Solution structure of IsTX. A male scorpion toxin from Opisthacanthus madagascariensis (Ischnuridae).
The novel sex-specific potassium channel inhibitor IsTX, a 41-residue peptide, was isolated from the venom of male Opisthacanthus madagascariensis. Two-dimensional NMR techniques revealed that the structure of IsTX contains a cysteine-stabilized alpha/beta-fold. IsTX is classified, based on its sequential and structural similarity, in the scorpion short toxin family alpha-KTx6. The alpha-KTx6 family contains a single alpha-helix and two beta-strands connected by four disulfide bridges and binds to voltage-gated K(+) channels and apamin-sensitive Ca(2+)-activated K(+) channels. The three-dimensional structure of IsTX is similar to that of Heterometrus spinifer toxin (HsTX1). HsTX1 blocks the Kv1.3 channel at picomolar concentrations, whereas IsTX has much lower affinities (10 000-fold). To investigate the structure-activity relationship, the geometry of sidechains and electrostatic surface potential maps were compared with HsTX1. As a result of the comparison of the primary structures, Lys27 of IsTX was conserved at the same position in HsTX1. The analogous Lys23 of HsTX1, the most critical residue for binding to potassium channels, binds to the channel pore. However, IsTX has fewer basic residues to interact with acidic channel surfaces than HsTX1. MALDI-TOF MS analysis clearly indicated that IsTX was found in male scorpion venom, but not in female. This is the first report that scorpion venom contains sex-specific compounds.


Capacitative Ca2+ influx in glial cells is inhibited by glycolytic inhibitors.
In non-excitable cells, stimulation of phosphoinositide (PI) turnover and inhibition of the endoplasmic reticulum (ER) Ca2+-ATPase are methods commonly used to deplete calcium stores, resulting in a capacitative Ca2+ influx (i.e., Ca2+ release-activated Ca2+ influx). Since this Ca2+ influx in glial cells has not been thoroughly investigated, we have used C6 glioma cells as a glial cell model to study this phenomenon. On adding cyclopiazonic acid (CPA) or thapsigargin (TG) (two ER Ca2+-ATPase inhibitors) in Ca2+-free medium, only a small transient increase in intracellular Ca2+ was seen. After depletion of the stored Ca2+, a marked Ca2+ influx, followed by a prolonged plateau, was seen on re-addition of extracellular Ca2+ ions (2 mM), i.e., capacitative Ca2+ influx. A similar effect was seen on adding ATP, known to deplete the inositol triphosphate (IP3)-sensitive Ca2+ store in C6 cells. After various degrees of store depletion, the amplitude of the capacitative Ca2+ influx was found to be highly dependent on the amount of Ca2+ remaining in the store. This Ca2+ influx was markedly inhibited by (1) La3+ and Ni2+, (2) SK&F 96365, econazole, and miconazole, and (3) membrane depolarization, clearly showing that this Ca2+ influx after store depletion in C6 cells is a capacitative mechanism. Interestingly, the capacitative Ca2+ influx can be inhibited by a reduction in intracellular ATP (ATPi) levels in glial cells. The role of ATPi in the capacitative Ca2+ influx is discussed.


[Comparison of the results of the treatment of patients with SSPE using various immunomodulating preparations].
The authors analysed the results of controlled treatment by three methods of patients in the 1st or 2nd phase of SSPE in a randomized group. The groups received: I. Propionibacterium granulosum KP-45 (interferon inducer) + isoprinosine, II--TFX (thymus extract) + isoprinosine, III--only isoprinosine. In all groups the treatment was continued during 6 months. The analysis of the clinical results of these methods failed to demonstrate a statistically significant superiority of any of these methods (among others, due to small number of cases) but an evident statistical tendency was revealed suggesting a better effectiveness of combined treatment (immunostimulator + isoprinosine) in relation to treatment with isoprinosine only. The final evaluation of the results requires further observations of these patients.


Severe venous and lymphatic obstruction after single-chamber pacemaker implantation in a patient with chest radiation therapy.
A 73-year-old woman with a history of paroxysmal atrial fibrillation, sinus node dysfunction, bilateral breast cancer, and extensive chest radiation developed progressive edema, dyspnea, and recurrent pleural effusions soon after single-chamber pacemaker implantation. Thoracentesis yielded a diagnosis of chylothorax, and progressive refractory anasarca developed. A computed tomography angiogram suggested obstruction of the superior vena cava and left subclavian vein despite outpatient therapeutic anticoagulation. Autopsy confirmed venous thrombosis, along with mediastinal fibrosis. The presumed etiology of the chylothorax and anasarca was obstruction of the atretic central venous structures following pacemaker implantation, critically impairing the already tenuous venous and lymphatic drainage. (PACE 2010; 520-524).


HL-60 cells degrade alpha-actinin to produce a fragment that promotes monocyte/macrophage maturation.
An amino-terminal fragment of alpha-actinin can promote monocyte/macrophage maturation. This fragment was initially isolated from media of HL-60 myeloid leukemia cells cultured on extracellular bone marrow matrix. To determine the source of this fragment in this culture system, we investigated whether HL-60 cells grown on bone marrow stroma have increased intracellular levels of alpha-actinin that may be released into the media during cell apoptosis. HL-60 cells grown on matrix showed no evidence of increased cellular alpha-actinin compared to cells grown on plastic substrata as measured by flow cytometry. In addition, there was no evidence of increased apoptosis as determined by DNA fragmentation assays or flow cytometry. However, 100 kD alpha-actinin was found in the extracellular matrix of bone marrow stroma by Western blot analysis and immunofluorescence microscopy. The alpha-actinin content in the stroma was markedly decreased after exposure to HL-60 cells. Furthermore, lysates of HL-60 cells or of peripheral blood monocytes can degrade exogenous alpha-actinin to produce a 31 kD fragment, which promotes monocyte/macrophage maturation. We conclude that when alpha-actinin is present in the extracellular matrix, it can be modified by HL-60 cells to produce a maturation promoting 31 kD fragment.


The effects of media on pharmaceutically relevant transporters in the human HT-29 adenocarcinoma cell line: does culture media need to be controlled?
The HT-29 cell line forms a confluent monolayer with tight junctions, but displays different phenotypes when cultured for 21 days in galactose-supplemented media (differentiated) versus glucose-supplemented media (dedifferentiated). This study is aimed at elucidating how media differences might affect selected drug transporter expression and peptide-based substrate transport toward reducing this variability. A vial of HT-29 cells was amplified and cultured over several passages in four different mediums (American Type Culture Collection recommended McCoy's 5A versus Dulbecco's modified Eagle's media containing glucose, galactose, or neither carbohydrate) with normal supplementation. Transporter mRNA expression was characterized at days 5 and 21 postseeding utilizing SABiosciences quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) drug transporter arrays. Transport studies using [H]histidine, [(3) H]glycylsarcosine, [(3) H]valacyclovir, and [(3) H]carnosine were performed to assess the functional effects of oligopeptide transporter expression changes in HT-29 cells grown in each media. qRT-PCR arrays illustrated variable, media-dependent transporter expression between both the initial and differentiated time points. Permeability studies illustrated considerable media-dependent differences in both paracellular and transcellular substrate fluxes. The results demonstrate that these cells exhibit differing monolayer characteristics and genotypic/phenotypic profile properties when cultured under different media. The results suggest a need for standardization of culture methodologies for reducing inter- and intralaboratory variability.


Linear IgA disease: successful treatment with erythromycin.
Conventional first-line treatments for linear IgA disease (and the related chronic immunobullous disease of childhood) include topical steroids and dapsone, both of which may be associated with potentially serious side-effects. Alternative anti-inflammatory therapies such as tetracycline and macrolide antibiotics, have been used to treat other immunobullous disorders and we now report an adult case of linear IgA disease and a paediatric case of mixed immunobullous disease of childhood that both responded to the macrolide antibiotic erythromycin. The mode of action is speculative and anti-inflammatory mechanisms are unclear. Nevertheless, from a clinical perspective, erythromycin may have a role in the treatment of linear IgA disease and could be considered ahead of many other, perhaps potentially more toxic, therapies.


Transgenic and knockout models for studying the role of lung antioxidant enzymes in defense against hyperoxia.
Although a role for antioxidant enzymes in preventing lung injury from hyperoxic exposure has been implicated in a number of early studies, a direct test for the hypothesis was not available. We intended to address this question using genetically modified mice in which the expression of a single antioxidant enzyme was either enhanced or diminished. We reasoned that if an antioxidant enzyme functions in protecting lung cells against oxidant-mediated injury, the level of its gene expression would correlate with the degree of tolerance to hyperoxia. Overexpression of functional human manganese superoxide dismutase (MnSOD) in lung alveolar type I and type II cells, fibroblasts, and capillary endothelial cells in strain B6C3 mice was achieved by incorporating a human beta-actin promoter-based MnSOD transgene into the mouse genome. However, MnSOD overexpression failed to prolong the survival of transgenic mice on exposure to greater than 99% oxygen compared with wild-type mice. In addition, mice deficient in copper-zinc superoxide dismutase or cellular glutathione peroxidase exhibited a marked sensitivity to numerous models of oxidant tissue injury but were not hypersensitive to hyperoxia. These data suggest that the role of these three antioxidant enzymes in preventing oxidant-mediated lung injury from hyperoxic exposure is negligible, and other cellular antioxidant enzymes and systems may be primarily used by the lungs in defense against hyperoxia.


Functionally Expression of Metalloproteinase in Taenia solium Metacestode and Its Evaluation for Serodiagnosis of Cysticercosis.
Parasite proteases have important roles in cleavage of host proteins during the invasion of host tissues and participate in the parasite's evasion from the host's immune response. The aim of the present study was to estimate a metalloproteinase properties of Taenia solium metacestode (TsMP) during host-parasite interactions, and evaluate its potential as a serodiagnostic antigen for cysticercosis. The cDNA coding for the mature catalytic domain of TsMP was cloned into pGEX-6P-1 expression vector. A recombinant glutathione S-transferase and TsMP fusion protein was induced. After refolding and purification, enzymatic properties of the recombinant metalloproteinase were observed. Immunoblot assay was processed to evaluate its potential as a serodiagnostic antigen for cysticercosis. The recombinant TsMP protein showed proteolytic activity, which preferred host extracellular matrix proteins such as collagen and fibronectin as degradable substrates. In immunoblot assay, 87.5% of sera from patients with cysticercosis showed strong reactivity. In sera from patients with other parasitic infections and from normal controls, it showed high specificity. TsMP might be involved in the processing of numerous host proteins and play an important role in the parasite life cycle. A single recombinant TsMP antigen could have a potential value for serodiagnosis of cysticercosis.


