Human cerebral endothelium: isolation and characterization of cells derived from microvessels of non-neoplastic and malignant glial tissue.
Human microvessels were isolated and cultured from non-neoplastic cerebral tissue specimens resected for the treatment of seizure disorders and from malignant glial tumors. After 1-2 weeks, cobblestone patterned plaques of cells were isolated and cultured from these microvessels. Cell lines positive for Factor VIII antigen and negative for glial fibrillary acidic protein were designated as endothelium. Endothelium from both tissue sources produced gamma-glutamyl transpeptidase in response to glial cell conditioned media. Tumor derived microvessel endothelium had decreased longevity in culture when compared to normal microvessel endothelium. Tumor derived endothelium also formed less extensive intercellular junctional complexes in vitro. The isolation and characterization of human cerebral microvessel endothelium derived from non-neoplastic tissue and glial tumors may lead to a further understanding of the role of endothelium in tumor growth and vascular permeability alterations.


Possible effect of the HLA-DQ2/DQ8 polymorphism on autoimmune parameters and lymphocyte subpopulation in recurrent pregnancy losses.
Recurrent pregnancy loss (RPL) affects 1-2 % of women. Allo- and autoimmune disorders are a recognized factor for RPL and poor pregnancy outcomes. There is a link between antiphospholipid syndrome (APS), Hashimoto's thyroiditis or coeliac disease, and pregnancy losses. The prevalence of the HLA-DQ2/DQ8 polymorphism and genetic susceptibility to the development of celiac disease may be higher in women who experience RPL. A total of 95 women who had experienced two or more miscarriages were qualified into the study: 49 women with the HLA-DQ2/DQ8 polymorphism as the study group, and 46 as the control group. The prenatal test results of the women were evaluated, which revealed that the foetuses from the study group had higher nuchal translucency measurements than those of controls (1.85 mm vs 1.50 mm; p = 0.0024). A higher level of anticardiolipin antibodies (aCL) in the IgG class (18.38 GP L vs 11.37 GP L; p = 0.0039) and antithyroid peroxidase antibodies (aTPO) (87.67 IU/mL vs 11.87 IU/mL; p = 0.0062) was observed when compared to the control group. The presence of the HLA-DQ2.2 polymorphism was observed when higher nuchal translucency measurements and a higher aTPO concentration occurred. A relationship between the aTPO concentration and a higher birth weight of newborns was also shown. No significant differences between the groups were observed for peripheral blood lymphocyte subsets. A statistically significant relationship between the HLA-DQ2/DQ8 polymorphism and the increased concentrations of indicators of autoimmune disorders was indicated.


[Analysis of the structure of cardiac rhythm during treatment of auricular fibrillation with digitalis].
The structure of cardiac rhythm was studied with the help of specialized computers during digitalization in 60 patients with atrial fibrillation of different etiology. The reduction of the heart contractions rate under digitalization is accompanied by certain changes in the structure of cardiac rhythm: the arrhythmic pattern of the ventricular contractions increases with a predominant growth of the number of long R--R intervals, the transitions from short intervals to longer ones become sharper, and portions of a relatively stable ventricular rhythm appear. Three main types of dynamics of the rhythm structure were distinguished on the basis of the changes in the interval R--R histogram. The described changes in the structure of cardiac rhythm are not specific, but when Digitalis drugs are used alone they can be used as additional criteria for digitalization.


Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study.
Bone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients. We retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model. The median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268-5.841, P = 0.010). Alcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.


Two-dimensional speckle tracking echocardiography demonstrates improved myocardial function after intravenous infusion of bone marrow mesenchymal stem in the X-Linked muscular dystrophy mice.
Bone marrow mesenchymal stem cells (BMSCs) are commonly used in regenerative medicine. However, it is not clear whether transplantation of BMSCs can improve cardiac function of the X-Linked Muscular Dystrophy Mice (mdx) and how to detect it. We aimed to investigate the role of speckle tracking echocardiography (STE) in detecting cardiac function of the BMSCs-transplanted mdx in comparison with the untreated mdx. The experimental mice were divided into the BMSCs-transplanted mdx, untreated mdx, and control mice groups (n = 6 per group). The BMSCs were transplanted via tail vein injections into a subset of mdx at 20 weeks of age. After four weeks, the cardiac functional parameters of all the mice in the 3 groups were analyzed by echocardiography. Then, all the mice were sacrificed, and the cardiac tissues were harvested and analyzed by immunofluorescence. The serum biochemical parameters were also analyzed to determine the beneficial effects of BMSCs transplantation. Traditional echocardiography parameters did not show statistically significant differences after BMSCs transplantation for the three groups of mice. In comparison with the control group, mdx showed significantly lower left ventricular (LV) STE parameters in both the long-axis and short-axis LV images (P < 0.05). However, BMSCs-transplanted mdx showed improvements in several STE parameters including significant increases in a few STE parameters (P < 0.05). Immunofluorescence staining of the myocardium tissues showed statistically significant differences between the mdx and the control mice (P < 0.05), and the mdx transplanted with BMSCs demonstrated significantly improvement compared with the untreated mdx (P < 0.05). This study demonstrated that the early reduction in the LV systolic and diastolic function in the mdx were accurately detected by STE. Furthermore, our study demonstrated that the transplantation of BMSCs significantly improved myocardial function in the mdx.


Effects of artificial sweeteners on insulin release and cationic fluxes in rat pancreatic islets.
Beta-L-glucose pentaacetate, but not alpha-D-galactose pentaacetate, was recently reported to taste bitter and to stimulate insulin release. This finding led, in the present study, to the investigation of the effects of both bitter and non-bitter artificial sweeteners on insulin release and cationic fluxes in isolated rat pancreatic islets. Sodium saccharin (1.0-10.0 mM), sodium cyclamate (5.0-10.0 mM), stevioside (1.0 mM) and acesulfame-K (1.0-15.0 mM), all of which display a bitter taste, augmented insulin release from islets incubated in the presence of 7.0 mM D-glucose. In contrast, aspartame (1.0-10.0 mM), which is devoid of bitter taste, failed to affect insulin secretion. A positive secretory response to acesulfame-K was still observed when the extracellular K+ concentration was adjusted to the same value as that in control media. No major changes in 86Rb and 45Ca outflow from pre-labelled perifused islets could be attributed to the saccharin, cyclamic or acesulfame anions. It is proposed that the insulinotropic action of some artificial sweeteners and, possibly, that of selected hexose pentaacetate esters may require G-protein-coupled receptors similar to those operative in the recognition of bitter compounds by taste buds.


Social network and social support characteristics amongst individuals recently discharged from acute psychiatric units.
This study compares the social support network of a diagnostically heterogeneous group of community mental health service users recently discharged from acute inpatient units, with that of a mental health service user comparison group with no history of hospital admission. Social data were elicited by a structured interview schedule (the Social Network Schedule). It was observed that the study group was characterized by smaller overall social networks, particularly within the primary network, but conversely the group had a greater proportion of service user peer contact. Few differences in perceived social support between groups were observed, although the study group reported fewer confidants. The implications of the study for nursing staff are discussed.


Polymicrobial infections and microbial patterns in infected nonunions - a descriptive analysis of 42 cases.
Frequencies of polymicrobial infection and pathogens evidenced in course of infected nonunion treatment are largely unknown. Therefore, this study aims at investigating microbial patterns in infected nonunions. Surgically treated patients with long bone infected nonunion admitted between January 2010 and March 2018 were included in the study. Microbiological culture and polymerase-chain-reaction results of tissue samples of initial and follow-up revision surgeries were assessed and compared with patient and treatment characteristics. Forty two patients with a mean age of 53.9 ± 17.7 years were included. In six patients (14.3%) polymicrobial infection was evident. A change of pathogens evidenced in course of the treatment occurred in 21 patients (50%). In 16 patients (38.1%) previously detected bacteria could be determined by microbial testing after further revision surgery. Staphylococcus aureus was most often detected (n = 34, 30.6%), followed by Enterococcus spp. (n = 25, 22.5%) and Staphylococcus epidermidis (n = 18, 16.2%). Five Staphylococcus aureus were resistant to methicillin (MRSA). In patients without polymicrobial infection or further germ detection in course of the treatment, 86.4% of the infections were due to Staphylococcus spp.. Infections due to Streptococcus spp. and gram-negative bacteria were only present in patients with polymicrobial infection and germ-change in course of the treatment. A low rate of polymicrobial infections was evidenced in the present study. Germ-change often occurs in course of revision surgeries. Prospective studies with more sensitive diagnostic tools are necessary to elucidate the therapeutical relevance of microbiological testing results for surgical as well as medical treatment in infected nonunions.


Macrophage responses to silk.
Silk fibers have potential biomedical applications beyond their traditional use as sutures. The physical properties of silk fibers and films make it a promising candidate for tissue engineering scaffold applications, particularly where high mechanical loads or tensile forces are applied or in cases where low rates of degradation are desirable. A critical issue for biomaterial scaffolds is biocompatibility. The direct inflammatory potential of intact silk fibers as well as extracts was studied in an in vitro system. The results indicate that silk fibers are largely immunologically inert in short- and long-term culture with RAW 264.7 murine macrophage cells while insoluble fibroin particles induced significant TNF release. Soluble sericin proteins extracted from native silk fibers did not induce significant macrophage activation. While sericin did not activate macrophages by itself, it demonstrated a synergistic effect with bacterial lipopolysaccharide. The low level of inflammatory potential of silk fibers makes them promising candidates in future biomedical applications.


Tips for children's better cooperation during the examination of the head and neck: A Delphi method.
To obtain and rate tips for the head and neck examination in children. A two-round Delphi method study was conducted to survey 13 practising paediatric otolaryngologists (PO) in North America and Europe to obtain tips on how to approach a 2- to 6-year-old child for head and neck examination. The tips were rated by the PO according to their frequency of utilization and usefulness on a scale of 1 (high) to 6 (low). One-sample Wilcoxon signed rank tests were used to evaluate each tip according to frequency of use and success rate. "Top Tips" were identified when both their Wilcoxon p-values were still significant, after a Bonferroni correction. An exact chi-square test for equality of proportions was used to determine the age groups for which satisfactory tips are to be favoured. The panellists rated forty-three tips. Seven tips obtained a p-value ≤0.001 for the frequency of use and usefulness in all age groups with an emphasis on the initial moments: eye contact, mood assessment, approach behaviour and strategy. Six more tips proved to be satisfactory for specific age groups without reaching the top tip significance level. Seven tips to approach a 2- to 6-year-old child reached a top consensus between the experts. Initial eye contact with the child and mood assessment are essential for a satisfactory outcome. The use of a gentle approach with explanation of each step of the physical exam and avoidance of pain are also important.


