concentration of an amyloidogenic intermediate of β2m with C-terminal unfolding (β2m92-99) in serum samples from 10 patients undergoing hemodialysis (HD). We utilized capillary electrophoretic analysis, surface plasmon resonance and enzyme-linked immunosorbent assay. We confirmed the normal core structure of ΔN6β2m with a commercial monoclonal anti-β2m antibody. In addition, using the specific monoclonal antibody for the C-terminal peptide, i.e. mAb 92-99, we confirmed unfolding in the C-terminal region of ΔN6β2m. On the basis of these findings, we established an ELISA to measure β2m92-99 using ΔN6β2m as a standard molecule in circulation. However, we did not detect β2m92-99 in serum from 10 HD patients, despite the absence of uremic inhibitors in the serum.


Flavin-catalyzed generation of diimide: an environmentally friendly method for the aerobic hydrogenation of olefins.
The first green and practical method for "aerobic hydrogenation" involving the use of hydrazine and an organocatalyst is described. Olefins can be hydrogenated by treatment with hydrazine in the presence of a 5-ethyl-3-methyllumiflavinium perchlorate (FlEt+.ClO4-) catalyst under O2 atmosphere to give the corresponding hydrogenated products in excellent yields along with environmentally benign water and molecular nitrogen as the only waste products.


Fusion extracted features from deep learning for identification of multiple positioning errors in dental panoramic imaging.
Dental panoramic imaging plays a pivotal role in dentistry for diagnosis and treatment planning. However, correctly positioning patients can be challenging for technicians due to the complexity of the imaging equipment and variations in patient anatomy, leading to positioning errors. These errors can compromise image quality and potentially result in misdiagnoses. This research aims to develop and validate a deep learning model capable of accurately and efficiently identifying multiple positioning errors in dental panoramic imaging. This retrospective study used 552 panoramic images selected from a hospital Picture Archiving and Communication System (PACS). We defined six types of errors (E1-E6) namely, (1) slumped position, (2) chin tipped low, (3) open lip, (4) head turned to one side, (5) head tilted to one side, and (6) tongue against the palate. First, six Convolutional Neural Network (CNN) models were employed to extract image features, which were then fused using transfer learning. Next, a Support Vector Machine (SVM) was applied to create a classifier for multiple positioning errors, using the fused image features. Finally, the classifier performance was evaluated using 3 indices of precision, recall rate, and accuracy. Experimental results show that the fusion of image features with six binary SVM classifiers yielded high accuracy, recall rates, and precision. Specifically, the classifier achieved an accuracy of 0.832 for identifying multiple positioning errors. This study demonstrates that six SVM classifiers effectively identify multiple positioning errors in dental panoramic imaging. The fusion of extracted image features and the employment of SVM classifiers improve diagnostic precision, suggesting potential enhancements in dental imaging efficiency and diagnostic accuracy. Future research should consider larger datasets and explore real-time clinical application.


General practitioners' use of magnetic resonance imaging: an open randomized trial comparing telephone and written requests and an open randomized controlled trial of different methods of local guideline dissemination.
To determine the impact and cost-effectiveness of telephone versus written access to magnetic resonance imaging (MRI), and of different strategies for disseminating locally produced guidelines, upon requests by general practitioners (GPs) for knee and lumbar spine investigation. Two sequential pragmatic open cluster-randomized trials were conducted within 39 general practices. The outcome measure in each trial was concordance of request with local guidelines. Trial 1: practices requested MRI by telephone or in writing. Trial 2: all practices received guidelines, plus either: a practice-based seminar, practice-specific audit feedback, both seminar and feedback, or neither. A total of 414 requests were assessed in the two trials. Trial 1: telephone access cost pound4.86 more per request but rates of concordant requests were equivalent (65%/64%: telephone/written). Trial 2: compared to the control group, costs per practice were pound1911 higher in seminar group, pound1543 higher in feedback group and pound3578 higher for those receiving both. Concordance was greater following the intervention (74% vs 65%; P < 0.05), but there was no difference between the four study groups. Method of access did not affect concordance. Written access was more cost-effective. Seminars and feedback were no more effective in modifying practice than guidelines alone, which was thus the most cost-effective option.


Water sources and their protection from the impact of microbial contamination in rural areas of Beijing, China.
Bacterial contamination of drinking water is a major public health problem in rural China. To explore bacterial contamination in rural areas of Beijing and identify possible causes of bacteria in drinking water samples, water samples were collected from wells in ten rural districts of Beijing, China. Total bacterial count, total coliforms and Escherichia coli in drinking water were then determined and water source and wellhead protection were investigated. The bacterial contamination in drinking water was serious in areas north of Beijing, with the total bacterial count, total coliforms and Escherichia coli in some water samples reaching 88,000 CFU/mL, 1,600 MPN/100 mL and 1,600 MPN/100 mL, respectively. Water source types, well depth, whether the well was adequately sealed and housed, and whether wellhead is above or below ground were the main factors influencing bacterial contamination levels in drinking water. The bacterial contamination was serious in the water of shallow wells and wells that were not closed, had no well housing or had a wellhead below ground level. The contamination sources around wells, including village dry toilets and livestock farms, were well correlated with bacterial contamination. Total bacterial counts were affected by proximity to sewage ditches and polluting industries, however, proximity to landfills did not influence the microbial indicators.


[Dopamine beta hydroxylase. Value and limits of its study in neurology].
Plasma dopamine-beta-hydroxylase was studied in 96 subjects, 33 of them controls and 63 of them patients (Parkinson's disease, chronic chorea, torsion dystonia, postural tremor and epilepsy). Only the epileptics showed a significant decrease in the average level of dopamine-beta-hydroxylase activity in comparison with the controls. During the cold test, DBH did not vary except in one case. On the other hand, during epileptic attacks, DBH activity underwent considerable fluctuations. Therefore, except in special pathological conditions, such as epileptic attacks, measurement of plasma or serum DBH activity is of limited value for neurological pathology and is not a good indication of the activity of the sympathetic nervous system.


Determination of antioxidant activity in foods and beverages by reaction with 2,2'-diphenyl-1-picrylhydrazyl (DPPH): collaborative study First Action 2012.04.
A colorimetric method for the determination of total antioxidant activity in a variety of foods and beverages was validated in both a single-laboratory validation and a collaborative laboratory validation study. The procedure involved extraction of the antioxidants directly into a methanol-water solution containing a known amount of 2,2'-diphenyl-1-picrylhydrazyl (DPPH), thus promoting the rapid reaction of extracted materials with DPPH. The reaction was monitored by spectrophotometric measurement of the absorbance loss at 517 nm. Antioxidant activity was quantified relative to a dilution series of vitamin E analog standards (Trolox), which were analyzed in parallel simultaneously with the food and beverage samples. The antioxidant activities of the samples ranged from 131 to 131 000 micromole Trolox equivalents/100 g. Statistical analysis of the results showed that nine of the 11 matrixes gave acceptable HorRat values, indicating that the method performed well in these cases. The acceptable matrixes include pomegranate juice, blueberry juice, carrot juice, green tea, wine, rosemary spice, ready-to-eat cereal, and yogurt. Two samples failed the HorRat test: the first was an almond milk that had an antioxidant level below the practical LOQ for the method; the second was a sample of canola oil with added omega-3 fatty acid that was immiscible in the reaction medium.