[SEB--an instrument for the assessment of therapeutic processes in inpatient psychotherapy].
The Stationserfahrungsbogen (Record Sheet and Questionnaire on the experience of the inpatient therapeutic process--SEB) is an instrument to assess process aspects during inpatient psychotherapy. Weekly presentation and completion of the sheet shows changes in selected aspects of patient experience. 38 items cover the following aspects (scales): relations with the therapeutic team, relations with the individual therapist, group climate (cohesion), attention from fellow patients, intensity of treatment, therapeutic rules, self-efficacy. The questionnaire can be applied in clinical and research areas and is also useful for quality management of therapeutic institutions. Single-case studies using SEB facilitate clinical discussion and understanding of therapeutic processes. In psychotherapy research the instrument can be used to assess common and specific factors of therapeutic effects. By comparison with norm scores and SEB can also be used for the evaluation of process and outcome quality. The questionnaire can be applied economically and with good patient compliance. It is objective and has clinical validity and is of great informative value. Internal consistency of the individual scales is good to satisfactory.


Piroxicam-induced regression of azoxymethane-induced aberrant crypt foci and prevention of colon cancer in rats.
Piroxicam has been shown to prevent azoxymethane (AOM)-induced aberrant crypt foci and colon cancer in rats. In this communication we evaluate whether piroxicam can also cause regression of precancerous lesions identified as aberrant crypt foci, thus preventing the occurrence of cancer. Male Fischer-344 rats were administered 0.125 g/kg piroxicam in their diet starting either 1 week prior to or 12 weeks after a single subcutaneous injection of AOM (30 mg/kg body wt). The yield of aberrant crypt foci and of colon adenomas and adenocarcinomas was determined at 5, 12, 27 and 37 weeks after administering the AOM respectively. When piroxicam was administered starting 1 week prior to AOM the yield of aberrant crypt foci at the three initial time points was reduced. When the administration of piroxicam was delayed until 12 weeks after AOM the yield of aberrant crypt foci was reduced from 53.8 +/- 8.1 foci/colon at 12 weeks to 11.1 +/- 2.0 at 27 weeks. At 37 weeks after administering AOM the yield of colon tumors was 0.59 +/- 0.11 tumors/animal, while in rats administered piroxicam beginning either 1 week prior to or 12 weeks after AOM the yield was similarly reduced to 0.14 +/- 0.07 and 0.17 +/- 0.07 tumors/animal respectively. Thus piroxicam was demonstrated not only to prevent, but also to cause regression of aberrant crypt foci, both of which were associated with the prevention of colon tumors.


Understanding the Gastrointestinal Protective Effects of Polyphenols using Foodomics-Based Approaches.
Plant polyphenols are rich sources of natural anti-oxidants and prebiotics. After ingestion, most polyphenols are absorbed in the intestine and interact with the gut microbiota and modulated metabolites produced by bacterial fermentation, such as short-chain fatty acids (SCFAs). Dietary polyphenols immunomodulatory role by regulating intestinal microorganisms, inhibiting the etiology and pathogenesis of various diseases including colon cancer, colorectal cancer, inflammatory bowel disease (IBD) and colitis. Foodomics is a novel high-throughput analysis approach widely applied in food and nutrition studies, incorporating genomics, transcriptomics, proteomics, metabolomics, and integrating multi-omics technologies. In this review, we present an overview of foodomics technologies for identifying active polyphenol components from natural foods, as well as a summary of the gastrointestinal protective effects of polyphenols based on foodomics approaches. Furthermore, we critically assess the limitations in applying foodomics technologies to investigate the protective effect of polyphenols on the gastrointestinal (GI) system. Finally, we outline future directions of foodomics techniques to investigate GI protective effects of polyphenols. Foodomics based on the combination of several analytical platforms and data processing for genomics, transcriptomics, proteomics and metabolomics studies, provides abundant data and a more comprehensive understanding of the interactions between polyphenols and the GI tract at the molecular level. This contribution provides a basis for further exploring the protective mechanisms of polyphenols on the GI system.


Winter stem xylem pressure in walnut trees: effects of carbohydrates, cooling and freezing.
Pressure transducers were attached to twigs of orchard trees and potted trees of walnut (Juglans regia L.) to measure winter stem xylem pressures. Experimental potted trees were partially defoliated in the late summer and early autumn to lower the amount of stored carbohydrates. Potted trees were placed in cooling chambers and subjected to various temperature regimes, including freeze-thaw cycles. Xylem pressures were inversely proportional to the previous 48-h air temperature, but positively correlated with the osmolarity of the xylem sap. Defoliated trees had significantly lower concentrations of stored carbohydrates and significantly lower xylem sap osmolarities than controls. Plants kept at 1.5 degrees C developed xylem pressures up to 40 kPa, just 7% of the theoretical osmotic pressure of the xylem sap. However, exposure to low, nonfreezing temperatures followed by freeze-thaw cycles resulted in pressures over 210 kPa, which was 39% of the theoretical osmotic pressure. A simple osmotic model could account for the modest positive winter pressures at low, nonfreezing temperatures, but not for the synergistic effects of freeze-thaw cycles.


1,3-Aminoalkoxylation and phenolation/dimerization of maleimide-derived Morita-Baylis-Hillman adduct of isatin via domino azidation-Michael addition/aza-Diels-Alder reaction.
NaN3-ROH/ArOH has been found to be an efficient reagent for 1,3-amino alkoxylation and 1,3-amino phenolation of a maleimide-derived MBH adduct of isatin via domino azidation-Michael addition. Following this protocol, with NaN3-formalin, a one-pot synthesis of 3-spiro-1,2-dihydropyrrolooxazine-5,7-dione-oxindole has been achieved. In an aprotic medium, the reaction underwent an unusual amino dimerization via an aza-Diels-Alder reaction of a common allylic imine intermediate.


[Integration of tuberculosis care into general hospitals in the United States].
In Japan we are now urged to rethink and reform the present ward-centered institutional system of clinical service for tuberculosis (TB). To provide useful information for this rethinking and reform, we performed a literature review of the process of integrating TB service into general hospitals in the US. Literature review. The process of integrating TB service into general hospitals in USA began around 1970, and continued until around 1980, when it was almost complete. From the experience and opinions of the authors reviewed, the following points were found to be important to successful integration: establishing an efficient outpatient department, maintaining patients' adherence to treatment, using a long-term care facility for TB patients requiring long-term in-hospital care, planning a program for integration of care fully in advance, individualizing the program according to the region, adopting a phased step-by-step program, educating hospital staff and securing financial support from governments. The reform of tuberculosis wards in Japan will occur at the same time as the reform of the country's TB control program, and will provide a good opportunity to improve our program.


Vaccination against influenza with recombinant hemagglutinin expressed by Schizochytrium sp. confers protective immunity.
For the rapid production of influenza vaccine antigens in unlimited quantities, a transition from conventional egg-based production to cell-based and recombinant systems is required. The need for higher-yield, lower-cost, and faster production processes is critical to provide adequate supplies of influenza vaccine to counter global pandemic threats. In this study, recombinant hemagglutinin proteins of influenza virus were expressed in the microalga Schizochytrium sp., an established, fermentable organism grown in large scale for the manufacture of polyunsaturated fatty acids for animal and human health applications. Schizochytrium was capable of exporting the full-length membrane-bound proteins in a secreted form suitable for vaccine formulation. One recombinant hemagglutinin (rHA) protein derived from A/Puerto Rico/8/34 (H1N1) influenza virus was evaluated as a vaccine in a murine challenge model. Protective immunity from lethal challenge with homologous virus was elicited by a single dose of 1.7, 5 or 15 µg rHA with or without adjuvant at survival rates between 80-100%. Full protection (100%) was established at all dose levels with or without adjuvant when mice were given a second vaccination. These data demonstrate the potential of Schizochytrium sp. as a platform for the production of recombinant antigens useful for vaccination against influenza.


Clinical and laboratory evaluation of schistosomiasis mansoni patients in Brazilian endemic areas.
A total of 60% of the territory of Alagoas (AL) is considered endemic for the occurrence of schistosomiasis and the classification of clinical forms of the disease are not known. This paper aimed to evaluate an endemic schistosomiasis population in AL, taking into account the prevalence, classification of the clinical forms and the results of laboratory analyses. The sample consisted of residents in endemic areas. The participants were submitted to a stool examination by the Kato-Katz technique and the diagnosis was based on the reading of two microscopic slides for each sample. The patients whose examinations were positive for schistosomiasis mansoni were submitted to a clinical examination and blood collection. Based on this examination, 8.11% of the study population were positive for schistosomiasis. The medium parasite load was 79.1 +/- 174.3 eggs. The intestinal (90.57%) and hepatointestinal (9.43%) forms were found at statistically significant levels (p < 0.001). The results of the present study update information on schistosomiasis in the city of Rio Largo. These data, although referring only to three locations in that city, suggest a decrease either in the parasite load or in the severity of clinical forms.


RNA editing and short variant of serotonin 2C receptor mRNA in neuronally differentiated NG108-15 cells.
Two types of serotonin 2C subtype receptor mRNA, receptor-type and short variant, has been reported. The expression of the receptor-type mRNA could be detected as well as the short variant in NG108-15 cells by using a high temperature stable reverse transcriptase and the expression of the receptor-type mRNA was enhanced in drug-induced neuronal differentiated cells. The deleted sequence of the short variant include the RNA editing site by adenosine deaminase. Analysis of the sequence at the editing site revealed that the mRNA of undifferentiated cells was highly edited at sites A and B and that cytosine deaminase activity may also be involved in neuronal differentiation.


Inhibition of cellular proliferation by cyclosporin A during compensatory renal growth: flow cytometric analysis.
Cell cycle analysis using flow cytometer (FCMX) was performed to evaluate the influence of cyclosporin A (CsA) on cellular proliferation during compensatory renal growth (CRG) in uninephrectomized (Ux) rats. CsA (50 mg/kg/day) was administered subcutaneously for 7 days and animals were scarificed 0, 12, 24, 48, 72, 120 and 168 h after Ux. The percent changes in the S (DNA synthesis) and G2M (DNA replication) phases in the contralateral kidney were analyzed. The cortical cells entering the S and G2M phases showed significant differences between CsA and vehicle groups (p = 0.0001, p = 0.001, respectively), but the medullary cells entering the S and G2M phases showed no significant differences between the 2 groups (p = 1.000, respectively). In the cortex, the CsA group showed a significant decrease in the S (at 12, 72 and 120 h) and G2M phases (at 24, 72 and 120 h) compared to the vehicle group (p < 0.05, respectively), but there was no significant difference in the medulla. In conclusion, cellular proliferation is suppressed in cortical cells by CsA.


