Differential effectiveness of a practice change intervention to improve antenatal care addressing alcohol consumption during pregnancy: Exploratory subgroup analyses within a randomised stepped-wedge controlled trial.
A practice change intervention demonstrated improvements in the provision of antenatal care addressing alcohol consumption. The aim of this study was to explore whether the effectiveness of the intervention differed between subgroups of pregnant women and types and location of maternity services. Post-hoc exploratory subgroup analyses of the outcomes from a randomised stepped-wedge controlled trial conducted with all public maternity services within three sectors of a local health district in Australia. Two outcomes (receipt of alcohol assessment and complete care) measured at two visit types (initial and subsequent) were included in analyses. Logistic regression models explored interactions between pre-post differences and subgroups of women (age, Aboriginal origin, education level, disadvantage, gravidity and alcohol consumption in pregnancy) and services (geographic remoteness, service and provider type/s) that have been reported to be associated with variation in guideline implementation. Surveys from 5694 women were included in the analyses. For the initial visit, no significant differential intervention effects between subgroups of women or type/location of services were found for either outcome. For subsequent visits, the intervention effect differed significantly only between Aboriginal origin subgroups (Aboriginal OR: 1.95; 95% CI: 0.99-3.85; non-Aboriginal OR: 5.34; 95% CI: 4.17-6.83; p<0.01) and women's alcohol consumption in pregnancy subgroups (consumed alcohol OR: 1.28; 95% CI: 0.59-2.78; not consumed alcohol OR: 5.22; 95% CI: 4.11-6.65; p<0.001) for assessment of alcohol consumption. These exploratory results suggest that the intervention may have had similar effects between different subgroups of women and types and location of services, with the exception of women who were non-Aboriginal and women who had not consumed alcohol, for whom the intervention was potentially more effective. The practice change intervention could be implemented with different maternity service and provider types to effectively support improvements in antenatal care addressing alcohol consumption. These exploratory results provide further data for hypothesis generation regarding targeted areas for the testing of additional strategies that enable Aboriginal women to benefit equally from the intervention, and to ensure those women most in need of care, those consuming alcohol during pregnancy, have their care needs met.


Environment-friendly management of textile mill wastewater sludge using epigeic earthworms: Bioaccumulation of heavy metals and metallothionein production.
In the present study, Eudrilus eugeniae and Perionyx excavatus were used for vermistabilization of textile mill sludge in different combinations with cowdung for 60 days. A higher percentage of metal removal was observed in earthworm treated mixtures for cadmium (54.5%) followed by copper (36.0%), chromium (37.0%) and zinc (35.9%). Vermistabilized textile mill sludge + cowdung (1:1) showed a maximum percentage increase in total NPK, a significant (P < 0.05) increase in bacteria, fungi, and actinomycetes with a better earthworm survival rate. A higher amount of metallothionein protein was produced by E. eugeniae than P. excavatus. Further, 100% textile mill sludge showed a number of histological abnormalities like degeneration of cells, cellular debris, and uneven cellular compartmentation while textile mill sludge with cowdung showed normal earthworm histology. Results suggest that textile mill sludge + cowdung (1:1) combination is suitable for vermistabilization of textile mill sludge.


Versatile end effector for laparoscopic robotic scrub nurse.
Integrating robotic scrub nurses in the operating room has the potential to help overcome staff shortages and limited use of available operating capacities in hospitals. Existing approaches of robotic scrub nurses are mainly focused on open surgical procedures, neglecting laparoscopic procedures. Laparoscopic interventions offer great potential for the context-sensitive integration of robotic systems due to possible standardization. However, the first step is to ensure the safe manipulation of laparoscopic instruments. A robotic platform with a universal gripper system was designed to pick up and place laparoscopic as well as da Vinci[Formula: see text] instruments in an efficient workflow. The robustness of the gripper system was studied using a test protocol, which included a force absorption test to determine the operational safety limits of the design and a grip test to determine the system performance. The test protocol shows results regarding force and torque absorption capabilities of the end effector, which are essential when transferring an instrument to the surgeon to enable a robust handover. The grip tests show that the laparoscopic instruments can be safely picked up, manipulated and returned independent of unexpected positional deviations. The gripper system also enables the manipulation of da Vinci[Formula: see text] instruments, opening the door for robot-robot interaction. Our evaluation tests have shown that our robotic scrub nurse with the universal gripper system can safely and robustly manipulate laparoscopic and da Vinci[Formula: see text] instruments. The system design will continue with the integration of context-sensitive capabilities.


Whole genome sequence analysis of bacteriophage P1 that infects the Lactobacillus plantarum.
Phage P1 was isolated from the abnormal fermented liquid using Lactobacillus plantarum (L. plantarum) IMAU10120. To date, genetic knowledge regarding L. plantarum phage diversity is still limited, and further in-depth sequencing analysis of isolated L. plantarum phages can fill this gap. Here, we investigated the whole genome sequence of L. plantarum phage P1, sequenced by Illumina HiSeq platform, to decipher its genomic characteristics and putative DNA packaging mechanism. It was revealed that phage P1 was 73,787 bp in length, which was composed of linear double-stranded DNA (dsDNA), and the GC content was 39.17%. Its genome contained 86 coding sequences for various functions, such as adsorption, injection, replication, assembly, and release. Moreover, it was observed that L. plantarum phage P1 utilized the 'cohesive ends' DNA packaging mechanism. This study furthered the genomic knowledge of L. plantarum phages and provided some basis for the control of L. plantarum phages in the dairy fermentation industry.


Anti-inflammatory drugs and variceal bleeding: a case-control study.
Non-steroidal anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices is a major complication of cirrhosis of the liver. To investigate the role, using a case-control study, of NSAIDs in first bleeding episodes associated with oesophageal or cardial varices in cirrhotic patients. A structured interview was conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal varices and 75 cirrhotic controls with oesophageal varices who had never bled. Cirrhotic patients who were admitted for bleeding related to portal hypertension were more likely to have used NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases (21 of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p = 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds ratio = 2. 9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001, odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables independently associated with the risk of bleeding. Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone.


Colour Stability of Various Types of Acrylic Teeth Exposed to Coffee, Tea and Cola.
Acrylic teeth of dentures are prone to discoloration due to frequent exposure to different colouring solutions in the oral environment. Thus, in order to maintain their aesthetic appearance, they must possess high colour stability while exposed to colorant solutions. To compare the colour stability of three different brands of acrylic teeth following immersion in coffee, tea and cola. This in vitro experimental study was conducted on 90 acrylic teeth in three groups (n = 30) of Ivoclar (Italy), PolyDent (Slovenia) and Apple (Iran). The teeth were immersed in coffee, cola and tea for one, three and six weeks (the teeth were not in contact with each other). Colour parameters were assessed before and after immersion using a spectrophotometer, and overall change in colour parameters was calculated. The overall colour change (ΔE) of the three groups at different time points was analyzed using one-way ANOVA. Pairwise comparisons were performed using Tukey's test. Coffee caused the greatest colour change in Apple acrylic teeth after six weeks (mean ΔE of 4.6 for coffee and 3.4 for tea and cola). Tea caused an almost equal colour change in the three groups. The greatest colour change in the Ivoclar teeth occurred in cola after six weeks (mean ΔE of 3.3, 3.4 and 2.8 for cola, tea and coffee, respectively). The greatest ΔE occurred at six weeks and was the highest in Apple, followed by PolyDent and then Ivoclar teeth in coffee (mean ΔE of 4.6, 3.4 and 3.3, respectively p < 0.001). Despite the significant colour change in the three groups, ΔE in Ivoclar group was within the clinically acceptable range of ≤ 3.3. A slight colour change was expected regarding the Apple and PolyDent acrylic teeth clinically.


Measuring the swelling behavior of polymer microspheres with different cross-linking densities and the medium-dependent color changes of the resulting latex crystal films.
We measured the size changes of cross-linked polymer microspheres of narrow size distribution with different cross-linking densities by the in situ swelling method. The swelling behavior of these cross-linked polymer microspheres revealed that their maximal swelling degree linearly decreased as a function of the cross-linker content from 6.65 at 1.36 mol% to 2.43 at 3.25 mol%. By means of UV-vis spectra, we observed the spectral changes of the latex crystal films composed of these cross-linked polymer microspheres when we filled the interstices of the latex crystal films with different fluid media. Some succeeding peak shifts were observed, which may have resulted from the movement or the swelling of the polymer microspheres in the latex crystals.


Diabetes medications and cardiovascular outcome trials: Lessons learned.
The US Food and Drug Administration's current standards require that new diabetes medications demonstrate cardiovascular safety in large, long-term trials. New drugs that have been assessed in such trials are changing the management of type 2 diabetes.


First person: a mental health mission to post-earthquake El Salvador.
In this article the author excerpts and discusses salient quotes or moments from the journal he compiled while visiting El Salvador in February 2001 as head of Disaster Psychiatry Outreach (DPO) to assist survivors of a major earthquake. This case discussion of a single disaster mental health response exemplifies key issues related to both short and long term mental health service delivery to disaster affected communities.


Impact of 'free-from' and 'healthy choice' labeled versions of chocolate and coffee on temporal profile (multiple-intake TDS) and liking.
Product reformulation for obtaining "free-from" or "healthy choice" versions may confer significant changes in sensory characteristics which could not meet consumer expectations in terms of sensory perception. Therefore, this paper aims to evaluate the influence of formulations of different product categories on their dynamic sensory profile and consumer acceptability. A sensory panel of 23 semi-trained assessors evaluated two product categories, chocolate and milk coffee, using Temporal Dominance of Sensations (TDS) over three consecutive intakes/sips (multiple-intake TDS) on two replications. TDS allowed us to describe the dynamic profile of classic products over the three intakes and to identify differences in the sensory temporal profile compared to their 'healthier choice' reformulated versions. For the chocolate category, increasing the cocoa and the reduction of lactose content mainly influenced the dominance of sweetness, dairy, cocoa, crunchy and bitterness attributes. No sugar addition and absence of caffeine (decaffeinated version) in ready to drink milk coffee beverage modified temporal perception of sweetness, bitterness, coffee flavor and smoothness texture. Higher overall liking averages were associated with the dominant attributes of chocolate with a higher level of cacao and milk coffee decaffeinated. The obtained results of the present work suggest that the multiple-intake TDS technique can be applied for the evaluation of different food categories, helping to develop healthier products and predicting the liking.