In Vitro Cleavage Assays using Purified Recombinant Drosophila Caspases for Substrate Screening.
Caspases are very specific cell death proteases that are involved in apoptotic and non-apoptotic processes. While the role of caspases during apoptosis has been very well defined and many apoptotic proteolytic substrates of caspases have been identified and characterized, the role of caspases for non-apoptotic processes is not well understood. In particular, few non-apoptotic substrates of caspases have been identified thus far. Here, in order to facilitate the identification and characterization of potential caspase substrates, a protocol that allows the testing of candidate substrates in caspase cleavage assays in vitro is described. This protocol includes the production and purification of recombinant caspase proteins, the production of the candidate substrates either recombinantly or in a cell-free expression system, and the actual in vitro cleavage reaction followed by SDS-PAGE and immunoblotting. This protocol is tailored for the Drosophila caspases Dronc and Drice but can easily be adapted for caspases from other organisms, including mammals.


Topical use of 5-fluorouracil for treatment of squamous cell carcinoma of the external genitalia of horses: 11 cases (1988-1992).
Ten horses with histologically confirmed squamous cell carcinoma (SCC) and 1 horse with presumptive SCC of the external genitalia were treated with a combination of surgical debridement and topical administration of 5-fluorouracil, or with topical treatment alone. Tumor remission was obtained in all horses except 1 in which owner compliance was deficient, and no recurrences have been reported. Topical use of 5-fluorouracil as a chemotherapeutic agent for treatment of genital lesions of SCC in horses should be considered as a viable alternative to radical surgical excision.


Binary prefix for sampling frequency offset estimation in dispersive optical transmissions.
We propose and experimentally demonstrate a method for sampling frequency offset (SFO) estimation in optical communication systems based on periodically inserted identical binary prefix. Different from conventional cyclic prefix, binary prefix provides not only high tolerance to chromatic dispersion in dispersive fiber transmission, but also the ability to estimate SFO by simple receiver-side digital signal processing. Moreover, this binary prefix based scheme is generally applicable to any advanced modulation formats. A proof-of-concept experiment is conducted to quantify the accuracy and tolerance of the scheme in estimating SFO. It is found that over a wide SFO range up to 341 ppm, the estimation error is kept under 20 ppb and signals are recovered with the same quality as with zero-offset sampling. The experimental results also confirm that this method is tolerant to link signal-to-noise ratio loss and dispersion, showing no additional penalty after transmission over a 40-km standard single-mode fiber at 1550 nm.


[A pivotal role of activated hepatic macrophage in the progression of alcoholic liver disease].
Our clinical and experimental research results indicated the possibility that gut-derived endotoxin contributes to the development of alcoholic liver disease. Long-term ethanol consumption resulted in an enhanced secretory function of hepatic macrophage accompanied by an ultrastructural feature of activation. The liver of rats fed on ethanol-diet were found to have an enhanced ability to produce CINC-1 (rat IL-8) after endotoxin injection. This chemokine may contribute to neutrophil recruitment into the liver in alcoholic liver injury. Females exhibited a greater ability to produce CINC-1 than males, and this fact may account for the gender difference in susceptibility to alcohol-related liver disease.


Determination of phospholipids in olive oil by 31P NMR spectroscopy.
A nondestructive analytical method based on NMR spectroscopy was developed for the determination of phospholipids in olive oil. The phospholipids extracted from virgin olive oil with a mixture of ethanol/water (2:1 v/v) were identified and quantified by high resolution (31)P NMR spectroscopy. The main phospholipids found in olive oil were phosphatidic acid, lyso-phosphatidic acid, and phosphatidylinositol. Validation of the (31)P NMR methodology for quantitative analysis of phospholipids in olive oil was performed. Sensitivity was satisfactory with detection limits of 0.25-1.24 mumol /mL. In addition, the composition of fatty acids in phospholipids model compounds and those in olive oil samples was estimated by employing one- and two-dimensional (1)H NMR. The results indicated that the fatty acid composition in phospholipids and triacylglycerols of olive oil was similar.


Current Status of Drug Targets and Emerging Therapeutic Strategies in the Management of Alzheimer's Disease.
Alzheimer's disease (AD) is a chronic neurodegenerative disease affecting the elderly. AD is associated with a progressive decline in memory and cognitive abilities, drastic changes in behavioural patterns and other psychiatric manifestations. It leads to a significant decline in the quality of life at personal, household as well as national level. Although AD was described about hundred years back and multiple theories have been proposed, its exact pathophysiology is unknown. There is no cure for AD and the life expectancy of AD patients remains low at 3-9 years. An accurate understanding of the molecular mechanism(s) involved in the pathogenesis of AD is imperative to devise a successful treatment strategy. This review explains and summarises the current understanding of different therapeutic strategies based on various molecular pathways known to date. Different strategies based on anti-amyloid pathology, glutamatergic pathway, anti-tau, neuroprotection through neurotrophic factors and cholinergic neurotransmission have been discussed. Further, the use of anti-inflammatory drugs, nutraceuticals, and dietary interventions has also been explained in the management of AD. It further describes different pharmacological and dietary interventions being used in treating and/or managing AD. Additionally, this article provides a thorough review of the literature for improving the therapeutic paradigm of AD.


Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis.
Chronic pulmonary infection with Pseudomonas aeruginosa (PA) develops in most patients with cystic fibrosis (CF) and is associated with a poor prognosis. Much effort has been directed toward treating the chronic infection, but it is almost impossible to eradicate it once established; therefore, prevention is preferable. Since 1989 CF patients at the Danish CF Center in Copenhagen have been treated with an intensive three-step-protocol consisting of colistin inhalations and oral ciprofloxacin at the time of initial PA colonization. This study compares 48 patients treated according to this intensive protocol with 43 historic controls. The study was carried out over 44 months and included 218 patient-years. Only 16% of the treated patients developed chronic PA infection after 3 1/2 years compared with 72% of the control patients (Kaplan Meier estimate, P < 0.005, log rank test). This indicates that aggressive treatment prevented or delayed chronic PA infection in 78% of the patients for 3 1/2 years. Furthermore, aggressive treatment maintained or increased pulmonary function (forced vital capacity and forced expiratory volume in 1 second in percent of predicted values) during the year after inclusion compared with the control group, in which pulmonary function declined (P < 0.01, Mann-Whitney test). Although some of the treated patients eventually developed chronic PA infection, these patients had significantly better pulmonary function at the onset of chronic PA infection compared with control patients (P < 0.001, Mann-Whitney test). When the different steps in the intensive three-step-protocol were analyzed, there was a trend suggesting that 3 months of high-dose treatment with colistin inhalation and oral ciprofloxacin produced the best results in terms of postponement or prevention of chronic PA infection (P < 0.05).