Endocytosis of the recombinant tissue plasminogen activator alteplase by hepatic endothelial cells.
The glycoprotein tissue-type plasminogen activator (t-PA, alteplase, CAS 105857-23-6) is a serine protease consisting of 527 amino acids and can activate plasminogen to plasmin, which subsequently dissolves the fibrin network of a thrombus. This activation occurs selectively on the thrombus, making recombinant t-PA a very effective agent in the treatment of thromboembolic disorders. t-PA has a short in vivo half-life and is rapidly removed from the circulation by the liver. The catabolism of t-PA involves receptor-mediated endocytosis and intracellular degradation in several cell types of the liver namely hepatic endothelial, parenchymal and Kupffer cells. Liver endothelial cells have been reported to possess a specific uptake system for t-PA based on the recognition of the high mannose carbohydrate structures on Asn117. To further elucidate the involvement of the mannose receptor on sinusoidal endothelial cells in the hepatic catabolism of t-PA and to identify the mechanisms involved, biochemical as well as electron microscopic studies were performed. The biochemical studies revealed that the removal of the mannose side chain in t-PA significantly reduced its clearance and degradation in isolated perfused livers. The binding of t-PA to preparations of primary hepatocytes and liver cell membranes could not be competed for by various sugars and glycoproteins, and was not dependent on the presence of carbohydrates on the molecule. This ruled out a major relevance of the sugar moieties of t-PA in its recognition by liver cells that were not of endothelial origin.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of coenzyme Q10 on tissue distribution of archaeosomes, and pegylated archaeosomes, administered to mice by oral and intravenous routes.
The biodistribution of orally and intravenously administered archaeosomes in mice was compared to that of archaeosomes containing either coenzyme Q10 (archaeosome-CoQ10), polyethylene glycol (archaeosome-PEG), or PEG plus CoQ10 (archaeosome-PEG-CoQ10). The archaeosome formulations were prepared by a reverse-phase evaporation method using the total polar lipids from the archaeobacterium Methanosarcina mazei. In the case of oral gavage, the most striking observation was that a significantly (p < 0.05) higher concentration (42.28+/-4.17%) of administered dose was found in the stomach content 3 h after administration of unmodified archaeosomes, as compared to that of archaeosome-CoQ10 (16.98+/-2.48%) and archaeosome-PEG-CoQ10 (5.8 +/-4.05"/ vesicles. This correlated with an increased uptake, notably of the archaeosome-PEG-CoQ 0 vesicles.,into liver and spleen; however, no more than 7% of the administered dose was found in liver, spleen and blood at any time point studied. In the case of intravenous administration, a significantly higher percentage of injected dose of unmodified archaeosomes was found in the liver (66.4 +/-.92%) and spleen (11.445+/-.68%) at 48 h, compared to archaeosome-CoQ10, archaeosome-PEG, and archaeosome-PEG-CoQ10 vesicles. The combination of PEG and CoQ10 significantly prolonged the circulation of archaeosomes in the blood, but after 48 h the amount of the vesicle marker in blood had declined to only about 0.5% of administered dose. These data indicate that the biodistribution of archaeosome formulations given orally or intravenously can be altered significantly by incorporating PEG or CoQ 10, alone or in combination, and these vesicles have the potential to act as a carrier for therapeutics and vaccines.


[The trends on the mortality for esophagus and stomach cancers in Linzhou city from 1988 to 2003].
Using the data on death for esophagus and stomach cancers in Linzhou cancer registration system, the mortality was described as well as the changing trend was analyzed. 18 240 death recorders for the both cancers during 1988 to 2003 were drawn from Linzhou cancer registration system. Of which, 10138 cases were esophageal cancer and 8102 cases were gastric cancer. Then data were stratified by sex, age, year and then linked to demographic classifications. The mortalities of two topographic site cancers were calculated and the age-adjusted rates were calculated by direct standardization to the world population. The Joinpoint model was used to get the estimated annual percent change (EAPC) of the age-adjusted rates, so to estimate the death rate change trends of both cancers in population of Linzhou city. In 2003, the age-adjusted mortalities of esophageal cancer and gastric cancer were 68.47 per 100,000 and 57.01 per 100,000 respectively of Linzhou city. From 1988 to 2003 the death rates for both of cancers had showed the decline trends. The EAPC of the mortality for esophageal cancer was -3.82 (-4.81 - -2.82, P < 0.001) and that for gastric cancer was -2.95 (-4.16 - -1.73, P < 0.001) respectively. The declining trend in was observed the mortality of esophageal and gastric cancer in Linzhou by this study.


Myelin-forming ability of Schwann cell-like cells induced from rat adipose-derived stem cells in vitro.
Although Schwann cell (SC) transplantation can enhance peripheral and central nerve repair experimentally, it is difficult to generate sufficient SC quickly for clinical application. So alternative cell systems for SC are desired. SC-like cells induced from adipose-derived stem cells (ADSC) may be one of the ideal alternative cell systems for SC. However, myelin-forming ability, which is the most important characteristics and function of SC, has not been investigated in SC-like cells from ADSC up to now. In this experiment, ADSC were harvested from rat inguinal fat pad. Rat ADSC were fibroblast-like in shape, almost all the cells expressed mesodermal marker fibronectin, and only few cells expressed neural stem cell marker nestin. A mixture of glial growth factors (Heregulin, bFGF, PDGF and forskolin) could induce rat ADSC into SC-like cells. SC-like cells were spindle-like in shape and expressed glial markers GFAP and S100, similar to genuine SC. When intracellular cAMP was increased, SC-like cells could express myelin protein p0. More importantly, when co-cultured with rat pheochromocytoma cell line (PC12 cells), SC-like cells could induce the differentiation of PC12 cells rapidly and form myelin structures with PC12 cells in vitro. Our data further demonstrated that SC-like cells from ADSC were able to form myelins and these cells may benefit the treatment of peripheral and central nerve injuries.


Uncertainty forecasts improve weather-related decisions and attenuate the effects of forecast error.
Although uncertainty is inherent in weather forecasts, explicit numeric uncertainty estimates are rarely included in public forecasts for fear that they will be misunderstood. Of particular concern are situations in which precautionary action is required at low probabilities, often the case with severe events. At present, a categorical weather warning system is used. The work reported here tested the relative benefits of several forecast formats, comparing decisions made with and without uncertainty forecasts. In three experiments, participants assumed the role of a manager of a road maintenance company in charge of deciding whether to pay to salt the roads and avoid a potential penalty associated with icy conditions. Participants used overnight low temperature forecasts accompanied in some conditions by uncertainty estimates and in others by decision advice comparable to categorical warnings. Results suggested that uncertainty information improved decision quality overall and increased trust in the forecast. Participants with uncertainty forecasts took appropriate precautionary action and withheld unnecessary action more often than did participants using deterministic forecasts. When error in the forecast increased, participants with conventional forecasts were reluctant to act. However, this effect was attenuated by uncertainty forecasts. Providing categorical decision advice alone did not improve decisions. However, combining decision advice with uncertainty estimates resulted in the best performance overall. The results reported here have important implications for the development of forecast formats to increase compliance with severe weather warnings as well as other domains in which one must act in the face of uncertainty.


Growth of Mycobacterium avium in human monocytes: identification of cytokines which reduce and enhance intracellular microbial growth.
Human monocytes were isolated by standard procedures and their ability to harbor growth of two virulent strains of Mycobacterium avium, TMC724 and TMC7479, was assessed in the absence or presence of cytokines. Both strains of mycobacteria, especially the M. avium TMC7479, grew progressively in untreated human monocytes. Inclusion of certain macrophage-activating cytokines, such as interferon-gamma in the presence of indomethacin or 1.25(OH2)-vitamin D3 (calcitriol) led to significant reductions in bacterial growth at 7 days post-infection. Conversely, treatment of human monocytes with interleukin-(IL) 1, macrophage-colony stimulating factor or IL 3 led to an increased permissiveness of these cells for M. avium. Moreover, these cytokines were shown to increase dramatically extracellular M. avium growth in vitro in tissue culture medium. Further, inclusion of antibodies against IL 1 beta and IL 6 in untreated infected monocytes monolayers led to a reduced growth of M. avium, suggesting that infected monocytes produce factors which enhance their susceptibility to M. avium. Overall, my findings suggest that cytokines may play a bidirectional role in atypical mycobacterial infections, by either increasing or decreasing resistance of the monocyte.


Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons.
A hallmark of glioblastoma multiforme (GBM) is neoangiogenesis, mediated by the overexpression of vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, like bevacizumab, prolong progression-free survival in GBM, however, this treatment has been reported to be associated with a decline in neurocognitive function. Therefore, this study focused on the effects of bevacizumab on neuronal function and plasticity. We analyzed neuronal membrane properties and synaptic plasticity in rat hippocampal slices, as well as spine dynamics in dissociated hippocampal neurons, to examine the impact of bevacizumab on hippocampal function and viability. VEGF inhibition resulted in profound impairments in hippocampal synaptic plasticity as well as reductions in dendritic spine number and length. Physiological properties of hippocampal neurons were also affected. These effects of VEGF blockade on hippocampal function may play a role in compromising memory and information processing and thus, may contribute to neurocognitive dysfunction in GBM patients treated with bevacizumab.