Modulation of human blood lymphocyte cytotoxicity by the phorbol ester tumor promoter P(Bu)2: increase of target binding, impairment of effector recycling, and activation of lytic potential which is independent of IL-2.
Treatment of lymphocytes with the tumor promotor P(Bu)2 enhanced their target-binding capacity. In the conventional 51Cr-release assay, the cytotoxic potential of lymphocytes pretreated with P(Bu)2 for a short time was reduced while after prolonged treatment their function was increased. The peak of lytic potential was attained after 15 hr of exposure. Comparison of the cytotoxic results obtained in suspension and immobilized conjugate assays suggested that P(Bu)2 treatment causes an impairment of the recycling capacity of lymphocytes. After prolonged exposure, the lytic machinery became activated as reflected by the reduced time elapsing after contact between effectors and targets and the delivery of lethal hit. The activation was also observed in the immobilized agarose assay. It was reflected by the elevated proportion of damaged targets that were bound to the treated lymphocytes. The P(Bu)2- and interferon-induced augmentation of lytic potential is achieved through different mechanisms. Combination treatment applied to the effectors in sequence (first P(Bu)2 followed by interferon), resulted in an additive effect. Similarly, simultaneous treatment with IL-2 and P(Bu)2 also gave an additive increase in cytotoxicity. Addition of antibodies directed against IL-2 did not abrogate the P(Bu)2 effect. Consequently, neither interferon nor IL-2 are involved in the phorbol ester-induced cytotoxic function.


Significance of the adrenergic system in the regulation of vasopressin secretion in rat neurohypophyseal tissue cultures.
The effects of adrenaline (A) and noradrenaline (NA) on vasopressin (VP) secretion were studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP contents of the supernatant media were determined by radioimmunoassay after a 1 or 2-h incubation. Significantly increased VP levels were detected in the tissue culture media following the administration of A (an alpha+beta(2)-receptor agonist), depending on the dose of A. The VP secretion elevation was totally blocked by the previous administration of phentolamine (an alpha(1)+alpha(2)-receptor antagonist) or corynanthine (an alpha(1)-receptor antagonist). Yohimbine (an alpha(2)-receptor antagonist) did not influence the VP secretion increase induced by A. After the administration of NA (a beta+alpha(1)-receptor agonist), a VP secretion elevation was again detected, but the degree of enhancement proved smaller than that of the VP secretion increase induced by A. Propranolol (a beta(1)+beta(2)-receptor antagonist) before NA administration prevented the VP secretion increase. Atenolol (a beta(1)-receptor antagonist) did not block the VP secretion elevation induced by NA. Corynanthine (an alpha(1)-receptor antagonist) treatment before NA administration reduced the NA-induced VP enhancement, because NA has an alpha(1)-receptor agonist character in addition to its main character (a beta-receptor agonist). Surprisingly, the administration of pindolol (a beta(1)+beta(2)-receptor antagonist) enhanced VP secretion. This contradictory effect can be explained in that pindolol not only acts as a blocker, but also exerts "intrinsic sympathomimetic action" and a strong adrenergic agonist effect. Pindolol before NA administration significantly increased the NA-induced VP elevation. Mainly the alpha(1)- and beta(2)-adrenergic receptors are involved in the A- or NA-induced increase of VP secretion in isolated NH tissue cultures. The results indicate that VP release is influenced directly by the adrenergic system, and the adrenergic control of VP secretion from the NH tissue in rats can occur at the level of the posterior pituitary.


Chronic Exposure to Normobaric Hypoxia Increases Testosterone Levels and Testosterone/Cortisol Ratio in Cyclists.
The aim of this study was to analyze the effects of the "live high, train low" method (LH−TL) and intermittent hypoxic training (IHT) on testosterone (T) and cortisol (C) levels in cyclists. Thirty cyclists participated in the experiment. The LH−TL group (n = 10) was exposed to normobaric hypoxia (FiO2 = 16.3%) for 11−12 h a day and trained in normoxia for 3 weeks. In the IHT group (n = 10), participants followed the IHT routine three times a week for 3 weeks in normobaric hypoxia (FiO2 = 16.3%). The control group (N; n = 10) followed the same training protocol in normoxia. The LH−TL training was found to significantly increase (p < 0.05) T levels and the testosterone/cortisol (T/C) ratio during the experiment. The area under the curve (AUC) calculated for T levels over 4 weeks was significantly (p < 0.05) higher in the LH−TL group, by 25.6%, compared to the N group. The results also indicated a significant correlation (r = 0.53; p < 0.05) between AUC for T levels over 4 weeks and ∆ values of hemoglobin (HGB) in the LH−TL group. Overall, the findings show that LH−TL training at a moderate simulated altitude contributes to an increase in T levels and T/C ratio in athletes, which is a beneficial change stimulating anabolic processes and erythropoiesis.


Serological identification of adult T-cell leukaemia-associated antigens.
Adult T-cell leukaemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Several clinical observations suggest that some tumour-associated antigens in ATL may be recognised by the immune system. In this study, we performed the serological screening of an expression library to identify ATL-associated antigens by using materials from a unique ATL patient with long-term stable disease. Among five distinct genes isolated, serine/arginine protein kinase 1 (SRPK1), which has been reported to have a restricted normal tissue distribution, was found to be overexpressed in most acute type ATL samples, but not in chronic type ATL or in normal peripheral blood mononuclear cells by real-time reverse transcription polymerase chain reaction. Interestingly, the overexpression of SRPK1 in aggressive types of ATL was more exclusively observed at the protein level than at the mRNA level. Autologous antibody to SRPK1 was confirmed in the ATL patient using Western blot analysis with plasma, but not detected in asymptomatic HTLV-I carriers or in healthy volunteers. These results indicate that SRPK1 may be useful for the development of therapeutic and diagnostic methods for patients with ATL.


Promoting the reduction of CO2 to formate and formaldehyde via gas-liquid interface dielectric barrier discharge using a Zn0.5Cd0.5S/CoP/multiwalled carbon nanotubes catalyst.
A Zn0.5Cd0.5S (ZCS) solid solution was prepared using a hydrothermal method, in which CoP nanowires were added as a co-catalyst and co-deposited with multiwalled carbon nanotubes (MWNTs) on sponge to prepare a series of ZCS/CoP/MWNTs/sponge electrodes. The microstructures of catalysts were analyzed to confirm ZCS and CoP were successfully loaded in MWNTs/sponge. The CO2 reduction products (formate and formaldehyde) produced via dielectric barrier discharge (DBD) using the different catalysts proved that the introduction of the CoP nanowires co-catalyst can enhance the catalytic activity of ZCS/MWNTs/sponge in the DBD system. Using 10% CoP and a ZCS/CoP concentration of 2.5 g·L-1, the resulting ZCS/CoP/MWNTs/sponge catalyst exhibited the best catalytic of CO2 reduction ability toward formate (7894.6 μmol·L-1) and formaldehyde (308.5 μmol·L-1) after 60 min of discharge, respectively. The proposed DBD catalytic mechanism for the reduction of CO2 was analyzed according to the Tafel slope, density functional theory calculations, photocurrent density and plasma reaction process. Furthermore, the application of the DBD catalytic technology for CO2 capture and reduction was shown to be efficient in a seawater system, and as such, it could be useful for marine CO2 storage and conversion.


[Cloning and sequencing of CTP synthetase cDNA from Chinese hamster cells].
The CTP synthetase cDNA was cloned from Chinese hamster lung cells V79. By comparison of the amino acid sequence of CTP synthetase with the counterpart of other species published, it was show that the CTP synthetase was a highly conserved and stable gene among the mammalian cells, but more differences of the CTP synthetase sequence could be seen between procaryotic and eukaryotic cells. This phenomenon suggested that the catalysing model of the enzyme might have some small differences in the organisms.


Degradation of aniline by ferrous ions activated persulfate: Impacts, mechanisms, and by-products.
Wastewater contains a large number of anions and organics which can scavenge reactive radicals and limit the application of sulfate radical-based advanced oxidation processes (SR-AOPs) in practical engineering. Here, we studied the removal rate and mechanism of aniline by SR-AOPs in different influencing factors, such as sodium persulfate dosage, ferrous ions dosage, solution pH, Cl-, HCO3-, NO3-, and other organic matter. By recognizing and analyzing free radicals, we concluded that SO4•- plays a major role in aniline degradation. The aniline removal rate increased with the initial concentrations of persulfate and ferrous ions, but aniline degradation was inhibited by excessive dosage. The aniline removal rate by ferrous-ions-catalyzed persulfate was higher under acidic conditions and could be improved under alkaline conditions if no ferrous ions were added. The addition of bicarbonate ions inhibited aniline removal, and the addition of nitrate ions barely caused the effect. While the addition of chloride ions promoted aniline degradation, which was confirmed that HClO generated from the reacting of Cl- and persulfate played a key role. However, TOC indicated that aniline was not completely mineralized in the process. Further analysis of the products from GC-MS demonstrated that chloride-ion additions produced some harmful halogenated by-products. Our results can act as a basis for developing processes for the aniline degradation in wastewater.


Layer by layer assembly of biotinylated protein networks for signal amplification.
Described herein is a unique and inexpensive method that outperforms commercial methods that amplify the streptavidin-biotin recognition event. Amplification induced by streptavidin and biotinylated protein causes the formation of a large detectable polymer. This approach enjoys a 100-fold decrease in detection limit in comparison with the commercial methods.


A novel myotropic peptide from the skin secretions of the tree frog, Polypedates pingbianensis.
A novel myotropic peptide, polypedatein, was purified and characterized from the skin secretions of the tree frog, Polypedates pingbianensis. Its primary structure, TLLCKYFAIC, was determined by Edman degradation and mass spectrometry. Polypedatein was subjected to bioassays including myotropic, antimicrobial, and serine protease inhibitory activities, which are related with many amphibian skin bioactive peptides. It was found to elicit concentration-dependent contractile effects on isolated rat ileum. cDNA clones encoding the precursor of polypedatein were isolated by screening a skin cDNA library of P. pingbianensis and then sequenced. The amino acid sequence deduced from the cDNA sequences matches well with the result from Edman degradation. BLAST search revealed that the sequence of polypedatein did not show similarity to known protein or peptide sequences. Especially, polypedatein does not contain conserved structural motifs of other amphibian myotropic peptides, such as bradykinins, bombesins, cholecystokinin (CCK), and tachykinins, indicating that polypedatein belongs to a novel amphibian myotropic peptide family. The signal peptide of the precursor encoding polypedatein shows significant sequence identity to that of other amphibian skin defensive peptides, such as antimicrobial peptides, bradykinins, lectins, and serine protease inhibitors, suggesting that polypedatein belongs to a novel amphibian myotropic peptide family. Polypedatein is also the first bioactive peptide from the genus of the frog, Polypedates.