Nicolau syndrome caused by Glatiramer.
Injection-site reactions to glatiramer are common and include erythema, pruritus, pain, or induration. Additionally, the present systematic review of the literature documents 20 cases of Nicolau syndrome following glatiramer, a rare but potentially severe skin reaction. Abdomen and thighs are the most frequently affected areas (80% of reported cases), and permanent skin damage has been observed in 30% of cases. Recurrences are rare (<10%).


Sensitization of the UPR by loss of PPP1R15A promotes fibrosis and senescence in IPF.
The unfolded protein response (UPR) is a direct consequence of cellular endoplasmic reticulum (ER) stress and a key disease driving mechanism in IPF. The resolution of the UPR is directed by PPP1R15A (GADD34) and leads to the restoration of normal ribosomal activity. While the role of PPP1R15A has been explored in lung epithelial cells, the role of this UPR resolving factor has yet to be explored in lung mesenchymal cells. The objective of the current study was to determine the expression and role of PPP1R15A in IPF fibroblasts and in a bleomycin-induced lung fibrosis model. A survey of IPF lung tissue revealed that PPP1R15A expression was markedly reduced. Targeting PPP1R15A in primary fibroblasts modulated TGF-β-induced fibroblast to myofibroblast differentiation and exacerbated pulmonary fibrosis in bleomycin-challenged mice. Interestingly, the loss of PPP1R15A appeared to promote lung fibroblast senescence. Taken together, our findings demonstrate the major role of PPP1R15A in the regulation of lung mesenchymal cells, and regulation of PPP1R15A may represent a novel therapeutic strategy in IPF.


Endangered Vancouver Island marmots (Marmota vancouverensis): sentinels of atmospherically delivered contaminants to British Columbia, Canada.
We characterized legacy and new contaminants in the highly endangered Vancouver Island (British Columbia, Canada) marmot and found generally low blood and fat concentrations of a complex mixture of pesticides, polychlorinated biphenyls (PCBs), -dibenzo-p-dioxins (PCDDs), -dibenzofurans (PCDFs), polybrominated biphenyls (PBBs), polybrominated diphenyl ethers (PBDEs), and polychlorinated naphthalenes (PCNs) in their tissues. The dominance of the more volatile alpha-hexachlorocyclohexane (HCH) and hexachlorobenzene (HCB) pesticides and the lesser chlorinated PCB congeners suggests that atmospheric processes largely explain the contamination of this high-altitude herbivore.


Cytokeratins in normal thymus and thymic epithelial tumors.
Thymus consists of some distinct epithelial cells that contain different sets of cytokeratins (CK). Epithelium-derived tumors maintain the expression of some of the CK of the specific nontransformed cells. Therefore, it seems reasonable to hypothesize that thymic epithelial tumors may differentiate toward distinct subsets of intrathymic epithelial cells in terms of CK expression. Eighty-one thymomas and 14 thymic carcinomas were studied immunohistologically using monoclonal antibodies specific for a single CK or a CK pair. Thymic epithelial neoplasms could not be distinguished from each other on the basis of the profile of CK expression because the degree of overlap was extensive. However, polygonal cell thymomas differentiate toward a CK13-positive cortical subset that is rare in normal thymus. Spindle cell thymomas differentiate toward a CK13-positive medullary subset. Mixed cell thymomas are comprised of a CK13-positive medullary subset and a CK13-negative medullary subset, both of which are typical in normal thymus. CK18 was expressed to a greater extent on the epithelium of thymic carcinomas than on that of thymomas. Polygonal cell thymomas more frequently were invasive than spindle and mixed cell thymomas. There is a possibility that the epithelium of polygonal cell thymomas is immature because it is a phenotypically unusual subset in normal thymus. A thymic carcinoma arising in a thymoma has been reported, although the relationship between the thymoma and the thymic carcinoma was not clear. Nevertheless, given the similar cellular differentiation of thymoma and thymic carcinoma, CK18-positive epithelium in thymomas may be transformed into thymic carcinoma cells in certain conditions.


Comparative study on cytochrome P-450 of yeasts using specific antibodies to cytochromes P-450alk and P-450(14DM).
The occurrence of cytochrome P-450(14DM) (lanosterol 14 alpha-demethylase) and cytochrome P-450alk (long-chain alkane terminal hydroxylase) in various yeast strains was determined with immunological procedures. Cytochrome P-450(14DM), which is constitutive or housekeeping enzyme playing an essential role in ergosterol biogenesis, was found in all yeast strains so far tested. Cytochromes P-450(14DM) from different species of yeast were immunologically different, although they may have had a few common antigenic sites. In contrast, cytochrome P-450alk was detected only in the alkane-assimilating yeasts.


The impact of unemployment on school leavers' perception of health. Mediating effect of financial situation and social contacts?
The main purpose of this paper is to explore whether unemployment influences adolescents' subjective perception of health and whether perceived financial stress and social contacts can mediate the effect of employment status on health. We are also interested in the differences in financial situation and social contacts between unemployed secondary school leavers and their employed and studying counterparts. Data were obtained from 844 adolescents (mean age 19.6) from Slovakia. The effect of unemployment on several health indicators was measured and subsequently controlled for perceived financial strain of respondents and their social contacts. The results showed highest financial strain among unemployed, whereas only small differences in social contacts were found between three groups. Negative influence of unemployment on perceived health of respondents was confirmed. Nevertheless, strong influence was found only on long-term well-being and mental health. Financial situation and social contacts contributed to the prediction of almost all health outcomes, and to some extent mediated the effect of unemployment. Although unemployment was found to have a negative impact on health of adolescents, sufficiency of social contacts and good financial situation seem to decrease this effect and protect the health of unemployed people.


Anticholinesterase effect and toxicity of bis(trichloromethyl) sulfone (N-1386 Biocide) in rats.
The oral LD50 for bis(trichloromethyl) sulfone (N-1386 Biocide) in male rats was 691 mg/kg. Deaths occurred 1-5 days after treatment and signs of toxicity suggestive of an anticholinesterase effect were noted. However, neither plasma cholinesterase nor brain acetylcholinesterase was inhibited 2, 4 or 24 hours after a single, oral dose of 500 mg/kg. Atropine (300 mg/kg, s.c.) or scopolamine (670 mg/kg, s.c.) pretreatments did not protect against the acute lethality of bis(trichloromethyl) sulfone although signs of toxicity were alleviated by both pretreatments. Bis(trichloromethyl) sulfone produced in vitro inhibition of rat plasma cholinesterase and brain acetylcholinesterase. The inhibition was competitive in brain. IC50's for these 2 enzymes were 8 microM in plasma and 25 microM in brain. In summary, bis(trichloromethyl) sulfone produced in vitro cholinesterase inhibition not demonstrated in vivo. Doses of anticholinergic compounds that ameliorated many toxic signs did not protect against lethality produced by bis(trichloromethyl) sulfone.


Responsiveness to hormone, growth factor and drug treatment of a human breast cancer cell line: comparison between early and late cultures.
Growth rate, morphology, and responsiveness to mitogenic stimuli and pharmacological treatments were evaluated in early and late cell passages derived from the same clone of the widely used MCF-7 human breast adenocarcinoma cell line. Our results indicate dissimilarities between early (E) and late (L) passages for some of the parameters analyzed. The cells that underwent many subcultivations grew faster than the others; both appeared homogeneous in size and shape. The E cells, subcultured for almost 1 yr, displayed higher sensitivity to the mitogenic action of both estradiol, according to the level of estrogen receptor, and insulin-like growth factor-I than did the L cells, kept in culture for more than 10 yr. Cell responsiveness to two drugs, a novel steroid antiestrogen and a polysulfonated distamycin A derivative, was more pronounced in the early cultures only at the longer time of exposure to the higher concentration of the estrogen antagonist. In addition, a drug-induced inhibition of insulin-like growth factor-I binding to its receptor was shown in both E and L cells, the latter being less sensitive than the former when exposed to the antiestrogen. Finally, MCF-7 E and L cells showed similar behavior when drug-induced apoptosis was tested.


TripleFRET measurements in flow cytometry.
A frequently used method for viewing protein interactions and conformation, Förster (fluorescence) resonance energy transfer (FRET), has traditionally been restricted to two fluorophores. Lately, several methods have been introduced to expand FRET methods to three species. We present a method that allows the determination of FRET efficiency in three-dye systems on a flow cytometer. TripleFRET accurately reproduces energy transfer efficiency values measured in two-dye systems, and it can indicate the presence of trimeric complexes, which is not possible with conventional FRET methods. We also discuss the interpretation of energy transfer values obtained with tripleFRET in relation to spatial distribution of labeled molecules, specifically addressing the limitations of using total energy transfer to determine molecular distance.


p53 expression in human rectal tissue after radiotherapy: upregulation in normal mucosa versus functional loss in rectal carcinomas.
In vitro, ionizing radiation of epithelial cells leads to upregulation of wild-type p53 and subsequent induction of p21(waf1). The effect of radiotherapy (RT) on the expression of these proteins in patients is unknown. We assessed the influence of RT on the expression of p53 and p21(waf1) in normal mucosa and rectal carcinomas in vivo. Tumor and normal tissue samples were derived from rectal cancer patients randomized in a clinical trial in which the value of preoperative RT was evaluated. p53 and p21(waf1) expression was determined in 51 irradiated and 52 nonirradiated patients using immunohistochemistry. In normal mucosa, both p53 and p21(waf1) were strongly upregulated after RT compared with the expression in unirradiated normal tissue (p <0.001). In tumor cells, no significant difference in the expression of p53 or p21(waf1) was found in the irradiated vs. nonirradiated group. In the few rectal tumors with wild-type p53, induction of p53 after RT did not necessarily lead to upregulation of p21(waf1). These findings demonstrate that in normal mucosa, a functional p53-p21(waf1) pathway is present, whereas in tumor cells it is defective in almost all cases because of either p53 mutation or down- or upstream disruption in tumors with wild-type p53. Therefore, we believe that the role of p53 expression as a single prognostic marker in rectal cancer needs reconsideration.