Correlation of membrane order and dynamics derived from time-resolved fluorescence measurements with solute permeability.
The relevance of order and dynamics of phospholipid bilayer membranes as detected with fluorescent probe molecules embedded in the membranes for describing their permeability properties was studied. Order parameters (S) and rotational diffusion coefficients (Dperpendicular) of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in unilamellar vesicles were determined by time-resolved fluorescence spectroscopy. Vesicles consisting of combinations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine, 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine, egg sphingomyelin and cholesterol were studied at 288, 298, and 308 degrees K. Permeability coefficients (P) of the model permeant D-[14C]mannitol were determined. A model was proposed for correlating P with both S and Dperpendicular, where S is linked to the average free surface area per lipid molecule and Dperpendicular reflects lipid thermal motion and, thus, redistribution rate of free surface area of the bilayer. P values ranging from 0.9 to 12.4 x 10(-11) cm/s were well described by the model. This supports the notion that permeation depends on membrane structural and dynamic properties. While changes in both S and Dperpendicular, at relative significance varying with the situation, appeared responsible for the effect of lipid composition on permeability, the effect of temperature on P was related primarily to Dperpendicular. P correlated better with S and Dperpendicular obtained with TMA-DPH rather than DPH. The location of the fluorescent probe molecules within the membranes is discussed as the cause for this difference.


YorkieCA overexpression in the posterior silk gland improves silk yield in Bombyx mori.
The traditional hybrid breeding techniques can no longer meet the increasing demands for silk production by the silkworm, Bombyx mori, and further improvement of the silk yield will depend on modern molecular breeding techniques. Here, we report improved silk yield in transgenic silkworms overexpressing the oncogene YorkieCA specifically in the posterior silk gland (PSG). The YorkieCA cDNA was ligated downstream of the hr3 enhancer and the fibroin L-chain (Fil) promoter, then inserted into a piggyBac vector for transgene. Overexpression of YorkieCA in the PSG significantly increased the weight of the PSG, and also increased the weight of the cocoon, larval body, and pupal body to decreasing degrees. Overexpression of YorkieCA up-regulated the Yorkie target genes resulting in increased cell size, endomitosis, the number of protein synthesis organelles, the expression of fibroin genes in the PSG, and eventually silk yield. Additionally, as we reported previously using the binary GAL4/UAS system, transgenic silkworms overexpressing Ras1CA with the hr3 enhancer and the Fil promoter also showed improved silk yield. Unfortunately, the hybrid progeny of YorkieCA-overexpressing silkworms and Ras1CA-overexpressing silkworms did not show overlapping improved silk yield due to the failure to increase expression of both Yorkie and Ras1.


A benchmark of parametric methods for horizontal transfers detection.
Horizontal gene transfer (HGT) has appeared to be of importance for prokaryotic species evolution. As a consequence numerous parametric methods, using only the information embedded in the genomes, have been designed to detect HGTs. Numerous reports of incongruencies in results of the different methods applied to the same genomes were published. The use of artificial genomes in which all HGT parameters are controlled allows testing different methods in the same conditions. The results of this benchmark concerning 16 representative parametric methods showed a great variety of efficiencies. Some methods work very poorly whatever the type of HGTs and some depend on the conditions or on the metrics used. The best methods in terms of total errors were those using tetranucleotides as criterion for the window methods or those using codon usage for gene based methods and the Kullback-Leibler divergence metric. Window methods are very sensitive but less specific and detect badly lone isolated gene. On the other hand gene based methods are often very specific but lack of sensitivity. We propose using two methods in combination to get the best of each category, a gene based one for specificity and a window based one for sensitivity.


Molecular Mechanisms of Neurodegenerative Diseases Induced by Human Retroviruses: A Review.
PROBLEM STATEMENT: Infection with retroviruses such as human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1) have been shown to lead to neurodegenerative diseases such as HIV-associated dementia (HAD) or neuroAIDS and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), respectively. APPROACH: HIV-1-induced neurologic disease is associated with an influx of HIV-infected monocytic cells across the blood-brain barrier. Following neuroinvasion, HIV-1 and viral proteins, in addition to cellular mediators released from infected and uninfected cells participate in astrocytic and neuronal dysregulation, leading to mild to severe neurocognitive disorders. RESULTS: The molecular architecture of viral regulatory components including the Long Terminal Repeat (LTR), genes encoding the viral proteins Tat, Vpr and Nef as well as the envelope gene encoding gp120 and gp41 have been implicated in 'indirect' mechanisms of neuronal injury, mechanisms which are likely responsible for the majority of CNS damage induced by HIV-1 infection. The neuropathogenesis of HAM/TSP is linked, in part, with both intra-and extracellular effectors functions of the viral transactivator protein Tax and likely other viral proteins. Tax is traditionally known to localize in the nucleus of infected cells serving as a regulator of both viral and cellular gene expression. CONCLUSION/RECOMMENDATIONS: However, recent evidence has suggested that Tax may also accumulate in the cytoplasm and be released from the infected cell through regulated cellular secretion processes. Once in the extracellular environment, Tax may cause functional alterations in cells of the peripheral blood, lymphoid organs and the central nervous system. These extracellular biological activities of Tax are likely very relevant to the neuropathogenesis of HTLV-1 and represent attractive targets for therapeutic intervention.


Filarial Coinfection Is Associated With Higher Bacterial Burdens and Altered Plasma Cytokine and Chemokine Responses in Tuberculous Lymphadenitis.
Filarial infections are known to modulate cytokine responses in pulmonary tuberculosis by their propensity to induce Type 2 and regulatory cytokines. However, very little is known about the effect of filarial infections on extra-pulmonary forms of tuberculosis. Thus, we have examined the effect of filarial infections on the plasma levels of various families of (IL-1, IL-12, γC, and regulatory) cytokines and (CC and CXC) chemokines in tuberculous lymphadenitis coinfection. We also measured lymph node culture grades in order to assess the burden of Mycobacterium tuberculosis in the two study groups [Fil+ (n = 67) and Fil- (n = 109)]. Our data reveal that bacterial burden was significantly higher in Fil+ compared to Fil- individuals. Plasma levels of IL-1 family (IL-1α, IL-β, IL-18) cytokines were significantly lower with the exception of IL-33 in Fil+ compared to Fil- individuals. Similarly, plasma levels of IL-12 family cytokines -IL-12 and IL-23 were significantly reduced, while IL-35 was significantly elevated in Fil+ compared to Fil- individuals. Filarial infection was also associated with diminished levels of IL-2, IL-9 and enhanced levels of IL-4, IL-10, and IL-1Ra. Similarly, the Fil+ individuals were linked to elevated levels of different CC (CCL-1, CCL-2, CCL-3, CCL-11) and CXC (CXCL-2, CXCL-8, CXCL-9, CXCL-11) chemokines. Therefore, we conclude that filarial infections exert powerful bystander effects on tuberculous lymphadenitis, effects including modulation of protective cytokines and chemokines with a direct impact on bacterial burdens.