Levels of PCB 126 and PCB 153 in plasma and tissues in goats exposed during gestation and lactation.
The aim of the present study was to gain knowledge about the disposition of the PCB congeners 126 and 153 in a goat model where pregnant does were given oral doses of PCB from day 60 of gestation until delivery. The goat kids were thus exposed to PCB during gestation and lactation. The doses of PCB 153 and PCB 126 were 98 and 49 ng/kg body wt/day, respectively. PCB levels were measured in plasma from the does at day 90 of gestation and at delivery, and in plasma from the kids at birth and four weeks post partum. Concentrations of PCB were analysed in brain, liver and fat tissue from the does six weeks after delivery and in liver and fat tissue from the kids at nine months of age. The ratio of estimated body burden to ingested dose in the does, was 0.95 +/- 0.07 for PCB 153 and 0.41 +/- 0.03 for PCB 126. Approximately 9% of PCB 153 and 6% of PCB 126 was transferred from the mothers to their kids during gestation and lactation. Prenatal exposure contributed to a much lower fraction of the body burden than postnatal PCB intake via milk, due to the fact that almost 100% of the PCB 153 transferred from the does to kids was transferred via milk, and the PCB 126 intake via milk was threefold higher than the calculated body burden. The hepatic PCB 126 concentration in both does and kids was significantly higher than the concentration in fat, in contrast to PCB 153, where the highest concentrations were found in fat. A significant difference in body burden between the does at delivery, the newborn kids, and the kids at four weeks of age, did not influence the plasma concentration of PCB 153 on a fat weight basis, which showed no difference with sampling time. Our results suggest that PCB 126 and PCB 153 have different pharmacokinetic properties. The higher levels of PCB 126 in liver tissue compared to fat tissue confirm the concept of hepatic sequestration. The similar blood concentration of PCB 153 in the does at delivery and their newborn kids despite the considerable difference in body burden, suggests a high degree of placental transfer. This supports previous observations that low molecular weight, lipid-soluble, non-polar chemicals reach the fetus to the greatest possible extent. For PCB 153, the body burden may provide the appropriate dose metric at steady state, but may give a minor underestimation of PCB 126 at low environmental exposure levels due to hepatic sequestration.


Factors affecting population dynamics of leaf beetles in a subarctic region: The interplay between climate warming and pollution decline.
Understanding the mechanisms by which abiotic drivers, such as climate and pollution, influence population dynamics of animals is important for our ability to predict the population trajectories of individual species under different global change scenarios. We monitored four leaf beetle species (Coleoptera: Chrysomelidae) feeding on willows (Salix spp.) in 13 sites along a pollution gradient in subarctic forests of north-western Russia from 1993 to 2014. During a subset of years, we also measured the impacts of natural enemies and host plant quality on the performance of one of these species, Chrysomela lapponica. Spring and fall temperatures increased by 2.5-3°C during the 21-year observation period, while emissions of sulfur dioxide and heavy metals from the nickel-copper smelter at Monchegorsk decreased fivefold. However, contrary to predictions of increasing herbivory with climate warming, and in spite of discovered increase in host plant quality with increase in temperatures, none of the beetle species became more abundant during the past 20years. No directional trends were observed in densities of either Phratora vitellinae or Plagiodera versicolora, whereas densities of both C. lapponica and Gonioctena pallida showed a simultaneous rapid 20-fold decline in the early 2000s, remaining at very low levels thereafter. Time series analysis and model selection indicated that these abrupt population declines were associated with decreases in aerial emissions from the smelter. Observed declines in the population densities of C. lapponica can be explained by increases in mortality from natural enemies due to the combined action of climate warming and declining pollution. This pattern suggests that at least in some tri-trophic systems, top-down factors override bottom-up effects and govern the impacts of environmental changes on insect herbivores.


Is there still a future for neurokinin 3 receptor antagonists as potential drugs for the treatment of psychiatric diseases?
Selective non-peptide antagonists for the neurokinin 3 (NK(3)) receptor first became available about twenty years ago. Although the understanding of the role of the NK(3) receptor in the brain has been greatly complicated by marked species differences in its distribution and by pharmacological heterogeneity, studies with brain-penetrant non-peptide NK(3) receptor antagonists in animals have indicated that these compounds may find utility in a number of psychiatric diseases, including schizophrenia, anxiety and depressive disorders. However, clinical studies with selective NK(3) receptor antagonists in these psychiatric conditions have been disappointing and they were unable to confirm the promising therapeutic potential from animal studies, thereby questioning the therapeutic utility of these compounds for CNS disorders. The purpose of this article is to provide a critical overview of the available data on NK(3) receptor antagonists in the psychiatry research and development field, by reviewing the behavioral and neurochemical effects of these agents in both preclinical and clinical studies.


Which search are you on? Adapting to color while searching for shape.
Human observers adjust their attentional control settings when searching for a target in the presence of predictable changes in the target-defining feature dimension. We investigated whether observers also adapt to changes in a nondefining target dimension. According to feature integration theory, stimuli that are unique in their environment in a single feature dimension can be detected with little effort. In two experiments, we studied how observers searching for such singletons adapt their attentional control settings to a dynamical change in a nondefining target dimension. Participants searched for a shape singleton and freely chose between two targets in each trial. The two targets differed in color, and the ratio of distractors colored like each target varied dynamically across trials. A model-based analysis with a Bayesian estimation approach showed that participants adapted their target choices to the color ratio: They tended to select the target from the smaller color subset, and switched their preference both when the color ratio changed between gray and heterogeneous colors (Exp. 1) and when it changed between red and blue (Exp. 2). Participants thus tuned their attentional control settings toward color, although the target was defined by shape. We concluded that observers spontaneously adapted their behavior to changing regularities in the environment. Because adaptation was more pronounced when color homogeneity allowed for element grouping, we suggest that observers adapt to regularities that can be registered without attentional resources. They do so even if the changes are not relevant for accomplishing the task-a process presumably based on statistical learning.


Relationship between dietary quality, determined by DASH score, and cardiometabolic health biomarkers: A cross-sectional analysis in adults.
The relationship between dietary patterns and cardiometabolic disease is of increasing interest. However, limited data regarding the association between dietary quality and biomarkers of cardiometabolic health exist. Therefore the aim of this work was to examine potential associations between dietary quality, assessed using the Dietary Approaches to Stop Hypertension (DASH) dietary quality score, adiposity and biomarkers of glucose homeostasis, lipoprotein metabolism and inflammation in a cross-sectional sample of 1493 men and women. Anthropometric measurements included BMI, hip and waist circumference (WC). Serum acute-phase reactants, adipocytokines, pro-inflammatory cytokines and white blood cell (WBC) counts were determined. Lipoprotein particle size and subclass concentrations were measured using nuclear magnetic resonance (NMR) spectroscopy. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Higher dietary quality was associated with lower BMI (P < 0.05), WC (P < 0.001), tumour necrosis factor α (TNF-α), interleukin 6 (IL-6), WBC and plasminogen activator inhibitor-1 (PAI-1) concentrations (P < 0.01) and reduced insulin resistance (P < 0.05). In addition less small low density lipoprotein (LDL) and small high density lipoprotein (HDL) particles and less large very low density lipoprotein (VLDL) particles were observed among those with better dietary quality (P < 0.001). Individuals in the top DASH quartile had a 54% and 48% lower likelihood of central obesity and metabolic syndrome (MetS), respectively, than those in the lowest DASH quartile (P < 0.05). Our data suggest that higher quality diet is associated with improved adiposity measures and a less insulin resistant, pro-inflammatory, pro-thrombotic and pro-atherogenic cardiometabolic profile which may impact on central obesity and MetS risk. These findings, which may be of clinical and public health significance in terms of dietary approaches to promote cardiometabolic health, warrant further examination.


Acute Basilar Artery Occlusion with Underlying High-Grade Basilar Artery Stenosis: Multimodal Endovascular Therapy in a Series of Seven Patients.
Acute basilar artery occlusion is associated with high rates of major morbidity and mortality. In rare cases, the underlying pathology is a high-grade stenosis of the basilar artery. We report on a series of seven cases with occluded high-grade basilar artery stenosis who received endovascular therapy at our center. Our prospective database since October 2009 until September 2013 was screened for patients with acute basilar artery occlusion and underlying high-grade stenosis who underwent endovascular therapy. Case files were retrospectively reviewed for clinical, outcome, and technical data. Seven patients were identified who suffered from an acute basilar artery occlusion based on a high-grade stenosis between October 2009 and September 2013. These patients were treated with an acute stenting of the basilar artery with or without a preceding mechanical thrombectomy. Median age was 75 (53-83) years; median prethrombectomy National Institute of Health Stroke scale score was 19 (7-28). A successful recanalization result defined as modified Thrombolysis In Cerebral Infarction grade 2b or higher was achieved in all cases. Two of the seven patients had a procedural complication consisting of a vessel dissection after angioplasty. A good clinical outcome according to the Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT) study criteria was achieved in three of the seven patients. One patient died during hospitalization in the acute phase. Mechanical thrombectomy combined with acute stenting of the basilar artery is technically feasible and may be an effective therapeutic option in the rare case of an acutely occluded high-grade stenosis of the basilar artery in patients with an otherwise poor prognosis.


The Enigma of Extreme Traumatism: Trauma, Exclusion and their Impact on Subjectivity.
My aim is to discuss the immediate effects of extreme trauma and to speculate on its long term effects. The formulations associated with the Post Traumatic Stress Syndrome generate an overly medicalized view of trauma, grossly underestimating its devastating impact. Catastrophic traumatic experience rips a hole in the representational continuity of psychic life; neither representations nor narrations are generated. Instead, a representational emptiness occurs, such that what has taken place cannot be shared or transmitted. The cathartic word becomes a robotic mocking of the interchange between human beings. There is no internalization, no ability to make the experience subjective. The resulting deep splitting in the psyche is characteristic of extreme traumatism, and its balance or perpetual working through is elaborated in this paper.


