Health Resource Utilization among Patients with Type 2 Diabetes Mellitus In Nigeria: An Analysis from the International Diabetes Management Practice Study (IDMPS).
To assess the data on health resource utilization collected from patients with T2DM in Nigeria, within the seventh wave (2016) of the International Diabetes Management Practices Study (IDMPS). In this cross-sectional study, adults (≥25 years) with T2DM, who had requisite diabetes treatment data and were attended by participating physicians during the two-week recruitment period, were included. Thirty-one participating physicians enrolled 304 eligible patients (mostly 40-60 years of age) with the duration of T2DM ranging from 1 to 31 years (median: 7). Only 34.2% (102/298) patients possessed health insurance and 46.8% (138/295) co-paid for medications outside the insurance. About 70.1% of patients had T2DM-related complications; 19.7% of patients were hospitalized in the past 12 months due to these complications. Altogether, 275 patients with T2DM received oral glucose-lowering drugs, with (88/275) or without (187/275) insulin. The cost of medications/strips was the reason reported for not achieving glycemic targets in ~60.0% (50/84) insulin users and 54.3% (114/210) patients self-monitoring blood glucose, respectively. Specialists in diabetes care attended to a lower number of patients/day than non-specialists (31.61±30.74 vs. 49.25±49.64). Most of the specialists (14/22; 63.6%) reported insulin use in 20%-40% patients; while non-specialists (6/9; 66.6%) reported insulin use in <20% patients. In Nigeria, low insurance coverage and high out-of pocket payments for healthcare limit access to healthcare. Physicians are overburdened and medical resources trained in diabetes care seem insufficient. These findings highlight the need to formulate effective healthcare strategies for patients with T2DM.


Experiment and computer-aided simulation: complementary tools to understand exercise metabolism.
During the last two decades the concept of the MLSS (maximal lactate steady state) has been established. The MLSS detects the highest level of the BLC (blood lactate concentration) and the corresponding workload (MLSS workload) that can be maintained over time without continual BLC accumulation. In spite of a lack of experimental and/or theoretical foundation, it has been speculated that the level of the MLSS may decrease with increasing performance capacity. The potential inter-relationship between performance capacity and BLC response to prolonged constant workload will be analysed based on a recent study, which provided evidence that the MLSS is independent of performance whereas MLSS workload increases with performance capacity, and by a computer-aided simulation. The simulated model modifies and combines previous theories put forward to explain the response of BLC to exercise and incorporates a theory about limiting factors of oxygen transport to the muscle cell. Simulations consider the BLC response to selected prolonged constant workloads while paying special respect to changes in body structure and substrate utilization, which are generally accepted as limiting factors of performance capacity. This complex modulation of appearance and disappearance of lactate during constant prolonged exercise seems to support the experimental results, which indicated independence between MLSS and performance capacity.


Reasons for improved survival from ovarian cancer in New South Wales, Australia, between 1980 and 2003: implications for cancer control.
We analyzed New South Wales Central Cancer Registry data for 1980-2003, to determine time trends in case fatality from ovarian cancer, after adjusting for stage, histological, and sociodemographic factors, and to consider service-delivery and research implications. After adjusting for covariates, the relative risk (95% confidence limit) of ovarian-cancer death reduced to 0.51 (0.46, 0.57) for 1999-2003 compared with 1980-1983. Relative risks were higher for adenocarcinomas and other specified and unspecified cancers than serous carcinomas, but lower for endometrioid carcinomas, sex cord-stromal and germ cell tumors. The probability of diagnosis with localized as opposed to more advanced disease was lower in older patients, the lowest socioeconomic stratum, women born in non-English-speaking countries, and more recent diagnostic periods. Approximately 61% of ovarian cancers had distant metastases at diagnosis in 1999-2003. Poorer survivals apply to older patients. Research directed at finding an effective screening test for epithelial ovarian cancer remains a priority.


Distribution of S1-nuclease sensitive sites and double-strand breaks in gamma-irradiated lambda-DNA.
Double-strand breaks and regions with unpaired bases (S1-nuclease sensitive sites) are formed in the DNA of gamma-irradiated lambda-phages. The frequency of both events was determined in the various fragments produced after digestion with a restriction enzyme (Eco RI). The results show that both types of radiation damage are randomly distributed in the DNA molecule. There is no hint that the S1 sites are formed in preferred regions of the lambda-genome.


Neurodevelopmental Assessment in Kindergarten in Children Exposed to General Anesthesia before the Age of 4 Years: A Retrospective Matched Cohort Study.
Animal studies demonstrate general anesthetic (GA) toxicity in the developing brain. Clinical reports raise concern, but the risk of GA exposure to neurodevelopment in children remains uncertain. The authors undertook a retrospective matched cohort study comparing children less than 4 yr of age exposed to GA to those with no GA exposure. The authors used the Early Development Instrument (EDI), a 104-component questionnaire, encompassing five developmental domains, completed in kindergarten as the outcome measure. Mixed-effect logistic regression models generated EDI estimates for single versus multiple GA exposure and compared both single and multiple exposures by the age of 0 to 2 or 2 to 4 yr. Known sociodemographic and physical confounders were incorporated as covariates in the models. A total of 18,056 children were studied: 3,850 exposed to a single GA and 620 exposed to two or more GA, who were matched to 13,586 nonexposed children. In children less than 2 yr of age, there was no independent association between single or multiple GA exposure and EDI results. Paradoxically, single exposure between 2 and 4 yr of age was associated with deficits, most significant for communication/general knowledge (estimate, -0.7; 95% CI, -0.93 to -0.47; P < 0.0001) and language/cognition (estimate, -0.34; 95% CI, -0.52 to -0.16; P < 0.0001) domains. Multiple GA exposure at the age of 2 to 4 yr did not confer greater risk than single GA exposure. These findings refute the assumption that the earlier the GA exposure in children, the greater the likelihood of long-term neurocognitive risk. The authors cannot confirm an association between multiple GA exposure and increased risk of neurocognitive impairment, increasing the probability of confounding to explain the results.


Physcomitrium patens Infection by Colletotrichum gloeosporioides: Understanding the Fungal-Bryophyte Interaction by Microscopy, Phenomics and RNA Sequencing.
Anthracnose caused by the hemibiotroph fungus Colletotrichum gloeosporioides is a devastating plant disease with an extensive impact on plant productivity. The process of colonization and disease progression of C. gloeosporioides has been studied in a number of angiosperm crops. To better understand the evolution of the plant response to pathogens, the study of this complex interaction has been extended to bryophytes. The model moss Physcomitrium patens Hedw. B&S (former Physcomitrella patens) is sensitive to known bacterial and fungal phytopathogens, including C. gloeosporioides, which cause infection and cell death. P. patens responses to these microorganisms resemble that of the angiosperms. However, the molecular events during the interaction of P. patens and C. gloeosporioides have not been explored. In this work, we present a comprehensive approach using microscopy, phenomics and RNA-seq analysis to explore the defense response of P. patens to C. gloeosporioides. Microscopy analysis showed that appressoria are already formed at 24 h after inoculation (hai) and tissue colonization and cell death occur at 24 hai and is massive at 48 hai. Consequently, the phenomics analysis showed progressing browning of moss tissues and impaired photosynthesis from 24 to 48 hai. The transcriptomic analysis revealed that more than 1200 P. patens genes were differentially expressed in response to Colletotrichum infection. The analysis of differentially expressed gene function showed that the C. gloeosporioides infection led to a transcription reprogramming in P. patens that upregulated the genes related to pathogen recognition, secondary metabolism, cell wall reinforcement and regulation of gene expression. In accordance with the observed phenomics results, some photosynthesis and chloroplast-related genes were repressed, indicating that, under attack, P. patens changes its transcription from primary metabolism to defend itself from the pathogen.


The size matters? A computational tool to design bivalent ligands.
Bivalent ligands are increasingly important such as for targeting G protein-coupled receptor (GPCR) dimers or proteolysis targeting chimeras (PROTACs). They contain two pharmacophoric units that simultaneously bind in their corresponding binding sites, connected with a spacer chain. Here, we report a molecular modelling tool that links the pharmacophore units via the shortest pathway along the receptors van der Waals surface and then scores the solutions providing prioritization for the design of new bivalent ligands. Bivalent ligands of known dimers of GPCRs, PROTACs and a model bivalent antibody/antigen system were analysed. The tool could rapidly assess the preferred linker length for the different systems and recapitulated the best reported results. In the case of GPCR dimers the results suggest that in some cases these ligands might bind to a secondary binding site at the extracellular entrance (vestibule or allosteric site) instead of the orthosteric binding site. Freely accessible from the Molecular Operating Environment svl exchange server (https://svl.chemcomp.com/). Supplementary data are available at Bioinformatics online.


Cancer incidence near municipal solid waste incinerators in Great Britain.
By use of the postcoded database held by the Small Area Health Statistic Unit, cancer incidence of over 14 million people living near 72 municipal solid waste incinerators in Great Britain was examined from 1974-86 (England), 1974-84 (Wales) and 1975-87 (Scotland). Numbers of observed cases were compared with expected numbers calculated from national rates (regionally adjusted) after stratification by a deprivation index based on 1981 census small area statistics. Observed-expected ratios were tested for decline in risk with distance up to 7.5 km. The study was conducted in two stages: the first involved a stratified random sample of 20 incinerators; the second the remaining 52 incinerators. Over the two stages of the study was a statistically significant (P<0.05) decline in risk with distance from incinerators for all cancers combined, stomach, colorectal, liver and lung cancer. Among these cancers in the second stage, the excess from 0 to 1 km ranged from 37% for liver cancer (0.95) excess cases 10(-5) per year to 5% for colorectal cancer. There was evidence of residual confounding near the incinerators, which seems to be a likely explanation of the finding for all cancers, stomach and lung, and also to explain at least part of the excess of liver cancer. For this reason and because of a substantial level of misdiagnosis (mainly secondary tumours) found among registrations and death certificates for liver cancer, further investigation, including histological review of the cases, is to be done to help determine whether or not there is an increase in primary liver cancer in the vicinity of incinerators.