Paracoccidioidomycosis Mimicking Sarcoidosis: A Review of 8 Cases.
Sarcoidosis is a multisystem disorder that is characterized by noncaseous epithelioid cell granulomas, which may affect almost any organ. Thoracic involvement is common and accounts for most of the morbidity and mortality associated with this disease. The diagnosis is based on exhaustive exclusion of differential diagnoses, particularly granulomatous infections. We report data on eight patients with paracoccidioidomycosis mimicking sarcoidosis. Five patients presented with a chronic pulmonary type infection and three had a disseminated form after immunosuppressive treatment. The mycological diagnosis in noncaseating granulomas is emphasized and reviewed.


A late onset adult seizure due to intracerebral needle: case-based update.
Late-onset seizure due to intracerebral needle is a rare entity. Most of them were clinically asymptomatic and rarely presented with seizure. Sewing needles are used in homicidal attempt in infancy or early childhood before the closure of the fontanels. Because of sociologic, politic, and scientific deficiencies subject remained untouched. We tried shedding some light on this ambiguous phenomenon. We report a 54-year-old man who was admitted to our neurosurgery outpatient department with epilepsy due to a sewing needle located in the left frontal lobe of the brain and made extensive literature review. Patient's physical and neurological examinations were completely normal. All biochemical and hematological tests were normal. Cranial tomography demonstrated a linear density at the left frontal lobe compatible with a sewing needle. Patient was followed-up with antiepileptic treatment with no seizure. Sixty cases from up-to-date literature and past cases were reviewed. Patients' ages differ from 4 days to 70 years. Our review showed four cases treated with antibiotics, 19 patients went to surgery, and others just followed-up with antiepileptic and other drugs. Literature needs an autopsy series for a more intimate estimation. Due to psychosocial and legitimacy problems, matter should be handled cautiously and law enforcement agencies must be informed. Follow-up with medication is the first line of treatment with asymptomatic patients. Treatment is dictated by clinic onset, physical examination, and patient consent.


Impacts of moisture content during ozonation of soils containing residual petroleum.
We tested the effect of soil moisture content on the efficiency of gas-phase ozonation for two types of soils containing residual petroleum. For the first soil (BM2), having a total petroleum hydrocarbons (TPH) concentration of 18,000mg/kg soil, a moisture content of 5% benefited oxidation, giving the highest efficiency of ozonation for TPH removal and for producing soluble and biodegradable products. In contrast, higher moisture content hindered O3 from oxidizing reactive materials in the second soil (BM3), which had a higher TPH concentration, 33,000mg/kg soil. This trend was documented by less TPH removal, less generation of soluble and biodegradable organic products, and a carbon balance that showed retarded carbon oxidation. An unexpected phenomenon was smoldering during ozonation of air-dried (<1% moisture) BM3, which did not occur with the same moisture conditions for BM2. BM3 smoldered was due to its higher TPH content, low heat buffering, and more release of volatiles with low self-ignition points. Smoldering did not occur for ≥ 5% water content, as it suppressed the temperature increase needed to volatilize the organics that initiated smoldering. The findings underscore the importance of controlling water content during ozonation to optimize the effectiveness of ozonation and prevent smoldering.


Formation of purine photoproducts in a defined human DNA sequence.
The formation of DNA base damages by broad spectrum ultraviolet irradiation (250-400 nm) was investigated using a defined sequence of human DNA. The irradiated, 92 base pair, 3'-end of the human alphoid segment was incubated with an enzyme fraction purified from bacteriophage T4-infected E. coli. As previously reported, analysis of reaction products by sequencing gels showed enzymic incision of purine-containing photoproducts as well as pyrimidine cyclobutane photodimers. The purine-incising activity does not require metal ions and was unaffected by beta-mercaptoethanol or dithiothreitol. The formation of the purine photoproducts is independent of buffer; these lesions are produced by irradiation of DNA in Tris, Hepes or phosphate buffers. They are produced at biologically significant wavelengths between 260 to 300 nm. Only low levels were detected above or below this range. The formation of purine photoproducts is dose dependent with similar yields at some specific loci to pyrimidine dimers. These results suggest that purine-containing photoproducts could be of consequence in ultraviolet carcinogenesis.


Validating Signs and Symptoms From An Actual Mass Casualty Incident to Characterize An Irritant Gas Syndrome Agent (IGSA) Exposure: A First Step in The Development of a Novel IGSA Triage Algorithm.
• Chemical exposures daily pose a significant threat to life. Rapid assessment by first responders/emergency nurses is required to reduce death and disability. Currently, no informatics tools for Irritant Gas Syndrome Agents (IGSA) exposures exist to process victims efficiently, continuously monitor for latent signs/symptoms, or make triage recommendations. • This study uses actual patient data from a chemical incident to characterize and validate signs/symptoms of an IGSA Syndrome. Validating signs/symptoms is the first step in developing new emergency department informatics tools with the potential to revolutionize the process by which emergency nurses manage triage victims of chemical incidents. Chemical exposures can pose a significant threat to life. Rapid assessment by first responders/emergency nurses is required to reduce death and disability. Currently, no informatics tools for irritant gas syndrome agents (IGSA) exposures exist to process victims efficiently, continuously monitor for latent signs/symptoms, or make triage recommendations. This study describes the first step in developing ED informatics tools for chemical incidents: validation of signs/symptoms that characterize an IGSA syndrome. Data abstracted from 146 patients treated for chlorine exposure in one emergency department during a 2005 train derailment and 152 patients not exposed to chlorine (a comparison group) were mapped to 93 possible signs/symptoms within 2 tools (WISER and CHEMM-IST) designed to assist emergency responders/emergency nurses with managing hazardous material exposures. Inferential statistics (χ2/Fisher's exact test) and diagnostics tests were used to examine mapped signs/symptoms of persons who were and were not exposed to chlorine. Three clusters of signs/symptoms are statistically associated with an IGSA syndrome (P < .01): respiratory (shortness of breath, wheezing, coughing, and choking); chest discomfort (tightness, pain, and burning), and eye, nose and/or throat (pain, irritation, and burning). The syndrome requires the presence of signs/symptoms from at least 2 of these clusters. The latency period must also be considered for exposed/potentially exposed persons. This study uses actual patient data from a chemical incident to characterize and validate signs/symptoms of an IGSA syndrome. Validating signs/symptoms is the first step in developing new ED informatics tools with the potential to revolutionize the process by which emergency nurses manage triage victims of chemical incidents.


Navigating the boundaries between metabolism and epigenetics in trypanosomes.
Epigenetic marks enable cells to acquire new biological features that favor their adaptation to environmental changes. These marks are chemical modifications on chromatin-associated proteins and nucleic acids that lead to changes in the chromatin landscape and may eventually affect gene expression. The chemical tags of these epigenetic marks are comprised of intermediate cellular metabolites. The number of discovered associations between metabolism and epigenetics has increased, revealing how environment influences gene regulation and phenotype diversity. This connection is relevant to all organisms but underappreciated in digenetic parasites, which must adapt to different environments as they progress through their life cycles. This review speculates and proposes associations between epigenetics and metabolism in trypanosomes, which are protozoan parasites that cause human and livestock diseases.


Percutaneous subclavian vein catheterization for hemodialysis: a report of 57 insertions.
The authors report an analysis of 57 subclavian vein catheterizations for hemodialysis. A total of 51 patients (34 men, 17 women) kept the Cobe single- and double-lumen catheters for 1,726 days. The youngest patient was eighteen and the oldest seventy-two years of age. There were no catheter-related deaths. Complications were encountered in 9 patients. The only life-threatening complication was cardiac arrest, which occurred during flushing of the catheter. The patient was successfully revived. The other complications were pneumothorax and hydrothorax in 1 patient, catheter site infection in 5 patients, and arrhythmias in 2 patients, which stopped after readjustment of the catheter tips. Their experience indicates that percutaneous subclavian vein catheterization is safe and provides quick access for hemodialysis with no morbidity and mortality if done correctly, patiently, and meticulously. The authors believe that this should be the first choice in patients with reversible renal failure and in patients with chronic renal failure, who are usually elderly and medically compromised, till a permanent vascular access is ready for use.


Structural development of the fictional narratives of African American preschoolers.
This study examined the structural development of African American preschoolers' narratives. It also investigated the effect of background variables (e.g., gender, maternal education, stimulation and responsiveness of the home environment, and whether or not the child lived in poverty) on the children's narratives. Sixty-five children completed a story-retelling task at age 4 and again at kindergarten entry. Narratives were then coded for story grammar elements. Four-year-olds narrated some attempts to solve the problem and some elements of the story ending. At kindergarten entry, children had higher total narrative scores and included more of every type of story grammar element except relationship. Overall, narratives were not related to background variables. The Bus Story Language Test (C. Renfrew, 1991) appears to be an assessment tool that is sensitive to structural growth in African American children's narratives from 4 years to kindergarten entry.


Effective modulation of the haematopoietic toxicity associated with zidovudine exposure to murine and human haematopoietic progenitor stem cells in vitro with lithium chloride.
The drug zidovudine (AZT), a synthetic thymidine analogue, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has induced haematopoietic toxicity manifested by anaemia, neutropenia, frequent thrombocytopenia, and overall bone-marrow suppression. The monovalent cation lithium has been shown to be an effective agent capable of modulating several aspects of haematopoiesis such as the induction of neutrophilia, thrombopoiesis, and protection against suppression of haematopoietic progenitor stem cells following exposure to anticancer drugs and/or radiation in the treatment of malignant disease. We here report the results of studies designed to evaluate the effectiveness of lithium in reversing and/or protecting against either murine or human bone marrow derived haematopoietic progenitors, i.e. (CFU-GM, CFU-Meg, and BFU-E) when co-cultured in the presence of zidovudine in vitro. Lithium chloride (LiCl) reversed zidovudine toxicity to either murine or human derived CFU-GM and CFU-Meg that was optimal at a concentration of 1 mM (P less than 0.05). However, the addition of lithium failed to influence zidovudine toxicity toward either murine or human BFU-E. In summary, these results support the scant clinical studies that have described the presence of neutrophilia and/or thrombopoiesis in zidovudine-treated AIDS patients receiving lithium. In addition, these data further confirm the need for more detailed evaluation of lithium as an adjuvant agent to reduce the haematopoietic toxicity associated with the use of antiviral therapy in HIV-infected patients.