A novel antioxidant 3,7-dihydroxy-isoflav-3-ene (DHIF) inhibits neointimal hyperplasia after vessel injury attenuating reactive oxygen species and nuclear factor-kappaB signaling.
Reactive oxygen species (ROS) contribute to neointimal smooth muscle proliferation by yet to be defined mechanisms. We examined the effects of a novel isoflavone 3,7-dihydroxy-isoflav-3-ene (DHIF) on development of neointimal lesions in relation to ROS elevations and cell signaling in injured arteries. Carotid arteries of rabbits treated with vehicle or DHIF were injured with a balloon catheter and effects on proliferation, apoptosis, vessel structure, ROS, NF-kappaB activation, cyclooxygenase and gene expression examined. Seven days after injury proliferating neointimal cells were reduced by 35% (P<0.05) whilst medial cell proliferation was attenuated by 16% (P<0.05). ROS levels were elevated fourfold in injured arteries of vehicle-treated rabbits. Treatment with DHIF prevented this elevation (P<0.05). Also, NF-kappaB was activated in neointimal cells from vehicle-treated rabbits, demonstrated by nuclear accumulation of NF-kappaB-p65. DHIF not only attenuated its nuclear accumulation but also suppressed NF-kappaB-p65 expression in neointimal cells. This was accompanied by a doubling of apoptotic cell numbers (P<0.05). Expression of cyclooxygenases Cox-1 and Cox-2 were also attenuated, by 74% and 50%, respectively (P<0.05), as was MCP-1. The antiproliferative effects of DHIF persisted at 14 days, and 28 days after injury neointima growth was attenuated by 50% (P<0.05). Thus, ROS stimulates neointima growth via mechanisms involving NF-kappaB activation, cyclooxygenases and MCP-1. DHIF's ability to attenuate NF-kappaB activation suggests that it may not only be useful in preventing restenosis but also in attenuating atherosclerosis.


Computed tomography in management of medulloblastomas.
The neuroradiological studies of 116 patients with histologically verified medulloblastomas, which had been examined with plain and contrast-enhanced computed tomography (CT), were reviewed. The typical CT appearances of a well-defined, hyperdense enhancing mass in the vermis, with surrounding oedema, occurred in 60% of this series. Atypical features include calcification (17%), cystic or necrotic regions (47%) or poorly defined margins and lack of enhancement (7%). Such features in a vermis mass presenting in the first decade, especially in a boy, should not be considered against the diagnosis of medulloblastoma, but may be misleading when the tumour predominantly involves a cerebellar hemisphere.


Prenatal fetal abdominal ultrasonography and diagnosis.
Despite the advent of gray scale recording, the feasibility and advantages of antenatal fetal ultrasound diagnosis have not received sufficient attention. This paper describes ultrasound fetal abdominal anatomy and illustrates prenatal diagnosis based on anatomical landmarks.


Long-term follow-up records.
Having accumulated a very large series of patients' records over a period of 60 years, some involving three generations of a family, the author has selected cases that illustrate the opportunities to observe the progress of patients from infancy for more than half a century. This unique opportunity has included a variety of clinical conditions such as congenital syphilis, cretinism, acute osteomyelitis, and pink disease and represents a long term follow-up of conditions which reflect both the paediatrics of the past and the changes in the pattern of disease which have occurred in the course of 60 years.


Impact of tumour size on prognosis of upper urinary tract urothelial carcinoma after radical nephroureterectomy: a multi-institutional analysis of 795 cases.
To evaluate the prognostic impact of tumour size on survival outcomes in upper urinary tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Data on 795 patients treated with RNU for UTUC from seven centres were retrospectively analysed with focus on tumour size. Clinicopathological features and relevant prognostic factors were compared between patients with tumours ≤3.0 cm and those with tumours >3.0 cm in size. The primary endpoints were cancer-specific survival (CSS), disease recurrence-free survival (RFS) and overall survival (OS). At a median follow-up of 32 months, 313 (39.4%) patients died from UTUC, 321 (40.4%) developed cancer recurrence, and 359 (45.1%) died from all causes. Tumour size >3.0 cm was associated with unfavourable clinicopathlogical features. Kaplan-Meier analysis showed that tumour size was significantly correlated with worse CSS, RFS and OS (all P < 0.001). Multivariate analysis showed that tumour size was an independent predictor of CSS (hazard ratio [HR] 2.296; P < 0.001), RFS (HR 2.193; P < 0.001) and OS (HR 2.417; P < 0.001). Tumour size >3.0 cm was a significant predictor of CSS, RFS and OS after RNU for patients with UTUC. Further studies are warranted before tumour size is included in risk prediction tools.


Transrectal ultrasonography for prostatic cancer: its value in staging and monitoring the response to radiotherapy and chemotherapy.
Current methods to evaluate the size and local extent of prostatic cancer are imprecise. Quantitative assessments of changes after therapy are unreliable. We have used transrectal ultrasonography in 50 patients with clinically localized prostatic cancer to determine the value of this imaging technique in staging the local tumor and in monitoring the response of the tumor to therapy. Transverse images of the prostate were obtained at 5 mm. intervals, and were used to determine the size and shape of the prostate, irregularity or discontinuity of the capsule, extracapsular extension of tumor and invasion into the seminal vesicles. Ultrasonography proved highly accurate in staging. Among 18 previously untreated patients whose tumor appeared to be confined to the prostate by rectal examination 8 (44 per cent) had extension beyond the prostate by ultrasonography, which was confirmed by operative findings. Serial ultrasonograms were performed before and after definitive radiotherapy in 7 patients and chemotherapy in 6 patients. In response to therapy the prostate decreased in size and resumed a more normal, symmetrical shape, the capsule reformed and thickened, the degree of extracapsular extension diminished and the seminal vesicles became normal. Maximal reduction in the size of the prostate usually occurred by 9 months after radiotherapy and by 3 months after chemotherapy. In patients with prostatic cancer transrectal ultrasonography is highly accurate in staging and offers an objective monitor of the response to therapy.


Nonlinearities of the human ERG reflected by Wiener kernels.
The Electroretinograms (ERGs) of three subjects were represented by first- and second-order Wiener kernels using the analytical procedures previously reported for lower vertebrate (Marmarelis and Naka, 1973) and invertebrate (McCann, 1974) retinal studies. The variances between the kernel estimates were relatively small, yet the second-order kernels were relatively large. The significance of the nonlinearities reflected by each second-order kernel was assessed by comparing the predicted response to the white-noise stimulus obtained using a first-order kernel with that obtained using a second-order kernel.


Modified Haigis Formula Effective Lens Position Equation for Ciliary Sulcus-Implanted Intraocular Lenses.
To investigate the effect of a modified Haigis formula effective lens position equation on improving refractive outcomes in eyes with ciliary sulcus-implanted intraocular lenses (IOLs). Retrospective cross-sectional study. One hundred thirty-two eyes of 132 consecutive patients who underwent phacoemulsification with implantation of a ZA9003 (Abbott Medical Optics Inc, Santa Ana, California, USA; 69 eyes) or AR40e (Abbott Medical Optics Inc; 63 eyes) IOL in the ciliary sulcus were enrolled. The modified effective lens position (ELP) equation based on the corneal radius (CR) (ELP - β0 - β1 × CR, where β0 and β1 are parameters in the linear regression analysis) was obtained using linear regression analysis in each IOL group, and was applied to the other IOL group in order to evaluate its effect on refractive outcomes in an independent data set. The median absolute error (MedAE) was predicted using the modified effective lens position equation and was compared with that predicted using the adjusted IOL power. The modified effective lens position equation was ELP + 11.662 - 1.6225 × CR in the ZA9003 group and ELP + 10.606 - 1.4817 × CR in the AR40e group. The MedAE that was predicted using the modified effective lens position equation (0.34 diopter [D] in the ZA9003 group and 0.42 D in the AR40e group) was significantly smaller than that predicted using the adjusted IOL power (0.47 D in the ZA9003 group and 0.66 D in the AR40e group) (P < .001 and P = .005, respectively). IOL power calculation using the modified Haigis formula effective lens position equation improved refractive outcomes in eyes with sulcus-implanted IOLs.


Recombinant tissue plasminogen activator for the treatment of spontaneous adult intraventricular hemorrhage.
Intraventricular hemorrhage (IVH) has a poor prognosis with mortality rates of between 80 and 100% when all four ventricles are involved. Fibrinolytic therapy has been reported to improve overall outcome. Patients with severe primary IVH were treated by direct intraventricular injection of recombinant tissue plasminogen activator (rt-PA) into the lateral ventricles, followed by cerebrospinal fluid (CSF) drainage if the intracranial pressure rose above 20 mm Hg. Over a 15-month period from 1995 through 1996, 10 patients were treated, (4 male and 6 female, mean age 35 years; range, 21-55 years). The mean Glasgow Coma Scale score on admission was 6 (range, 4-8) and the mean Graeb score for severity of IVH on the first CT scan was 10 (range, 8-12). Angiography was negative in five cases but identified arteriovenous malformations in three, a post-traumatic pseudoaneurysm in one, and Moya-moya disease in one. The mean total dose requirement of rt-PA was 8.25 mg (range, 6-12 mg) with a significant reduction in the mean Graeb score after 7 days to 3.9 (range, 2-7, p<0.0001). Outcome at 3 months was death in one case (mortality 10%), severe disability in two (20%), moderate disability in three (30%), and good result in four (40%). Four patients (40%) required subsequent CSF shunting. No complications of rehemorrhage, infection, or catheter obstruction were encountered. Intraventricular fibrinolysis with rt-PA seems to be safe and effective for the treatment of severe IVH.


cAMP regulates vasopressin-induced AQP2 expression via protein kinase A-independent pathway.
The regulation of AVP-induced AQP2 expression was investigated in the present study. AVP administration induced AQP2 expression in a dose-dependent manner in association with an increase in intracellular cAMP concentration. PKA activity was stimulated by AVP but PKA inhibitors did not block the upregulation of AQP2 expression. However, AVP also activated both ERK and CREB pathways, and ERK inhibitor attenuated the upregulation of AQP2 expression. These results therefore indicate that the effect of AVP stimulation to upregulate AQP2 expression involves a PKA-independent pathway.