Overestimation of physical activity among a nationally representative sample of underactive individuals with diabetes.
Using data from the national Health and Retirement Study, we sought to: (a) estimate the proportion of the US adults with diabetes above the age of 50 who do not meet physical activity guidelines but believe they are sufficiently active; and (b) examine demographic and health-related correlates of such "overestimation." Respondents who were classified as underactive according to a detailed activity inventory but reported exercising at least the "right amount," were designated as overestimating their physical activity. Multiple logistic regression was used to examine the association of demographic and health-related correlates with the odds of overestimation. Fifty-four percent of the survey sample did not meet physical activity guidelines, and one quarter of this underactive group overestimated their physical activity. The adjusted odds of overestimation were higher among respondents who held the perception that they were about the right weight or underweight [odds ratio (OR)=2.42; 95% confidence interval (CI), 1.49-3.94), who had good or better self-assessed diabetes control (OR=1.84; 95% CI, 1.12-3.04), and who were Black or Hispanic (OR=1.89; 95% CI, 1.13-3.16). Experiencing shortness of breath reduced the odds of overestimation (OR=0.34; 95% CI, 0.19-0.61). Overestimation of physical activity is common among adults with diabetes, and is associated with the perceptions that one is about the right weight and that one has good control of diabetes, and with being Black or Hispanic. Clinicians should be aware that these factors may affect their patients' beliefs about how much physical activity is adequate.


In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R-roscovitine) in mantle cell lymphomas.
Mantle cell lymphoma (MCL) has the worst prognosis of all B-cell lymphomas and has poor response to conventional therapy. It is characterized by the presence of a chromosomal translocation t(11:14) (q13;q32) which results in deregulated cyclin D1 expression. Since defects in cell cycle regulation and apoptosis are primary events in MCL, small-molecule inhibitors of cdks-cyclins may play an important role in the therapy of this disorder. CYC202 (Seliciclib, R-roscovitine; Cyclacel Ltd., Dundee, UK) is a purine analogue and a selective inhibitor of the cdk2-cyclin E as well as cdk7-cyclin H and cdk9-cyclin T. The activity of CYC202 was tested in four human MCL cell lines: REC, Granta-519, JeKo-1 and NCEB-1. The effect of CYC202 on the cell cycle and on apoptosis-, cell-cycle- and transcription-regulation-related proteins was assessed. The IC50 was 25 microM for REC, Granta-519 and JeKo-1 cells and 50 microM for NCEB-1 cells. CYC202 caused an accumulation of cells in the G2-M phase of the cell cycle and apoptosis. CYC202 caused down-regulation of cyclin D1 and Mcl-1 protein levels, possibly because of the inhibition of transcription elongation. Our data suggest that CYC202 is an active agent in MCL. The concomitant decrease of the phosphorylated and total forms of RNA polymerase II suggests that this could be the main mechanism mediating the biological effects of CYC202 in MCL cells. The drug might represent a new therapeutic agent in this lymphoma subtype.


Effects of cyano-substituents on the molecular packing structures of conjugated polymers for bulk-heterojunction solar cells.
The molecular packing structures of two conjugated polymers based on alkoxy naphthalene, one with cyano-substituents and one without, have been investigated to determine the effects of electron-withdrawing cyano-groups on the performance of bulk-heterojunction solar cells. The substituted cyano-groups facilitate the self-assembly of the polymer chains, and the cyano-substituted polymer:PC71BM blend exhibits enhanced exciton dissociation to PC71BM. Moreover, the electron-withdrawing cyano-groups lower the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) levels of the conjugated polymer, which leads to a higher open circuit voltage (V(OC)) and a lower energy loss during electron transfer from the donor to the acceptor. A bulk-heterojunction device fabricated with the cyano-substituted polymer:PC71BM blend has a higher V(OC) (0.89 V), a higher fill factor (FF) (51.4%), and a lower short circuit current (J(SC)) (7.4 mA/cm(2)) than that of the noncyano-substituted polymer:PC71BM blend under AM 1.5G illumination with an intensity of 100 mW cm(-2). Thus, the cyano-substitution of conjugated polymers may be an effective strategy for optimizing the domain size and crystallinity of the polymer:PC71BM blend, and for increasing V(OC) by tuning the HOMO and LUMO energy levels of the conjugated polymer.


Are spontaneous epidural haematoma in sickle cell disease a rare complication? A report of two new cases.
Sickle cell anaemia, an autosomal recessive disease relatively common among the black races, gives rise sometimes to neurological complications. Among these, spontaneous epidural haematoma constitutes a rare event that is not always easy to treat in the Third world conditions. Two new cases are described and their pathology is compared with the five already described cases in the literature. A vaso-occlusive pathological process as in the orbital compression syndrome is thought to be implicated in the generation of the spontaneous epidural haematoma. When facing an epidural haematoma as a complication of sickle cell disease in a hospital of the Third world conditions, a cautious attitude towards surgery should be observed because of the high complication rate. If the relation between the haematoma and the anaemia is not immediately apparent, we are in favour of starting treatment with antibiotics.


Novel polymer nanowire crystals of diketopyrrolopyrrole-based copolymer with excellent charge transport properties.
The first demonstration of polymer nanowire (PNW) crystals based on a diketopyrrolopyrrole-based copolymer (i.e., PDTTDPP), and their application to field-effect transistors (FETs) is reported. Remarkably, transmission electron microscopy and selected area electron diffraction analyses of the PNW reveal its single-crystalline (SC) nature. FETs fabricated of a SC PNW exhibit a maximal charge carrier mobility of ≈7.00 cm(2) V(-1) s(-1) , which is almost one order of magnitude higher than that of the thin-film transistors made of the same polymer (PDTTDPP).


Occupational asthma: "the big picture".
With more than 200 agents inducing occupational asthma, an organized approach to identify the impact of both low- and high-molecular-weight agents is important. In this report, our goal is to explain the general categories of the sensitizing agents, present guidelines regarding what might be expected when exposures and sensitization occur, and present a number of references that can be explored to find information regarding the outcome of those with these illnesses.


Voltage-gated proton channels in microglia.
Microglia, macrophages that reside in the brain, can express at least 12 different ion channels, including voltage-gated proton channels. The properties of H+ currents in microglia are similar to those in other phagocytes. Proton currents are elicited by depolarizing the membrane potential, but activation also depends strongly on both intracellular pH (pH(i)) and extracellular pH (pH(o)). Increasing pH(o) or lowering pH(i) promotes H+ channel opening by shifting the activation threshold to more negative potentials. H+ channels in microglia open only when the pH gradient is outward, so they carry only outward current in the steady state. Time-dependent activation of H+ currents is slow, with a time constant roughly 1 s at room temperature. Microglial H+ currents are inhibited by inorganic polyvalent cations, which reduce H+ current amplitude and shift the voltage dependence of activation to more positive potentials. Cytoskeletal disruptive agents modulate H+ currents in microglia. Cytochalasin D and colchicine decrease the current density and slow the activation of H+ currents. Similar changes of H+ currents, possibly due to cytoskeletal reorganization, occur in microglia during the transformation from ameboid to ramified morphology. Phagocytes, including microglia, undergo a respiratory burst, in which NADPH oxidase releases bactericidal superoxide anions into the phagosome and stoichiometrically releases protons into the cell, tending to depolarize and acidify the cell. H+ currents may help regulate both the membrane potential and pH(i) during the respiratory burst. By compensating for the efflux of electrons and counteracting intracellular acidification, H+ channels help maintain superoxide anion production.


Pest categorisation of Leucinodes pseudorbonalis.
The EFSA Panel on Plant Health performed a pest categorisation of the snout moth Leucinodes pseudorbonalis Mally, Korycinska, Agassiz, Hall, Hodgetts & Nuss (Lepidoptera: Crambidae), for the territory of the EU. This species is not included in the EU Commission Implementing Regulation 2019/2072. This oligophagous species, which feeds on fruit and leaves of Solanum aethiopicum (Ethiopian eggplant) and S. melongena (eggplant), is known to occur in sub-Saharan Africa (Angola, Liberia, Senegal, Uganda). Adults oviposit on leaves and newly hatched caterpillars can bore into shoots, causing wilting and dieback, before moving into the fruit, which they tunnel. Damage may be visible only if the fruit is cut open. A single aubergine can be infested by up to 20 larvae. Mature larvae abandon the fruit to pupate in a cocoon in the soil. Adult moths fly for short distances only in darkness. Potential entry pathways for L. pseudorbonalis, such as Solanum spp. plants for planting and soil/growing media are regulated and can be considered as closed. The fruit and leaves pathways remain open from countries where L. pseudorbonalis is known to occur. Indeed, this species was intercepted in the EU with S. aethiopicum eight times from January to June 2021. Should L. pseudorbonalis enter the EU, host availability (S. melongena) and climatic conditions in some limited areas of southern EU Member States could allow this species to successfully establish and spread within these areas. Economic impact in aubergine production is anticipated if establishment occurs. L. pseudorbonalis satisfies the criteria that are within the remit of EFSA to assess for this species to be regarded as a potential Union quarantine pest. Because this is a recently described species, there are knowledge gaps related to the biology of this moth and its distribution. However, these gaps do not affect the conclusions of this categorisation.


[Electrocardiographic abnormalities in left pneumothorax].
Pneumothorax is a frequent complication among patients under mechanical ventilation or undergoing various invasive procedures. Its prevalence in intensive care units ranges from 3% to 14%. The electrocardiographic abnormalities described in left pneumothorax include poor precordial R-wave progression, precordial T wave inversion, phasic QRS voltage variation. QRS voltage ratio (aVF/DI) greater than 2 has high sensitivity and specificity. Electrocardiographic changes are secondary to several factors including clockwise rotation axis of the heart, dilated right ventricle, posterior displacement of the mediastinum, hypoxemia, and decreased coronary blood flow. We here describe a patient with left pneumothorax whose electrocardiographic features successfully reversed upon pneumothorax resolving.