Identification of efficient and sequence specific bimolecular artificial ribonucleases by a combinatorial approach.
Chemically modified nucleotide monomers were incorporated into adjacent terminal positions of two separate oligonucleotides complementary to an RNA target; all possible combinations of the catalytic units were tested, resulting in an artificial nuclease that showed high activity and catalytic turnover.


An inexact multistage fuzzy-stochastic programming for regional electric power system management constrained by environmental quality.
Electric power system involves different fields and disciplines which addressed the economic system, energy system, and environment system. Inner uncertainty of this compound system would be an inevitable problem. Therefore, an inexact multistage fuzzy-stochastic programming (IMFSP) was developed for regional electric power system management constrained by environmental quality. A model which concluded interval-parameter programming, multistage stochastic programming, and fuzzy probability distribution was built to reflect the uncertain information and dynamic variation in the case study, and the scenarios under different credibility degrees were considered. For all scenarios under consideration, corrective actions were allowed to be taken dynamically in accordance with the pre-regulated policies and the uncertainties in reality. The results suggest that the methodology is applicable to handle the uncertainty of regional electric power management systems and help the decision makers to establish an effective development plan.


Adjusting HIV prevalence estimates for non-participation: an application to demographic surveillance.
HIV testing is a cornerstone of efforts to combat the HIV epidemic, and testing conducted as part of surveillance provides invaluable data on the spread of infection and the effectiveness of campaigns to reduce the transmission of HIV. However, participation in HIV testing can be low, and if respondents systematically select not to be tested because they know or suspect they are HIV positive (and fear disclosure), standard approaches to deal with missing data will fail to remove selection bias. We implemented Heckman-type selection models, which can be used to adjust for missing data that are not missing at random, and established the extent of selection bias in a population-based HIV survey in an HIV hyperendemic community in rural South Africa. We used data from a population-based HIV survey carried out in 2009 in rural KwaZulu-Natal, South Africa. In this survey, 5565 women (35%) and 2567 men (27%) provided blood for an HIV test. We accounted for missing data using interviewer identity as a selection variable which predicted consent to HIV testing but was unlikely to be independently associated with HIV status. Our approach involved using this selection variable to examine the HIV status of residents who would ordinarily refuse to test, except that they were allocated a persuasive interviewer. Our copula model allows for flexibility when modelling the dependence structure between HIV survey participation and HIV status. For women, our selection model generated an HIV prevalence estimate of 33% (95% CI 27-40) for all people eligible to consent to HIV testing in the survey. This estimate is higher than the estimate of 24% generated when only information from respondents who participated in testing is used in the analysis, and the estimate of 27% when imputation analysis is used to predict missing data on HIV status. For men, we found an HIV prevalence of 25% (95% CI 15-35) using the selection model, compared to 16% among those who participated in testing, and 18% estimated with imputation. We provide new confidence intervals that correct for the fact that the relationship between testing and HIV status is unknown and requires estimation. We confirm the feasibility and value of adopting selection models to account for missing data in population-based HIV surveys and surveillance systems. Elements of survey design, such as interviewer identity, present the opportunity to adopt this approach in routine applications. Where non-participation is high, true confidence intervals are much wider than those generated by standard approaches to dealing with missing data suggest.


A glimmer of hope? Evaluation of time for non-genitourinary medicine physicians to diagnose HIV infection in patients presenting with HIV-related illness.
A study conducted in 2002-2003 at three UK south coast hospitals measuring the length of time for non-genitourinary medicine physicians to diagnose HIV when patients presented with an HIV-related illness, found a median time to diagnosis of four days with 70% of diagnoses being made within seven days. This retrospective cohort study of all patients newly diagnosed with HIV between 1 January 2010 and 31 December 2011 was conducted at the same three hospitals. Thirty-seven patients were newly diagnosed with HIV in non-genitourinary (GU) medicine inpatient and outpatient settings (24 men, 13 women), with a mean age of 43 years. The median time to diagnosis was one day (interquartile range of 0-4 days), with 81% of diagnoses made within seven days of first presentation. Late diagnosis of HIV remains a significant challenge, but delayed diagnosis in a patient admitted with an HIV-related illness is reducing in this setting.


Automated tool detection with deep learning for monitoring kinematics and eye-hand coordination in microsurgery.
In microsurgical procedures, surgeons use micro-instruments under high magnifications to handle delicate tissues. These procedures require highly skilled attentional and motor control for planning and implementing eye-hand coordination strategies. Eye-hand coordination in surgery has mostly been studied in open, laparoscopic, and robot-assisted surgeries, as there are no available tools to perform automatic tool detection in microsurgery. We introduce and investigate a method for simultaneous detection and processing of micro-instruments and gaze during microsurgery. We train and evaluate a convolutional neural network for detecting 17 microsurgical tools with a dataset of 7500 frames from 20 videos of simulated and real surgical procedures. Model evaluations result in mean average precision at the 0.5 threshold of 89.5-91.4% for validation and 69.7-73.2% for testing over partially unseen surgical settings, and the average inference time of 39.90 ± 1.2 frames/second. While prior research has mostly evaluated surgical tool detection on homogeneous datasets with limited number of tools, we demonstrate the feasibility of transfer learning, and conclude that detectors that generalize reliably to new settings require data from several different surgical procedures. In a case study, we apply the detector with a microscope eye tracker to investigate tool use and eye-hand coordination during an intracranial vessel dissection task. The results show that tool kinematics differentiate microsurgical actions. The gaze-to-microscissors distances are also smaller during dissection than other actions when the surgeon has more space to maneuver. The presented detection pipeline provides the clinical and research communities with a valuable resource for automatic content extraction and objective skill assessment in various microsurgical environments.


Nonsteroidal anti-inflammatory drugs use and risk of Parkinson disease: A dose-response meta-analysis.
Previous studies have indicated that nonsteroidal anti-inflammatory drugs (NSAIDs) use is associated with Parkinson disease risk, but presented controversial results.Medline, Embase, Web of Science, and the Cochrane Database were searched update to November 2017. Key data were extracted from eligible studies. A dose-response meta-analysis was conducted for synthesizing data from eligible studies.Fifteen eligible studies were included in this meta-analysis. NSAIDs use was not associated with Parkinson disease risk [relevant risk (RR): 0.06; 95% confidence interval (95% CI), 0.91-1.02]. Subgroup analysis showed that aspirin use (RR: 1.14; 95% CI, 0.98-1.30) or ibuprofen use (RR: 1.01; 95% CI, 0.88-1.17) was not associated with Parkinson disease risk; however, the use of non-aspirin NSAIDs was significantly associated with Parkinson disease risk (RR:0.91; 95% CI, 0.84-0.99). Furthermore, NSAIDs use was not associated with the risk of Parkinson disease in female (RR: 0.99; 95% CI, 0.83-1.17) and male (RR: 1.01; 95% CI, 0.88-1.16). In addition, a dose-response showed per 1 number of prescription incremental increase in NSAIDs use was not associated with the risk of Parkinson disease (RR: 0.96; 95% CI, 0.91-1.02), per 1 year of duration of NSAIDs use incremental increase was not associated with the risk of Parkinson disease (RR: 0.98; 95% CI, 0.92-1.03), and per 1 dosage of NSAIDs use incremental increase was not associated with the risk of Parkinson disease (RR: 0.98; 95% CI, 0.95-1.02).NSAIDs use was not associated with the risk of Parkinson disease. The potency and the cumulative NSAIDs use did not play critical roles.


Direct observation of positron capture process at the positron source of the superKEKB B-factory.
A direct simultaneous detection of electron ([Formula: see text]) and positron ([Formula: see text]) bunches was successfully performed using wideband beam monitors and a detection system at the [Formula: see text] capture section of the SuperKEKB B-factory. The time intervals between the secondary-generated [Formula: see text] and [Formula: see text] bunches were measured to investigate their dynamical capture process. The results show that the time intervals were measured in the range of 20-280 ps on average, and the line-order switch of the [Formula: see text] and [Formula: see text] bunches and their dynamical phase-slip process in the axial direction were clearly observed as a function of the capture phase of accelerating structures. In this report, the dynamical capture and phase-slip process for the [Formula: see text] and [Formula: see text] bunches under the two-bunch acceleration scheme is described in detail. This study opens up a new window for direct observation of the [Formula: see text] and [Formula: see text] capture process at any present and future [Formula: see text] sources.


Linking entries in protein interaction database to structured text: the FEBS Letters experiment.
The corpus of the scientific literature has reached such size that a lot of useful data, dispersed throughout millions different articles, are now hard to recover. For instance, many articles in the biological domain describe relationships between entities (gene, proteins, small molecules, etc.) yet this crucial information cannot be efficiently used because of the difficulties in retrieving it automatically from unstructured text. Databases are striving to capture this valuable information and to organize it in a structured format ready for automatic analysis. However, the current database model, based on manual curation, is not sustainable because the limited support is not compatible with complete and accurate coverage of published information. Several proposals have been put forward to increase the efficiency and accuracy of the curation process. Here we present an experiment, designed by the editorial board of FEBS Letters, aimed at integrating each manuscript with a structured summary precisely reporting, with database identifiers and predefined controlled vocabularies, the protein interactions reported in the manuscript. The authors play an important role in this process as they are requested to provide structured information to be appended, in the form of human-readable paragraphs, at the end of traditional summaries. It is envisaged that the structured text will become an integral part of Medline abstracts. In 6 months time the experience gained with this experiment will form the basis for a community discussion to propose a widely accepted strategy for information storage and retrieval.