Identification of the active-site peptide of 2,3-dihydroxybenzoic acid decarboxylase from Aspergillus oryzae.
The non-oxidative decarboxylation of aromatic acids is a poorly understood reaction. The transformation of 2,3-dihydroxybenzoic acid to catechol in the fungal metabolism of indole is a prototype of such a reaction. 2,3-Dihydroxybenzoic acid decarboxylase (EC 184.108.40.206) which catalyzes this reaction was purified to homogeneity from anthranilate induced cultures of Aspergillus oryzae using affinity chromatography. The enzyme did not require cofactors like NAD+, PLP, TPP or metal ions for its activity. There was no spectral evidence for the presence of enzyme bound cofactors. The preparation, which was adjudged homogeneous by the criteria of SDS-PAGE, sedimentation analysis and N-terminal analysis, was characterized for its physicochemical and kinetic parameters. The enzyme was inactivated by group-specific modifiers like diethyl pyrocarbonate (DEPC) and N-ethylmaleimide (NEM). The kinetics of inactivation by DEPC suggested the presence of a single class of essential histidine residues, the second order rate constant of inactivation for which was 12.5 M-1 min-1. A single class of cysteine residues was modified by NEM with a second order rate constant of 33 M-1 min-1. Substrate analogues protected the enzyme against inactivation by both DEPC and NEM, suggesting the location of the essential histidine and cysteine to be at the active site of the enzyme. The incorporation of radiolabelled NEM in a differential labelling experiment was 0.73 mol per mol subunit confirming the presence of a single essential cysteine per active-site. Differentially labelled enzyme was enzymatically cleaved and the peptide bearing the label was purified and sequenced. The active-site peptide LLGLAETCK and the N-terminal sequence MLGKIALEEAFALPRFEEKT did not bear any similarity to sequences reported in the Swiss-Prot Protein Sequence Databank, a reflection probably of the unique primary structure of this novel enzyme. The sequences reported in this study will appear in the Swiss-Prot Protein Sequence Databank under the accession number P80402.


Focusing x-ray spectrograph for laser fusion experiments.
X-ray spectra from laser fusion targets are normally measured with flat crystal (nonfocusing) spectrographs. We describe here the characteristics of a focusing spectrograph which is capable of recording wide band spectra with significantly higher sensitivity. Measuring spectra in the (10-11) A range from glass microballoons imploded by a two-beam Nd:Glass laser system we find intensity per unit area on film about 100 times higher with a curved mica than with a flat mica spectrograph.


Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions.
Thyroid carcinoma, which is rare in pediatric patients (age 0-18 years) but more common in adolescent and young adult (AYA) patients (age 15-39 years), carries the potential for morbidity and mortality. Hybrid-capture-based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety-three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of these MTC patients with novel alterations in RET experienced clinical benefit from vandetanib treatment. CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy. The Oncologist 2017;22:255-263 IMPLICATIONS FOR PRACTICE: The detection of diverse clinically relevant genomic alterations in the majority of pediatric, adolescent, and young adult patients with thyroid carcinoma in this study suggests that comprehensive genomic profiling may be beneficial for young patients with papillary, anaplastic, or medullary thyroid carcinoma, particularly for advanced or refractory cases for which clinical trials involving molecularly targeted therapies may be appropriate.


Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination.
Lyme disease is the most common vector-borne disease in North America and Europe. The clinical manifestations of Lyme disease vary based on the genospecies of the infecting Borrelia burgdorferi spirochete, but the microbial genetic elements underlying these associations are not known. Here, we report the whole genome sequence (WGS) and analysis of 299 B. burgdorferi (Bb) isolates derived from patients in the Eastern and Midwestern US and Central Europe. We develop a WGS-based classification of Bb isolates, confirm and extend the findings of previous single- and multi-locus typing systems, define the plasmid profiles of human-infectious Bb isolates, annotate the core and strain-variable surface lipoproteome, and identify loci associated with disseminated infection. A core genome consisting of ~900 open reading frames and a core set of plasmids consisting of lp17, lp25, lp36, lp28-3, lp28-4, lp54, and cp26 are found in nearly all isolates. Strain-variable (accessory) plasmids and genes correlate strongly with phylogeny. Using genetic association study methods, we identify an accessory genome signature associated with dissemination in humans and define the individual plasmids and genes that make up this signature. Strains within the RST1/WGS A subgroup, particularly a subset marked by the OspC type A genotype, have increased rates of dissemination in humans. OspC type A strains possess a unique set of strongly linked genetic elements including the presence of lp56 and lp28-1 plasmids and a cluster of genes that may contribute to their enhanced virulence compared to other genotypes. These features of OspC type A strains reflect a broader paradigm across Bb isolates, in which near-clonal genotypes are defined by strain-specific clusters of linked genetic elements, particularly those encoding surface-exposed lipoproteins. These clusters of genes are maintained by strain-specific patterns of plasmid occupancy and are associated with the probability of invasive infection.


Association Between Smoking and Serum GlycA and High-Sensitivity C-Reactive Protein Levels: The Multi-Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
Inflammation is suggested to be a central feature of atherosclerosis, particularly among smokers. We studied whether inflammatory biomarkers GlycA and high-sensitivity C-reactive protein are associated with cigarette smoking. A total of 11 509 participants, 6774 from the MESA (Multi-Ethnic Study of Atherosclerosis) and 4735 from ELSA-Brasil (The Brazilian Longitudinal Study of Adult Health) were included. We evaluated the cross-sectional association between multiple measures of smoking behavior and the inflammatory biomarkers, GlycA and high-sensitivity C-reactive protein, using regression models adjusted for demographic, anthropometric, and clinical characteristics. Participants were 57.7±11.1 years old and 46.4% were men. Never, former, and current smokers comprised 51.7%, 34.0%, and 14.3% of the population, respectively. Multivariable-adjusted mean absolute difference in GlycA levels (μmol/L) with 95% confidence interval (CI) were higher for former (4.1, 95% CI, 1.7-6.6 μmol/L) and current smokers (19.9, 95% CI, 16.6-23.2 μmol/L), compared with never smokers. Each 5-unit increase in pack-years of smoking was associated with higher GlycA levels among former (0.7, 95% CI, 0.3-1.1 μmol/L) and current smokers (1.6, 95% CI, 0.8-2.4 μmol/L). Among former smokers, each 5-year increase in time since quitting smoking was associated with lower GlycA levels (-1.6, 95% CI, -2.4 to -0.8 μmol/L) and each 10-unit increase in number of cigarettes/day was associated with higher GlycA among current smokers (2.8, 95% CI, 0.5-5.2 μmol/L). There were similar significant associations between all measures of smoking behavior, and both log-transformed GlycA and high-sensitivity C-reactive protein. Acute and chronic exposure to tobacco smoking is associated with inflammation, as quantified by both GlycA and high-sensitivity C-reactive protein. These biomarkers may have utility for the study and regulation of novel and traditional tobacco products.


Suppression of acute and chronic inflammation by orally administered prostaglandins.
Oral administration of a stable analog of prostaglandin E1 (PGE1) 15-(S)-15-methyl-prostaglandin E1, can suppress both chronic adjuvant-induced polyarthritis and acute immune complex-induced vasculitis in a dose dependent manner. Histopathologic studies of tibiotarsal joints from rats with adjuvant disease showed suppression of arthritis in animals treated with the PGE1 analog from time of adjuvant challenge. This study represents the first demonstration of suppressed experimental polyarthritis by an orally administered prostaglandin. Suppression of the acute immune complex-induced vasculitis was demonstrated using 15- methyl-PGE1 administered orally 12 hours prior to antigen-antibody challenge. Diminution of tissue injury resulting from immune complex-induced vasculitis is reflected by a decrease in vaso-permeability, indicating suppressed vascular damage in animals treated with prostaglandin. These studies demonstrate the potential use of orally active prostaglandins as an antiinflammatory agent.


The value of color-map virtual touch tissue imaging (CMV) in the differential diagnosis of benign and malignant breast lesions.
Researchers have evaluated the virtual touch tissue imaging (VTI) value in the diagnosis of breast lesions, mostly based on gray-scale. This study aimed to evaluate the value of color-map virtual touch tissue imaging (CMV) in the diagnosis of breast lesions. We retrospectively analyzed the VTI images of 55 breast lesions in 49 female patients who underwent an examination of breast lesions in our hospital from January 2019 to December 2019. The pathological results were taken as the gold standard. The receiver operating characteristic (ROC) curve of CMV was analyzed, and its diagnostic performance was evaluated. Weighted Kappa (k) statistics were used to assess the inter-observer agreement for CMV. A total of 55 breast lesions were included, including 19 malignant lesions and 36 benign lesions. Multivariate analysis showed that patients with higher CMV scores (P = 0.014, odds ratio [OR] = 13.667, 95% confidence interval = 1.702-109.773) were independent predictors of breast cancer. The sensitivity, specificity, and the area under curve (AUC) of CMV were 94.47%, 72.22%, and 0.912. The CMV's inter-observer agreement was almost perfect among radiologists with different work experience (k = 0.854, standard error = 0.049, 95% CI = 0.758-0.950). CMV has high accuracy and repeatability in the diagnosis of malignant breast lesions.


Differential expression of secretagogin immunostaining in the hippocampal formation and the entorhinal and perirhinal cortices of humans, rats, and mice.
Secretagogin (SCGN) is a recently discovered calcium-binding protein belonging to the group of EF-hand calcium-binding proteins. SCGN immunostaining has been described in various regions of the human, rat and mouse brain. In these studies, it has been reported that, in general, the patterns of SCGN staining differ between rodents and human brains. These differences have been interpreted as uncovering phylogenetic differences in SCGN expression. Nevertheless, an important aspect that is not usually taken into account is that different methods are used for obtaining and processing brain tissue coming from humans and experimental animals. This is a critical issue since it has been shown that post-mortem time delay and the method of fixation (i.e., perfused vs. nonperfused brains) may influence the results of the immunostaining. Thus, it is not clear whether differences found in comparative studies with the human brain are simply due to technical factors or species-specific differences. In the present study, we analyzed the pattern of SCGN immunostaining in the adult human hippocampal formation (DG, CA1, CA2, CA3, subiculum, presubiculum, and parasubiculum) as well as in the entorhinal and perirhinal cortices. This pattern of immunostaining was compared with rat and mouse that were fixed either by perfusion or immersion and with different post-mortem time delays (up to 5 hr) to mimic the way the human brain tissue is usually processed. We found a number of clear similarities and differences in the pattern of labeling among the human, rat, and mouse in these brain regions as well as between the different brain regions examined within each species. These differences were not due to the fixation.