A dose-dependent pharmacokinetic study on caffeic acid in rabbits after intravenous administration.
The dose-dependent pharmacokinetics of caffeic acid (CA) were studied in rabbits. Three different doses (5, 10, and 25 mg kg-1) were administered intravenously to six rabbits each. The concentration-time profiles for CA could be fitted by a two-compartment model for each dose. The results showed that total-body clearance and elimination rate constant from the central compartment (k10) after a 5 mg kg-1 dose were greater than those after the other two doses. Furthermore, the terminal elimination half-life (beta half-life) and mean residence time (MRT) after a 5 mg kg-1 dose were less than after the other doses. The AUC value increased linearly with dose within the range of 10-25 mg kg-1. Most of the unchanged caffeic acid was excreted in the urine within 2 h. The percentage of unchanged caffeic acid excreted in the urine was 63.4, 60.0, and 55.4% after doses of 5, 10, and 25 mg kg-1, respectively, which was not significantly different. However, significant differences in the renal clearances and renal excretion rate constants were observed with a 5 mg kg-1 dose compared to the other doses. On the other hand, nonrenal clearances and nonrenal excretion rate constants showed no dose-related differences. The differences observed in total-body clearance, k10, beta half-life, and MRT between a 5 mg kg-1 dose and the other doses can be explained on the basis of the differences in renal clearance and renal excretion rate constants.


An In Situ Evaluation of Different CAM Plants as Plant Microbial Fuel Cells for Energy Recovery in the Atacama Desert.
Excess energy derived from photosynthesis can be used in plant microbial fuel cell (PMFC) systems as a sustainable alternative for the generation of electricity. In this study, the in situ performance of CAM (Crassulacean acid metabolism) plants in Calama, in the Atacama Desert, was evaluated for energy recovery using PMFCs with stainless steel AISI 316L and Cu as electrodes. The plant species evaluated included Aloe perfoliata, Cereus jamacaru, Austrocylindropuntia subulata, Agave potatorum, Aloe arborescens, Malephora crocea, and Kalanchoe daigremontiana. Among the plant species, Kalanchoe daigremontiana demonstrated significant potential as an in situ PMFC, showing a maximum cell potential of 0.248 V and a minimum of 0.139 V. In addition, the cumulative energy for recovery was about 9.4 mWh m-2 of the electrode. The use of CAM plants in PMFCs presents a novel approach for green energy generation, as these plants possess an inherent ability to adapt to arid environments and water-scarce areas such as the Atacama Desert climate.


The validity of the multi-informant approach to assessing child and adolescent mental health.
Child and adolescent patients may display mental health concerns within some contexts and not others (e.g., home vs. school). Thus, understanding the specific contexts in which patients display concerns may assist mental health professionals in tailoring treatments to patients' needs. Consequently, clinical assessments often include reports from multiple informants who vary in the contexts in which they observe patients' behavior (e.g., patients, parents, teachers). Previous meta-analyses indicate that informants' reports correlate at low-to-moderate magnitudes. However, is it valid to interpret low correspondence among reports as indicating that patients display concerns in some contexts and not others? We meta-analyzed 341 studies published between 1989 and 2014 that reported cross-informant correspondence estimates, and observed low-to-moderate correspondence (mean internalizing: r = .25; mean externalizing: r = .30; mean overall: r = .28). Informant pair, mental health domain, and measurement method moderated magnitudes of correspondence. These robust findings have informed the development of concepts for interpreting multi-informant assessments, allowing researchers to draw specific predictions about the incremental and construct validity of these assessments. In turn, we critically evaluated research on the incremental and construct validity of the multi-informant approach to clinical child and adolescent assessment. In so doing, we identify crucial gaps in knowledge for future research, and provide recommendations for "best practices" in using and interpreting multi-informant assessments in clinical work and research. This article has important implications for developing personalized approaches to clinical assessment, with the goal of informing techniques for tailoring treatments to target the specific contexts where patients display concerns. (PsycINFO Database Record


Progress in desmin-related myopathies.
Desmin-related myopathies are sporadic and familial neuromuscular conditions of considerable clinical heterogeneity uniformly marked by the pathologic accretion of desmin, often in a filamentous fashion. A large variety of other proteins, some of them cytoskeletal, also accrue. Morphologically, two types may be distinguished, one characterized by inclusions such as cytoplasmic and spheroid bodies or desmin-dystrophin plaques and another marked by granulofilamentous material. The genetic spectrum of desmin-related myopathies is quite diverse in that missense mutations and deletions in the desmin gene and a missense mutation in the alpha-B crystallin gene have been detected and several genes on other chromosomes have been mapped; the encoded protein products of these genes, however, are unknown. Accumulation of desmin and other proteins appears to be due to impaired nonlysosomal proteolysis. Mutant desmin that appears to be hyperphosphorylated seems to act as a seed protein for filament aggregation, inducing formation of inclusions and granulofilamentous material in these conditions. This condition is part of the group of disorders known as "surplus protein myopathies."


Extracellular ATP causes of loss of L-selectin from human lymphocytes via occupancy of P2Z purinocepters.
Lymphocytes from normal subjects or patients with chronic lymphocytic leukemia are known to possess receptors for extracellular ATP termed P2Z purinoceptors whose physiological role is undefined. Addition of extracellular ATP (50-500 microM) to both normal and leukemic lymphocytes caused loss of binding of monoclonal antibodies to L-selectin (CD62L) on the cell surface. UTP, ADP, and adenosine (all at 500 microM) had no effect on L-selectin expression. Several features of the ATP-induced loss of L selectin indicate that this effect is mediated by lymphocyte P2Z purinoceptors. First the loss was attenuated in isotonic NaCl medium compared to 150 mM KCl medium. Second the loss of L-selectin was immediately halted by addition of Mg2+ ions in molar excess of ATP. The most potent nucleotide causing L-selectin loss was benzoylbenzoic ATP (> 10 microM) which is also the most potent agonist for the P2Z purinoceptor. Finally preincubation of lymphocytes with oxidized ATP, an irreversible inhibitor of P2Z purinoceptors, also inhibited ATP induced loss of L-selectin. Extracellular ATP is known to open an ion channel associated with the P2Z purinoceptor on B-lymphocytes which allows influx of Ca2+. However, ATP-induced loss of L-selectin did not require extracellular Ca2+. Moreover addition of the calcium ionophore, ionomycin, had minimal effect on L-selectin expression. Staurosporine (500 nM), an inhibitor of protein kinase C, inhibited only 10% of ATP induced loss of L-selectin but completely inhibited the loss of L-selectin caused by 50 nM PMA. Thus extracellular ATP interacts with lymphocyte P2Z purinoceptors which leads to shedding of L-selectin via a pathway which requires neither Ca2+ influx nor activation of protein kinase C. ATP may have a physiological role in the loss of L-selectin which occurs during the interactions of lymphocytes with other cells.


Proteolytic processing of dextransucrase of Leuconostoc mesenteroides.
Various dextransucrase molecular mass forms found in enzyme preparations may sometimes be products of proteolytic activity. Extracellular protease in Leuconostoc mesenteroides strains NRRL B-512F and B-512FMC dextransucrase preparations was identified. Protease had a molecular mass of 30 kDa and was the predominant form derived from a high molecular mass precursor. The production and activity of protease in culture medium was strongly dependent on pH. When L. mesenteroides dextransucrase (173 kDa) was hydrolyzed by protease, at pH 7 and 37 degrees C, various dextransucrase forms with molecular masses as low as 120 kDa conserving dextransucrase activity were obtained.


The distribution of myeloperoxidase, eosinophil cationic protein, albumin and urea in sequential bronchoalveolar lavage.
The distribution of myeloperoxidase (MPO) and eosinophil cationic protein (ECP), secreted from activated neutrophils and eosinophils, was estimated in bronchoalveolar lavage fluid in a sequential lavage study performed on 12 healthy subjects. Four 50 ml aliquots were sequentially injected into the right middle lobe and immediately aspirated. Recent studies, using radiological methods, have revealed proximal airway distribution of the first infused lavage aliquot, and more peripheral distribution of the following ones. We found significantly higher concentrations of MPO (p less than 0.001) and ECP (p less than 0.001) in the first aspirated aliquots as compared to the following three. These findings are compatible with the concept that these substances are, to a substantial part, distributed to the surface of the proximal airways. In contrast, the sequential recovery of albumin and urea showed a homogeneous recovery pattern. The findings were compatible with those of a small series of sixteen 10 ml lavage aliquots, sequentially infused and aspirated, also indicating a continuous diffusion of these small molecules through the lung membranes into the lavage fluid during the lavage process. We conclude that the difference in recovery pattern and distribution on the bronchial surface makes albumin and urea unsuitable as denominators in ratios to MPO and ECP, for the estimation of quantitative local concentration in epithelial lining fluid.


[Retrospective and comparative study of pneumococcal bacteremia in patients with chronic hepatopathy].
The chronic hepatopathy predispose to severe infections due to Streptococcus pneumoniae, including bacteremia. We have reviewed the clinic characteristics and outcome of 34 patients without HIV infection and compared with 140 HIV-negative patients with pneumococcal bacteremia. From 34 patients with chronic liver diseases, 27 were male (79%) and 7 female (21%), aged from 33 to 83 years. In 16 cases the origin of hepatopathy were alcoholic. The majority of the patients had fever (85%). From 29 isolations of S. pneumoniae in which a sensibility study was available, 5 (17%) were resistant to penicillin. Among 27 (79%) cases of chronic hepatopathy, the bacteremia was associated with pneumonia; 5 (18%) cases had roentgenographic evidence of multiple-lobe involvement, and 6 (18%) had peritonitis. The independent factors associated with pneumococcal bacteremia in chronic hepatopathy patients were elevated concentrations of amino-transferases (p < 0.001), alcoholism (p < 0.001) and bacteremic peritonitis (p = 0.007). The overall case of fatality and bacteremia-related mortality rate were higher among patients with chronic hepatopathy than control group, without statistic signification (38% vs 25%; and 29% vs 24% of control group, respectively). The presence of septic shock was poor prognosis (mortality rate: 83% [10/12]; p < 0.001). The multilobar involvement was associated with high mortality rate (60%; p = 0.1). Pneumococcal bactermia in patients with chronic hepatopathy have a high mortality rate; however clinical outcome is similar to patients without chronic hepatopathy.