[Improvement of the diagnostic accuracy in patients with suspected rheumatic disease by preselection in the early arthritis clinic : An alternative to the appointment service point model of the Healthcare Improvement Act].
The diagnosis and treatment of inflammatory rheumatic diseases can be delayed by a long waiting period for an appointment with a rheumatologist. This study investigated whether preselection of patients in an early arthritis clinic is a suitable tool to improve this situation. In 2006 an early arthritis clinic was founded by the Collaborating Center of Rheumatology in Halle (Saale). General practitioners refer patients by using a special registration form that helps to identify patients with an early joint swelling or inflammatory back pain. Patients are then allocated to a pool of participating rheumatologists and are seen by one of them within 2 weeks. For our scientific evaluation the data of 248 patients from the early arthritis clinic and data of 187 regular patients were gathered by means of an additional questionnaire for rheumatologists and patients. In the early arthritis clinic 40.3 % of patients received the diagnosis of an inflammatory rheumatic disease compared with 19.3 % in the control group. In the latter group 51 % were diagnosed as having degenerative joint or spine disorders compared with 22 % in patients from the early arthritis clinic; however, 61 % of patients who were referred to the early arthritis clinic did not fulfill the criteria of the registration form. On the other hand, patients in this group fulfilling these criteria had an inflammatory rheumatic disease in 68.1 % of the cases. The mean duration of symptoms at the time of first rheumatological consultation was significantly shorter in the early arthritis clinic than in the control group (6 vs. 39 months). Our data demonstrate that the preselection of patients can serve as a useful instrument to guide the referral of patients to rheumatologists. The high percentage of patients who did not fulfil the criteria of the registration form indicates that a further improvement of this form is necessary and stresses the need for intensive communication between rheumatologists and general practitioners. Early arthritis clinics may be an alternative to the current efforts of the legislative authorities to improve specialist care by centralized distribution of specialist appointments.


IDENTIFCATION AND VALIDATION OF NOVEL microRNA MOLECULE FROM THE PELODISCUS SINENSIS BY BIOINFORMATICS APPROACHES.
MicroRNAs (miRNAs) are a group of endogenous, short non-coding RNAs with the length of about 22 nt, which mediate gene expression at the post-transcriptional level through mRNA degradation or translational repression. Among them, some are highly evolutionally conserved in the animal kingdom; this provides a powerful strategy for identifying miRNAs in new species. The Chinese soft-shelled turtle (Pelodiscus sinensis) is one of the most important freshwater aquaculture reptilian species in China, but related miRNAs have not been identified up to now. In the present study, a total of 10 Pelodiscus sinensis miRNAs were identified according to Pelodiscus sinensis ESTs and GSSs information in NCBI database by bioinformatics approaches. The RT-PCR-based assays were performed and found that 10 Pelodiscus sinensis miRNAs were expressed. Using these miRNAs, 22 target genes were identified. These genes encode 22 proteins involved in metabolism, signal transduction, transcriptional regulation, and development. These miRNAs and their targets will serve as useful resources for their, functional analyses in miRNA-regulated processes in Pelodiscus sinensis breeding and genetic research.


The cerebellar contribution to eye movements based upon lesions: binocular three-axis control and the translational vestibulo-ocular reflex.
The study of human cerebellar patients and monkeys with experimental cerebellar lesions has taught us much about the role of the cerebellum in normal ocular motor control. Here we emphasize recent findings that point to a role for the cerebellum in (1) the control of the three-dimensional axis about which the eye rotates in response to visual and vestibular stimuli, and (2) the generation of the translational VOR. Findings in cerebellar patients include abnormalities of eye torsion during attempted fixation that suggest a cerebellar role in the control of torsion so that Listing's law is obeyed. Abnormal torsion during vertical pursuit suggests that central processing of information for smooth pursuit may be based upon a phylogenetically old, semicircular canal coordinate scheme. Inappropriate and disconjugate vertical and torsional eye movements ("cross-coupling") occur during brief, high-acceleration rotations of the head. This suggests a role for the cerebellum in the binocular control of the rotation axis of the VOR. Finally, abnormalities of the modulation of the translational VOR with near viewing in cerebellar patients, but with sparing of the very initial 25-30 msec of response, suggests an important role for the cerebellum in the translational VOR.


Size structure of populations within populations: leaf number and size in crowded and uncrowded Impatiens pallida individuals.
We compared the size distributions of leaves on naturally-occurring crowded and experimentally thinned "uncrowded" individuals of Impatiens pallida in southeastern Pennsylvania. Crowding decreased the number of leaves on individual plants and altered the distribution of leaf size. Crowded individuals had smaller leaves, but the size (length) inequality of the leaf population did not change. The relationships between the height of a plant and the mean and maximum length of its leaves were significantly different for crowded and uncrowded plants. There were weak positive relationships between height and total leaf area, and height and total number of leaves for uncrowded plants, whereas crowded plants showed tighter but curvilinear relationships between these variables. Our results point out the strengths and the limitations of viewing canopies as populations of modules.


An unidentified macromolecular inhibitory constituent of calcium oxalate crystal growth in human urine.
We have detected and isolated a macromolecular constituent in normal human urine possessing calcium crystal growth inhibitory activity. The purification procedure consisted of two anion exchange chromatographies and one affinity chromatography. The crystal growth inhibitor was found to be heterogeneous in net charge as well as in size. It has not been identified. It is not an uronic acid-containing glycosaminoglycan, hitherto presumed to be responsible for the inhibitory activity. Whether an urinary fragment of inter-alpha-trypsin inhibitor is responsible has yet to be resolved.


Plasma prolactin measurement is not indicated in women in the routine investigation of uncomplicated infertility.
Measurement of plasma prolactin frequently forms part of the routine investigation of infertile couples. In 315 consecutive women attending an infertility clinic in a university teaching hospital, all of those with increased plasma prolactin concentrations would have been detected from their symptoms. All women with prolactin concentrations in the range 500--800 miu l(minus sign1) appeared to be ovulating. These data support previous proposals in guidelines published by both the European Society for Human Reproduction and Embryology (ESHRE, 1996) and the Royal College of Obstetricians and Gynaecologists (RCOG, 1998) that there is no benefit in measuring plasma prolactin in the investigation of infertility in women who are menstruating normally and have no other clinical indications.


Passport for care: implementing the survivorship care plan.
Approximately 12,000 children in the United States are diagnosed with cancer each year, and roughly 75% of these patients become long-term survivors. The Passport for Care was developed to support these survivors and their health care providers.


Identification of nanominerals and nanoparticles in burning coal waste piles from Portugal.
A range of carbon nanoparticles, agglomerates and mineral phases have been identified in burning coal waste pile materials from the Douro Coalfield of Portugal, as a basis for identifying their potential environmental and human health impacts. The fragile nature and fine particle size of these materials required novel characterization methods, including energy-dispersive X-ray spectrometry (EDS), field-emission scanning electron microscope (FE-SEM), and high-resolution transmission electron microscopy (HR-TEM) techniques. The chemical composition and possible correlations with morphology of the nanominerals and associated ultra-fine particles have been evaluated in the context of human health exposure, as well as in relation to management of such components in coal-fire environments.


The default response to uncertainty and the importance of perceived safety in anxiety and stress: An evolution-theoretical perspective.
From a combined neurobiological and evolution-theoretical perspective, the stress response is a subcortically subserved response to uncertainty that is not 'generated' but 'default': the stress response is 'always there' but as long as safety is perceived, the stress response is under tonic prefrontal inhibition, reflected by high vagally mediated heart rate variability. Uncertainty of safety leads to disinhibiting the default stress response, even in the absence of threat. Due to the stress response's survival value, this 'erring on the side of caution' is passed to us via our genes. Thus, intolerance of uncertainty is not acquired during the life cycle, but is a given property of all living organisms, only to be alleviated in situations of which the safety is learned. When the latter is deficient, generalized unsafety ensues, which underlies chronic anxiety and stress and their somatic health risks, as well as other highly prevalent conditions carrying such risks, including loneliness, obesity, aerobic unfitness and old age.


Analysis of FOXO1A as a candidate gene for type 2 diabetes.
The human forkhead box O1A (FOXO1A) gene on chromosome 13q14.1 is a key transcription factor in insulin signaling in liver and adipose tissue and plays a central role in the regulation of key pancreatic beta-cell genes including IPF1. We hypothesized that sequence variants of FOXO1A contribute to the observed defects in hepatic and peripheral insulin action and altered beta-cell compensation that characterize type 2 diabetes (T2DM). To test this hypothesis, we screened the three exons, 3' untranslated region, and 5' flanking region for sequence variants in Caucasian and African-American individuals with early onset (<45 years) T2DM. We identified only six variants; none altered the coding sequence, and except for one variant in the 3' untranslated region, they were rare or absent in Caucasians. To increase coverage of the gene, we selected seven additional variants in the large first intron and 5' flanking region, thus providing 13 variants that spanned 116.4kb. Based on frequency and linkage disequilibrium patterns in a subset of individuals, we selected eight SNPs to type in a Caucasian population comprising 192 unrelated nondiabetic control individuals and 192 individuals with T2DM, and 10 SNPs to type in 182 controls and 352 diabetic individuals of African-American ancestry. No variant was associated with T2DM (African-Americans, p>0.08; Caucasians, p>0.09). Of the 8 Caucasian SNPs, six comprised a single haplotype block spanning over 100kb and including most of the large first intron. In contrast, no block was observed among SNPs typed in African-Americans. No haplotype was associated with T2DM. FOXO1A variation is rare and is unlikely to contribute to T2DM in either Caucasian or African-American populations.


Cardiovascular risk as defined in the 2003 European blood pressure classification: the assessment of an additional predictive value of pulse pressure on mortality.
This study determines the predictive value of brachial pulse pressure for cardiovascular stroke and coronary mortality in a large population categorized by blood pressure level. The population was composed of 69,989 subjects aged more than 50 years and divided into 'optimal', 'normal' and 'normal high' normotensive subjects, and grades 1, 2, 3 hypertensive subjects as defined in the 2003 European Guidelines for Management of Hypertension. Hazard ratios for mortality were evaluated using Cox regression models before and after adjustment for pulse pressure. To further assess the role of pulse pressure in mortality, subjects were also classified as 'normotensive' and 'hypertensive' whether they were with or without elevated pulse pressure (> or =60 mmHg). By comparison with 'optimal' values, before adjustment for pulse pressure, the hazard ratio for cardiovascular, coronary and stroke mortality increased markedly for blood pressure groups as defined by the European blood pressure classification. For cardiovascular and coronary mortality, the hazard ratio was significant both in the 'high normal' and hypertensive ranges. For stroke mortality, hazard ratio was significant only in the hypertensive ranges. After adjustment to pulse pressure, hazard ratio remained unmodified for stroke mortality. For coronary mortality, the risk was attenuated in 'high normal' and all hypertensive groups. A study of the pulse pressure classification in subjects dichotomized as normotensive and hypertensive subjects indicated that pulse pressure was an independent risk factor for cardiovascular mortality. Increased pulse pressure predicts cardiovascular mortality, acting more on coronary than cerebral vessels. This finding involves all blood pressure ranges, including subjects with low diastolic but normal systolic blood pressure.