The Correlation between Depression, Balance, and Physical Functioning Post Stroke.
Depression, imbalance, and physical disability are among the serious stroke sequels. The objective of this study was to examine the correlation between depression, balance, and self-reported physical performance in patients post stroke. The Arabic versions of the Beck Depression Inventory (BDI), Dynamic Gait Index (A-DGI), and physical Stroke Impact Scale-16 version 3 were administered to a convenience sample of patients post stroke. The correlation between the mentioned measures was calculated using the Pearson coefficient. Additionally, the Kruskal-Wallis test was used to find out if the distribution of measurement scores differs among BDI levels of depression intensity or among Orpington Prognostic Scale (OPS) levels of stroke severity. Sixty-one patients with stroke (mean age [standard deviation] = 64 [12] years, 39 male) were recruited. Significant moderate correlations were found between BDI and A-DGI, BDI and Stroke Impact Scale (SIS), and A-DGI and physical SIS. Additionally, the distribution of the A-DGI and the physical SIS scores showed significant differences among BDI levels of depression intensity. Moreover, the distribution of the BDI, A-DGI, and physical SIS scores showed significant differences among OPS levels of stroke severity. Depressive symptoms were found frequent among people post stroke and were associated with balance and self-reported physical performance.


Ecosystem Services in the Nemunas Delta: Differences in Perceptions of Farmers, Birdwatchers and Scientists.
Engaging relevant stakeholders to identify ecosystem services is an important step in ensuring better management actions and nature protection. In this study, we involved three stakeholder groups that gave their opinions on different aspects regarding the usage, threats and protection of ecosystem services in the Nemunas Delta region (south-eastern Baltic Sea). Opinions from 178 respondents, representing local farmers, birdwatchers and scientists were collected in order to evaluate the importance of ecosystem services and to distinguish the most effective actions to sustain them. Despite many differences, there was a clear consensus among all three respondent groups about the importance of some ecosystem services such as water quality, water cycle, habitats for migratory animals, existence value, nature watching, subject for education and research and recreation. Birdwatchers appeared to be helpful in ecosystem services evaluation for their experience-based knowledge in this study region, but the differing perceptions of different groups on the majority of ecosystem services showed how important it is to include more than one stakeholder group in the assessment. The respondents did not agree about the actions needed to sustain ecosystem services--this highlights a need for compromises between anthropogenic activities and environmental protection, while an agreement on the necessity (willingness) to preserve natural values points to future development directions for the Nemunas Delta Region.


Solvothermal synthesis of bifunctional carbon dots for tartrazine and Fe(III) detection from chamomile residue by ternary DES pretreatment.
A ternary deep eutectic solvent (DES) consisting of choline chloride, lactic acid, and urea in a molar ratio of 1:2:2 was used to pretreat chamomile residue, followed by carbon dots (CDs) preparation using a one-pot solvothermal method. The CDs prepared under the suitable conditions had a high quantum yield of 47.34% and could be used as a bifunctional fluorescent probe for the detection of tartrazine and Fe(III). The concentration of tartrazine or Fe(III) had a good linear relationship with the fluorescence intensity of CDs that the determination coefficient (R2) was 0.9957 and 0.9943, and the limit of detection (LOD) was 40 nM and 119 nM, respectively. After verifying the different fluorescence quenching mechanisms of CDs by these two substances, a quantitative analysis was performed on real samples with recoveries of 90.70%∼104.29%. Overall, this study provided a promising technology for chemical conversion from low-cost chamomile residue to attractive bifunctional fluorescent probe.


Does withholding aspirin for one week reduce the risk of post-sphincterotomy bleeding?
Complications of endoscopic sphincterotomy are closely related to the endoscopic technique. To date, there have been no studies to indicate that aspirin increases the risk of bleeding after endoscopic sphincterotomy. To compare the incidence of post-sphincterotomy bleeding in patients with and without prior aspirin therapy. Eight hundred and four patients were recruited into this retrospective study: 124 patients continued to take aspirin until the day of sphincterotomy (Group 1), 116 patients had their aspirin discontinued for 1 week before sphincterotomy (Group 2) and 564 patients had never taken aspirin (Group 3). The primary outcome analysed was the incidence of post-sphincterotomy bleeding. Sixty-seven patients (8.3%) developed post-sphincterotomy bleeding. The incidences of post-sphincterotomy bleeding in Groups 1, 2 and 3 were 9.7%, 9.5% and 3.9%, respectively. Group 1 showed significantly increased post-sphincterotomy bleeding when compared with Group 3 (P=0.01), and the risk was also significantly increased when Group 2 was compared with Group 3 (P=0.01). However, there was no significant difference in post-sphincterotomy bleeding between Groups 1 and 2 (P=0.96). Aspirin therapy increased the risk of post-sphincterotomy bleeding. Withholding aspirin for 1 week before endoscopic sphincterotomy did not seem to decrease the risk of post-sphincterotomy bleeding.


Anesthesia penile tumescence test.
This article describes a simple method which we have found useful in helping to diagnose psychogenic impotence.


The effect of itraconazole on the pharmacokinetics of lorlatinib: results of a phase I, open-label, crossover study in healthy participants.
Background The third-generation tyrosine kinase inhibitor lorlatinib is approved for the treatment of ALK-positive metastatic NSCLC. CYP3A plays a major role in lorlatinib metabolism; therefore, a drug-drug interaction study was warranted to evaluate the impact of the strong CYP3A inhibitor, itraconazole, on lorlatinib plasma exposure. Methods This phase 1, open-label, 2-period, crossover study estimated the effects of itraconazole on the plasma pharmacokinetics and safety of lorlatinib in healthy participants (NCT02838264). Single-dose lorlatinib 50 mg (n = 2), 75 mg (n = 2) and 100 mg (n = 12) was administered in Period 1. In Period 2, itraconazole oral solution 200 mg/day was administered on Days 1-11, and single-dose lorlatinib on Day 5. Blood samples were collected up to 168 h after lorlatinib dosing. Results During daily dosing with itraconazole (Period 2), the ratios of the adjusted geometric means for area under the plasma concentration-time profile extrapolated to infinity (AUCinf) and maximum plasma concentration (Cmax) of single-dose lorlatinib 100 mg were 141.79% (90% confidence interval, 128.71%, 156.21%) and 124.39% (110.20%, 140.41%), respectively, compared with Period 1 (lorlatinib alone). Lorlatinib was well tolerated alone and with itraconazole. No serious adverse events or withdrawals were reported. Conclusions Co-administration of itraconazole and lorlatinib increased the plasma exposure of lorlatinib relative to lorlatinib alone in healthy participants. Therefore, concomitant use of lorlatinib with strong CYP3A inhibitors should be avoided. If this combination is unavoidable, the starting dose of lorlatinib should be reduced from 100 mg to 75 mg.


Functionality of wrapping defects in soluble proteins: what cannot be kept dry must be conserved.
Soluble proteins preserve their structure only if a sufficient number of non-polar groups are clustered around the backbone hydrogen bonds, protecting them from water attack. When these bonds are not properly wrapped or dehydrated intramolecularly, structural integrity can be preserved through binding partnerships. This is because insufficiently wrapped hydrogen bonds are inherently adhesive and become better shielded upon protein-ligand association. Thus, we postulate that deficiently wrapped hydrogen bonds are functionally relevant. Two findings that support this conjecture are: (a) there is a statistically relevant linear correlation between the number of defects in a folding domain and its proteomic connectivity, obtained from large-scale two-hybrid experiments; (b) the residues paired by under-wrapped hydrogen bonds are highly conserved. The high mutational sensitivity of under-wrapped regions can be rationalized, since their structural integrity relies on their propensity to behave as binding sites, in turn, a consequence of their adhesiveness. Thus, the regions in soluble protein structure that cannot be kept dry in water tend to be conserved.


Synthesis and in vitro and in vivo characterization of highly β1-selective β-adrenoceptor partial agonists.
β-Adrenoceptor antagonists boast a 50-year use for symptomatic control in numerous cardiovascular diseases. One might expect highly selective antagonists are available for the human β-adrenoceptor subtype involved in these diseases, yet few truly β1-selective molecules exist. To address this clinical need, we re-evaluated LK 204-545 (1), (1) a selective β1-adrenoceptor antagonist, and discovered it possessed significant partial agonism. Removal of 1's aromatic nitrile afforded 19, a ligand with similar β1-adrenoceptor selectivity and partial agonism (log KD of -7.75 and -5.15 as an antagonist of functional β1- and β2-mediated responses, respectively, and 34% of the maximal response of isoprenaline (β1)). In vitro β-adrenoceptor selectivity and partial agonism of 19 were mirrored in vivo. We designed analogues of 19 to improve affinity, selectivity, and partial agonism. Although partial agonism could not be fully attenuated, SAR suggests that an extended alkoxyalkoxy side chain, alongside substituents at the meta- or para-positions of the phenylurea, increases ligand affinity and β1-selectivity.


Positive crossmatches--when is it safe to transplant?
There is no doubt that the interpretation of a positive lymphocytotoxic crossmatch test has changed over the past 10-15 years. It is now generally accepted that the original dogma put forward in the mid-1960s "that a renal transplant must not be performed in the presence of a positive lymphocytotoxic crossmatch" is no longer tenable, and many positive crossmatch transplants have already been successfully carried out. However, the precise conditions under which such a transplant can be performed are still not fully understood. Some factors which should be considered when deciding whether or not to transplant in the presence of a positive crossmatch are: (1) the specificity of the antibody, and this can be HLA class I, class II or non-HLA; (2) the time interval between the last positive crossmatch serum and transplantation; and (3) the immunoglobulin class of the antibody, either IgG or IgM.


The association of air pollution with height: Evidence from Hong Kong's "Children of 1997" birth cohort.
Within populations, height is positively associated with economic success and in economically developed populations inversely associated with health. Recent studies also suggest air pollution may result in higher bone turnover markers among children, which may affect growth. However, few studies have investigated the effect of air pollution on height or growth rate. We therefore assessed the associations of several air pollutants with height at different ages. We simultaneously assessed associations of particulate matter with a diameter of 10 micrometers or less (PM10 ), sulfur dioxide (SO2 ), nitric oxide (NO), and nitrogen dioxide (NO2 ) in utero, in infancy, and in childhood with height at different ages (∼9, ∼11, ∼13, and ∼15 years), in a population-representative birth cohort "Children of 1997" (n = 8327) from the developed non-Western setting of Hong Kong with relatively high air pollution and short children, using partial least square regression. After considering multiple comparison, higher SO2 in childhood was associated with shorter height at ∼13 years (-0.20 cm, 99% CI -0.32 to -0.06). This difference was not evident at ∼15 years. These observations suggest that air pollution may affect the trajectory of growth and development rather than final height, with corresponding implications for health in later life.


Specific effect of zinc ions on DNA polymerase activity of avian myeloblastosis virus.
The effect of selected cations on DNA synthesis by DNA-polymerase of avian myeloblastosis virus (AMV) was studied. Zinc ions at low concentration (0.2mM) in the assay system enhanced the activity about 2 x fold and at higher concentration (2.0 mM) inhibited the activity completely. In contrast, addition of lithium and potassium salts produced inhibitory effects in this ionic concentration range. Replacement of K+ ion had an inhibitory effect on the activity.