Ribo-ODDR: oligo design pipeline for experiment-specific rRNA depletion in Ribo-seq.
Ribosome Profiling (Ribo-seq) has revolutionized the study of RNA translation by providing information on ribosome positions across all translated RNAs with nucleotide-resolution. Yet several technical limitations restrict the sequencing depth of such experiments, the most common of which is the overabundance of rRNA fragments. Various strategies can be employed to tackle this issue, including the use of commercial rRNA depletion kits. However, as they are designed for more standardized RNAseq experiments, they may perform suboptimally in Ribo-seq. In order to overcome this, it is possible to use custom biotinylated oligos complementary to the most abundant rRNA fragments, however currently no computational framework exists to aid the design of optimal oligos. Here, we first show that a major confounding issue is that the rRNA fragments generated via Ribo-seq vary significantly with differing experimental conditions, suggesting that a 'one-size-fits-all' approach may be inefficient. Therefore we developed Ribo-ODDR, an oligo design pipeline integrated with a user-friendly interface that assists in oligo selection for efficient experiment-specific rRNA depletion. Ribo-ODDR uses preliminary data to identify the most abundant rRNA fragments, and calculates the rRNA depletion efficiency of potential oligos. We experimentally show that Ribo-ODDR designed oligos outperform commercially available kits and lead to a significant increase in rRNA depletion in Ribo-seq. Ribo-ODDR is freely accessible at https://github.com/fallerlab/Ribo-ODDR. Supplementary data are available at Bioinformatics online.


Error analysis of tissue resistivity measurement.
We identified the error sources in a system for measuring tissue resistivity at eight frequencies from 1 Hz to 1 MHz using the four-terminal method. We expressed the measured resistivity with an analytical formula containing all error terms. We conducted practical error measurements with in-vivo and bench-top experiments. We averaged errors at all frequencies for all measurements. The standard deviations of error of the quantization error of the 8-bit digital oscilloscope with voltage averaging, the nonideality of the circuit, the in-vivo motion artifact and electrical interference combined to yield an error of +/- 1.19%. The dimension error in measuring the syringe tube for measuring the reference saline resistivity added +/- 1.32% error. The estimation of the working probe constant by interpolating a set of probe constants measured in reference saline solutions added +/- 0.48% error. The difference in the current magnitudes used during the probe calibration and that during the tissue resistivity measurement caused +/- 0.14% error. Variation of the electrode spacing, alignment, and electrode surface property due to the insertion of electrodes into the tissue caused +/- 0.61% error. We combined the above errors to yield an overall standard deviation error of the measured tissue resistivity of +/- 1.96%.


Neural mechanisms underlying the clasp-knife reflex in the cat. I. Characteristics of the reflex.
1. The goal of this study was to characterize the clasp-knife reflex by the use of stretch and isometric contraction of ankle extensor and flexor muscles in decerebrated cats with bilateral dorsal hemisections of their spinal cords at segment T12. 2. Stretch of an extensor muscle evoked inhibition in both homonymous and synergistic extensor muscles. The similarities between homonymous and synergistic inhibition suggest that similar neural mechanisms were responsible. 3. Homonymous and synergistic clasp-knife inhibition showed several characteristic features: 1) inhibition was evoked only by large stretches that produced significant muscle force. Short stretches that did not produce large forces evoked only excitation; 2) the magnitude of clasp-knife inhibition increased with increasing initial motor output, as reflected in the level of rectified EMG; 3) the time course of reflex inhibition evoked by ramp-and-hold stretch was characterized by segmentation of EMG during ramp stretch, dynamic overshoot of inhibition at the end-of-ramp stretch, and slow but usually complete decay of inhibition during maintained stretch; 4) inhibition persisted beyond the termination of stretch, and 5) inhibition showed adaptation to repeated stretch. 4. Isometric contraction of the soleus or medial gastrocnemius, produced by electrical stimulation of the muscle nerve, also evoked powerful synergistic-reflex inhibition via similar mechanisms as stretch-evoked, clasp-knife inhibition. Stretch evoked a greater degree of inhibition than did contraction, indicating that receptors responsive to both stretch and contraction contribute to clasp-knife inhibition. 5. The reflex effects produced by stretching the soleus or medial gastrocnemius were not confined to the homonymous and close synergistic muscles. Extensor muscles were inhibited and flexor muscles were excited throughout the hindlimb, which paralleled the pattern of a flexion-withdrawal reflex evoked by cutaneous stimulation. 6. Stretch of a flexor muscle, the tibialis anterior, evoked the same spatial pattern and time course of reflex action as stretch of an extensor muscle--inhibition of extensor muscles and excitation of flexor muscles throughout the hindlimb, including homonymous excitation of the tibialis anterior. 7. We conclude that neither Golgi tendon organs nor secondary spindle afferents are likely to contribute significantly to clasp-knife inhibition because their responses to stretch and isometric contraction differ from the reflex actions evoked by stretch and contraction.(ABSTRACT TRUNCATED AT 400 WORDS)


Acquisition of Carbapenemase-Producing Enterobacteriaceae in Solid Organ Transplantation Recipients.
Carbapenemase-producing Enterobacteriaceae (CPE) can lead to life-threatening outcomes with rapid spread of the carbapenemase gene in solid organ transplantation (SOT) recipients because of limitations of available antibiotics. We examined the characteristics and importance of CPE acquisition in SOT recipients with large numbers of CPE isolates. Between November 2015 and October 2016, 584 CPE isolates were found in 37 recipients and verified by carbapenemase gene multiplex polymerase chain reaction (PCR). One hundred recipients with at least 2 negative results in carbapenemase PCR for stool surveillance and no CPE isolates in clinical samples were retrospectively included. Most CPE isolates were Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (546, 93.5%). The most frequent transplantation organ was lung (43.3%), and the most common sample with CPE isolates other than stool was respiratory tract (22.6%). The median time between SOT and first CPE acquisition was 7 days. All-cause mortality was significantly higher in recipients with CPE than in those without CPE (24.3% vs 10.0%; P = .03). In multivariate regression analysis, stool colonization of vancomycin-resistant Enterococci and/or Clostridium difficile during 30 days before SOT (odds ratio [OR], 3.28; 95% CI, 1.24-8.68; P = .02), lung transplantation (OR, 4.50; 95% CI, 1.19-17.03; P = .03), and intensive care unit stay ≥2 weeks (OR, 6.21; 95% CI, 1.72-22.45; P = .005) were associated with acquisition of CPE. Early posttransplantation CPE acquisition may affect the clinical outcome of SOT recipients. Careful screening for CPE during the early posttransplantation period would be meaningful in recipients with risk factors.


Toward automatic robot programming: learning human skill from visual data.
We propose a novel approach to program a robot by demonstrating the task multiple number of times in front of a binocular vision system. We track artificially-induced features appearing in the image plane due to nonimpedimental color stickers attached at different fingertips and wrist joint, in a simultaneous feature detection and tracking framework. A Kalman filter does the tracking by recursively predicting the tentative feature location and a higher order statistics (HOS)-based data clustering algorithm extracts the feature. A fast and efficient algorithm for the vision system thus developed processes a binocular video sequence to obtain the trajectories and the orientation information of the end effector from the images of a human hand. The concept of trajectory bundle is introduced to avoid singularities and to obtain an optimal path.


Operative techniques in association with arrhythmia surgery in patients with congenital heart disease.
Arrhythmia surgery in patients with congenital disease is challenged by the range of anatomic variants, arrhythmia types, and intramyocardial scar location. Experimental and clinical studies have elucidated the mechanisms of arrhythmias for accessory connections, atrial fibrillation, atrial reentry tachycardia, nodal reentry tachycardia, focal or automatic atrial tachycardia, and ventricular tachycardia. The surgical and transcatheter possibilities are numerous, and the congenital heart surgeon should have a comprehensive understanding of all arrhythmia types and potential methods of ablation. The purpose of this article is to introduce resternotomy techniques for safe mediastinal reentry and to review operative techniques of arrhythmia surgery in association with congenital heart disease.


Protein-protein interaction network evaluation for identifying potential drug targets.
As pathogens evolve effective schemes to overcome the effect of antibiotics, the prevalent "one drug and one drug target" approach is falling behind. We propose novel strategies for identifying potential multiple-drug targets in pathogenic protein-protein interaction (PPI) networks with the goal of disrupting known pathways/complexes. Given a set S of pathogenic pathways/complexes, we first consider computing the minimum number of proteins (with no human orthologs) whose removal from the PPI network disrupts all pathways/complexes. Unfortunately, even the best approximation algorithms for this (NP-hard) problem return too many targets to be practical. Thus, we focus on computing the optimal tradeoff (i.e., maximum ratio) between the number of disrupted essential pathways/complexes and the protein targets. For this "sparsest cut" problem, we describe two polynomial time algorithms with respective approximation factors of |S| and O(√ n) (n: number of nodes). On the Escherichia coli PPI network with nine essential (signaling) paths from the KEGG database, our algorithms show how to disrupt three of them by targeting only three proteins (two of them essential proteins). We also consider the case where there are no available essential pathways/complexes to guide us. In order to maximize the number of disrupted "potential" pathways/complexes, we show how to compute the smallest set of proteins whose removal partitions the PPI network into two almost-equal sized subnetworks so as to maximize the number of potential pathways/complexes disrupted. This approach yields 28 potential targets (four of them known drug targets) on the E. coli PPI network whose removal partitions it to two subnetworks with relative sizes of 1-5.