Endoplasmic reticulum stress in the pathogenesis of early-onset pre-eclampsia.
Recent data have provided molecular evidence of high levels of endoplasmic reticulum stress in non-laboured placentas from cases of early-onset pre-eclampsia. Endoplasmic reticulum stress is intricately linked to oxidative stress, and the two often share the same aetiology. In the case of pre-eclampsia this is likely to be placental malperfusion, secondary to deficient conversion of the spiral arteries. Endoplasmic reticulum stress activates a number of signalling pathways aimed at restoring homeostasis, but if these attempts fail then the apoptotic machinery may be activated. The potential consequences for placental development and function are numerous and diverse. Inhibition of protein synthesis results in lower levels of many kinases, growth factors and regulatory proteins involved in cell cycle control, and experiments in vitro reveal that endoplasmic reticulum stress slows cell proliferation. Chronic, low levels of stress during the second and third trimesters may therefore result in a growth restricted phenotype. Higher levels of endoplasmic reticulum stress lead to activation of pro-inflammatory pathways, a feature of pre-eclampsia that may contribute to maternal endothelial cell activation. These findings emphasise the complexity of cellular responses to stress, and the need to approach these in a holistic fashion when considering therapeutic interventions.


Trichroic prism assembly for separating and recombining colors in a compact projection display.
A trichroic prism assembly design, believed to be new, is proposed and demonstrated. This new design has the advantages of low s- and p-polarization dependence in the reflectance spectra of the optical coatings. Hence it can be used for both color separation and color recombination with polarization change. This new trichroic prism assembly is especially useful in a compact color projector employing reflective liquid-crystal light valves.


Production, characteristics and mode of action of hemopoietic growth inhibitors in myeloid leukemias.
The best characterized hemopoietic growth inhibitors in myeloid leukemias are leukemia associated inhibitor (LAI) and leukemia inhibitory activity (LIA). Both are normal cell products overproduced in leukemia. LIA is identical with acid isoferritins and LAI is not identical with LIA. They act in different ways to inhibit normal stem cell growth. The overproduction of these putative normal regulators may explain the suppression of normal hemopoiesis typical of myeloid leukemias. Modulation of the production and the action of LAI and LIA may have potential therapeutic value in leukemia.


Accurate gamma-ray spectrometry measurements of the half-life of 92Sr.
Studies of the nuclear fuel cycle require an accurate knowledge of the energy release from the decay of radioactive nuclides produced in a reactor, including precise half-life data for the short-lived radionuclides. Moreover, short-lived fission products are crucial for fission rate distribution measurements performed in low-power facilities, such as EOLE and MINERVE of CEA Cadarache [Fougeras, P., 2005. EOLE, MINERVE and MASURCA facilities and their associated neutron experimental programs. In: 13th International Conference on Nuclear Engineering, Beijing, China, 16-20 May 2005], and their nuclear decay data need to be known to high precision. For these reasons, the half-life of (92)Sr has been measured to solve a recently observed inconsistency identified with the quoted value in the main nuclear applications libraries (including JEFF3.1): T(1/2)=2.71+/-0.01 h [Parsa, B., Ashari, A., Goolvard, L., Nobar, Y.M., 1971. Decay scheme of 2.71 h (92)Sr. Nucl. Phys. A 175, 629-640]. An overestimation of 4.5% has been identified in this work, based on two independent methods. Specific gamma-ray spectrometry measurements on activated fissile foils have been carried out, using two HPGe detectors. Influencing factors such as net area measurements of photopeaks, pulse pile-up accuracy and dead time corrections in the presence of decaying activity are discussed. A new value has been obtained by combining eight series of measurements: T(1/2)=2.594+/-0.006 h. The uncertainty has been reduced by a factor of two with respect to previous evaluations. This measured value also shows good agreement with the most recent studies of T(1/2)=2.627+/-0.009 h [Nir-El, Y., 2003. Private Communications. Soreq Research Centre, Yavne, Israel].


Impact of polishing system on surface roughness of different ceramic surfaces after various pretreatments and bracket debonding.
Evaluating various polishing methods after bracket debonding and excessive attachment material removal for different ceramics and pretreatments. Zirconia (ZrO2), leucite (LEU) and lithium disilicate (LiSi) specimens were pretreated with a) silica coated alumina particles (CoJet); LEU and LiSi additionally with b) hydrofluoric acid (HF), c) Monobond Etch&Prime (MEP), d) silicium carbide grinder (SiC) before bracket bonding, shearing off, ARI evaluation, excessive attachment material removal and polishing with i) Sof-Lex Discs (Soflex), ii) polishing paste (Paste), iii) polishing set (Set). Before/after polishing surface roughness (Ra) was measured with a profilometer. Martens hardness parameter were also assessed. Irrespective of pretreatment Ra of LEU increased the most, followed by LiSi and ZrO2 (p < 0.001, SiC: p = 0.012), in accordance with the measured Martens hardness parameter. CoJet/SiC caused greater roughness as HF/MEP (p < 0.001). The ZrO2 surface was rougher after polishing with Paste/Set (p < 0.001; p = 0.047). Ra improved in the LEU/CoJet, LEU/SiC and LiSi/SiC groups with Soflex/Set (p < 0.001), in the LiSi/CoJet and LEU/HF groups by Soflex (p = 0.003, p < 0.001) and worsened by Paste (p = 0.017, p < 0.001). Polishing of HF or MEP pretreated LiSi with Set increased Ra (p = 0.001, p < 0.001), so did Paste in the LEU/MEP group (p < 0.001). Paste couldn't improve the surfaces. Soflex was the only method decreasing Ra on rough surfaces and not causing roughness worsening. Polishing of LEU/LiSi after MEP, LEU after HF pretreatment doesn´t seem to have any benefit. To avoid long-term damage to ceramic restorations, special attention should be paid to the polishing method after orthodontic treatment.


Peptic ulcer disease among dyspeptic patients at endoscopy unit, University of Gondar hospital, Northwest Ethiopia.
Dyspepsia is a common complaint in upper gastrointestinal disorders. It is described as predominant epigastric pain lasting for at least one month. Globally, peptic ulcer disease occurs in 3.5-32% of patients with dyspepsia. Helicobacter pylori (H. pylori) infection and non-steroidal anti-inflammatory drugs/aspirin use are the widely known risk factors for peptic ulcer disease. There was no recent document on H. pylori infection rate among patients with peptic ulcer disease in Ethiopia. This study aimed to determine magnitude and associated factors of peptic ulcer disease among dyspeptic patients in Northwest Ethiopia. An institutional-based cross sectional study was conducted at the University of Gondar hospital, Northwest Ethiopia. A convenience sampling method was used to recruit 218 study subjects. A pre-designed semi-structured questionnaire was used to extract clinical information. Olympus flexible fiber-optic endoscope (Olympus, GIF-E 600, Olympus Corp., Hamburg, Germany) was used to confirm the presence of peptic ulcer disease. Diagnosis of active H. pylori infection was made using the fecal H. pylori Antigen 25 T Card Test (Anamol Lab., Pvt. Ltd., Palghar, India). The Data were entered into EPI Info version 220.127.116.11, and then exported to SPSS version 20 for analysis. Explanatory variables associated with peptic ulcer disease were analyzed by applying logistic regression model. P value < 0.05 was used to declare significant association. A total of 218 dyspeptic patients who underwent upper gastrointestinal endoscopic evaluations were included in the study. The mean (+ SD) age of patients was 42 ± 16.4 years. Forty nine percent (95% CI 42.4-56.2) of dyspeptic patients had active H. pylori infection. Peptic ulcer disease was diagnosed in 35% (95% CI 31.4-39.2) of patients with dyspepsia. H. pylori infection (AOR = 6.298, 95% CI 2.965-13.378, P value < 0.001) and NSAIDs/ASA use (AOR = 6.252, 95% CI 2.925-13.362, P value < 0.001) were identified as risk factors for peptic ulcer disease. Medical treatment of peptic ulcer disease should target treatment of H. pylori infection and cautious use of non-steroidal anti-inflammatory drugs/aspirin.


Native myocardial longitudinal (T1 ) relaxation time: Regional, age, and sex associations in the healthy adult heart.
To use magnetic resonance imaging (MRI) at two field strengths to assess healthy adults' regional myocardial noncontrast (native) T1 relaxation time distribution, and global myocardial native T1 between sexes and across age groups. In all, 84 healthy volunteers underwent MRI at 1.5T and 3.0T. T1 maps were acquired in three left ventricular short axis slices using an optimized modified Look-Locker inversion recovery investigational prototype sequence. T1 measurements in msec were calculated from 16 regions-of-interest, and a global T1 value from all evaluable segments per subject. Associations were assessed with a multivariate linear regression model. In total, 1297 (96.5%) segments were evaluable at 1.5T and 1263 (94.0%) segments at 3.0T. Native T1 was higher in septal than lateral myocardium (1.5T: 956.3 ± 44.4 vs. 939.2 ± 54.2 msec; P < 0.001; 3.0T: 1158.2 ± 45.9 vs. 1148.9 ± 56.9 msec; P = 0.012). Native T1 decreased with increasing age in females but not in males. Among lowest age tertile (<33 years) global native T1 was higher in females than in males at 1.5T (960.0 ± 20.3 vs. 931.5 ± 22.2 msec, respectively; P = 0.003) and 3.0T (1166.5 ± 19.7 vs. 1130.2 ± 20.6 msec; P < 0.001). No sex differences were observed in upper age tertile (≥55 years) at 1.5T (937.7 ± 25.4 vs. 934.7 ± 22.3 msec; P = 0.762) or 3.0T (1153.0 ± 30.0 vs. 1132.3 ± 23.5 msec; P = 0.056). Association of global native T1 to age (P = 0.002) and sex (P < 0.001) was independent of field strength and body size. In healthy adults, native T1 values are highest in the ventricular septum. Global native T1 was inversely associated with age in women, but not in men. J. Magn. Reson. Imaging 2016;44:541-548.