Respiratory and olfactory turbinals in feliform and caniform carnivorans: the influence of snout length.
To enhance bite force at the canines, feliform carnivorans have short rostra relative to caniform carnivorans. Rostral reduction in feliforms results in less rostrocaudal space for the maxilloturbinals, the complex set of bones involved in conditioning inspired air and conserving water. It is unknown whether the maxilloturbinals might show adaptations to adjust for this loss, such as greater complexity than what is observed in longer snouted caniforms. To understand the impact of rostral shortening on turbinals in feliforms, we used high resolution CT scans to quantify turbinal surface areas (SA) in 16 feliforms and compared them with published data on 20 caniforms. Results indicate that feliforms have reduced maxilloturbinal SA for their body mass relative to caniforms, but comparable fronto-ethmoturbinal SA. However, anterior portions of the ethmoturbinals in feliforms extend forward into the snout and are positioned within the respiratory pathway. When the SA of these anterior ethmoturbinals is added to maxilloturbinal SA to produce an estimated respiratory SA, feliforms and caniforms are similar in respiratory SA. This transfer of ethmoturbinal SA to respiratory function results in feliforms having less estimated olfactory SA relative to caniforms. Previous work on canids found a positive association between olfactory surface area and diet, but this was not found for felids. Results are consistent with feliforms having somewhat reduced olfactory ability relative to caniforms. If confirmed by behavioral data, the relative reduction in olfactory SA in many feliforms may reflect a greater reliance on vision in foraging relative to caniforms.


Droplet Impact Dynamics on Lubricant-Infused Superhydrophobic Surfaces: The Role of Viscosity Ratio.
In this study, the spreading and retraction dynamics of impacting droplets on lubricant-infused PTFE surfaces were investigated through high-speed imagery. Superhydrophobic Polytetrafluoroethylene (PTFE) surfaces with randomly rough microstructures were prepared by sanding PTFE. Several silicone oils with different viscosities were infused into the structures of superhydrophobic PTFE surfaces. A glycerin and water solution was used for the impacting droplets. The viscosity ratio between the impinging droplet and infused oil layer was varied from 0.06 to 1.2. The droplet impact dynamics on lubricant-infused surfaces were found to change as the viscosity of the infused silicone oil layer was decreased. These changes included an increase in the spreading rate of the droplet following impact, an increase to the maximum spreading diameter, and an increase to the retraction velocity after the droplet reached its maximum diameter. These variations in the impact dynamics were most significant as the viscosity ratio became larger than one and are likely due to the reduction of viscous losses between the oil and water phases during the spreading and retraction of the impacting droplet. Using a scaling analysis which takes into account the role of energy dissipation in the impact dynamics, all the data for the maximum diameter of the droplet on lubricant-infused PTFE surfaces were found to collapse onto a single master curve. Finally, measurements of the dynamic advancing and receding contact angle were made during spreading and retraction of the droplet. These measurements showed the expected Cox-Voinov-Tanner scaling of contact angle for the high oil viscosity, low viscosity ratio lubricant infused surfaces. However, like the superhydrophobic surface, little changes in either the dynamic advancing or receding contact angle were observed for droplets spreading on the surface infused with the lowest viscosity oil.


Healthcare use and costs among Medicare enrollees on pirfenidone versus nintedanib for idiopathic pulmonary fibrosis.
Aim: Compare healthcare utilization and costs between Medicare beneficiaries with idiopathic pulmonary fibrosis (IPF) receiving pirfenidone or nintedanib. Methods: Retrospective cohort study of Medicare beneficiaries (100% Research Identifiable Files) with IPF who initiated pirfenidone or nintedanib between 15 October 2014 and 31 December 2015. Inverse probability of treatment weighting using propensity scores adjusted for baseline covariates. Outcomes: hospitalization and monthly costs. Results: Hazard and incidence rate ratios (95% CI) for all-cause (0.79 [0.68-0.91]; 0.69 [0.59-0.82]) and respiratory-related (0.80 [0.65-0.97]; 0.71 [0.57-0.90]) hospitalizations favored pirfenidone versus nintedanib. Monthly inpatient costs were lower for pirfenidone versus nintedanib patients; outpatient and pharmacy costs were similar. Conclusion: In patients with IPF, pirfenidone compared with nintedanib has a moderate but significant protective effect on hospitalization, corresponding to lower inpatient costs.


Regulation of Gene Expression by SAR of Silkworm Attacus ricini rRNA Gene.
The 1 kb scaffold-attachment region (SAR) at 5' non-transcription region of rRNA gene of silkworm Attacus ricini was cloned into eukaryotic expression vector pLu, which contained luciferase report gene and neo(R) selecting marker. After transfection of constructs into NIH3T3 cell line by using cation liposome, the luciferase activity was monitored to check the SAR's function. The results demonstrated that the SAR could enhance gene expression up to 15-fold in stable transformed cells, but no obvious gene expression was observed in transient transfection. Its effect on gene expression appeared to requirechromosomal integration. Southwestern blotting experiments showed that SAR specifically bound to nuclear matrix proteins of NIH3T3 cells. The binding with nuclear matrix may be necessary for SAR function of transcriptional enhancement.


[Multidisciplinary therapy using interferon and immunological evaluation for glioma patients: two-color analysis of T cell subsets].
We have employed IAR therapy [combination of postirradiation, chemotherapy and interferon (IFN)] for malignant glioma patients. Changes of lymphocyte fractions in patients were evaluated before and after IAR therapy, using a recently developed two-color analysis. Eight malignant glioma patients received irradiation, chemotherapy (ACNU) and immunotherapy (OK-432 and IFN-beta). Peripheral blood lymphocytes taken during hospitalization with IAR therapy (first half and latter half), and every 3 to 6 months for 2 years at the longest after IAR therapy were double-stained with FITC- and PI-labelled antibodies and two-color analysis was conducted by a FACS Analyzer. Six patients out of 8 survived for 6 months to 2 years, 2 died after 3 and 6 months, respectively. Leu-2a (suppressor/cytotoxic T), especially Leu-2a+ 15- (cytotoxic T) showed a high value. Leu-2a level decreased during treatment, and both Leu-2a+ 15- and Leu-2a+ 15+ (suppressor T) values decreased. Two thirds of the patients showing an increased Leu-2a+ 15+ level died. Leu 3a (helper/inducer T), especially Leu-3a+ 8+ (inducer T) level decreased, but Leu-3a+ 8- (helper T) level increased during treatment. The level decreased in the worse patients. Leu-3a/Leu-2a ratio was low, but it increased during treatment as compared with the results of conventional therapy. Leu-7, Leu-11a, NK activity, and gamma-IFN productivity were further studied. Treatment combined with IFN revealed an influence on the T cells resulting in an increase of helper T level and suppression of suppressor T level.


Epidemiology and primary prevention of thyroid cancer.
The purpose of this review is to provide an account of our present knowledge about the epidemiology of nonmedullary thyroid carcinoma, to discuss the effects of environment, lifestyle and radiation on the risk of developing thyroid cancer, and to discuss aspects on primary prevention of the disease. In areas not associated with nuclear fallout, the annual incidence of thyroid cancer ranges between 2.0-3.8 cases per 100,000 in women and 1.2-2.6 per 100,000 in men, women of childbearing age being at highest risk. Low figures are found in some European countries (Denmark, Holland, Slovakia) and high figures are found in Iceland and Hawaii. Differences in iodine intake may be one factor explaining the geographic variation, high iodine intake being associated with a slightly increased risk of developing thyroid cancer. In general, lifestyle factors have only a small effect on the risk of thyroid cancer, a possible protective effect of tobacco smoking has been recently reported. Because of the (small) increase in risk of thyroid cancer associated with iodination programs, these should be supervised, so that the population does not receive excess iodine. The thyroid gland is highly sensitive to radiation-induced oncogenesis. This is verified by numerous reports from survivors after Hiroshima and Nagasaki, the Nevada, Novaja Semlja and Marshal Island atmospheric tests, and the Chernobyl plant accident, as well as by investigations of earlier medical use of radiation for benign diseases in childhood. These reports are summarized in the review. There appears to be a dose-response relation for the risk of developing cancer after exposure to radioactive radioiodine. The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. Thus, the incidence of thyroid cancer in children in the Belarus area was less than 1 case per million per year before the Chernobyl accident, increasing to a peak exceeding 100 per million per year in certain areas after the accident. It is a social obligation of scientists to inform the public and politicians of these risks. All nuclear power plants should have a program in operation for stockpiling potassium iodide for distribution within 1-2 days after an accident.


Community and Hospital Acquired Pneumonia.
Community-acquired pneumonia is the most common cause of death among infectious diseases, and responsible for millions of hospitalizations annually. Pneumonia may be classified based on how it is acquired, etiology, and clinical presentation. Chest radiographs are the gold standard for initial imaging evaluation and chest computed tomography plays an important role in diagnostic problem-solving and evaluation of complicated and treatment-resistant pneumonia. Follow-up imaging with chest radiographs or computed tomography post-illness resolution may be used to identify treatment-resistant inflammation or unidentified underlying malignancies.


Wide and fast dispersion tuning of a picosecond OPO based on aperiodic quasi-phase matching using an axially chirped volume Bragg grating.
We report on a widely tunable synchronously pumped picosecond optical parametric oscillator (OPO) combining an aperiodically poled MgO-doped LiNbO3 crystal as a broadband gain medium and an axially chirped volume Bragg grating as a spectral filtering dispersive element. Translation of the Bragg grating along the beam axis enables wavelength tuning over 215 nm around 3.82 μm and provides spectral narrowing. Rapid continuous tuning over 150 nm in 100 ms is demonstrated.


Auxological standards in bone dysplasias.
A variety of heritable bone dysplasias have been identified, affecting a total of 3-4.5 in 10,000 new-born individuals. Many of these dysplasias affect fetal growth and growth during infancy, with linear growth and body proportions being affected. Taken together, the effects of such dysplasias often result in a reduced adult height. Currently, radiographic criteria are used to distinguish between different dysplasias. However, additional clinical findings are often required to make a specific diagnosis. Molecular and genetic techniques may also be used to confirm a particular diagnosis. However, the specific genetic defect underlying each disorder has yet to be identified for the majority of disorders.


Follow-Up Treatment After Inpatient Therapy of Patients With Unipolar Depression-Compliance With the Guidelines?
To date, there is only a limited number of studies evaluating the implementation and effects of treatment guidelines. Therefore, this study aimed to determine how many patients diagnosed with a major depression were treated in compliance with the German treatment guideline after hospital treatment, and whether a deviation from the guideline resulted in a less favorable development. Five hundred two patients, which originally participated in the INDDEP-study, were included. Data were collected at admission and discharge from eight different psychosomatic (psychotherapeutic) hospitals in Germany as well as 3 months and 1 year after hospital treatment. Data on depressive symptomatology were assessed by QIDS-C (clinical interviews). By phone interviews, the clinical course and the outpatient treatments were assessed. Statistical analyses compared patients who were treated in compliance with the German treatment guideline with those who were not. Seventy-nine point one percent of the outpatient treatments complied with the treatment guideline. Eleven point eight percent of the patients were treated with medication only, 60.2% with psychotherapy only, and 28.0% with a combination. There was no difference in the clinical outcome (depression) with regard to guideline compliance. Cases in which deviation from the guideline occurred (20.9%) were younger and had a less severe depressive symptomatology at admission and after hospital treatment. After treatment in a psychosomatic hospital or day hospital, the majority of patients with a depressive disorder received adjacent treatment in accordance with the German guideline and with a clear focus on psychotherapy. Deviations from the guideline did not result in a less favorable course of the illness. ISRCTN20317064, retrospectively registered 31.07.2012.