A Smartphone App to Support Sedentary Behavior Change by Visualizing Personal Mobility Patterns and Action Planning (SedVis): Development and Pilot Study.
Prolonged sedentary behavior is related to a number of risk factors for chronic diseases. Given the high prevalence of sedentary behavior in daily life, simple yet practical solutions for behavior change are needed to avoid detrimental health effects. The mobile app SedVis was developed based on the health action process approach. The app provides personal mobility pattern visualization (for both physical activity and sedentary behavior) and action planning for sedentary behavior change. The primary aim of the study is to investigate the effect of mobility pattern visualization on users' action planning for changing their sedentary behavior. The secondary aim is to evaluate user engagement with the visualization and user experience of the app. A 3-week user study was conducted with 16 participants who had the motivation to reduce their sedentary behavior. Participants were allocated to either an active control group (n=8) or an intervention group (n=8). In the 1-week baseline period, none of the participants had access to the functions in the app. In the following 2-week intervention period, only the intervention group was given access to the visualizations, whereas both groups were asked to make action plans every day and reduce their sedentary behavior. Participants' sedentary behavior was estimated based on the sensor data of their smartphones, and their action plans and interaction with the app were also recorded by the app. Participants' intention to change their sedentary behavior and user experience of the app were assessed using questionnaires. The data were analyzed using both traditional null hypothesis significance testing (NHST) and Bayesian statistics. The results suggested that the visualizations in SedVis had no effect on the participants' action planning according to both the NHST and Bayesian statistics. The intervention involving visualizations and action planning in SedVis had a positive effect on reducing participants' sedentary hours, with weak evidence according to Bayesian statistics (Bayes factor, BF+0=1.92; median 0.52; 95% CI 0.04-1.25), whereas no change in sedentary time was more likely in the active control condition (BF+0=0.28; median 0.18; 95% CI 0.01-0.64). Furthermore, Bayesian analysis weakly suggested that the more frequently the users checked the app, the more likely they were to reduce their sedentary behavior (BF-0=1.49; r=-0.50). Using a smartphone app to collect data on users' mobility patterns and provide real-time feedback using visualizations may be a promising method to induce changes in sedentary behavior and may be more effective than action planning alone. Replications with larger samples are needed to confirm these findings.


Association in multifactorial traits: how to deal with rare observations?
To detect the role of a candidate gene for a trait in a sample of individuals, we may test SNP haplotype or diplotype effects. For a limited sample size, many haplotype or diplotype categories may contain few individuals. This involves a power decrease when testing the association between the trait and the haplotypes or diplotypes as these categories provide little additional information while increasing the degrees of freedom. The present paper proposes a new strategy to group rare categories based on a measure of similarity between haplotypes or diplotypes and compares it to two other possible strategies to deal with rare categories: a SNP selection strategy based on haplotype diversity, and a grouping strategy that pools all rare categories into a single baseline group. This comparison is performed by means of simulation under four scenarios. We show that this new strategy shows the largest increase in power irrespective of the model underlying the candidate gene in the studied trait. This strategy therefore provides a powerful alternative to currently used methods to reduce the number of rare categories.


[Cigarette smoking, use of snuff and other risk behaviour among students].
Different prevalences of cigarette smoking and use of snus between University students and non-students, may supply us with information about the diffusion stage of the epidemic. User characteristics and involvement in other risk behaviour influences their status as diffusion agents. 1 655 students at the University of Oslo responded to a postal questionnaire about their tobacco, alcohol and drug use, gambling habits, physical activity and incidence of anxiety and depression. Data on tobacco habits of similarly aged youth outside University were obtained from Statistics Norway. The response rate was 57 %. The proportion of daily smokers was significantly lower among students (men [10 %], women [9.6 %]), than among non-students (men [27 %], women [28 %]). The proportion of snuff users (daily + occasionally) for women was almost three times higher among students (12 %) than non-students (3.8 %). For men the results were different (28 % snuff users among students and 33 % among non-students). The quit-rate for smoking among students was higher for daily (46 %) and former users (61 %) of snus, than among students who had not used snus (34 %). Cigarette smoking increased with drug abuse, alcohol consumption, physical inactiveness, reduced mental health, and absence of parity. Use of snus was a typical male phenomenon, and increased with alcohol consumption and drug abuse. The diffusion of the snus epidemic seems to be in an early stage for women, while for men it may already have reached a level of maturity. The high proportion of previous smokers among snus users, indicates that snus may affect the prevalence and frequency of smoking in a population. Groups with a low social impact seem to have a higher prevalence of smokers, both in general and among students, while the opposite is the case for snus users.


Assessment of the charge selectivity of glomerular basement membrane using Ficoll sulfate.
The extent to which the glomerular basement membrane (GBM) contributes to the charge selectivity of the glomerular capillary wall has been controversial. To reexamine this issue, the size and charge selectivity of filters made from isolated rat GBM were assessed, using polydisperse Ficoll and Ficoll sulfate as test macromolecules. Ficoll sulfate, a novel tracer with spherical shape synthesized for this purpose, exhibited little or no binding to serum albumin, thereby avoiding a major difficulty that has been reported with dextran sulfate. The sieving coefficients of Ficoll sulfate were not different from those of Ficoll at physiological ionic strength, although the values for Ficoll sulfate were depressed at low ionic strength. These results confirm that the GBM possesses fixed negative charges but suggest that its charge density is insufficient to confer significant charge selectivity under physiological conditions, where electrostatic interactions are relatively well screened. The sieving coefficients of Ficoll sulfate and Ficoll were elevated significantly and by similar amounts when bovine serum albumin (BSA) was present in the retentate at 4 g/dl. This could be explained as the combined effect of two nonspecific physical factors, namely, the reduction in filtration velocity due to the osmotic pressure of BSA and the effect on macromolecular partitioning of repulsive solute-solute interactions. The view that BSA does not affect the intrinsic properties of the GBM is supported also by the absence of an effect on the hydraulic permeability of isolated GBM. The sieving coefficient of BSA was roughly half that of Ficoll or Ficoll sulfate of similar Stokes-Einstein radius. Given the finding of negligible charge selectivity, this difference may be attributed to the nonspherical shape of albumin. The results suggest that, to the extent that isolated GBM is similar to GBM in vivo, the charge selectivity of the glomerular capillary wall must be due to the endothelial and/or epithelial cell layers.


CSF somatostatin-like immunoreactivity in dementia.
Concentrations of somatostatin-like immunoreactivity (SLI) in CSF were reduced in Alzheimer's disease (AD) and multi-infarct dementia (p less than 0.01), but not in normal-pressure hydrocephalus, Parkinson's disease, and Huntington's disease. This suggests that reduced SLI content in AD cerebral cortex is reflected in CSF. Chromatographic characterization of CSF SLI showed no differences between AD and controls. Concentrations of SLI in AD patients overlapped those in both normal subjects and patients with multi-infarct dementia, so that changes in CSF SLI have no diagnostic specificity.


11beta-Hydroxysteroid dehydrogenase: a regulator of glucocorticoid response in osteoporosis.
Until recently it was assumed that there was a direct relationship between the level of glucocorticoids in the circulation and the levels within tissue. The identification and characterisation of local glucocorticoid modifying enzymes in a range of tissues however demonstrated that tissue levels of glucocorticoids can be regulated independently of circulating levels. This appears to be the case in bone where the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes are expressed. Glucocorticoids are actively generated within osteoblasts by the 11beta-HSD1 enzyme and this generation increases with proinflammatory cytokines, glucocorticoids, and probably with age. Measures of enzyme activity can predict the response of bone formation markers to therapeutic glucocorticoids. This review summarises the data relating to 11beta-HSD expression and activity in human bone and describes how this has implications for age-related, inflammation-associated, and glucocorticoid-induced osteoporosis.


Differential expression of a β-1,4-endoglucanase induced by diet change in the foliar nematode Aphelenchoides fragariae.
We identified and characterized a β-1,4-endoglucanase, Afr-ENG-1, in the foliar nematode Aphelenchoides fragariae that is differentially expressed when the nematode feeds on fungi or plants. When individuals from hosta plants were transferred to a fungus culture, expression of the enzyme decreased 1,812-fold after five generations on the fungus diet. Afr-eng-1 was readily detected in the genome of 75% of nematodes from the plant population but only in 38% of the diet-changed population. The gene cannot be detected in nematodes maintained on fungus for over 100 generations. Diet was also associated with changes in nematode body size and in the severity of symptoms caused on hosta leaves. Plant-diet nematodes caused larger lesions and were longer and thinner than fungus-diet nematodes. Nematodes moved from a plant diet to a fungus diet for five generations had the same body size as the nematodes that had fed on the fungus for 100 generations. Full-length sequences of Afr-eng-1 were obtained and found to encode a glycosyl hydrolase family 5 protein. This is the first β-1,4-endoglucanase and plant-parasitism-related gene described in the genus Aphelenchoides.


A role for alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid GluR1 phosphorylation in the modulatory effects of appetitive reward cues on goal-directed behavior.
Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor regulation has been shown to be critically involved in synaptic plasticity underlying learning and memory. This regulation occurs through trafficking of the receptor and modulation of the receptor's channel properties, both of which depend on protein phosphorylation. Using homologous recombination (knock-in) techniques we targeted two phosphorylation sites on the AMPA-GluR1 receptor: the Ser831 site, phosphorylated by calcium calmodulin-dependent protein kinase II/protein kinase C, and the Ser845 site, phosphorylated by protein kinase A. Mice with mutations that prevented phosphorylation at one or both of these sites were tested on a single-outcome Pavlovian-instrumental transfer task often used to assess the acquisition of incentive motivation by cues for food reinforcement. Mice were separately trained to associate a Pavlovian cue with food and to perform an instrumental lever-press response to earn that same reward. During a transfer test, the cue was presented while the mice were lever-pressing under extinction conditions. Whereas wild-type control mice showed substantial enhancement of lever-pressing when the cue was presented (i.e. showed Pavlovian-instrumental transfer), mice with mutations at both of these phosphorylation sites showed no evidence of such transfer. By contrast, mice with either serine site mutated alone showed normal transfer. These results suggest critical roles for GluR1 phosphorylation pathways in a form of incentive learning that can play an important part in regulating normal motivated behavior as well as maladaptive behaviors such as addiction and eating disorders.


Spurious elevation of automated leukocyte counts induced by Fluosol DA 20%.
During studies with Fluosol DA 20% (FDA) in rats, an artifactual leukocytosis was observed when an impedance type electronic cell counter was used. The effect was found to be directly related to the duration of the interval between addition of an erythrocyte lysing fluid and counting, observed up to 11 d after transfusion with FDA, blood cell associated, reproducible in vitro, FDA concentration dependent, temperature dependent, and present when human blood was used instead of rat blood. Microscopically, the effect appears to be the result of agglutination of lysed erythrocyte membranes due to the interaction of erythrocytes, the emulsion component of FDA, and the quaternary ammonium salt component of the lysing fluid. These data suggest that FDA causes subtle changes in erythrocytes and raises the possibility that other cells may be similarly affected.