The effect of intermaxillary fixation on leukocyte zinc, serum trace elements and nutritional status of patients undergoing maxillofacial surgery.
Mononuclear cell (MNC), polymorphonuclear cell (PMNC) and serum zinc levels were studied in 17 oral surgical patients with intermaxillary fixation. Serum copper, iron, selenium and bromide concentrations were also measured together with common indices of nutritional status. Nine patients received nutritional counselling. Eight patients had, in addition, oral supplementation with a commercial formula. No changes in intracellular or serum zinc levels were seen during the study period. A statistically significant decrease was seen in mean body weight with subsequent changes in anthropometry. Maximal mean weight loss was 6.0 +/- 3.8% in control group and 3.8 +/- 2.7% in supplemental group. The impaired oral intake due to intermaxillary fixation does not interfere significantly with zinc status as estimated by MNC, PMNC or serum zinc levels. The reduction in body weight and anthropometric indices in the relatively short fixation period may be clinically significant in some patients. Supplementation with a commercial formula helps to maintain the nutritional status of these patients.


Historical analysis of Newfoundland dog fur colour genetics.
This article makes use of digitized historic newspapers to analyze Newfoundland dog fur colour genetics, and fur colour variations over time. The results indicate that contrary to the accepted view, the 'Solid' gene was introduced into the British population of Newfoundland dogs in the 1840s. Prior to that time, the dogs were white and black (Landseer) or white and brown, and thus spotted/spotted homozygotes. Due to 'Solid' being dominant over 'spotted', and selective breeding, today the majority of Newfoundland dogs are solid black. Whereas small white marks on the chest and/or paw appears to be a random event, the historical data supports the existence of an 'Irish spotted' fur colour pattern, with white head blaze, breast, paws and tail tip, in spotted/spotted homozygotes.


Double high-dose chemotherapy with adriamycin, paclitaxel, cyclophosphamide, and thiotepa followed by autologous peripheral blood stem cell transplantation in women with metastatic breast cancer.
To determine the feasibility, time to progression, and event-free survival, twenty-two women with metastatic breast cancer received two cycles of high-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) early after first-line induction chemotherapy. The median age of the ten (45.5%) pre- and 12 (54.5%) postmenopausal women was 48 (range: 33-60) years. Sixteen patients (72.7%) had at least two or more metastatic sites involved. Protocol induction and mobilization chemotherapy including granulocyte-colony stimulating-factor (G-CSF) consisted of two cycles with adriamycin (60 mg/m(2)) i.v. and paclitaxel (200 mg/m(2)) i.v. After collection of at least 4 x 10(6)/kg bodyweight peripheral blood stem cells, the first HDCT-course of adriamycin (60 mg/m(2)), paclitaxel (200 mg/m(2)) cyclophosphamide (4 g/m(2)), and thiotepa (800 mg/m(2)) (ATCT) was given to at least stable disease (SD) patients. Six to eight weeks later, the second HDCT-ATCT was administered. Each HDCT-cycle was followed by PBSCT with a median of 3.81 x 10(6)/kg bodyweight CD-34 positive cells (range: 1.85-10.38). All women showed median leukocyte engraftment (>1,000 x 10(9)/l) on day +9.4 (range: 7-13) and median platelet engraftment (>20,000 x 10(9)/l) on day +12.3 (range: 8-15). There were no apparent differences in the clinical course and non-hematologic toxicity between the two HDCT-cycles. Of the 21 patients evaluable for response, eight (38.1%) patients achieved complete remission (CR), ten (47.6%) patients showed a partial remission (PR), two patients (9.5%) no change, and one patient (4.8%) progressive disease. After a median observation time of 36 (range 28-55) months, six (28.6%) women are alive, four (19.0%) of them in continuous CR, including two women with stable bone lesions, respectively, and 15 (71.4%) died due to progressive disease. Median time to progression (TTP) was 8 (range 4-19) months. A high initial response rate of early HDCT, including the most active drugs adriamycin and paclitaxel, can be achieved with tolerable toxicity in metastatic breast cancer. New approaches for maintaining primary tumor response achieved with efficacious high-dose chemotherapy are warranted.


In vivo selection of human renal cell carcinoma cells with high metastatic potential in nude mice.
Studies were made to determine whether the orthotopic implantation of human renal cell carcinoma cells (HRCC) into nude mice will produce distant metastases, thus allowing for the selection of variant cells with high metastatic potential. The parental SN12C line was established in culture from a surgical specimen of HRCC. The renal subcapsule (RSC) of adult nude mice was injected with SN12C cells; the mice were killed when they became moribund. Cell lines were established from either single or multiple lung HRCC metastases. The intravenous injection of many (but not all) of the metastasis-derived lines produced significantly more experimental metastases than did the parental cells. The injection of cells into the RSC demonstrated that, in general, cells derived from spontaneous metastases were more metastatic than cells of the parental line. Hence adult nude mice can be used to select HRCC cells with high metastatic potential. These HRCC variant lines offer a good model for studying the cell properties of metastatic HRCC.


Peripheral-arterial tonometry for assessing endothelial function in relation to dietary habits.
Peripheral-arterial tonometry (PAT) provides, with good reproducibility, measures of nitric oxide-mediated endothelial response, which correlate with flow-mediated dilation (FMD) findings obtained by brachial artery ultrasound. Few data about the ability of exploring endothelial function by PAT in relation to dietary habits are available. The aim of this study was to evaluate natural logarithm of reactive hyperemia index (lnRHI) in subjects referred for primary prevention, in relation to classic risk factors, in particular to adherence to Mediterranean diet and red wine consumption. The study population was composed of 95 consecutive clinically stable subjects in primary prevention for cardiovascular diseases. All subjects underwent medical questionnaire, clinical examination, and PAT for endothelial function evaluation. A significant inverse correlation between lnRHI values and body mass index (r = -0.284; P = 0.022) was found. We described a gradual reduction in lnRHI values, corresponding to the increase in the number of risk factors (0.75 [0.31-1.26], 0.66 [0.25-0.97], 0.63 [0.37-1.19], 0.48 [0.32-0.71], 0.43 [0.31-0.91], respectively, for none, 1, 2, 3, and 4 cardiovascular risk factors; P = 0.004). A significant positive correlation between score of adherence to Mediterranean diet and lnRHI values was found (r = 0.307; P = 0.002). Higher adherence to Mediterranean diet was found in subjects with lnRHI values greater than 0.40 in comparison to others (39 [27-50] vs 33 [28-45], respectively; P = 0.064). The lnRHI values were significantly higher in regular drinkers in comparison to nonregular drinkers (0.46 [0.25-0.83] vs 0.70 [0.32-1.26], respectively; P < 0.0001).Relationship between reactive hyperemia index and red wine consumption remained statistically significant even after adjustment for age, sex, body mass index, smoking habit, hypertension, and adherence to Mediterranean diet. Our findings strengthen the ability of PAT to evaluate alterations of endothelium response to ischemia, in relation to physiological and clinical conditions, so indicating possible usefulness to optimize and personalize risk stratification.


Ameliorative effect of selenium nanoparticles on testicular toxicity induced by cisplatin in adult male rats.
Cisplatin (Cis) is a treatment for testicular germ-cell tumors (TGCTs). Unfortunately, it causes testicular toxicity due to releasing reactive oxygen species (ROS) causing damage to testicular cells and chromosomes. The current study aimed to investigate the ameliorative effect of selenium nanoparticles (SeNPs) against cisplatin testicular toxicity in male rats by assessment of body weight, testis weight, oxidative stress markers in testis homogenates as (malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione reduced (GSH), Glutathione peroxidase (GSH ∼ PX) and Catalase (CAT)), gene expression, testosterone concentration (T), sperm characteristics (count, motility and abnormality) and testicular histopathology. Methods: Thirty adult male rats divided equally into four groups; a single dose intraperitoneally injection of cisplatin (10 mg/kg) and selenium nanoparticles (2 mg/kg/day) were administrated alone or in combination. Cis group showed a decrease in body weight, testis weight, antioxidant activities (SOD, GSH, GSH ∼ PX and CAT), T concentration and steroidogenetic expression, the data recorded an increase in MDA levels and sperm abnormality, meanwhile histopathology of testis sections showed degenerative changes in the seminiferous tubules. The co-administration of selenium nanoparticles ameliorated the harmful effects of cisplatin. In conclusion; SeNPs through its antioxidant potential may be useful to prevent the testicular toxicity induced by cisplatin to the rat testis by reducing oxidative stress.


Do speakers have access to a mental syllabary? ERP comparison of high frequency and novel syllable production.
The transformation of an abstract phonological code into articulation has been hypothesized to involve the retrieval of stored syllable-sized motor plans. Accordingly, gestural scores for frequently used syllables are retrieved from memory whereas gestural scores for novel and possibly low frequency syllables are assembled on-line. The present study was designed to test this hypothesis. Participants produced disyllabic pseudowords with high frequency, low frequency and non-existent (novel) initial syllables. Behavioral results revealed slower production latencies for novel than for high frequency syllables. Event-related potentials diverged in waveform amplitudes and global topographic patterns between high frequency and low frequency/novel syllables around 170 ms before the onset of articulation. These differences indicate the recruitment of different brain networks during the production of frequent and infrequent/novel syllables, in line with the hypothesis that speakers store syllabic-sized motor programs for frequent syllables and assemble these motor plans on-line for low frequency and novel syllables.


Scheduling and Modeling a Cognitive Assessment Guide for Screening AD by Primary Care Physicians.
New research data on Alzheimer's Disease define it as a clinicobiological entity, which has a long preclinical and presymptomatic phase. Emphasis has been given in early detection and diagnosis, which will allow professionals, caregivers and patients themselves to plan and adjust better to the response of the disease. Primary care physicians, who most often are the first to witness and perceive cognitive impairment, may play a central role in the diagnostic procedure, but frequently they are reluctant to be engaged to the screening procedure. The aim of this study is to model a practical guideline for mental assessment and screening, which will be part of a whole step-to-step medical instruction policy for primary care physicians. After a careful review of the literature, we propose a two-visits approach. This approach combines the measures to be administered in each visit, with a detailed list of close-ended questions on the factors concerning Alzheimer's screening. The tests are automatically available to the physician through hyperlink connection and the scores are immediately calculated. Clinical trials will follow to test the validity of the proposed guidance.