Phenolic glycosides from Viscum angulatum.
Three new glycosides, pinocembrin 7-O-apiosyl(1-->5)apiosyl(1-->2)-beta-D-glucopyranoside (1), 2',3',4',3' '-tetramethoxy-1,3-diphenylpropane 5',4' '-di-O-beta-D-glucopyranoside (2), and rhamnocitrin 3-O-apiosyl(1-->5)apiosyl(1-->2)-[alpha-L-rhamnopyranosyl(1-->6)]-beta-D-glucopyranoside (3), were isolated from Viscum angulatumalong with viscumneoside V, naringenin, and homoeriodictyol. Their structures were established by spectral and chemical methods.


Strategies for improving safety performance in construction firms.
Over the years many prevention management practices have been implemented to prevent and mitigate accidents at the construction site. However, there is little evidence of the effectiveness of individual or combined practices used by companies to manage occupational health and safety issues. The authors selected a sample of 1180 construction firms and 221 individual practices applied in these companies to analyze their effectiveness reducing injury rates over a period of four years in Chile. Different methods were used to study this massive database including: visual analyses of graphical information, statistical analyses and classification techniques. Results showed that practices related to safety incentives and rewards are the most effective from the accident rate viewpoint, even though they are seldom used by companies; on the other hand, practices related to accidents and incidents investigation had a slight negative impact on the accident rate because they are frequently used as a reactive measure. In general, the higher the percentage of prevention practices implemented in a strategy, the lower the accident rate. However, the analysis of the combined effect of prevention practices indicated that the choice of the right combination of practices was more important than just the number of practices implemented.


Regulation of blood-brain tumor barrier permeability by calcium-activated potassium channels.
The blood-brain tumor barrier (BTB) limits the delivery of therapeutic drugs to brain tumors. We demonstrate in a rat brain tumor (RG2) model an enhanced drug delivery to brain tumor following intracarotid infusion of bradykinin (BK), nitric oxide (NO) donors, or agonists of soluble guanylate cyclase (sGC) and calcium-dependent potassium (K(Ca)) channels. We modulated K(Ca) channels by specific agonists and agents that produce NO and cGMP in situ to obtain sustained enhancement of selective drug delivery to brain tumors. Intracarotid infusion of BK or 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS-1619) significantly enhanced BTB permeability (K(i)) to [(14)C]alpha-aminoisobutyric acid in the brain tumor area but not in normal brain tissue. The K(i) increase achieved by BK, NS-1619, NO donors, or the sGC activator 3-(5'-hydroxymethyl-2'furyl)-1-benzylindazole (YC-1) was significantly attenuated when coinfused with a K(Ca) channel antagonist, iberiotoxin. Immunoblot and immunolocalization studies demonstrate overexpression of K(Ca) channels in tumor cells and capillaries compared with normal brain. The potentiometric assays demonstrate the functional activity of K(Ca) channels in rat brain endothelial and glioma cells. Additionally, we show that BK and NS-1619 significantly increased the density of transport vesicles in the cytoplasm of brain tumor capillary endothelia and tumor cells. The cleft indices and cleft area indices in rat tumor capillaries were significantly higher than in normal brain capillaries, and BK infusion did not alter these indices. These data demonstrate that the cellular mechanism for K(Ca) channel-mediated BTB permeability increase is due to accelerated formation of pinocytotic vesicles, which can transport drugs across BTB. We conclude that K(Ca) channels serve as a convergence point in the biochemical regulation of BTB permeability.


Congestive heart failure due to traumatic arteriovenous fistula--two case reports.
Arteriovenous fistulas are abnormal connections between the high-pressure and high-resistance arterial system and the venous system with opposite features. Due to its lower resistance, the blood preferentially flows via the fistula rather than through the capillary bed. The amount of shunt flow depends on its size and proximity to the heart. Due to the increase in circulating volume, progressive dilation develops in the whole vascular system proximal to the shunt. Cardiomegaly and venous distention may return to normal after surgical repair of this vascular abnormality. Two cases are presented of heart failure due to traumatic arteriovenous fistula, one of which was between the right renal artery and inferior vena cava and the other between the left renal artery and renal vein.


Hypertrophic osteopathy associated with an intrathoracic neoplasm in a rabbit.
Hypertrophic osteopathy associated with an intrathoracic neoplasm was diagnosed in a 7.5-year-old spayed female White New Zealand rabbit. The rabbit was examined because it had a swollen foot and was anorectic. An intrapulmonary mass as well as periosteal proliferation in the tarsometatarsal region were observed on radiography. Histologic examination of necropsy specimens was used to confirm the diagnosis of hypertrophic osteopathy secondary to metastatic adenocarcinoma of the lungs. To the author's knowledge, hypertrophic osteopathy has not been reported in lagomorphs, but should be considered as a differential diagnosis in lame rabbits.


Chronic treatment with D1 and D2 dopamine receptor agonists: combined treatments interact to differentially affect brain levels of monoamines.
Recent evidence of functional interactions between D1 and D2 dopamine receptor subtypes has led to the concept that many of the behavioural effects of dopamine agonists occur only with activation of both receptor subtypes. Thus, combined treatment with dopamine agonists selective for each of the D1 and D2 receptors may be an effective therapy for Parkinson's disease, chiefly characterized by loss of central dopamine-containing neurons. In addition, recent hypotheses of the possible pathogenesis of this disorder have suggested that metabolism of dopamine by monoamine oxidase in the presynaptic terminal may contribute to the loss of dopaminergic cells, through the production of reactive by-products. Therefore, the effects of chronic (15 day) treatment of rats with different doses of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, a D2 receptor agonist), SKF 38393 (a D1 receptor partial agonist) or combinations of both drugs on levels of brain monoamines and some of their acidic metabolites were investigated. Little or no effects of the drugs were observed on measures of dopamine or noradrenaline when given separately, while each selective agonist dose-dependently reduced serotonin levels. Combined treatment with the two agonists produced profound effects on the catecholamines, but with no effect on 3,4-dihydroxyphenylacetic acid, the metabolite of dopamine produced by monoamine oxidase. In addition, the effects of combined treatment on serotonin levels were opposite of those of the drugs given independently. Concomitant treatment of animals with both D1 and D2 receptor agonists can therefore increase tissue levels of dopamine without increasing the potentially harmful metabolism of dopamine by monoamine oxidase.


The 'healthy immigrant effect': breastfeeding behaviour in Ireland.
The benefits of breastfeeding for babies, mothers and society have been demonstrated in a large scientific literature. Irish rates of breastfeeding are amongst the lowest in Europe (in 2010, Ireland had the lowest breastfeeding initiation rate of 14 European countries). One of the most distinctive features of breastfeeding behaviour in Ireland is the large difference in breastfeeding rates between immigrants to Ireland and the Irish-born. Data from the 2010 Irish National Perinatal Reporting System show that just 46.1% of Irish-born mothers were breastfeeding at hospital discharge, in comparison with 84.2% of immigrant mothers. Descriptive patterns suggest that breastfeeding behaviour in Ireland may exhibit a 'healthy immigrant' effect, whereby the health status and behaviours of immigrants are better than the native-born on arrival, but converge to native levels as length of time since migration increases. Using nationally representative data from two cohorts of children in Ireland, the purpose of this article is to examine the evidence for a 'healthy immigrant' effect with respect to breastfeeding behaviour. The results indicate that immigrants are significantly more likely to breastfeed than Irish-born mothers, but that immigrant breastfeeding rates converge towards Irish-born rates of breastfeeding as length of time since migration increases. The decline in breastfeeding behaviour among immigrants to Ireland with length of time since migration highlights the need for appropriate interventions aimed at countering the particular negative attitudes to breastfeeding that are observed in Irish society.