Substituting random forest for multiple linear regression improves binding affinity prediction of scoring functions: Cyscore as a case study.
State-of-the-art protein-ligand docking methods are generally limited by the traditionally low accuracy of their scoring functions, which are used to predict binding affinity and thus vital for discriminating between active and inactive compounds. Despite intensive research over the years, classical scoring functions have reached a plateau in their predictive performance. These assume a predetermined additive functional form for some sophisticated numerical features, and use standard multivariate linear regression (MLR) on experimental data to derive the coefficients. In this study we show that such a simple functional form is detrimental for the prediction performance of a scoring function, and replacing linear regression by machine learning techniques like random forest (RF) can improve prediction performance. We investigate the conditions of applying RF under various contexts and find that given sufficient training samples RF manages to comprehensively capture the non-linearity between structural features and measured binding affinities. Incorporating more structural features and training with more samples can both boost RF performance. In addition, we analyze the importance of structural features to binding affinity prediction using the RF variable importance tool. Lastly, we use Cyscore, a top performing empirical scoring function, as a baseline for comparison study. Machine-learning scoring functions are fundamentally different from classical scoring functions because the former circumvents the fixed functional form relating structural features with binding affinities. RF, but not MLR, can effectively exploit more structural features and more training samples, leading to higher prediction performance. The future availability of more X-ray crystal structures will further widen the performance gap between RF-based and MLR-based scoring functions. This further stresses the importance of substituting RF for MLR in scoring function development.


The nature of the interactions of pyridostigmine with the nicotinic acetylcholine receptor-ionic channel complex. I. Agonist, desensitizing, and binding properties.
The actions of pyridostigmine (Pyr), an anticholinesterase agent, were studied on the acetylcholine (ACh) receptor-ion channel complex and on the electrically excitable membrane of the frog cutaneous pectoris and sartorius muscles and the chronically denervated soleus muscle of the rat. Pyr at concentrations of 0.2-0.4 mM potentiated the indirect evoked muscle twitch and at concentrations greater than or equal to 0.8 mM depressed the indirect twitch with an IC50 of about 2 mM. Twitch depression produced by Pyr was reversed slowly, and after a 60-min wash only 59% of the control muscle twitch had returned. Pyr did not affect either the membrane potential or the muscle action potential. Pyr had several effects at the neuromuscular junction of the frog and rat. It decreased the peak amplitude of the end-plate current (EPC) in a voltage- and concentration-dependent manner. In contrast to diisopropylfluorophosphate, which depresses the EPC amplitude and induces a double exponential decay of the EPC and miniature end-plate current (MEPC), Pyr produced a marked prolongation of the time constants of EPC and MEPC decay while maintaining a single exponential decay. The decrease caused by Pyr of indirect twitch tension, EPC amplitude, and ACh sensitivity indicates mechanisms which limit the number and/or properties of conducting channels. The drug decreased channel conductance and prolonged channel lifetime as revealed by Fourier analysis of ACh-induced end-plate current fluctuations. An altered form of the conducting species induced by Pyr appears to be responsible for either the apparent agonist-induced depolarization or its ability to increase the affinity of ACh for its recognition site. Pyr was also found to inhibit the binding of ACh and alpha-bungarotoxin to receptor-rich membrane from the electric organ of Torpedo nobiliana, and to have a higher affinity for the receptor than for the ion channel binding sites. These actions are distinct from acetylcholinesterase inhibition caused by the agent. Strong evidence suggests that the direct influences of the agent on neuromuscular transmission involve at least three distinct, although possibly interacting, mechanisms: (a) a weak agonist action, (b) the formation of desensitized receptor-complex intermediates, and (c) the alteration of the conductance properties of active channels.


A comparison of two sphygmomanometers that may replace the traditional mercury column in the healthcare workplace.
Alternatives to the traditional, but possibly toxic mercury sphygmomanometer are needed for accurate blood pressure measurements in the medical workplace. We compared the performance of two commercially available potential replacements for the mercury column; an anaeroid manometer (Baum & Co) and an automated oscillometric device (Omron HEM-907), using the mercury sphygmomanometer as a standard, in the same participants. Two independent observers performed simultaneous triplicate blood pressure readings for 512 participants. The average difference and standard deviation of the difference comparing the mercury column vs. the anaeroid and automated devices were calculated for each of the three paired systolic and diastolic blood pressure readings. Both devices met the Association for the Advancement of Medical Instrumentation criteria for sphygmomanometers (<5 mmHg average difference, <8 mmHg standard deviation of the difference) for all three readings. Compared with the mercury standard, there were no significant differences (by paired t-test) with the anaeroid device (-0.83/0.73 mmHg, P=0.25/0.09), but the automated device slightly overestimated systolic blood pressure (by 2.12 mmHg, P=0.002) and underestimated diastolic blood pressure (by 2.36 mmHg, P=0.0002). The first reading was significantly higher and had a larger standard deviation than the second or third readings across all manometers. The automated device performed as well as an anaeroid manometer operated by well trained, experienced observers. The two alternative devices to the mercury sphygmomanometer examined in this study may be potential replacement devices for blood pressure measurement.


[Cost-effectiveness study of olanzapine pamoate: Mirror-image analysis after one year].
Olanzapine pamoate has a higher cost of treatment than the oral form and requires administration in a hospital setting (unlike other long-acting antipsychotics), and the cost-effectiveness of this treatment may be questioned. Many scientific societies and national health systems are increasingly interested in the pharmacoeconomic impact of health products. The search for efficacy of a treatment can be done in two ways: medico-economic modeling studies or observational studies i.e. randomized controlled trials or mirror studies. The models are based on theoretical models from published clinical data simulating the course and evolution of patient health conditions, which benefit from a particular therapeutic strategy. Even if the design of observational mirror studies makes it possible to get closer to the clinical reality by observing the patient before and after the initiation of the treatment, the majority of the pharmacoeconomic studies published on olanzapine pamoate are modeling works that do not reflect actual conditions of care. The Guillaume Régnier Hospital Center in Rennes has a large cohort of patients treated with olanzapine pamoate: 121 instauration treatments are recorded from April 1, 2010 to Mars 1, 2015. The objective of this study is to evaluate the cost-effectiveness of olanzapine pamoate in actual clinical practice. This is a one-year cost-effectiveness retrospective observational mirror-image study of a cohort of 52 patients with schizophrenia who were treated for at least three months with olanzapine pamoate. The primary efficacy endpoint is the differential in the number of full-time hospitalizations before and after the introduction of olanzapine pamoate versus the hospital cost differential. The secondary criteria are the difference of the number of the days spent in hospital and the number of outpatient consultations between the year preceding the injection and the year following it. The results were calculated on the general cohort and within 2 subgroups: patients treated for more than one year and those receiving less than one year of treatment with olanzapine pamoate. Fifty-two patients were included (median age=35 years, sex ratio H/F=2.7) and only 38.5% discontinued treatment. For patients who maintained long-acting treatment, they received a dosage of 25mg oral olanzapine (min=7.5mg, max=60mg), 5mg more medially than the group having stopped the olanzapine pamoate (20mg; min=10mg, max=40mg). The majority of these patients were receiving off-label authorized marketing doses of oral olanzapine, whereas 22% of them had off-label dosages of olanzapine pamoate. The main causes of discontinuation were symptom persistence, loss of vision and the occurrence of adverse effects (including weight gain and sedation). Olanzapine pamoate significantly reduced the number of hospitalizations compared to the previous management strategy (1 less hospitalization, P<0.001 in patients treated more than one year and in the general cohort). As a logical consequence the number of hospitalization days in day care increased after the establishment of this long-acting antipsychotic with hospital reserve status (18 in median; min=0, max=159). We observed a non-statistically significant tendency of decrease in the number of days of full-time hospitalization and an increase in the number of ambulatory procedures, particularly in patients who have maintained the treatment for one year. This efficiency had a non-significant additional cost of €3361 per year. There was an average multiplication by 8,5 of the drug cost a year later in the general cohort (5.5 in the group of patients treated less than one year and 10.4 in the group of patients who maintained it a year). There was a 23,2% average increase in the cost of hospitalization in the general cohort (3.75 % in patients who maintained treatment compared to 48.9% in patients who discontinued treatment). By its mirror design, the study was placed in real conditions of care of the patient with schizophrenia. A total of 61.5% of patients maintained treatment with olanzapine pamoate for a minimum of one year. This APAP is more effective without significantly increasing the cost compared to the previous therapeutic strategy (including oral olanzapine). The additional cost is partly due to the administration restriction in a hospital setting in relation to risk of Post-Injection Delirium/Sedation Syndrom (PDSS). There is currently no acceptable efficiency limit. The results of this cost-effectiveness analysis cannot be extrapolated to the other long-acting antipsychotics since it is the only one with hospital reserve status. The current limitations of medico-economics in psychiatry derive from the heterogeneity of clinical forms and the management of mental pathologies.


Which MRI Score and Technique Should Be Used for Assessing Crohn's Disease Activity?
Magnetic resonance (MR) enterography is assuming an increasingly important and central role in the management of patients with Crohn's disease, as it is not only involved in diagnosis and staging of the disease but also allows for patients' follow-up, evaluating the response to therapy, and predicting disease outcomes. Several MR scores have been developed but unfortunately there is no globally accepted score. The most widely used scores are the Magnetic Resonance Index of Activity (MaRIA) score, the London score, the Nancy score, and the Clermont score; however, there are multiple differences between these tools in terms of the assessed radiological items, fasting, administration of oral or intravenous contrast, and the use of diffusion-weighted images. Here we reviewed the main characteristics of each MR scoring system to clarify which is the most appropriate score for monitoring disease activity in both clinical practice and clinical trials.