Survey of referral patterns and attitudes toward hyperbaric oxygen treatment among Danish oncologists, ear, nose and throat surgeons and oral and maxillofacial surgeons.
In head and neck cancer patients with late radiation injury, hyperbaric oxygen (HBO) is used for therapeutic or prophylactic reasons against soft-tissue and osteoradionecrosis (ORN). Twenty-nine departments of oncology, ENT, oral and maxillofacial (OMF) surgery were surveyed using the Enalyzer tool (www.enalyzer.com), of whom 21 responded. Data were incomplete in four returns. Within the previous year, 14 departments had referred at least one patient for hyperbaric oxygen therapy (HBOT). There appears to be a generally positive attitude in Danish OMF, ENT and oncology departments towards referral of patients with ORN for HBOT. However, there is an increasing desire for better evidence for its role in head and neck cancer in the prevention and treatment of soft-tissue injury and osteonecrosis following radiotherapy.


Effect of L-carnitine and soybean oil on growth performance and body composition of early-weaned pigs.
Two experiments were conducted to evaluate the effect of dietary L-carnitine on growth performance and body composition of early-weaned pigs. In Exp. 1, 120 weanling pigs (initially 5.6 kg and 19 +/- 2 d of age) were allotted in a 3 x 2 factorial with four pigs per pen and five replications (pens) per treatment. Main effects from d 0 to 14 after weaning included dietary L-carnitine (0, 500, or 1,000 ppm) and soybean oil (0 to 10%). From d 14 to 35 after weaning, levels were reduced to 0, 250, or 500 ppm L-carnitine and 0 or 5% soybean oil. No L-carnitine x soybean oil interactions were observed (P > .10). From d 0 to 14, L-carnitine and soybean oil had no effect (P > .10) on pig performance. From d 14 to 35 and d 0 to 35, gain:feed ratio (G/F) improved (linear, P < .05) with increasing dietary L-carnitine; however, ADG and ADFI were not affected. Soybean oil improved ADG and G/F (P < .05) from d 14 to 35 and ADG from d 0 to 35. In Exp. 2, 180 weanling pigs (initially 6.0 kg and 22 +/- 2 d of age) were allotted in a 2 x 3 factorial. Pigs were fed either 0 or 1,000 ppm L-carnitine from d 0 to 14 after weaning and then pigs fed each of these diets were fed diets containing 0, 250, or 500 ppm L-carnitine from d 14 to 35. No interactions occurred between feeding L-carnitine from d 0 to 14 and performance observed from d 14 to 35. From d 0 to 14 after weaning, L-carnitine increased ADG (P < .08) and ADFI (P < .02). From d 14 to 35, ADFI decreased (linear, P < .05) and G/F increased (quadratic, P < .05) as dietary L-carnitine increased. Cumulative (d 0 to 35) ADFI decreased (linear, P < .05) and G/F increased (linear, P < .05) with increasing L-carnitine. On d 35, 14 pigs from each of four selected treatments (0 or 1,000 ppm L-carnitine from d 0 to 14 followed by either 0 or 500 ppm from d 14 to 35) were slaughtered, and carcass composition was recorded. Carcass moisture and CP percentages were not influenced (P > .10) by dietary L-carnitine. However, pigs fed 1,000 ppm L-carnitine from d 0 to 14 had less (P < .05) carcass lipid and daily lipid accretion on d 35 whether they were fed L-carnitine from d 14 to 35 or not. These results suggest that dietary L-carnitine improves G/F and reduces carcass lipid accretion in early-weaned pigs.


LYZL6, an acidic, bacteriolytic, human sperm-related protein, plays a role in fertilization.
Lysozyme-like proteins (LYZLs) belong to the c-type lysozyme/α-lactalbumin family and are selectively expressed in the mammalian male reproductive tract. Two members, human sperm lysozyme-like protein (SLLP) -1 and mouse LYZL4, have been reported to contribute to fertilization but show no bacteriolytic activity. Here, we focused on the possible contribution of LYZL6 to immunity and fertilization. In humans, LYZL6 was selectively expressed by the testis and epididymis and became concentrated on spermatozoa. Native LYZL6 isolated from sperm extracts exhibited bacteriolytic activity against Micrococcus lysodeikticus. Recombinant LYZL6 (rLYZL6) reached its peak activity at pH 5.6 and 15 mM of Na+, and could inhibit the growth of Gram-positive, but not Gram-negative bacteria. Nevertheless, the bacteriolytic activity of rLYZL6 proved to be much lower than that of human lysozyme under physiological conditions. Immunodetection with a specific antiserum localized the LYZL6 protein on the postacrosomal membrane of mature spermatozoa. Immunoneutralization of LYZL6 significantly decreased the numbers of human spermatozoa fused with zona-free hamster eggs in a dose-dependent manner in vitro. Thus, we report here for the first time that LYZL6, an acidic, bacteriolytic and human sperm-related protein, is likely important for fertilization but not for the innate immunity of the male reproductive tract.


Staff nurse empowerment and effort-reward imbalance.
The purpose of this study was to test an expanded model of Rosabeth Moss Kanter's Structural Theory of Organizational Behaviour (Kanter 1977; Laschinger, Finegan, Shamian and Wilk 2001) by examining the relationship between nurses' empowerment and their perceptions of effort-reward imbalance (Siegrist 1996). A sample of 112 staff nurses employed in teaching hospitals in Ontario participated in this study (58% return rate). A descriptive correlational survey design was used to collect data by eLiciting responses to five self-report instruments: the Conditions of Work Effectiveness II, the Job Activities Scale II, and the Organizational Relationships Scale II (Laschinger, Finegan, Shamian and Wilk 2001), the Effort-Reward Imbalance (ERI) scale (Siegrist and Peter 1999a) and a demographic questionnaire. Staff nurses were only moderately empowered, and 24.1% perceived their work to have more efforts than rewards, according to Siegrist's guidelines.


A multigene family that interacts with the amino terminus of plasmodium MSP-1 identified using the yeast two-hybrid system.
Merozoite surface protein 1 (MSP-1) is a high-molecular-weight protein expressed on the surface of the malaria merozoite in a noncovalent complex with other protein molecules. MSP-1 undergoes a series of proteolytic processing events, but no precise biological role for the various proteolytic fragments of MSP-1 or for the additional proteins present in the complex is known. Through the use of the yeast two-hybrid system, we have isolated genes encoding proteins that interact with a region of the amino-terminal proteolytic fragment of MSP-1 from the mouse parasite Plasmodium yoelii. This analysis has led to the isolation of two sequence-related molecules, one of which is the P. yoelii homologue of MSP-7 originally described in Plasmodium falciparum. BLAST analysis of the P. falciparum database has revealed that there are six related protein molecules present in this species encoded near each other on chromosome 13. In P. falciparum, we designated these molecules MSRP-1 to -5. Analysis of the P. yoelii database indicates a similar chromosomal organization for the two genes in the mouse parasite species. The three P. falciparum sequences with the highest degree of homology to the P. yoelii sequences isolated in the two-hybrid screen have been characterized at the molecular level (MSRP-1 to -3). Expression analysis indicated that the mRNAs are expressed at various levels in the different asexual stages. Immunofluorescence studies colocalized the expression of the MSRP molecules and the amino-terminal portion of MSP-1 to the surfaces of trophozoites. In vitro binding experiments confirmed the interaction between MSRP-1, MSRP-2, and the amino-terminal region of P. falciparum MSP-1.


Improvement of ventricular function after atrioventricular junction ablation in a patient with atrial flutter after Mustard's operation.
Arrhythmias are common problems following Mustard's operation for D-transposition of the great arteries. A 19-year-old male is presented who was diagnosed at birth with D-transposition of the great arteries and a right aortic arch and underwent a Mustard procedure at 12 months of age. He developed sinus node dysfunction and atrial flutter unresponsive to antiarrhythmic drugs and dual chamber pacing. Following complete heart block with radiofrequency catheter ablation of the atrioventricular junction, the patient's heart was paced in VVIR mode. Ventricular function improved after the ablation and persisted in two years' follow-up.


The Human Mixed Lineage Leukemia 5 (MLL5), a Sequentially and Structurally Divergent SET Domain-Containing Protein with No Intrinsic Catalytic Activity.
Mixed Lineage Leukemia 5 (MLL5) plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. Chromatin binding is ensured by its plant homeodomain (PHD) through a direct interaction with the N-terminus of histone H3 (H3). In addition, MLL5 contains a Su(var)3-9, Enhancer of zeste, Trithorax (SET) domain, a protein module that usually displays histone lysine methyltransferase activity. We report here the crystal structure of the unliganded SET domain of human MLL5 at 2.1 Å resolution. Although it shows most of the canonical features of other SET domains, both the lack of key residues and the presence in the SET-I subdomain of an unusually large loop preclude the interaction of MLL5 SET with its cofactor and substrate. Accordingly, we show that MLL5 is devoid of any in vitro methyltransferase activity on full-length histones and histone H3 peptides. Hence, the three dimensional structure of MLL5 SET domain unveils the structural basis for its lack of methyltransferase activity and suggests a new regulatory mechanism.