[Ultrastructural examinations of HeLa cells exposed to cadmium ions].
Destructive changes in cadmium-treated HeLa cells affecting practically all the cell structures and organelles, were observed. Side by side with it compensation and adaptation responses of cells, which in definite period reduced cell pathological effect of this microelement were revealed.


Recognition of emotional facial expressions in adolescents with anorexia nervosa and adolescents with major depression.
Anorexia nervosa (AN) has been suggested to be associated with abnormalities in facial emotion recognition. Most prior studies on facial emotion recognition in AN have investigated adult samples, despite the onset of AN being particularly often during adolescence. In addition, few studies have examined whether impairments in facial emotion recognition are specific to AN or might be explained by frequent comorbid conditions that are also associated with deficits in emotion recognition, such as depression. The present study addressed these gaps by investigating recognition of emotional facial expressions in adolescent girls with AN (n = 26) compared to girls with major depression (MD; n = 26) and healthy girls (HC; n = 37). Participants completed one task requiring identification of emotions (happy, sad, afraid, angry, neutral) in faces and two control tasks. Neither of the clinical groups showed impairments. The AN group was more accurate than the HC group in recognising afraid facial expressions and more accurate than the MD group in recognising happy, sad, and afraid expressions. Misclassification analyses identified subtle group differences in the types of errors made. The results suggest that the deficits in facial emotion recognition found in adult AN samples are not present in adolescent patients.


Photodegradative surfactants: photolyses of p-alkylbenzyltrimethylammonium and alkylbenzyldimethylammonium halides in aqueous solution.
A series of benzyl-containing ammonium salts, p-alkylbenzyltrimethylammonium halides (C(n)BA: 1a-c) and alkylbenzyldimethylammonium halides (C(n)AB: 2a-d), have been prepared and their photodegradabilities in aqueous solutions have been compared. The photolytic decomposition proceeded by heterolytic and homolytic cleavages of the benzyl-nitrogen bond. The conversion yields were almost the same for all surfactants, whereas the product yields were slightly dependent on the alkyl-chain length. After irradiation, C(8)BA (1b) and C(12)BA (1c) were converted to non-surfactants, whereas C(12)AB (2c) and C(16)AB (2d) still remained surface-active. Their solution properties were concomitantly changed.


The influences of ambient fine particulate matter constituents on plasma hormones, circulating TMAO levels and blood pressure: A panel study in China.
Considerable investigations have been carried out to address the relationship between ambient fine particulate matter (PM2.5) and blood pressure (BP) in patients with hypertension. However, few studies have explored the influence of PM2.5 and its constituents on Trimethylamine N-oxide (TMAO), an established risk factor for hypertension and cardiovascular disease (CVD), particularly in severely air-polluted areas. To explore the potential impact of PM2.5 constituents on BP, plasma hormones, and TMAO, a panel study was conducted to investigate changes in BP, plasma hormones, and TMAO in response to ambient air pollution exposure in stage 1 hypertensive young adults. Linear mixed effect models were used to estimate the cumulative effects of fine particulate matters (PM2.5) and its constituents on BP, plasma hormones and TMAO. We found that one interquartile range (IQR) (35 μg/m3) increase in 0-1 day moving-average PM2.5 concentrations was statistically significantly associated with elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) with estimated values of 0.13 (95% confidence interval (CI): 0.03 to 0.23) mmHg, 0.18 (95% CI: 0.08 to 0.28) mmHg, and 0.17 (95% CI: 0.09 to 0.26) mmHg, respectively. Hormone disturbance in the renin-angiotensin-aldosterone system was also associated with PM2.5 exposure. Elevated TMAO levels with an IQR increase for 0-4, 0-5, 0-6 moving-average concentrations of PM2.5 were found, and the increased values ranged from 26.28 (95% CI: 2.92 to 49.64) to 60.78 (31.95-89.61) ng/ml. More importantly, the PM2.5-bound metal constituents, such as manganese (Mn), titanium (Ti), and selenium (Se) showed robust associations with elevated BP and plasma TMAO levels. This study demonstrates associations between PM2.5 metal constituents and increased BP, changes in plasma hormones and TMAO, in stage 1 hypertensive young adults. Source control, aiming to reduce the emission of PM2.5-bound metals should be implemented to reduce the risk of hypertension and CVD.


Some characteristics of human adrenal microsomal 21-hydroxylase activity.
The following general characteristics of 21-hydroxylase activity were determined using pooled microsomes obtained from three glands. Enzyme activity exhibited a broad pH dependence, being optimal between pH 7.4-pH 7.8, and was maximal with NADPH in the range 2 to 4.75 X 10(-4)mol/l. No microsomal 21-hydroxylase activity was detected in the absence of NADPH or substrate and when heat denatured microsomes were employed. Enzyme activity was depressed by greater than 75% in the presence of 100% oxygen or nitrogen. In a second set of experiments, microsomal fractions were prepared individually from 7 glands. In the presence of 17 alpha-hydroxy progesterone (2.0 X 10(-7) and 2.0 X 10(-6)mol/l) product formation was linear with time for up to 90 s when the microsomal protein concentration was 5, 10 and 20 micrograms/ml. Between 5 and 30% of the substrate was converted during the first 60 s. In 5/7 of the glands the addition of the autologous cytosol (20 micrograms protein/ml) was without effect, and enzyme activity (using a 60 s reaction and either 2.0 X 10(-7) or 2 X 10(-6)mol/l 17 alpha-hydroxy progesterone was directly proportional to the microsomal protein concentration (range 0-20 micrograms/ml). With the other 2 adrenals 21-hydroxylation was not proportional to the same range of microsomal protein concentrations, although it became so upon the addition of cytosol, which significantly augmented activity. There was considerable variation in enzyme activity between glands from different individuals (Vmax ranging from 2.6 to 16.6 X 10(-9) mol/min/mg protein) and in the apparent Km's (from 0.22 to 1.1 X 10(-6)mol/l). In the two preparations sensitive to cytosol, the Vmax increased 2-fold, and the Km was 3 times lower. Cytosol was without effect upon the kinetic characteristics of the other 5 microsomal preparations. Ascorbic acid (1 X 10(-3) mol/l) depressed enzyme activity by 25-43% whereas oxidised and reduced glutathione (1 X 10(-3) mol/l) showed a slight and variable effect upon 21-hydroxylation.


Evaluation of a textile-based near infrared spectroscopy system in calf muscle oxygenation measurements.
We recently introduced a novel textile-based NIRS sensor (TexNIRS). Here, we evaluate TexNIRS in ten subjects (16 legs, age 28.5 ± 2.32 years, adipose tissue thickness (ATT) 4.17 ± 1.71 mm). Three venous occlusions at 50 mmHg were performed on their calf muscle. After 3 min of occlusion, oxy/deoxy hemoglobin concentration ([O₂Hb], [HHb]) changes were 3.71 ± 1.89/1.79 ± 1.08 μM; venous oxygen saturation (SvO₂) was 75 ± 9.7 %, oxygen consumption (VO₂) was 0.02 ± 0.01 mL/100 g/min, hemoglobin flow (HF) was 0.93 ± 0.48 μmol/100 mL/min, and blood flow (BF) was 2.01 ± 1.04 mL/100 mL/min. Our results are in good agreement with the literature, but the TexNIRS enables a much higher level of comfort.


Randomized trial comparing Internet-based training in cognitive behavioural therapy theory, assessment and formulation to delayed-training control.
There is a need for effective, scalable methods of training clinicians in evidence-based interventions, particularly for populations with significant barriers to accessing traditional methods of training (e.g., developing economies, non-English speaking geographically dispersed populations). Hence this study examined the effectiveness of Internet-based training (IBT) in cognitive behavioural therapy (CBT) theory, assessment and formulation for participants in Russia with limited previous knowledge or training in CBT. Participants (N = 63) were randomized to either immediate IBT (approximately three hours over the course of one month) or a delayed training control group. Participants were assessed immediately prior to and following the training/delay on (a) standardized role-play of a CBT assessment and (b) ability to construct CBT formulation of the role-play 'patient'. In addition the feasibility and acceptability of the training was assessed. Responses indicated that translated and subtitled IBT training was perceived by participants to be feasible and acceptable. Following the training those allocated to IBT scored significantly higher on measures of CBT assessment and formulation skills (between group effects sizes of d = 0.77-1.10) than those allocated to the control group. Participants reported IBT to be a feasible and acceptable form of CBT dissemination. An adaptation of the CTS used to rate a standardized role-play assessment demonstrated good inter-rater reliability. IBT may be an effective and scalable method of CBT dissemination with particular potential for training CBT skills in populations with significant barrier to accessing traditional methods of training.


Jobelyn® extends the life span and improves motor function in Drosophila melanogaster exposed to lipopolysaccharide via augmentation of antioxidant status.
Jobelyn® (JB), a dietary supplement, derived from polyphenol-rich leaf sheath of Sorghum bicolor, has been reported to attenuate sensorimotor deficits and oxidative stress evoked by complete Freund-adjuvant in mice. This present study evaluated its effects on the life span, motor function and changes in oxidative stress parameters as well as acetylcholinesterase activity in Drosophila melanogaster exposed to lipopolysaccharide (LPS). The flies (50 per vial), in 5 replicates were fed with LPS (250 μg/kg diet) alone or in combination with JB (0.25-1.0 mg/kg diet) daily for 7 days. The mortality rate and motor function were evaluated on day 7. The flies were afterwards processed for determination of oxidative stress parameters and acetylcholinesterase activity. The effects of JB (0.25-1.0 mg/g diet) on the longevity of Drosophila was also investigated wherein the flies were monitored daily for mortality throughout their lifespan. The flies exposed to LPS (250 μg/kg diet) had reduced life span and elevated oxidative stress when compared with control. However, JB (0.25 and 1.0 mg/kg diet) improved the motor function and also reduced the mortality rate of the flies exposed to LPS. It also restored the cellular antioxidant status and reduced acetylcholinesterase activity, accumulation of hydrogen peroxide as well as nitric oxide in Drosophila fed with LPS. JB also extended the longevity of the flies relative to control. The findings that JB improves motor function and extended the lifespan of Drosophila flies by boosting the antioxidant status and cholinergic function, suggest it might be helpful in delaying the onset of neuropsychiatric illnesses associated with the aging processes.