Membrane-embedded substrate recognition by cytochrome P450 3A4.
Cytochrome P450 3A4 (CYP3A4) is the dominant xenobiotic-metabolizing enzyme in the liver and intestine and is involved in the disposition of more than 50% of drugs. Because of its ability to bind multiple substrates, its reaction kinetics are complex, and its association with the microsomal membrane confounds our understanding of how this enzyme recognizes and recruits diverse substrates. Testosterone (TST) hydroxylation is the prototypical CYP3A4 reaction, displaying positive homotropic cooperativity with three binding sites. Here, exploiting the capability of accelerated molecular dynamics (aMD) to sample events in the millisecond regime, I performed >25-μs aMD simulations in the presence of three TST molecules. These simulations identified high-occupancy surface-binding sites as well as a pathway for TST ingress into the CYP3A4 active site originating in the membrane. Adaptive biasing force analysis of the latter pathway revealed a metastable intermediate that could constitute a third binding site at high TST concentrations. Prompted by the observation that interactions between TST and the G'-helix mobilize the ligand into the active site, a free-energy analysis of TST distribution in the membrane was conducted and revealed that the depth of the G'-helix is optimal for extracting TST. In summary, these simulations confirm separate, but adjacent substrate-binding sites within the enzyme and the existence of an auxiliary TST-binding site. The broader impact of these simulations is that they support a mechanism in which cytochromes P450 directly recruit membrane-solubilized substrates.


Quantifying the roughness on the free energy landscape: entropic bottlenecks and protein folding rates.
The prediction of protein folding rates and mechanisms is currently of great interest in the protein folding community. A close comparison between theory and experiment in this area is promising to advance our understanding of the physical-chemical principles governing the folding process. The delicate interplay of entropic and energetic/enthalpic factors in the protein free energy regulates the details of this complex reaction. In this article, we propose the use of topological descriptors to quantify the amount of heterogeneity in the configurational entropy contribution to the free energy. We apply the procedure to a set of 16 two-state folding proteins. The results offer a clean and simple theoretical explanation for the experimentally measured folding rates and mechanisms, in terms of the intrinsic entropic roughness along the populated folding routes on the protein free energy landscape.


Intracellular K+ activity, intracellular Na+ activity and maximum diastolic potential of canine subendocardial Purkinje cells from one-day-old infarcts.
The basis for the reduced maximum diastolic potential of canine cardiac subendocardial Purkinje fibers surviving one day after extensive transmural infarction was investigated, using double-barrel potassium and sodium ion-sensitive microelectrodes. The maximum diastolic potential of Purkinje fibers in infarct preparations from the left ventricular apex measured during the first hour of superfusion in a tissue bath was -50.1 +/- 13.7 mV, a value markedly reduced from the value in control Purkinje fibers from noninfarcted preparations (-85.0 +/- 4.5 mV). The intracellular potassium ion activity was reduced by 50.4 mM during this time (intracellular potassium ion activity equals 61.6 +/- 16.1 mM, as compared to control intracellular potassium ion activity of 112 +/- 19.8 mM). The potassium equilibrium potential was reduced by 16.0 mV (from -97.2 +/- 4.7 mV in controls to -81.2 +/- 6.9 mV), thus accounting for about one half of the reduction in the maximum diastolic potential. After 6 hours of superfusion, the maximum diastolic potential increased to -78.9 +/- 8.7 mV (still significantly less than control). The potassium equilibrium potential had largely recovered (-93.8 +/- 5.9 mV). The intracellular sodium ion activity of Purkinje fibers in the infarcts (15.6 +/- 6.9 mM) was elevated during the first hour of superfusion by 6.2 mM compared to control (9.4 +/- 2.6 mM), and this was only 12% as much as the initial intracellular potassium ion activity decrease. Sodium ion activity after 3-6 hours of superfusion was not significantly different than normal (12.1 +/- 4.9 mM). In conclusion, only a portion of the maximum diastolic potential changes can be explained by a reduction of the potassium equilibrium potential. It is likely that change(s) in the cell membrane sodium-potassium pump's function and in the membrane conductance are also involved. Furthermore, the lack of a compensatory increase in intracellular sodium ion activity accompanying the large reduction of intracellular potassium ion activity may be a consequence of the cellular acidosis, which is known to occur during myocardial ischemia.


Hospital-associated bacterial meningitis.
Eighteen of 349 cases (5.2 per cent) of bacterial meningitis seen between 1949 and 1973 were hospital-associated (developed after admission to the hospital). The patients were adults, usually males, and developed symptoms and signs of meningitis from 2 to 23 days (mean, 10.1 days) after hospital admission. The diagnosis of bacterial meningitis was made from less than 1 day to 15 days (mean, 4.8 days) after the onset of symptoms. Fourteen of the 18 patients had received antibiotics during the week prior to developing meningitis. Nine (50 per cent) had a chronic, noninfection, underlying illness. Diagnostic or surgical procedures involving the neuraxis or adjacent structures preceded the development of meningitis in 10 of the 18 patients (56 per cent). Only 6 of the 18 patients survived their infection. Prompt recognition, diagnosis, and therapy of hospital-associated meningitis in high-risk patients may reduce the significant mortality.


Antioxidant activity assay based on the inhibition of oxidation and photobleaching of L-cysteine-capped CdTe quantum dots.
Quantum dots (QDs) have recently been the focus of attention of many investigators for development of diagnostic tools in many research areas. In this work, we established a new QD-based assay to evaluate the antioxidant/polyphenolic activity. This assay is based on measurement of the inhibitory effect of the antioxidant/polyphenolic compounds on the UV-induced bleaching of CdTe QDs with L-cysteine capping. QDs exhibited excellent photostability without any UV exposure, while they bleached rapidly under UV irradiation. Generation of reactive oxygen species (ROS) under UV irradiation is probably the main cause of the photobleaching of QDs. By comparing the photostability of QDs in buffer solution in the absence and presence of sodium azide, as a known (1)O(2) quencher, the involvement of (1)O(2) in photobleaching of QDs was confirmed. The photobleaching effect induced by ROS could be reduced in the presence of antioxidant/polyphenolic compounds. We tested several antioxidant/polyphenolic compounds as well as known antioxidants such as trolox and 4 different types of tea. The results obtained by the QD-based assay revealed a very good correlation with the data acquired by Folin-Ciocalteu assay. Furthermore, a deeper understanding of the mechanism and the solution for photobleaching of QDs under UV irradiation might be very meaningful in promoting their clinical applications.