Muribaculaceae Genomes Assembled from Metagenomes Suggest Genetic Drivers of Differential Response to Acarbose Treatment in Mice.
The drug acarbose is used to treat diabetes and, by inhibiting α-amylase in the small intestine, increases the amount of starch entering the lower digestive tract. This results in changes to the composition of the microbiota and their fermentation products. Acarbose also increases longevity in mice, an effect that has been correlated with increased production of the short-chain fatty acids propionate and butyrate. In experiments replicated across three study sites, two distantly related species in the bacterial family Muribaculaceae were dramatically more abundant in acarbose-treated mice, distinguishing these responders from other members of the family. Bacteria in the family Muribaculaceae are predicted to produce propionate as a fermentation end product and are abundant and diverse in the guts of mice, although few isolates are available. We reconstructed genomes from metagenomes (MAGs) for nine populations of Muribaculaceae to examine factors that distinguish species that respond positively to acarbose. We found two closely related MAGs (B1A and B1B) from one responsive species that both contain a polysaccharide utilization locus with a predicted extracellular α-amylase. These genomes also shared a periplasmic neopullulanase with another, distantly related MAG (B2) representative of the only other responsive species. This gene differentiated these three MAGs from MAGs representative of nonresponding species. Differential gene content in B1A and B1B may be associated with the inconsistent response of this species to acarbose across study sites. This work demonstrates the utility of culture-free genomics for inferring the ecological roles of gut bacteria, including their response to pharmaceutical perturbations. IMPORTANCE The drug acarbose is used to treat diabetes by preventing the breakdown of starch in the small intestine, resulting in dramatic changes in the abundance of some members of the gut microbiome and its fermentation products. In mice, several of the bacteria that respond most positively are classified in the family Muribaculaceae, members of which produce propionate as a primary fermentation product. Propionate has been associated with gut health and increased longevity in mice. We found that genomes of the most responsive Muribaculaceae showed signs of specialization for starch fermentation, presumably providing them a competitive advantage in the large intestine of animals consuming acarbose. Comparisons among genomes enhance existing models for the ecological niches occupied by members of this family. In addition, genes encoding one type of enzyme known to participate in starch breakdown were found in all three genomes from responding species but none of the other genomes.


When should we perform colonoscopy to increase the adenoma detection rate?
The rate of adenoma detection is the most reliable quality indicator of colonoscopy. Studies have reported that colonoscopy performed in morning has a higher adenoma detection rate (ADR) than that performed in the afternoon. These studies have explained that several physician-related factors such as undergoing an emergency procedure the night before colonoscopy, accumulated workload, and increased fatigue level in the afternoon might have led to such finding. However, several opposing articles have indicated that the time of day and ADR is not quite related. Complex confounding factors can impact study results. Colonoscopy withdrawal time and bowel preparation quality are key factors. However, queue list numbers, participation of academic fellows, nurses' assistance, and the number of colonoscopies allocated per hour are also notable factors. Recently, an attempt has been made to homogenize the ADR in the morning and afternoon through artificial intelligence-assisted colonoscopy. This review article introduces the history of this long-debated topic, discusses points to consider in real-world practice, and suggests new ideas for planning future research. By understanding this issue, the rate of adenoma detection during colonoscopy is expected to be improved further.


Mediastinal bronchogenic cyst mimicking congenital lobar emphysema.
Bronchogenic cyst (BC) is a rare congenital malformation of the lung. Most patients remain asymptomatic until adulthood while some are symptomatic in the first few years of life. However, symptoms in newborn period are rare. We report a case of a 3-day-old preterm baby with respiratory distress diagnosed as congenital lobar emphysema on chest X-ray. A CT scan revealed a mediastinal cyst causing obstructive lobar emphysema. The cyst was excised and pathological examination was suggestive of BC.


Novel platelet ADP P2Y12 inhibitors in the treatment of acute coronary syndrome.
Inhibition of the platelet P2Y12 receptor plays an important role in the prevention of thrombotic complications of acute coronary syndrome and percutaneous coronary interventions. Despite clinical benefits with clopidogrel therapy in these high risk patients, efficacy of clopidogrel is limited by slow onset of action, variability in platelet inhibitory response and potential drug-drug interactions. Importantly, suboptimal platelet inhibition by clopidogrel is associated with worse prognosis. This underscores the need for alternate antiplatelet treatment strategies. A number of novel P2Y12 antagonists are approved or in advanced development and some have demonstrated superior platelet inhibition effect, clinical outcomes, and safety profile than clopidogrel in patients with acute coronary syndrome. The aim of this manuscript is to provide an overview on the current status in P2Y12 receptor inhibition and to review the pharmacology and clinical development of four of these agents: prasugrel, cangrelor, ticagrelor, and elinogrel.


Component Optimization of Neomycin Biosynthesis via the Reconstitution of a Combinatorial Mini-Gene-Cluster in Streptomyces fradiae.
Neomycin, a multicomponent aminoglycoside antibiotic, is mainly utilized in livestock husbandry and feed additives in animals. The antimicrobial potency of the main product neomycin B is higher than that of its stereoisomer neomycin C. However, the content of neomycin C as an impurity in the high-producing strain is relatively high, and its isolation or removal from neomycin B is quite difficult, which influences the widespread application of neomycin. In this work, the essential genes responsible for neomycin biosynthesis were evaluated and overexpressed to reduce the content of neomycin C. Among them, neoG and neoH are two novel regulatory genes for neomycin biosynthesis, aphA is a resistance gene, neoN encoding a radical SAM-dependent epimerase is responsible for the conversion of neomycin C to B using SAM as the cofactor, and metK is a SAM synthetase coding gene. We demonstrated that the reconstitution and overexpression of a mini-gene-cluster (PkasO*-neoN-metK-PkasO*-neoGH-aphA) could effectively reduce the accumulation of neomycin C from 19.1 to 12.7% and simultaneously increase neomycin B by ∼13.1% in the engineered strain Sf/pKCZ04 compared with the wild-type strain (Sf). Real-time quantitative polymerase chain reaction analysis revealed the remarkable up-regulation of the neoE, neoH, neoN, and metK genes situated in the mini-gene-cluster. The findings will pave a new path for component optimization and the large-scale industrial production of significant commercial antibiotics.


Discriminating between different acute chemical toxicities via changes in the daphnid metabolome.
Currently, there is widespread interest in exploiting "omics" approaches to screen the toxicity of chemicals, potentially enabling their rapid categorization into classes of defined mode of action (MOA). Direct infusion Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) metabolomics provides a sensitive and nontargeted analysis of potentially a thousand endogenous metabolites. Our previous work has shown that mass spectra can be recorded from whole-organism homogenate or hemolymph of single adult Daphnia magna. Here we develop multivariate models and discover perturbations to specific metabolic pathways that can discriminate between the acute toxicities of four chemicals to D. magna using FT-ICR MS metabolomics. We focus on model toxicants (cadmium, fenvalerate, dinitrophenol, and propranolol) with different MOAs. First, we confirmed that a toxicant-induced metabolic effect could be determined for each chemical in both the hemolymph and the whole-organism metabolome, with between 9 and 660 mass spectral peaks changing intensities significantly, dependent upon toxicant and sample type. Subsequently, supervised multivariate models were built that discriminated significantly all four acute metabolic toxicities, yielding mean classification error rates (across all classes) of 3.9 and 6.9% for whole-organism homogenates and hemolymph, respectively. Following extensive peak annotation, we discovered toxicant-specific perturbations to putatively identified metabolic pathways, including propranolol-induced disruption of fatty acid metabolism and eicosanoid biosynthesis and fenvalerate-induced disruption of amino sugar metabolism. We conclude that the metabolic profiles of whole-daphnid homogenates are more discriminatory for toxicant action than hemolymph. Furthermore, our findings highlight the capability of metabolomics to discover early-event metabolic responses that can discriminate between the acute toxicities of chemicals.


Primary resected meningiomas: relapses and proliferation markers.
Relapses of meningiomas are a well known phenomenon during follow-up. The significance of sex, age, surgical treatment and mitotic frequency with regard to relapses are still a matter of debate. The study included 125 meningioma patients who underwent surgical intervention between 1986 and 1997 They were in follow-up for 3, 5, 10 and 15 years; they were grouped as "stable" or "relapsing" tumours. The follow-up was based on magnetic resonance image (MRI) and tomodensitometry (TDM). The labelling index for Ki67 and PCNA (proliferation markers) was scored at resection. Risk factors for relapse were reviewed using univariate analysis and Cox hazards model. One hundred and twenty-five patients were under medical control of whom 26 showed a relapse. Among them 25 arose from subtotal resected tumours and 1 was a recurrence. Relapses comprised 16 females and 10 males. Tumour relapses at 3,5,10 and 15 years were, respectively, 8.8%, 13.6%, 17.6% and 20.8%. Proliferation markers, at group level, were statistically significantly different to distinguish stable from relapsing and malignant from benign meningiomas. Factors significantly associated with tumour relapse in univariate analysis were incomplete resection, histopathology and proliferation markers. In multivariate analysis the proliferation markers and incomplete resection were the only significant risk factors (p<0.05) for relapse. To avoid relapses of meningiomas, total resection is recommended. The resection type and proliferation markers are predictive factors for tumour relapse. The proliferation markers cannot be applied at the individual level.


Accuracy of routine echocardiographic measurements made by an inexperienced examiner through tele-instruction.
The reproducibility and accuracy of routine echocardiographic measurements made by an inexperienced doctor using tele-instruction were evaluated. Thirty-eight patients were first examined at a local hospital by an inexperienced doctor instructed by a specialist 450 km away at a university hospital. The specialist then examined the patients at the local hospital using the same equipment, after an average of 50 days. The accuracy of M-mode and quantitative Doppler measurements was comparable to that observed in reproducibility studies made under normal examination conditions. There were no systematic measurement errors. No important M-mode information was missed except evidence of left ventricular hypertrophy in six patients. In the two-dimensional examination there were differences of clinical significance in only three patients. There were no clinically important differences in the Doppler quantification of mitral and aortic regurgitation. Tele-instructed echocardiography is also an excellent educational tool, allowing an inexperienced examiner gradually to take responsibility for the local echocardiographic service.


Lone pair driven anisotropy in antimony chalcogenide semiconductors.
Antimony sulfide (Sb2S3) and selenide (Sb2Se3) have emerged as promising earth-abundant alternatives among thin-film photovoltaic compounds. A distinguishing feature of these materials is their anisotropic crystal structures, which are composed of quasi-one-dimensional (1D) [Sb4X6]n ribbons. The interaction between ribbons has been reported to be van der Waals (vdW) in nature and Sb2X3 are thus commonly classified in the literature as 1D semiconductors. However, based on first-principles calculations, here we show that inter-ribbon interactions are present in Sb2X3 beyond the vdW regime. The origin of the anisotropic structures is related to the stereochemical activity of the Sb 5s lone pair according to electronic structure analysis. The impacts of structural anisotropy on the electronic, dielectric and optical properties relevant to solar cells are further examined, including the presence of higher dimensional Fermi surfaces for charge carrier transport. Our study provides guidelines for optimising the performance of Sb2X3-based photovoltaics via device structuring based on the underlying crystal anisotropy.