A protein complex bearing an oxidase with napthalene dihydrodiol dehydrogenase activity is induced in Mucor circinelloides strain YR-1 during growth on polycyclic aromatic compounds.
Fungi are organisms capable of growing in a myriad of conditions and respond to counteract environmental cues. Several locations in the world are polluted with oil and its derivatives, and some microorganisms tolerant to these compounds have been isolated. Some fungi can grow in the presence of molecules such as polycyclic aromatic hydrocarbons as sole carbon sources. In this report, we further characterized the induced enzymes with phenanthrene from Mucor circinelloides YR-1 strain, isolated from a polluted field near a petrochemical facility in México. We identified a putative oxidase that is induced when growth with phenanthrene as sole carbon source at a pH of 8.5 and is NADP+ dependent. We show that this enzyme bears naphthalene dihydrodiol dehydrogenase activity with substrate preference for the cis-naphthalene over the trans-naphthalene, with an optimal pH in the range of 8-10. Mass spectrometry analysis revealed that the induced enzyme belongs to the NADP+ oxidase family enzymes with the typical Rossmann-fold for NADP+ binding. This enzyme seems to form a high molecular weight structure (~ 541 kDa) and with a monomer of 57 kDa, suggesting that the multimer is constituted of 10 subunits. Our findings contribute to understanding of the roles that dihydrodiol dehydrogenases have in organisms exposed to toxic compounds in the environment and can regulate their expression.


The cornified envelope of terminally differentiated human epidermal keratinocytes consists of cross-linked protein.
A small proportion of the protein of stratum corneum of human epidermal callus is insoluble even when boiled in solutions containing sodium dodecylsulfate and a reducing agent. This protein is present in the cornified envelope, a structure located beneath the plasma membrane. When cornified envelopes were dissolved by exhaustive proteolytic digestion and the products analyzed by chromatography, approximately 18% of the total lysine residues were found as the cross-linking dipeptide epsilon-(gamma-glutamyl) lysine. Labeled cornified envelope protein was synthesized by human epidermal keratinocytes allowed to differentiate terminally in culture. The extent of cross-linking, determined from the proportion of radioactive lysine in epsilon-(gamma-glutamyl) lysine after exhaustive proteolysis, was similar to that in stratum corneum. The properties of the cornified envelopes (insolubility in detergent and reducing agents, and solubility following proteolytic digestion) are readily explained by a structure consisting of a cross-linked protein lattice.


Beta-adrenergic receptor-dependent and -independent stimulation of adenylate cyclase is impaired during severe sepsis in humans.
a) To investigate the functional consequences of sepsis on the beta-adrenergic signal transduction in human circulating lymphocytes; b) to appreciate sepsis-associated catecholamine and cytokine release. Experimental, comparative study. Research laboratory in a university hospital. Healthy controls (n = 10); critically ill patients who were not septic (n = 7); septic patients with severe sepsis or septic shock (n = 11). Experiments were carried out using freshly isolated peripheral blood mononuclear cells (PBMC). We measured beta-adrenergic receptor (betaAR) number and affinity, and intracellular cAMP content at baseline and after the pharmacological stimulation of each component of the beta-adrenergic complex: betaAR with isoproterenol, Gs-protein with sodium fluoride (NaF), adenylate cyclase with forskolin. Catecholamine (adrenaline, noradrenaline) and cytokine (TNFalpha, IL-1alpha, IL-1beta, IL-6) serum levels were measured. In both septic and non-septic patients we observed a similar 40 % down-regulation of betaARs compared to controls, and a reduced basal and isoproterenol-stimulated cAMP accumulation (p < 0.05). The cAMP production elicited by NaF or forskolin was lower in septic patients than in the controls (p < 0.01). Forskolin-stimulated cAMP accumulation was significantly lower in septic patients than it was in non-septic ones (p < 0.001). Catecholamine serum concentrations were increased in the two patient groups without any significant difference. Elevated cytokine serum levels were detected in 45% of the septic patients (versus 14% of non-septic patients p < 0.05). Patients presenting with severe sepsis or septic shock have extended postreceptor defects of the beta-adrenergic signal transduction. This finding suggests a heterologous desensitization of adenylate cyclase stimulation.


Chemical characterization of the acid alteration of diesel fuel: Non-targeted analysis by two-dimensional gas chromatography coupled with time-of-flight mass spectrometry with tile-based Fisher ratio and combinatorial threshold determination.
The illicit chemical alteration of petroleum fuels is of keen interest, particularly to regulatory agencies that set fuel specifications, or taxes/credits based on those specifications. One type of alteration is the reaction of diesel fuel with concentrated sulfuric acid. Such reactions are known to subtly alter the chemical composition of the fuel, particularly the aromatic species native to the fuel. Comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS) is well suited for the analysis of diesel fuel, but may provide the analyst with an overwhelming amount of data, particularly in sample-class comparison experiments comprised of many samples. Tile-based Fisher-ratio (F-ratio) analysis reduces the abundance of data in a GC×GC-TOFMS experiment to only the peaks which significantly distinguish the unaltered and acid altered sample classes. Three samples of diesel fuel from differently branded filling stations were each altered to discover chemical features, i.e., analyte peaks, which were consistently changed by the acid reaction. Using different fuels prioritizes the discovery of features likely to be robust to the variation present between fuel samples and may consequently be useful in determining whether an unknown sample has been acid altered. The subsequent analysis confirmed that aromatic species are removed by the acid alteration, with the degree of removal consistent with predicted reactivity toward electrophilic aromatic sulfonation. Additionally, we observed that alkenes and alkynes were also removed from the fuel, and that sulfur dioxide or compounds that degrade to sulfur dioxide are generated by the acid alteration. In addition to applying the previously reported tile-based F-ratio method, this report also expands null distribution analysis to algorithmically determine an F-ratio threshold to confidently select only the features which are sufficiently class-distinguishing. When applied to the acid alteration of diesel fuel, the suggested per-hit F-ratio threshold was 12.4, which is predicted to maintain the false discovery rate (FDR) below 0.1%. Using this F-ratio threshold, 107 of the 3362 preliminary hits were deemed significantly changing due to the acid alteration, with the number of false positives estimated to be about 3. Validation of the F-ratio analysis was performed using an additional three fuels.


Tissue distribution of arsenic after subcutaneous implantation of arsenic trioxide pellet in rats.
In control rats, the arsenic level in the spleen and blood cells was 1.59 and 10.79 microgram/g wet tissue, respectively. In the kidney, lung, heart, brain, and hair, the arsenic level was lower than 1.1 microgram/g wet tissue. In rats in which a pellet containing 2 mg of arsenic tsioxide was implanted subcutaneously, the arsenic level in the spleen and blood cells was markedly high for at least 2 months after implantation; after 67 days of implantation, the arsenic level in the spleen and blood cells was 16.79 and 66.34 microgram/g wet tissue, respectively. In the kidney, liver, lung, heart, brain, and hair, the increase in arsenic after implantation was smaller than that in the spleen. In the plasma, arsenic was not detected before and after arsenic implantation. It is concluded that arsenic implanted subcutaneously concentrates in the blood cells, possibly in the red cells, in rats.


Possible consequences of genes of major effect: transient changes in the G-matrix.
Understanding the process of evolutionary divergence requires knowledge of the strength, form, and targets of selection, as well as the genetic architecture of the divergent traits. Quantitative genetic approaches to understanding multivariate selection and genetic response to selection have proven to be powerful tools in this endeavor, particularly with respect to short-term evolution. However, the application of quantitative genetic theory over periods of substantial phenotypic change is controversial because it requires that the requisite genetic parameters remain constant over the period of time in question. We show herein how attempts to determine the stability of key genetic parameters may be misled by the 'many genes of small effect' type of genetic architecture generally assumed in quantitative genetics. The presence of genes of major effect (GOMEs) can alter the genetic variance-covariance matrix dramatically for brief periods of time, significantly alter the rate and trajectory of multivariate evolution, and thereby mislead attempts to reconstruct or predict long term evolution.


Metabolomics for early detection of stress in freshwater alga Poterioochromonas malhamensis exposed to silver nanoparticles.
Silver nanoparticles (AgNPs) are one of the most used engineered nanomaterials. Despite progress in assessing their environmental implications, knowledge gaps exist concerning the metabolic perturbations induced by AgNPs on phytoplankton, essential organisms in global biogeochemical cycles and food-web dynamics. We combine targeted metabolomics, biouptake and physiological response studies to elucidate metabolic perturbations in alga Poterioochromonas malhamensis induced by AgNPs and dissolved Ag. We show time-dependent perturbation of the metabolism of amino acids, nucleotides, fatty acids, tricarboxylic acids, photosynthesis and photorespiration by both Ag-treatments. The results suggest that dissolved Ag ions released by AgNPs are the major toxicity driver; however, AgNPs internalized in food vacuoles contributed to the perturbation of amino acid metabolism, TCA cycle and oxidative stress. The metabolic perturbations corroborate the observed physiological responses. We highlight the potential of metabolomics as a tool for understanding the molecular basis for these metabolic and physiological changes, and for early detection of stress.


Apple peel intestinal atresia in siblings with ocular anomalies and microcephaly.
Two siblings who presented shortly after birth with signs of upper intestinal obstruction were successfully operated for apple peel jejunal atresia. In addition to intestinal malformations, both siblings exhibited severe microcephaly and ocular abnormalities not previously reported in this condition.


Neurochemical and histochemical studies of the effect of a lesion of the nucleus cuneiformis on the cholinergic innervation of discrete areas of the rat brain.
The innervation sites of the dorsal tegmental acetylcholinesterase (AChE)-containing pathway were examined in rats by combining histochemical and biochemical techniques. A lesion was placed in the nucleus cuneiformis (midbrain reticular formation) and brains were examined after 4 days survival for changes in AChE staining and choline acetyltransferase (ChAT) activity in discrete brain areas. An ipsilateral projection appears to exist to the anterior thalamic nuclei, lateral portion of the medial thalamic nucleus, parafascicular nucleus, pretectal nucleus, posterior thalamic nucleus, and deep layers of the superior colliculus. A possible bilateral innervation to the reticular nucleus of the thalamus and the dorsal and ventral lateral geniculates was found. The parallel use of AChE histochemistry and measurements of ChAT activity in discrete nuclei will be useful for future evaluation of cholinergic pathways.