Macrophage cell cycling: influence of proliferative state on the antibody-mediated activities of rat resident peritoneal macrophages.
Countercurrent centrifugal elutriation (CCE) was used to isolate fractions of rat resident peritoneal macrophages that were enriched in different phases of the cell cycle. The purpose was to assess the influence of the proliferative status of these cells on their antibody-mediated phagocytic activity. Autoradiographic analysis of the resident peritoneal cell population isolated 1 hr after an intravenous injection of [3H] thymidine showed that about 3% of the macrophages were in S-phase of the cell cycle. CCE yielded fractions of macrophages in which the proportions of S-phase cells ranged from 0% to about 10%. Results of flow cytometric analysis of propidium iodine-stained cells were consistent with the autoradiographic findings. Essentially all of the macrophages in the CCE fractions ingested antibody-coated particles, but there were marked differences in phagocytic capacity and in expression of Fc-receptors among discrete groups of cells. CCE fractions with the smallest cells and no S-phase macrophages ingested approximately six- to eightfold fewer particles than did macrophages from CCE fractions with the largest cells and enriched in S-phase macrophages. Similarly, smaller macrophages bound fewer antibody-coated particles than did larger macrophages. These results, which are identical to those previously reported for murine macrophage cell lines, show that the number of Fc-receptors and the phagocytic capacity of cycling resident peritoneal macrophages increase as the cells progress from G1 to G2. Thus, the proliferative state of macrophages does not determine whether they are phagocytic but rather their phagocytic capacity.


Phenotype and prognostic correlations of the converter region mutations affecting the β myosin heavy chain.
The prognostic value of genetic studies in cardiomyopathies is still controversial. Our objective was to evaluate the outcome of patients with cardiomyopathy with mutations in the converter domain of β myosin heavy chain (MYH7). Clinical characteristics and survival of 117 affected members with mutations in the converter domain of MYH7 were compared with 409 patients described in the literature with mutations in the same region. Twenty-five mutations were evaluated (9 in our families including 3 novel (Ile730Asn, Asp717Gly and Arg719Pro)). Clinical diagnoses were hypertrophic (n=407), dilated (n=15), non-compaction (n=4) and restrictive (n=5) cardiomyopathies, unspecified cardiomyopathy (n=11), sudden death (n=50) and 35 healthy carriers. One hundred eighty-four had events (cardiovascular death or transplant). Median event-free survival was 50±2 years in our patients and 53±3 years in the literature (p=0.27). There were significant differences in the outcome between mutation: Ile736Thr had fewer events than other mutations in the region (p=0.01), while Arg719Gln (p<0.01) had reduced event-free survival. Mutations in the converter region are generally associated with adverse prognosis although there are differences between mutations. The identification of a mutation in this particular region provides important prognostic information that should be considered in the clinical management of affected patients.


Changes in the microbiological and chemical characteristics of white bread during storage in paper packages modified with Ag/TiO2-SiO2, Ag/N-TiO2 or Au/TiO2.
Microbiological and chemical characteristics of white bread during storage in paper-packages modified with Ag/TiO2-SiO2, Ag/N-TiO2 or Au/TiO2 were investigated. The whiteness and the water retention of the modified packages were slightly superior to those exhibited by the reference sample, as the color of the composite was lighter. The water retention was very good especially for the Ag/TiO2-SiO2-paper. These improvements can be associated with the high specific surface area and with the low agglomeration tendency of Ag nanoparticles in comparison with the Au ones. The preservation activity of the composites for the bread storage is positively influenced by photoactivity and presence of nano-Ag. Packages Ag/TiO2-SiO2-paper and Ag/N-TiO2-paper can find their applicability for extending the shelf life of bread by 2 days as compared with the unmodified paper-package. No influence of the Au/TiO2 on the extending the shelf life of bread was observed.


Flank Pain as a Symptom of COVID-19.
The COVID-19 disease is spreading rapidly worldwide, and no vaccine or very effective drug has been found yet. However, the transmission rate of the disease can be reduced by taking precautions. Therefore, it is essential to detect the patients early to prevent the spread of the disease.1,2 We report a case of 26-year-old male patient who was admitted to our urology outpatient clinic with the complaint of flank pain and had incidental findings of COVID-19 in the lung bases on abdominal CT.


Effects of DA-9801 on the inflammation and apoptosis induced by angiotensin II in human dermal microvascular endothelial cells.
DA-9801, a plant-based drug used for the treatment of diabetic neuropathy, is known to improve angiotensin II (Ang II)-induced vascular endothelial cell dysfunction. However, the underlying mechanism is not fully understood. We aimed to determine whether the protective effect of DA-9801 against Ang II-induced endothelial cell dysfunction was mediated via inhibition of endothelial cell inflammation and apoptosis. Ang II-induced oxidative stress was attenuated by pretreatment of human dermal microvascular endothelial cells (HDMECs) with DA-9801. This prevented the Ang II-induced upregulation of NAD(P)H oxidase (the NOX4 and p22phox subunits) and reactive oxygen species. Further, pretreatment of HDMECs with DA-9801 ameliorated Ang II-mediated nuclear factor kappa B activity via prevention of the upregulation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. It also decreased the Ang II-stimulated increase in inducible nitric oxide synthase (NOS) and decreased endothelial NOS protein expression. DA-9801 decreased Ang II-induced upregulation of intercellular adhesion molecule 1, vascular adhesion molecule, and E-selectin in HDMECs. Moreover, TUNEL and annexin V-FITC fluorescence staining for apoptosis and the activities of caspases 9, 7, and 3 decreased in HDMECs pretreated with DA-9801, indicating that the drug enhanced anti-apoptotic pathways. Thus, DA-9801 modulated Ang II-induced endothelial cell dysfunction via inflammatory and apoptotic pathways.


Mechanical thrombectomy via direct carotid artery approach for the treatment of acute anterior circulation large vessel occlusion.
Mechanical thrombectomy (MT) has become an important treatment method for acute anterior circulation large vessel occlusion. The carotid artery approach is a fast and effective alternative when the transfemoral approach is difficult due to vascular variation. The present study reports on seven cases of acute anterior circulation stroke where direct carotid approach was used to obtain vascular access. Patients with acute anterior circulation large vessel occlusion treated via carotid artery access between January 2018 and January 2020 were retrospectively analyzed. Brain computed tomography (CT) and angiographic imaging results, indications for carotid artery approach and technical aspects of the method, modified thrombolysis in cerebral infarction (mTICI), procedure-related complications, and patient outcomes were evaluated. Seven patients were treated using a direct carotid artery approach. Among the seven cases, four patients were treated using percutaneous carotid artery puncture, and two patients were treated with emergency carotid artery incision and thrombectomy. The remaining case involved carotid artery puncture for MCA thrombectomy, followed by carotid artery incision for carotid artery thrombectomy. The carotid artery puncture point was exposed via surgical incision and sutured after MT. Modified Rankin Scale (MRS) scores 90 days after surgery showed good prognosis in three patients, poor prognosis in four patients. This case series highlights the advantage of using a transcarotid approach to bypass anatomical barriers to achieve faster reperfusion when the femoral approach is not possible. The carotid artery puncture point was surgically exposed and sutured to reduce the incidence of postoperative complications.


Reproductive outcome in 3 families with a satellited chromosome 4 with review of the literature.
We describe 3 families segregating for a translocation of the nucleolus organizer region (NOR) onto chromosome 4. Review of previously reported cases of translocations involving NOR and chromosome 4 shows that these translocations may be associated with variable reproductive outcomes. We provide evidence that imprinting is not the mechanism responsible for the variable reproductive outcomes in the case of satellited 4p chromosomes; this may offer indirect support for a ribosomal gene position effect. Translocated ribosomal genes may influence the expression of neighboring genes and could explain the variable phenotypes in individuals with satellited nonacrocentric chromosomes. We recommend that prenatal counseling of individuals with satellited nonacrocentric chromosomes should be cautious.


Inflammatory disorders associated with trisomy 8-myelodysplastic syndromes: French retrospective case-control study.
We report cases of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) with trisomy 8 associated with inflammatory and autoimmune diseases (IADs). Data for 21 patients with trisomy 8-MDS/MPN and IADs were analyzed and compared to 103 patients with trisomy 8-MDS/MPN without IADs. The median age of MDS/MPN patients with IADs was 67 [59-80]. The IADs were Behçet's-like disease in 11 (52%) patients, inflammatory arthritis in 4 (19%) and Sjögren's syndrome, autoimmune hemolytic anemia, aseptic abscess, periarteritis nodosa, Sweet's syndrome and unclassified vasculitis in one patient each. Overall, 17/21 (81%) patients with IADs received treatment (88% with steroids), with complete and partial response in 7/17 (35%) and 8/17 (47%), respectively. The effect of MDS treatment on IADs could be assessed in seven patients receiving azacytidine: five achieved remission and two partial response. As compared with the 103 trisomy 8-MDS/MPN cases without IADs, those with IADs were more often non-European (P = 0.005) and had poor karyotype (P < 0.001). We found no difference in overall survival or acute myeloid leukemia progression between trisomy 8-associated MDS/MPN with and without IADs. The spectrum of IADs associated with trisomy 8-positive MDS/MPN is dominated by Behçet's-like disease. Steroid therapy is effective, but mostly sparing therapies are necessary. Azacytidine could be an effective alternative.


Method development and analysis of retail foods for annatto food colouring material.
Analytical methods for the determination of the permitted food colouring annatto (E160b) have been developed or refined to encompass the wide range of food commodity types permitted to contain it. Specific solvent extraction regimens have been used depending upon the food commodity analysed and HPLC analysis techniques coupled with spectral confirmation have been used for the determination of the major colouring components. Qualitative and quantitative data on the annatto content of 165 composite and two single retail food samples covering a wide range of foods at levels above the limit of quantification (0.1 mg kg(-1)) is reported. Quantitative results are given for the major colour principals 9'-cis-bixin, 9'-cis-norbixin and trans-bixin. Semi-quantitative results are given for the minor bixin and norbixin isomers monocis- (not 9'-), di-cis- and trans-norbixin, for which authentic reference standards were not available. Repeat analyses (n = 4-9) of 12 different types of food commodity (covering the permitted range) spiked with annatto at levels between 1.7 and 27.7 mg kg(-1) gave mean recoveries between 61 and 96%. The corresponding relative SDs (RSD) were between 2.1 and 7.9%.