Proximal and distal environmental correlates of adolescent obesity.
The purpose of this study was to determine how proximal (home) and distal (neighborhood) environmental characteristics interact to influence obesity in early and middle adolescents. This was a descriptive, cross-sectional study using the 2007 National Survey of Children's Health (NCSH). Participants were 39,542 children ages 11 to 17 years. Logistic regressions were used to examine the relationship between adolescent obesity and environmental factors, the relative strength of these factors, and the influence of age and gender. Proximal environmental factors were stronger correlates of adolescent obesity than distal environmental factors. Sedentary behavior related to TV watching time at home was the strongest correlate of adolescent obesity overall (OR 1.13, 95% CI 1.11-1.15). Parks and playgrounds (OR 0.86, 95% CI 0.08-0.92), as well as recreation centers (OR 0.91, 95% CI 0.85-0.97) were significant distal environmental factor correlates. Girls and middle adolescents were at less risk for obesity than boys and early adolescents (OR 0.51, 95% CI 0.68-0.82; OR 0.75, 95% CI 0.68-0.96). The results of this study reveal the importance of proximal environmental characteristics on adolescent obesity relative to distal environmental characteristics. Obesity intervention strategies for adolescents should target sedentary behavior and opportunities for physical activity with a focus on early adolescents and boys.


Application of 3D printing in ear reconstruction with autogenous costal cartilage: A systematic review.
In recent years, 3D printing technology has been employed as a production method that builds materials layer upon layer, providing notable advantages in terms of individual customization and production efficiency. Autologous costal cartilage ear reconstruction has seen substantial changes due to 3D printing technology. In this context, this research evaluated the prospects and applications of 3D printing in ear reconstruction education, preoperative planning and simulation, the production of intraoperative guide plates, and other related areas. All articles eligible for consideration were sourced through a comprehensive search of PubMed, the Cochrane Library, EMBASE, and Web of Science from inception to May 22, 2023. Two reviewers extracted data on the manufacturing process and interventions. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the research. Database searching yielded 283 records, of which 24 articles were selected for qualitative analysis. The utilization of 3D printing is becoming increasingly widespread in autogenous costal cartilage ear reconstruction, from education to the application of preoperative design and intraoperative guide plates production, possessing a substantial influence on surgical training, the enhancement of surgical effects, complications reduction, and so forth. This study sought to determine the application value and further development potential of 3D printing in autologous costal cartilage ear reconstruction. However, there is a lack of conclusive evidence on its effectiveness when compared to conventional strategies because of the limited number of cohort studies and randomized controlled trials. Simultaneously, the evaluation of the effect lacks objective and quantitative evaluation criteria, with most of them being emotional sentiments and ratings, making it difficult to execute a quantitative synthetic analysis. It is hoped that more large-scale comparative studies will be undertaken, and an objective and standard effect evaluation system will be implemented in the future.


Multicenter evaluation of the Clostridium difficile TOX A/B TEST.
Clostridium difficile, the primary cause of nosocomial diarrhea in the United States and many other industrialized countries, is recognized as a major health concern because of its ability to cause severe intestinal disease leading to complications such as relapses and infections due to vancomycin-resistant enterococci. The disease results from two toxins, toxins A and B, produced by this pathogen. In this study, we evaluated the TOX A/B TEST, a new 1-h enzyme immunoassay (EIA) that detects toxins A and B. We compared the test with the tissue culture assay, which is recognized as the "gold standard" for C. difficile testing. Evaluations were performed in-house at TechLab, Inc. (Blacksburg, Va.) and off-site at four clinical laboratories. Of 1,152 specimens tested, 165 were positive by the TOX A/B TEST and tissue culture and 973 were negative by both tests. The sensitivity and specificity were 92.2 and 100%, respectively. The positive and negative predictive values were 100 and 98.6%, respectively, and the correlation of the TOX A/B TEST with tissue culture was 98.8%. When discrepant samples were resolved by culture, the sensitivity and specificity were 93.2 and 98.9%, respectively. The positive and negative predictive values were 100 and 98.8%, respectively, with a correlation of 99.0%. There were no specimens that were positive by the TOX A/B TEST and negative by tissue culture. Fourteen specimens were negative by the TOX A/B TEST but positive by tissue culture. Of these, two were negative by toxigenic culture, five were positive by toxigenic culture, and seven were not available for further testing. There were no indeterminate results, since the test does not have an indeterminant zone. In a separate study, 102 specimens that were positive by tissue culture and the TOX A/B TEST were examined in toxin A-specific EIAs. Two specimens that presumptively contained toxin A-negative, toxin B-positive (toxA-/toxB+) isolates were identified. One specimen was from a patient with a clinical history consistent with C. difficile infection. Isolates obtained from these specimens by selective culture on solid media and in broth tested toxA-/toxB+ when grown in brain heart infusion dialysis flasks, which stimulate in vitro production of both toxins. Our findings show that the TOX A/B TEST is suitable as a diagnostic aid for C. difficile disease because it correlates well with tissue culture and detects isolates that may be missed with toxin A-specific EIAs.


Centriolar SAS-5 is required for centrosome duplication in C. elegans.
Centrosomes, the major microtubule-organizing centres (MTOCs) of animal cells, are comprised of a pair of centrioles surrounded by pericentriolar material (PCM). Early in the cell cycle, there is a single centrosome, which duplicates during S-phase to direct bipolar spindle assembly during mitosis. Although crucial for proper cell division, the mechanisms that govern centrosome duplication are not fully understood. Here, we identify the Caenorhabditis elegans gene sas-5 as essential for daughter-centriole formation. SAS-5 is a coiled-coil protein that localizes primarily to centrioles. Fluorescence recovery after photobleaching (FRAP) experiments with green fluorescent protein (GFP) fused to SAS-5 (GFP-SAS-5) demonstrated that the protein shuttles between centrioles and the cytoplasm throughout the cell cycle. Analysis of mutant alleles revealed that the presence of SAS-5 at centrioles is crucial for daughter-centriole formation and that ZYG-1, a kinase that is also essential for this process, controls the distribution of SAS-5 to centrioles. Furthermore, partial RNA-interference (RNAi)-mediated inactivation experiments suggest that both sas-5 and zyg-1 are dose-dependent regulators of centrosome duplication.


Substance P-containing terminals in synaptic contact with cholinergic neurons in the neostriatum and basal forebrain: a double immunocytochemical study in the rat.
Antibodies against substance P and choline acetyltransferase (ChAT) have been used in a sequential double-immunocytochemical ultrastructural study of the rat forebrain. The peroxidase-anti-peroxidase procedure was used for both antigens, however, two different substrates for the peroxidase reactions were used. The substance P-immunoreactive sites were first localized using 3,3'-diaminobenzidine as the substrate, then the ChAT-immunoreactive sites were localized using benzidine dihydrochloride. The reaction product formed by the two substrates was distinguishable in both the light and electron microscopes. Using this procedure, the cell bodies and proximal dendrites of identified cholinergic neurons in the neostriatum were found to receive symmetrical synaptic input from substance P-immunoreactive boutons. A similar pattern of substance P-immunoreactive synaptic input was observed onto magnocellular basal forebrain cholinergic neurons in the ventral pallidum and ventromedial globus pallidus. In both the striatum and basal forebrain substance P-immunoreactive boutons were also seen in contact with structures that did not display ChAT immunoreactivity.


Pitfalls during the Embolization and Evaluation after the Embolization for the Skull Base Meningiomas.
Pitfall during the embolization and evaluation after the embolization for skull base meningiomas supplied by meningeal arteries of internal carotid artery (ICA) are reported. This study includes 15 cases of skull base meningiomas (two males and 13 females) that supplied by meningeal branches of internal carotid artery. The preoperative embolization was performed by these feeders. MRI findings and serum levels of C-reactive protein (CRP) after the embolization were examined. In ten patients among 15 patients the meningeal branches of ICA were dominant feeders. In ten patients out of 15 patients, the embolization from the meningeal branches of ICA was possible. Eight patients out of these ten patients were suffered from high fever and increase of serum level of CRP after the embolization. During the embolization for skull base meningiomas, the existence of collateral pathways between the ICA system and external carotid artery system were identified. The increase of serum levels of CRP might be recognized in the patients that effective embolization were performed.


Community-generated recommendations regarding the urban nutrition and tobacco environments: a photo-elicitation study in Philadelphia.
Overweight, obesity, and tobacco use are major preventable causes of disability, disease, and death. In 2010, 25% of Philadelphia adults smoked, and 66% were overweight or obese. To address these health threats, the Philadelphia Department of Public Health launched Get Healthy Philly, an initiative to improve the city's nutrition, physical activity, and tobacco environments. The objective of this assessment was to identify residents' perspectives on threats to health and opportunities for change in the local food and tobacco environments. Participants (N = 48) took photographs to document their concerns regarding Philadelphia's food and tobacco environments and participated in photo-elicitation interviews. We coded photographs and interview transcripts and identified key themes. Participants proposed interventions for nutrition 4 times more often than for tobacco. Participants spontaneously articulated the need for multilevel change consistent with the ecological model of health behavior, including changes to policies (food assistance program provisions to encourage healthful purchases), local and school environments (more healthful corner store inventories and school meals), and individual knowledge and behavior (healthier food purchases). Participants often required interviewer prompting to discuss tobacco, and they suggested interventions including changes in advertising (a local environmental concern) and cigarette taxes (a policy concern). Participants were well versed in the relevance to health of nutrition and physical activity and the need for multilevel interventions. Their responses suggested community readiness for change. In contrast, participants' more limited comments regarding tobacco suggested that prevention and control of tobacco use were perceived as less salient public health concerns.