Transformation of Cyanobacterial Biomolecules by Iron Oxides During Flash Pyrolysis: Implications for Mars Life-Detection Missions.
Answering the question of whether life ever existed on Mars is a key goal of both NASA's and ESA's imminent Mars rover missions. The obfuscatory effects of oxidizing salts, such as perchlorates and sulfates, on organic matter during thermal decomposition analysis techniques are well established. Less well studied are the transformative effects of iron oxides and (oxy)hydroxides, which are present in great abundances in the martian regolith. We examined the products of flash pyrolysis-gas chromatography-mass spectrometry (a technique analogous to the thermal techniques employed by past, current, and future landed Mars missions) which form when the cyanobacteria Arthrospira platensis are heated in the presence of a variety of Mars-relevant iron-bearing minerals. We found that iron oxides/(oxy)hydroxides have transformative effects on the pyrolytic products of cyanobacterial biomolecules. Both the abundance and variety of molecular species detected were decreased as iron substrates transformed biomolecules, by both oxidative and reductive processes, into lower fidelity alkanes, aromatic and aryl-bonded hydrocarbons. Despite the loss of fidelity, a suite that contains mid-length alkanes and polyaromatic hydrocarbons and/or aryl-bonded molecules in iron-rich samples subjected to pyrolysis may allude to the transformation of cyanobacterially derived mid-long chain length fatty acids (particularly unsaturated fatty acids) originally present in the sample. Hematite was found to be the iron oxide with the lowest transformation potential, and because this iron oxide has a high affinity for codeposition of organic matter and preservation over geological timescales, sampling at Mars should target sediments/strata that have undergone a diagenetic history encouraging the dehydration, dihydroxylation, and oxidation of more reactive iron-bearing phases to hematite by looking for (mineralogical) evidence of the activity of oxidizing, acidic/neutral, and either hot or long-lived fluids.


Prevalence and risk factor analysis of bovine hemoplasma infection by direct PCR in Eastern Hokkaido, Japan.
The prevalence and risk factors of 2 bovine hemoplasma species-Mycoplasma wenyonii (Mw) and "Candidatus Mycoplasma haemobos" (CMh)-were examined by direct PCR using whole blood samples collected from 343 cattle in Eastern Hokkaido, Japan. The sensitivity of the direct PCR assay was 10-fold higher than the standard PCR assay, detecting 5 copies of bovine hemoplasma DNA per reaction. An epidemiological survey of sampling location, living conditions, age and bovine leukemia virus antibody was performed to assess infection risk factors. The prevalence rates were 38.5% for Mw and 39.1% for CMh, respectively, with an overall prevalence rate of 64.7% for all bovine hemoplasma infections. Significant differences were found in sampling location, living conditions and age. Compared with pastured cattle, farmed cattle were significantly more susceptible to infection with total hemoplasma species (P<0.001), and were particularly susceptible to CMh (P<0.001). Cattle that were 1-3 years of age were more susceptible to infection with hemoplasma compared with other age groups. Bovine leukemia virus infection status was not significantly associated with hemoplasma infections. Blood examination revealed significantly lower RBC, Hb, and PCV levels, and a higher MCV in infected cattle than in noninfected cattle.


Results of 2 decades of injury surveillance and public release of data in the Australian Football League.
Injuries are common in all professional football codes (including soccer, rugby league and union, American football, Gaelic football, and Australian football). To report the epidemiology of injuries in the Australian Football League (AFL) from 1992-2012 and to identify changes in injury patterns during that period. Descriptive epidemiology study. The AFL commenced surveying injuries in 1992, with all teams and players included since 1996. An injury was defined as "any physical or medical condition that causes a player to miss a match in the regular season or finals (playoffs)." Administrative records of injury payments (which are compulsory as part of salary cap compliance) to players who do not play matches determined the occurrence of an injury. The seasonal incidence was measured in units of new injuries per club (of 40 players) per season (of 22 matches). There were 4492 players listed over the 21-year period who suffered 13,606 new injuries/illnesses and 1965 recurrent injuries/illnesses, which caused 51,919 matches to be missed. The lowest seasonal incidence was 30.3 new injuries per club per season recorded in 1993, and the highest was 40.3 recorded in 1998. The injury prevalence (missed matches through injury per club per season) varied from a low of 116.3 in 1994 to a high of 157.1 in 2011. The recurrence rate of injuries was highest at 25% in 1992 and lowest at 9% in 2012 and has steadily fallen across the 21 years (P < .01). The most frequent and prevalent injury was hamstring strain (average of 6 injuries per club per season, resulting in 20 missed matches per club per season; recurrence rate, 26%), although the rate of hamstring injuries has fallen in the past 2 seasons after a change to the structure of the interchange bench (P < .05). The rate of knee posterior cruciate ligament injuries fell in the years after a rule change to prevent knee-to-knee collisions in ruckmen (P < .01). Annual public reporting (by way of media release and reports available freely online) of injury rates, using units easily understood by laypeople, has been well received. It has also paved the way for rule changes with the primary goal of improving player safety.


Protective Mechanism of Leucine and Isoleucine against H2O2-Induced Oxidative Damage in Bovine Mammary Epithelial Cells.
Leucine and isoleucine possess antioxidative and anti-inflammatory properties. However, their underlying protective mechanisms against oxidative damage remain unknown. Therefore, in this study, the protective mechanism of leucine and isoleucine against H2O2-induced oxidative damage in a bovine mammary epithelial cell lines (MAC-T cells) were investigated. Briefly, MAC-T cells exposed or free to H2O2 were incubated with different combinations of leucine and isoleucine. The cellular relative proliferation rate and viability, oxidative stress indicators, and inflammatory factors were determined by specific commercial kits. The genes related to barrier functions was measured by real-time quantitative PCR. The protein expression differences were explored by 4D label-free quantitative proteomic analyses and validated by parallel reaction monitoring. The results revealed that leucine and isoleucine increased cell proliferation, total antioxidant status (TAS), and the relative mRNA expression of occludin, as well as decreased malondialdehyde (MDA), total oxidant status (TOS)/TAS, IL-6, IL-1β, and TOS. When leucine and isoleucine were combined, MDA, TOS/TAS, and the relative mRNA expression levels of claudin-1, occludin, and zonula occludens-1 increased when compared to leucine or isoleucine alone. Proteomics analyses revealed that leucine significantly upregulated the propanoate metabolism; valine, leucine, and isoleucine degradation; and thermogenesis pathways, whereas isoleucine significantly upregulated the peroxisome and propanoate metabolism pathways. In conclusion, leucine protected MAC-T cells from H2O2-induced oxidative stress by generating more ATP to supplement energy demands, and isoleucine improved the deficit in peroxisome transport and promoted acetyl-CoA production. The findings of this study enhance our understanding of the protective mechanisms of leucine and isoleucine against oxidative damage.