Cytochrome P450-dependent metabolism of l-deprenyl in monkey (Cercopithecus aethiops) and C57BL/6 mouse brain microsomal preparations.
The aim of the present investigation was to characterize the cytochrome P450 (CYP)-dependent metabolism of l-deprenyl by brain microsomal preparations obtained from two different animal models that have been extensively used in Parkinson's disease studies, namely monkey (Cercopithecus aethiops) and C57BL/6 mouse. In monkey brain microsomal fractions, the apparent Km values for methamphetamine formation from l-deprenyl were 67.8 +/- 1.0 and 72.0 +/- 1.6 microm, in the cortex and striatum, respectively. Similarly, for nordeprenyl formation from l-deprenyl, Km values in cortex and striatum were 21.3 +/- 3.2 and 27.3 +/- 4.0 microm, respectively. Both metabolic pathways appear to be more efficient in the cortex than in the striatum as the Vmax for microsomal preparation was lower in the striatum for the formation of both metabolites. The formation rate of l-methamphetamine was up to one order of magnitude greater than that of nordeprenyl. Inhibition analysis of both pathways in monkey brain suggested that l-methamphetamine formation is catalysed by CYP2A and CYP3A, whereas only CYP3A appears to be involved in nordeprenyl formation. With microsomal preparations from whole brain of C57BL/6 mice, the only l-deprenyl metabolite that could be detected was methamphetamine and the Km and Vmax values were similar to those determined in monkey cortex (53.6 +/- 2.9 microm and 33.9 +/- 0.4 pmol/min/mg protein, respectively). 4-Methylpyrazole selectively inhibited methamphetamine formation, suggesting the involvement of CYP2E1. In conclusion, the present study indicates that l-deprenyl is effectively metabolised by CYP-dependent oxidases in the brain, giving rise mainly to the formation of methamphetamine, which has been suggested to play a role in the pharmacological effects of the parent drug. The results also demonstrate that there are differences between species in CYP-dependent metabolism of l-deprenyl.


Elements of chronic disease management service system: an empirical study from large hospitals in China.
At present, more patients suffer from multiple chronic diseases. However, the hospital's existing chronic disease management is carried out according to the department. This means that a patient needs to go to more than one department for a chronic disease treatment. Therefore, this study proposes 6 dimensions (organizational management, medical service support, medical service, community alliance, self-management support, management information system) and 36 questions, to help evaluate the current chronic disease management system in China's large third-class hospitals. In this study, 143 survey samples from doctors and nurses were collected. A principal component analysis was used to extract three key elements of chronic disease management service delivery system (service management organization, management information system, medical core service). Then, multiple regression was used to establish the relationship model between the overall performance of the system and the main elements. Three key service nodes of the system (medical specialist support, patient tracking management and personalized intervention) were determined according to the weight of the regression model. The regression coefficients of the above three main elements show a similar impact on the overall performance of the system, but the key service nodes under each major element have relative differences, including medical specialist support, patient tracking management and personalized intervention. Finally, to establish a chronic disease management system with multiple departmental continuous care for chronic diseases, it is necessary to improve the chronic disease management system from three aspects of medical specialty support, patient tracking management and personalized intervention. This paper proposes corresponding improvement strategies.


Evaluation of posterior and total corneal astigmatism with colour-LED topography.
To characterise the posterior and total corneal astigmatism using colour point-source light-emitting diodes (LED) topography. In a prospective case series 400 eyes from 400 patients were evaluated by colour-LED topography. Only eyes with normal topographies were considered. The following parameters were studied: magnitude and distribution of SimK and posterior corneal astigmatism, correlation between SimK and posterior corneal astigmatism, and differences in magnitude and axis between total and anterior corneal astigmatism. The mean SimK corneal astigmatism was 1.21 ± 0.94 D. The mean posterior corneal astigmatism was 0.37 ± 0.24 D. Posterior astigmatism was vertically oriented in 68% of eyes. Twenty-two percent of eyes showed a posterior corneal astigmatism ≥ 0.50 D. The correlation coefficients between SimK and posterior corneal astigmatism were: r2 = 0.066; p = 0.371 in WTR eyes, r2 = 0.112; p = 0.173 in ATR eyes and r2 = -0.019; p = 0.879 in oblique eyes. A difference between SimK and total corneal astigmatism ≥ 0.50 D was found in 7% of eyes. A difference in axis between SimK and total corneal astigmatism ≥ 10° was found in 24% of eyes. The percentage of eyes with posterior corneal astigmatism ≥ 0.50 D and the differences between anterior and total corneal astigmatism were higher than those previously reported in the literature. Therefore, this study supports the consideration of total corneal astigmatism magnitude and axis is mandatory for a precise surgical correction of astigmatism.


Analysis of force profile during a maximum voluntary isometric contraction task.
This study analyses maximum voluntary isometric contraction (MVIC) and its measurement by recording the force profile during maximal-effort, 7-s hand-grip contractions. Six healthy subjects each performed three trials repeated at short intervals to study variation from fatigue. These three trials were performed during three separate sessions at daily intervals to look at random variation. A pattern of force development during a trial was identified. An initiation phase, with or without an initiation peak, was followed by a maintenance phase, sometimes with secondary pulses and an underlying decline in force. Of these three MVIC parameters, maximum force during the maintenance phase showed less random variability compared to intertrial fatigue variability than did maximum force during the initiation phase or absolute maximum force. Analysis of MVIC as a task, rather than a single, maximal value reveals deeper levels of motor control in its generation. Thus, force parameters other than the absolute maximum force may be better suited to quantification of muscle performance in health and disease.


Incidence of acute kidney injury in dogs with systemic mycotic infections treated with amphotericin B (1996-2020).
Amphotericin-B (AmB) is an essential medication for the treatment of life-threatening systemic mycoses but the incidence and risk factors for acute kidney injury (AKI) after its administration are not known in dogs. Determine the incidence of and risk factors for AKI in dogs receiving AmB. Fifty-one client owned dogs receiving AmB for the treatment of systemic mycoses. Retrospective study. Signalment, potential risk factors, AKI development (creatinine ≥0.3 mg/dL from baseline), drug formulation (deoxycholate [AmB-D] or lipid complex [ABLC]), dose, and treatment duration were recorded. The probability of an AKI diagnosis was evaluated using a log-rank test. The incidence of AKI and odds ratios were calculated for potential risk factors. Incidence of AKI was 5/12 (42%) for dogs receiving AmB-D and 14/39 (36%) for dogs receiving ABLC. Of the 19 dogs that developed AKI, 16 (84%) continued treatment after a pause in the planned dosing protocol. Fifty percent of dogs received a cumulative dose of 6.9 mg/kg for AmB-D and 22.5 mg/kg for ABLC (P < .01) at time of AKI diagnosis. ICU hospitalization (odds ratio [OR] 0.21, 95% confidence interval [CI]: 0.58-0.87) and inpatient status (OR 0.25, 95% CI: 0.07-0.86) were associated with decreased odds of AKI. Incidence of AKI with AmB is common but does not always preclude continued treatment. The incidence of AKI is similar between AmB-D and ABLC, but dogs receiving ABLC tolerated a higher cumulative total dose before AKI diagnosis.


A Threshold QuickDASH Score for Estimating a Diagnosis of Major Depression in Patients With Fingertip Injuries in the American and Dutch Population.
The aim was to determine the threshold Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score that estimates a diagnosis of major depression in patients with fingertip injuries in American and Dutch patients. In this observational cross-sectional study, 112 patients with a recent fingertip injury measured symptoms of depression with the Patient Health Questionnaire and upper extremity disability with the QuickDASH. In the US cohort, 8 of 56 patients had an estimated diagnosis of major depression. A threshold value of QuickDASH of 50 showed a sensitivity of 88% and a specificity of 81%, with a negative predicting value (NPV) of 95% for an estimated diagnosis of major depression. In the Dutch cohort, 7 of 56 patients had an estimated diagnosis of major depression. The same threshold score of 50 had a sensitivity of 71%, a specificity of 63%, and an NPV of 94%. We have found a correlation between experienced loss of function and an estimated diagnosis of major depression in patients with a fingertip injury. Referral to the primary care physician for further evaluation of depression in these patients is advised.


II - Prostaglandin hyperalgesia: the peripheral analgesic activity of morphine, enkephalins and opioid antagonists.
Morphine, enkephalins, nalorphine, naloxone and pentazocine are shown to have a peripheral analgesic effect. In our modification of the Randall-Selitto test these substances were 50--100 times more potent than a standard local anaesthetic, lidocaine. At this peripheral site, naloxone did not antagonize the effect of morphine. Morphine had a marked analgesic effect on the hyperalgesia induced by PGE2 and PGI2, BaCl2, Ca2+ ionophore A23187, isoprenaline but not on that induced by dibutyryl cyclic AMP. It was suggested that the peripheral analgesic effect of morphine is due to an inhibition of adenylate-cyclase activity.


An automatic flow system for NIR screening analysis of liquefied petroleum gas with respect to propane content.
This paper proposes a NIR spectrometric method for screening analysis of liquefied petroleum gas (LPG) samples. The proposed method is aimed at discriminating samples with low and high propane content, which can be useful for the adjustment of burn settings in industrial applications. A gas flow system was developed to introduce the LPG sample into a NIR flow cell at constant pressure. In addition, a gas chromatographer was employed to determine the propane content of the sample for reference purposes. The results of a principal component analysis, as well as a classification study using SIMCA (soft independent modeling of class analogies), revealed that the samples can be successfully discriminated with respect to propane content by using the NIR spectrum in the range 8100-8800 cm(-1). In addition, by using SPA-LDA (linear discriminant analysis with variables selected by the successive projections algorithm), it was found that perfect discrimination can also be achieved by using only two wavenumbers (8215 and 8324 cm(-1)). This finding may be of value for the design of a dedicated, low-cost instrument for routine analyses.


High rates of enteric protozoal infections in selected homosexual men attending a venereal disease clinic.
Stool specimens from 89 high-risk, sexually active homosexual men were screened for enteric protozoal cysts. Patients whose specimens contained nonpathogenic cysts were investigated further by examination of fresh purged specimens. A total of 27 of the initial specimens (30%) contained protozoal cysts. Twenty-three patients (26%) harbored pathogens. There were 18 cases (20%) of amebiasis and 11 cases (12%) of giardiasis. Six men (7%) had concurrent amebiasis and giardiasis. The presence of infections correlated with a history of anilingus but not with place of birth, travel, or history of symptoms. The exceptionally high rate of prevalence of intestinal protozoal infection in this population suggests that enteric protozoal infections are important among sexually transmitted diseases.