Construction of a FRAX® model for the assessment of fracture probability in Canada and implications for treatment.
We describe the creation of a FRAX® model for the assessment of fracture probability in Canadian men and women, calibrated from national hip fracture and mortality data. This FRAX tool was used to examine possible thresholds for therapeutic intervention in Canada in two large complementary cohorts of women and men. To evaluate a Canadian World Health Organization (WHO) fracture risk assessment (FRAX®) tool for computing 10-year probabilities of osteoporotic fracture. Fracture probabilities were computed from national hip fracture data (2005) and death hazards (2004) for Canada. Probabilities took account of age, sex, clinical risk factors (CRFs), and femoral neck bone mineral density (BMD). Treatment implications were studied in two large cohorts of individuals age 50 years and older: the population-based Canadian Multicentre Osteoporosis Study (4,778 women and 1,919 men) and the clinically referred Manitoba BMD Cohort (36,730 women and 2,873 men). Fracture probabilities increased with age, decreasing femoral neck T-score, and number of CRFs. Among women, 10.1-11.3% would be designated high risk based upon 10-year major osteoporotic fracture probability exceeding 20%. A much larger proportion would be designated high risk based upon 10-year hip fracture probability exceeding 3% (25.7-28.0%) or osteoporotic BMD (27.1-30.9%), and relatively few from prior hip or clinical spine fracture (1.6-4.2%). One or more criteria for intervention were met by 29.2-34.0% of women excluding hip fracture probability (35.3-41.0% including hip fracture probability). Lower intervention rates were seen among CaMos (Canadian Multicentre Osteoporosis Study) men (6.8-12.9%), but in clinically referred men from the Manitoba BMD Cohort, one or more criteria for high risk were seen for 26.4% excluding hip fracture probability (42.4% including hip fracture probability). The FRAX tool can be used to identify intervention thresholds in Canada. The FRAX model supports a shift from a dual X-ray absorptiometry (DXA)-based intervention strategy, towards a strategy based on fracture probability for a major osteoporotic fracture.


Decreased prevalence and age-specific risk factors for Toxoplasma gondii IgG antibodies in The Netherlands between 1995/1996 and 2006/2007.
To estimate the change in the seroprevalence and risk factors for toxoplasmosis in The Netherlands, a study was conducted in the general population in 2006/2007, similarly designed as a previous study in 1995/1996. Testing 5541 sera for IgG antibodies against Toxoplasma gondii showed a marked decrease of the overall seroprevalence to 26·0% [95% confidence interval (CI) 24·0-28·0], compared to 40·5% (95% CI 37·5-43·4) in 1995/1996. In women of reproductive age the seroprevalence decreased from 35·2% (95% CI 32·9-38·6) in 1995/1996 to 18·5% (95% CI 16·2-20·7) in 2006/2007, leaving the majority of pregnant women susceptible to primary infection with T. gondii and their babies to congenital toxoplasmosis. In participants aged ≥20 years, Toxoplasma seropositivity was associated with living in the Northwest, living in urban areas, low educational level, consumption of raw pork, keeping a cat, and not having occupational contact with clients or patients. For younger participants, risk factors were keeping sheep or cattle, consumption of raw unwashed vegetables and putting sand in the mouth.


Exercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection.
Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression. We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS. Healthy mice were subjected to 6weeks of motorized treadmill running. The Proteolipid protein (PLP)-induced transfer EAE model in mice was utilized. To assess effects of ET on systemic autoimmunity, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were transferred to naïve recipients. To assess direct neuroprotective effects of ET, PLP-reactive LN-T cells were transferred into recipient mice that were trained prior to EAE transfer or to sedentary mice. EAE severity was assessed in vivo and the characteristics of encephalitogenic LN-T cells derived from PLP-immunized mice were evaluated in vitro. LN-T cells obtained from trained mice induced an attenuated clinical and pathological EAE in recipient mice vs. cells derived from sedentary animals. Training inhibited the activation, proliferation and cytokine gene expression of PLP-reactive T cells in response to CNS-derived autoantigen, but strongly enhanced their proliferation in response to Concanavalin A, a non-specific stimulus. However, there was no difference in EAE severity when autoreactive encephalitogenic T cells were transferred to trained vs. sedentary recipient mice. ET inhibits immune system responses to an auto-antigen to attenuate EAE, rather than generally suppressing the immune system, but does not induce a direct neuro-protective effect against EAE.


[Properties of glucose isomerase from Streptomyces robeus S-606].
Optimal conditions of the glucose isomerase fixation in a cell are determined by thermal treatment of Str. robeus S-606 biomass. Under these conditions the maximal enzyme activation (by 50-55 percent) is simultaneously observed. Basic properties of glucose isomerase fixed inside the cell are studied in comparison with the enzymic cell-free extract of this enzyme. The pH-optimum for preparations coincides and is observed at pH 7.5; the temperature optimum for the soluble enzyme is 70 degrees C, and for the intracellular enzyme it is higher by 5 degrees C. Thermostability of the intracellular enzyme is also higher than that of the soluble one. The Michaelis constants are calculated for the glucose isomerase preparations in a form of producer cells and enzymic extract: they equal to 0.375 M and 0.285 M, respectively. A comparison of properties permits considering intracellular glucose isomerase as an immobilized enzymic preparation.


Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer.
Measurement of human urinary carcinogen metabolites is a practical approach for obtaining important information about tobacco and cancer. This review presents currently available methods and evaluates their utility. Carcinogens and their metabolites and related compounds that have been quantified in the urine of smokers or non-smokers exposed to environmental tobacco smoke (ETS) include trans,trans-muconic acid (tt-MA) and S-phenylmercapturic acid (metabolites of benzene), 1- and 2-naphthol, hydroxyphenanthrenes and phenanthrene dihydrodiols, 1-hydroxypyrene (1-HOP), metabolites of benzo[a]pyrene, aromatic amines and heterocyclic aromatic amines, N-nitrosoproline, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (NNAL and NNAL-Gluc), 8-oxodeoxyguanosine, thioethers, mercapturic acids, and alkyladenines. Nitrosamines and their metabolites have also been quantified in the urine of smokeless tobacco users. The utility of these assays to provide information about carcinogen dose, delineation of exposed vs. non-exposed individuals, and carcinogen metabolism in humans is discussed. NNAL and NNAL-Gluc are exceptionally useful biomarkers because they are derived from a carcinogen- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)- that is specific to tobacco products. The NNAL assay has high sensitivity and specificity, which are particularly important for studies on ETS exposure. Other useful assays that have been widely applied involve quantitation of 1-HOP and tt-MA. Urinary carcinogen metabolite biomarkers will be critical components of future studies on tobacco and human cancer, particularly with respect to new tobacco products and strategies for harm reduction, the role of metabolic polymorphisms in cancer, and further evaluation of human carcinogen exposure from ETS.


How to enhance nursing students' intention to use information technology: the first step before integrating it in nursing curriculum.
Today, in the 21st century, information technology has an important and critical role in the healthcare delivery system. Nursing educators already know and understand that they should integrate nursing informatics into the nursing curriculum to prepare future nurses for the new world of information technology. However, as of now, the core program of nursing studies in Israel does not put an emphasis on the skills required to properly use nursing informatics. The present research is the first step toward achieving this target by recognizing the importance of the human factor. The main goal is to examine the correlation between nursing students' attitudes and a number of variables: self-efficacy, threat, challenge, and innovativeness. This quantitative study used a convenience sample of nursing students in a bachelor's degree program at a large academic center in central Israel. Results show significant positive correlations between nursing students' attitudes to computer use and self-efficacy, a sense of challenge in using a computer, a sense of threat in using a computer, and previous experience with computers. The insights of these results will benefit nursing educators by helping them find creative ways to expose the students to the world of information technology and to improve the quality of future nurses.


A major gene for primary hypoalphalipoproteinemia.
Sixteen kindreds were ascertained through probands clinically determined to have primary hypoalphalipoproteinemia, characterized by bottom decile high-density lipoprotein cholesterol (HDL-c), but otherwise normolipidemic. Age- and sex-adjusted, standardized HDL-c levels on 64 individuals in 14 nuclear families in which the proband was a parent were analyzed using the unified mixed model of segregation analysis as implemented in the computer program POINTER. The analysis proceeded by using the likelihood of offspring conditional on the parental phenotypes (conditional likelihood), which appears to overcome the limitation of possible heterogeneity in the selection criteria and provides an appropriate correction for the ascertainment. In these families, the multifactorial contribution to the phenotype appears to be small and significant only in the offspring generation. Although it was not possible to resolve the dominance pattern at the major locus since none of a recessive, additive, or dominant hypothesis could be firmly rejected, these families provided clear evidence for a major gene. Genetic heterogeneity is still a possibility, even within "primary" hypoalphalipoproteinemia.


Potential Roles of Exosomes in the Development and Detection of Malignant Mesothelioma: An Update.
Malignant mesothelioma (MM) is a devastating cancer of mesothelial cells, caused by asbestos exposure. Limited knowledge regarding the detection of asbestos exposure and the early diagnosis of MM, as well as a lack of successful treatment options for this deadly cancer, project an immediate need to understand the mechanism(s) of MM development. With the recent discovery of nano-vesicles, namely exosomes, and their enormous potential to contain signature molecules representative of different diseases, as well as to communicate with distant targets, we were encouraged to explore their role(s) in MM biology. In this review, we summarize what we know so far about exosomes and MM based on our own studies and on published literature from other groups in the field. We expect that the information contained in this review will help advance the field of MM forward by revealing the mechanisms of MM development and survival. Based on this knowledge, future therapeutic strategies for MM can potentially be developed. We also hope that the outcome of our studies presented here may help in the detection of MM.


Instrumentation for the upgrade to the JET core charge-exchange spectrometers.
Charge-exchange spectroscopy on JET has become particularly challenging with the introduction of the ITER-like wall. The line intensities are weaker and contaminated by many nuisance lines. We have therefore upgraded the instrumentation to improve throughput and allow the simultaneous measurement of impurity and fuel-ion charge exchange by splitting the light between two pairs of imaging spectrometers using dichroic beam splitters. Imaging instruments allow us to stack 11 × 1 mm diameter fibres on the entrance slits without cross talk. CCD cameras were chosen to have 512 × 512 pixels to allow frame transfer times <0.2 ms which with minimum exposure times of 5 ms give tolerable smearing even without a chopper. The image plane is optically demagnified 2:1 to match the sensor size of these cameras. Because the image plane of the spectrometer is tilted, the CCD must also be tilted to maintain focus over the spectrum (Scheimpflug condition). To avoid transverse keystoning (causing the vertical height of the spectra to change across the sensor), the configuration is furthermore designed to be telecentric by a suitable choice of the lens separation. The lens configuration is built almost entirely from commercial off-the-shelf components, which allowed it to be assembled and aligned relatively rapidly to meet the deadline for in-vessel calibration in the JET shutdown.