A Review of Ginseng Clinical Trials Registered in the WHO International Clinical Trials Registry Platform.
Although ginseng has long been broadly used in clinical settings around the world, few clinical trials on ginseng have been conducted. The objective of this study was to provide a comprehensive evaluation of the characteristics of ginseng clinical trials registered in the WHO International Clinical Trials Registry Platform (ICTRP) as of December 2017 regarding their frequency, design, type of ginseng, dosage, duration, condition, funding sources, and publication status. A total of 134 ginseng clinical studies were registered from 2002 to 2017, of which 60.4% were completed and 23.1% are actively recruiting participants. A large number of trials were associated with aspects of high-quality trial design. Overall, 94% of the trials employed randomized allocation to study arms, 78.4% were double-blind studies using placebo as one of the control groups, and 71% were published as completed trials. Trials whose sample size was restricted to fewer than 100 participants accounted for 74.7% of the total. Of the primary funding sources for ginseng studies, 67.2% were nonindustry organizations. The ginseng clinical trials were heterogeneous with respect to ginseng species and variety, indications, dose, duration, and participant characteristics. Clearly, stricter and methodologically suitable studies are needed to demonstrate the efficacy and safety of ginseng.


Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells.
A series of artemisinin-related endoperoxides was tested for cytotoxicity to Ehrlich ascites tumor (EAT) cells using the microculture tetrazolium (MTT) assay. Artemisinin [1] had an IC50 value of 29.8 microM. Derivatives of dihydroartemisinin [2], being developed as antimalarial drugs (artemether [3], arteether [4], sodium artesunate [5], artelinic acid [6], and sodium artelinate [7]), exhibited a somewhat more potent cytotoxicity. Their IC50 values ranged from 12.2 to 19.9 microM. The presence of an exocyclic methylene fused to the lactone ring, as for artemisitene [9], led to higher cytotoxicity than 1. From the two epimeric 11-hydroxyartemisinin derivatives, the R form 12 showed a considerably higher cytotoxicity than the S form 13. Opening of the lactone ring of 1 dramatically reduced the cytotoxicity. The ether dimer 8 of 2 was the most potent cytotoxic agent, its IC50 being 1.4 microM. The variations in cytotoxicity between the structurally related compounds mostly correlated well with the theoretical capacity of radical formation and stabilization. In some cases lipophilicity or the presence of an electrophilic moiety seemed to have a determinant influence on cytotoxicity. The artemisinin-related endoperoxides showed cytotoxicity to EAT cells at higher concentrations than those needed for in vitro antimalarial activity, as reported in the literature.


Cross-cultural issues in European bioethics.
European biomedical ethics is often contrasted to American autonomy-based approaches, and both are usually distinguished as 'Western'. But at least three 'different voices' within European bioethics can be identified: the deontological codes of southern Europe (and Ireland), in which the patient has a positive duty to maximise his or her own health and to follow the doctor's instructions, whilst the physician is constrained more by professional norms than by patient rights; the liberal, rights-based models of Western Europe, in which the patient retains the negative right to override medical opinion, even if his or her mental capacity is in doubt; the social welfarist models of the Nordic countries, which concentrate on positive rights and entitlements to universal healthcare provision and entrust dispute resolution to non-elected administrative officials.


Potassium-stimulated taurine release and nitric oxide synthase activity during quinolinic acid lesion of the rat striatum.
The microdialysis technique was used to study the effect of nitric oxide synthase (NOS) activity on taurine release. Taurine release was characterized in rat striatum that was excitotoxically lesioned compared to normal conditions. The basal taurine level of the dialysate decreased during quinolinate (QUIN) lesion in parallel to the cell degeneration process. The K+-stimulated taurine concentration also decreased during QUIN-lesion, but to an extent that was different from that of basal values. K+-stimulated taurine levels were further markedly lowered by coapplication of the NOS inhibitor L-NAME in control and in lesioned animals up to 30 days after QUIN-injection. Postdegenerative tissue did not show any NOS-dependency in K+-induced taurine release. We conclude that a substantial part of K+-induced taurine release depends on NOS-activity both in normal brain tissue and in excitotoxically induced neurodegeneration. The main source of K+-induced taurine release in control rats are neurons but in lesioned animals are activated astroglial cells.


Conducting fresh whole blood transfusion training.
Fresh whole blood is the optimal resuscitation fluid for casualties in hemorrhagic shock according to the Committee on Tactical Combat Casualty Care and has demonstrated to improve outcomes in severely wounded patients. Like all medical interventions, fresh whole blood transfusions are not without risks, but similarly can be mitigated through increased training to develop provider knowledge and proficiency. To date, no literature has been published regarding the proper technique to conduct fresh whole blood transfusion training. This article provides a structured foundation to establish a standardized fresh whole blood transfusion training program to increase skill and preparedness for fresh whole blood protocol implementation. Using these techniques in a training environment, providers will be able to provide optimal resuscitation in hemorrhagic shock in austere environments.


Near-infrared spectroscopy in the assessment of cerebral oxygenation at high altitude.
Hypoxia plays a key role in the pathogenesis of acute mountain sickness (AMS), but individual susceptibility is variable and cerebral symptoms do not always correlate with PaO2 measurements. Cerebral hypoxia may be more relevant than PaO2. We studied trends in cerebral regional oxygen saturation by the technique of near-infrared spectroscopy in 20 subjects ascending rapidly to 4680 m. Subjects were enrolled in a placebo-controlled, double-blind trial of medroxyprogesterone for the prevention of AMS. The fall in cerebral oxygen saturation was less than in the periphery. At 4680 m, cerebral oxygenation correlated with peripheral saturation but not with PaCO2 or with cerebral symptoms scores. At 4680 m, subjects on medroxyprogesterone had higher cerebral and peripheral saturation compared with those on a placebo. We conclude that cerebral oxygenation monitored with the Critikon 2020 system provided important information on the complex relationship of hypoxia to AMS and that other factors, such as changes in blood flow or capillary permeability, may be equally important.


Ethylene causes transcriptomic changes in Synechocystis during phototaxis.
Ethylene is well known as a plant hormone, but its role in bacteria is poorly studied. We recently showed that Synechocystis sp. Strain PCC 6803 has a functional receptor for ethylene, ethylene response 1 (Etr1), that is involved in various processes such as phototaxis in response to directional light and biofilm formation. Here, we use RNA sequencing to examine the changes in gene transcripts caused by ethylene under phototaxis conditions. Over 500 gene transcripts across many functional categories, of approximately 3700 protein-encoding genes, were altered by application of ethylene. In general, ethylene caused both up- and downregulation of genes within a functional category. However, the transcript levels of amino acid metabolism genes were mainly upregulated and cell envelope genes were mostly downregulated by ethylene. The changes in cell envelope genes correlate with our prior observation that ethylene affects cell surface properties to alter cell motility. Ethylene caused a twofold or more change in 62 transcripts with the largest category of upregulated genes annotated as transporters and the largest category of downregulated genes annotated as glycosyltransferases which sometimes are involved in changing the composition of sugars on the cell surface. Consistent with changes in cell envelope, glycosyltransferase, and transporter gene transcripts, application of ethylene altered the levels of specific sugar moieties on the surface of cells. Light signaling from Etr1 involves two proteins (Slr1213 and Slr1214) and a small, noncoding RNA, carbon stress-induced RNA1 (csiR1). Application of ethylene caused a rapid, but transient, decrease in the transcript levels of etr1, slr1213, and slr1214 and a rapid and prolonged decrease in csiR1 transcript. Deletion of Slr1214 caused a large increase in csiR1 transcript levels and ethylene lowered csiR1 transcript. These data combined with prior reports indicate that ethylene functions as a signal to affect a variety of processes altering the physiology of Synechocystis cells.