Treatment of a traumatic leptomeningeal cyst in an adult with fibrinogen-based collagen.
Reports of traumatic leptomeningeal cysts (TLMC) are rare in adults. The standard treatment approach is craniectomy with careful exposure of the intact dural edges, followed by duroplasty. However, occasionally, the location of the TLMC makes achieving watertight duroplasty impossible. Herein, we report the case of a 28-year-old male who presented with a soft growing mass on the vertex of his head 16 months after the head trauma. Upon enhanced CT examination, a bony defect involving both the inner and outer table of the cranium was observed close to the sagittal sinus, and a well-defined cystic mass, 5 cm in diameter, was nested within the defect. The risks associated with extension craniotomy were high because the lesion was located superficial to the sagittal sinus, we opted to use fibrinogen-based collagen fleece (TachoCombR®) to repair the dural defect. Two months after surgery, the patient remained asymptomatic with a good cosmetic result. In cases like ours, when the defect is near the major sinuses and the risk of rupturing the sinus during watertight dural closure is high, fibrinogen-based collagen fleece (TachoComb®) is an effective alternative approach to standard dural suture techniques.


Transcriptome and metabolite profiling reveals the effects of Funneliformis mosseae on the roots of continuously cropped soybeans.
Arbuscular mycorrhizal fungi are the most widely distributed mycorrhizal fungi, which can form mycorrhizal symbionts with plant roots and enhance plant stress resistance by regulating host metabolic activities. In this paper, the RNA sequencing and ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) technologies were used to study the transcriptome and metabolite profiles of the roots of continuously cropped soybeans that were infected with F. mosseae and F. oxysporum. The objective was to explore the effects of F. mosseae treatment on soybean root rot infected with F. oxysporum. According to the transcriptome profiles, 24,285 differentially expressed genes (DEGs) were identified, and the expression of genes encoding phenylalanine ammonia lyase (PAL), trans-cinnamate monooxygenase (CYP73A), cinnamyl-CoA reductase (CCR), chalcone isomerase (CHI) and coffee-coenzyme o-methyltransferase were upregulated after being infected with F. oxysporum; these changes were key to the induction of the soybean's defence response. The metabolite results showed that daidzein and 7,4-dihydroxy, 6-methoxy isoflavone (glycine), which are involved in the isoflavone metabolic pathway, were upregulated after the roots were inoculated with F. mosseae. In addition, a substantial alteration in the abundance of amino acids, phenolic and terpene metabolites all led to the synthesis of defence compounds. An integrated analysis of the metabolic and transcriptomic data revealed that substantial alterations in the abundance of most of the intermediate metabolites and enzymes changed substantially under pathogen infection. These changes included the isoflavonoid biosynthesis pathway, which suggests that isoflavonoid biosynthesis plays an important role in the soybean root response. The results showed that F. mosseae could alleviate the root rot caused by continuous cropping. The increased activity of some disease-resistant genes and disease-resistant metabolites may partly account for the ability of the plants to resist diseases. This study provides new insights into the molecular mechanism by which AMF alleviates soybean root rot, which is important in agriculture.


Identification and characterization of zebrafish thrombocytes.
To analyse primary haemostasis in the zebrafish we have identified and characterized the zebrafish thrombocyte by morphologic, immunologic and functional approaches. Novel methods were developed for harvesting zebrafish blood with preservation of thrombocytes, and assaying whole blood adhesion/aggregation responses in microtitre plates. Light and electron microscopy of the thrombocyte illustrated morphological characteristics including the formation of aggregates, pseudopodia, and surface-connected vesicles analagous to the platelet canalicular system. Immunostaining with polyclonal antisera versus human platelet glycoproteins demonstrated the presence of glycoprotein Ib and IIb/IIIa-like complexes on the thrombocyte surface. Whole blood assays for adhesion/aggregation and ATP release showed ristocetin-induced adhesion without ATP release, and platelet agonist (collagen, arachidonic acid) induced aggregation with ATP release. Blood harvested from zebrafish treated with aspirin demonstrated inhibition of arachidonic acid induced aggregation and agonist induced ATP release, consistent with at least partial dependence on an intact cyclo oxygenase pathway. The combined morphologic immunologic and functional evidence suggest that the zebrafish thrombocyte is the haemostatic homologue of the mammalian platelet. Conservation of major haemostatic pathways involved in platelet function and coagulation suggests that the zebrafish is a relevant model for mammalian haemostasis and thrombosis.


Angloplasty revision: importance of genioplasty for narrowing of the lower face.
Angloplasty is the most common procedure in facial contouring surgery among Asians. However, to achieve satisfactory results during procedures aimed at altering the lower facial contour, the shape of the mandible and the chin area in particular is an important consideration. In cases of reoperation for further improvement after angloplasty, surgeons should consider performing a genioplasty to improve the shape of the chin. From March of 2010 to August of 2012, 52 women who were dissatisfied with results of angloplasty and wanted a slimmer lower face underwent genioplasty and revision angloplasty. The procedures included narrowing genioplasty and contouring of the lower border of the mandible from the parasymphysis area to the previously resected area. All patients were satisfied with their facial appearance, which had become slender when viewed from the front. There were no notable complications. No patient experienced permanent sensory numbness of the lower lip. Two patients complained of submental bulges and were treated postoperatively using laser-assisted liposuction. When performing revision surgery to restore the contour of the mandible, the surgeon should consider the shape of the mandible as a whole to create a slender face, which is achievable by simultaneous narrowing genioplasty and contouring of the lower border of the mandible. Therapeutic, IV.


Resection of nasopharyngeal angiofibroma with extranasal and extrapharyngeal involvement.
The authors report their own experiences with the diagnosis and therapy of 7 cases of nasopharyngeal angiofibroma with extranasal and extrapharyngeal involvement, thereby attempt to formulate the surgical approach for resection of huge nasopharyngeal angiofibroma with extensive involvement. The results suggested that appropriate surgical approach was of paramount importance for eliminating the tumor and may effectively reduce traumatic injury during the operation. Elective embolization of the vessels feeding the tumor could reduce bleeding and therefore increase the safety of the operation.


[Oncogeriatrics: an attempt to operational definition].
Comprehensive geriatric assessment (CGA) represents a multidisciplinary comprehensive evaluation of an older individual's functional status, comorbid medical conditions, cognition, psychological state, social support, nutritional status, and a review of the patient's medications. Initially, the use of a CGA in the care of older patients with cancer was based on an extrapolation of its ability to predict morbidity and mortality in the general geriatric population. More recently, however, accumulating data show the benefits of using a CGA particularly in patients with cancer to predict morbidity and mortality. Prospective trials evaluating the utility of a CGA to guide interventions to improve the quality of cancer care in older adults are justified.


Serum concentrations of allergen-specific IgE in horses with equine recurrent airway obstruction and healthy controls assessed by ELISA.
Equine recurrent airway obstruction (RAO), also known as heaves, is one of the most common respiratory problems in older horses. When RAO-affected horses stay pastured or in a dust-free environment for a prolonged time, clinical signs as well as airway inflammation wane. A number of environmental, immunologic, infectious, and genetic factors play an important role in the pathogenesis of RAO, and the immunologic basis of this disease is still poorly understood. The aim of this study was to investigate the concentrations of allergen-specific IgE in the serum of horses suffering from RAO and healthy controls. The study included a group of 14 adult Polish Konik horses, kept in a standardized environment, and divided into 2 groups: 7 horses which did not have any respiratory problems comprised the control group and 7 horses with a history of RAO constituted the study group. A clinical and laboratory evaluation, endoscopic examination, and bronchoalveolar lavage (BAL) were performed in all horses. Sera of all horses were tested against allergens from 9 molds and 3 mites using the Heska Allercept assay. In the serologic tests, a statistically significant difference between both groups was found for specific IgE against mites, wherein Tyrophagus putrescentia correlated most clearly with RAO. There was no difference between groups for IgE specific against molds. On the basis of our observations and results, we conclude that RAO is associated with increased serum concentrations of specific serum IgE against mites, in particular T putrescentia.


[Response properties of pulpal nerve fibers with different conduction velocities].
Tapering and branching of the nerve fibers cause the conduction velocity (CV) along the axon to be unequal. The purpose of this study was to investigate the response properties of the myelinated and unmyelinated nerve fibers in the cat tooth pulp. Electrophysiological recordings were made from the functional single fibers innervating the lower canine tooth pulp in 25 adult cats anesthetized with pentobarbital sodium after the application of four types of stimuli to the canine tooth. A total of 272 single pulpal nerve fibers was identified. A-fibers (n = 215) were divided into two groups: One (Ac, n = 55) consisting of the fibers whose intrapulpal CVs were less than 2 m/s and the extra-pulpal CVs of more than 2 m/s, and the other (At, n = 160) consisting of the fibers whose CVs were more than 2m/s both inside and outside the tooth pulp. Fifty-seven C-fibers (C) were also found. None of C, 47% of At and 46% of Ac responded to the rapid elevation of the temperature. None of At, 38% of Ac and 53% of C responded to the continuous heat. None of C, 20% of At and 20% of Ac responded to the hydrostatic pressure. None of At, 86% of Ac and all of C responded to bradykinin. These results suggest that the functional difference between the pulpal A-and C-fibers is not clear and that the Ac-fibers may complicate the dental and pulpal pain.


Heterogeneity of catalase in maturing and germinated cotton seeds.
To investigate possible charge and size heterogeneity of catalase (EC 220.127.116.11) in cotton (Gossypium hirsutum L. cv Deltapine 62), extracts of cotyledons from different developmental ages were subjected to nondenaturing polyacrylamide gel electrophoresis and isoelectric focusing. Special precautions (e.g. fresh homogenates, reducing media) were necessary to prevent artefacts due to enzyme modification during extraction and storage. When the gels were stained for enzyme activity, two distinct electrophoretic forms of catalase were resolved in extracts of maturing and mature cotton seeds. In germinated seeds, three additional cathodic forms were detected revealing a total of five electrophoretic variants. In green cotyledons, the two anodic forms characteristic of ungerminated seeds were less active; whereas, the most cathodic form was predominant. All forms of catalase were found in isolated glyoxysomes. Corresponding electrophoretic patterns were found on Western blots probed with anticatalase serum; no immunoreactive, catalytically inactive forms were detected. Western blots of sodium dodecyl sulfate-polyacrylamide gels revealed only one immunoreactive (55 kilodaltons) polypeptide in cotton extracts of all developmental ages. Results from isoelectric focusing and Ferguson plots indicate that the electrophoretic variants of catalase are charge isomers with a molecular weight of approximately 230,000.