Proximal aortic stiffness is related to left ventricular function and exercise capacity in patients with dilated cardiomyopathy.
Patients with heart failure (HF) show abnormal arterial stiffening. We examined 60 patients (52.1 +/- 12, 8 years) with non-ischaemic dilated cardiomyopathy (NIDC), New York Heart Association II-III, in sinus rhythm, left ventricular ejection fraction 30.1 +/- 8.6%, and 44 normals. All subjects underwent an echocardiographic study and a cardiopulmonary exercise test. We evaluated the segmental proximal aorta (AO) pulse wave velocity (PWV) in the region of aortic arch with a new echo-method: from the suprasternal view, the distance between ascending and descending AO was measured with two-dimensional ultrasound, and the aortic flow wave transit time (TT) was measured with pulsed-wave Doppler. Pulse wave velocity was calculated as aortic distance/TT. Patients showed increased PWV (7.4 +/- 2.9 vs. 4.8 +/- 1.1 m/s, P < 0.001), compared with controls. Patients with advanced left ventricular (LV) (restrictive or pseudo-normal filling pattern) diastolic dysfunction showed increased PWV (8.6 +/- 2.6 vs. 6.6 +/- 2.9 m/s, P = 0.01) and reduced peak and predicted (for age, sex, and body mass) VO(2) (both P < 0.001), compared with those with mild diastolic dysfunction (delayed relaxation filling pattern). Pulse wave velocity was significantly correlated with the LV mass (r = 0.32, P = 0.01), the peak spectral tissue Doppler imaging systolic wave (r = -0.34, P = 0.006), the LV diastolic filling pattern (r = 0.42, P = 0.001), and the peak (r = -0.47, P < 0.001) and predicted VO(2) (r = -0.579, P < 0.001). Patients with NIDC showed increased proximal aortic stiffness, which relates to LV systolic and diastolic function and exercise capacity. The echocardiographic assessment of the regional aorta PWV seems to be clinically important.


Period-adding route in sparkling bubbles.
Chains of bubbles are seen rising along the wall whenever champagne is poured into a glass. The careful observation of a given bubble chain often reveals that the interbubble distance suddenly changes during the degassing process, indicating different bubbling regimes in this elusive phenomenon of effervescence. We report the transitions between these different bubbling regimes that present sequences of multiple periods known as the period-adding route.


Cross-cultural adaptation and validation of the Danish 10-item Connor-Davidson Resilience Scale among hospital staff.
The 10-item Connor-Davidson Resilience Scale (CD-RISC 10) is a brief instrument measuring resilience in adults. The scale has shown sound psychometric properties in different populations and cultures. Our objectives were to cross-culturally adapt the CD-RISC 10 into Danish and to establish the psychometric properties of the Danish version in terms of internal consistency, construct validity and longitudinal validity. The CD-RISC 10 was translated using established guidelines. Employees ( N=272) at hospitals in the Central Denmark Region completed questionnaires at baseline and three months follow-up. Questionnaires included the translated Danish version of the CD-RISC 10 and the 10-item Perceived Stress Scale (PSS-10). Internal consistency was assessed by Cronbach's alpha and construct and longitudinal validity by correlating CD-RISC 10 and PSS-10 baseline scores and change scores from baseline to follow-up. The Danish CD-RISC 10 provides acceptable internal consistency (Cronbach's alpha = 0.87). Analysis of construct validity revealed a negative correlation with the PSS-10 at baseline ( r=-.63 [95%CI: -.70; -.55], p<.0001). Analysis of longitudinal validity similarly demonstrated a negative correlation on change scores from baseline to follow-up ( r=-.51 [95%CI: -.62; -.39], p<.0001). The scale has acceptable psychometric properties as an instrument for measuring resilience in a Danish-speaking population.


Antibiotic sensitivity of Salmonella strains from food-handlers in the period 1980-1988 in Italy.
Throughout the past nine years, between 1980 and 1988, we tested 1,205,257 food-handlers as Salmonella carriers in Milan. We isolated 20,286 Salmonella strains with annual average prevalence of 1.68%, fairly costant in recent years. The serotype isolated confirm the prevalence of minor Salmonella, such as S. thypimurium, S. panama, S. anatum, S. london, S. derby, S. infantis, S. heidelberg, S. bredeney, S. braenderup. The frequency of new strains decreased from 15 in 1980 to 1 in 1988 and these were infrequent serogroups. Salmonella strains isolated were generally sensitive to aminoglycoside antibiotics (tobramycin, netilmicin), while they were often resistant to rifampicin, aztreonam, and sometimes to cefuroxime and tetracycline with multiple-resistance.


Prospective and concurrent correlates of emotion perception in psychotic disorders: a naturalistic, longitudinal study of neurocognition, affective blunting and avolition.
This naturalistic study investigated longitudinal and cross-sectional symptomatic and neurocognitive correlates of social cognition indexed by emotion perception. Participants were 31 persons admitted to a psychiatric emergency ward due to acute psychosis. Positive and negative (i.e., affective blunting and avolition) symptoms were assessed at baseline and 12-month follow-up using the Positive and Negative Syndrome Scale. Participants completed neuropsychological assessments with alternative versions of the Repeatable Battery for the Assessment of Neuropsychological Status at baseline and at 12-month follow-up. Emotion perception was measured using the Face/Voice Emotion Test at 12-month follow-up. Correlational analyses (Spearman's rho) revealed strong and statistically significant associations between neurocognition and emotion perception (baseline r = 0.58, follow-up r = 0.43). Associations between positive symptoms and emotion perception were weak or non-existent (baseline r = 0.13, follow-up r = -0.01). Emotion perception was moderately, but not significantly, associated with affective blunting at follow-up (r = 0.33), but not at baseline (r = 0.21). The association with avolition was non-existent (baseline r = -0.05, follow-up r = 0.01). This study supports the notion that emotion perception has neurocognitive correlates. The cross-sectional trend level association with affective blunting suggests that the ability to perceive emotions might be related to, but dissociable from the ability to express emotions.


Accumulation of glyceryl ether lipids in Wolman's disease.
We have shown that ether-linked glycerolipids accumulated in the adrenal, liver, and spleen of a male Chinese infant with Wolman's disease; the increases were mainly in the alkyl and alk-1-enyl glycerolipids that did not contain phosphorus. Alkyldiacylglycerol accounted for a portion of the rise in the neutral alkylglycerols. The spleen also contained increased amounts of ether-linked phosphoglycerides of the alkyl and alk-1-enyl types. Organs from a Niemann-Pick patient were also included in this study; they did not show comparable rises in the content of ether-linked glycerolipids, suggesting the possibility that storage of these compounds may be characteristic of Wolman's disease, or a variant form thereof.


Milestones in the study of bladder tumors and the contribution of Sir Henry Thompson (1820-1904).
We tried through this paper to present briefly the history of the study of bladder tumors and to underline the contribution of Sir Henry Thompson - outstanding British urologist - on that field.