Noradrenergic modulation of basolateral amygdala neuronal activity: opposing influences of alpha-2 and beta receptor activation.
Substantial data exists demonstrating the importance of the amygdala and the locus ceruleus (LC) in responding to stress, aversive memory formation, and the development of stress-related disorders; however, little is known about the effects of norepinephrine (NE) on amygdala neuronal activity in vivo. The basolateral nucleus of the amygdala (BLA) receives dense NE projections from the LC, NE increases in the BLA in response to stress, and the BLA can also modulate the LC via reciprocal projections. These experiments examined the effects of noradrenergic agents on spontaneous and evoked responses of BLA neurons. NE iontophoresis inhibited spontaneous firing and decreased the responsiveness of BLA neurons to electrical stimulation of entorhinal cortex and sensory association cortex (Te3). Confirmed BLA projection neurons exhibited exclusively inhibitory responses to NE. Systemic administration of propranolol, a beta-receptor antagonist, decreased the spontaneous firing rate and potentiated the NE-evoked inhibition of BLA neurons. In addition, iontophoresis of the alpha-2 agonist clonidine, footshock administration, and LC stimulation mimicked the effects of NE iontophoresis on spontaneous activity. Furthermore, the effects of LC stimulation were partially blocked by systemic administration of alpha 2 and beta receptor antagonists. This is the first study to demonstrate the actions of directly applied and stimulus-evoked NE in the BLA in vivo, and provides a mechanism by which beta receptors can mediate the important behavioral consequences of NE within the BLA. The interaction between these two structures is particularly relevant with regard to their known involvement in stress responses and stress-related disorders.


Nanotechnology and Microtechnology in Drug Delivery Systems.
A special issue of the journal Dose-Response entitled "Nanotechnology and Microtechnology in Drug Delivery Systems" is proposed. In pharmaceutical studies, new and existing drugs continue to be investigated for their poor specificity, solubility, therapeutic index, and immunogenicity. In order to solve these problems, drug delivery systems are essential for controlled drug release. It has been shown that the size and shape (nano- or micro-) of drug carriers can affect a drug's circulation time, distribution, and cellular uptake. Hence, it is not surprising that nanotechnology and microtechnology have been explored as powerful tools for drug delivery in past decades. The main topics will be related to the technologies including microtechnology for the sustained release of drug, nanotechnology for the targeting delivery of drugs, new polymer materials nanotechnology, nanotechnology in drugs combination application, and so on.


[Classification of hypoxia, hypo-, and hypercapnia].
The new classifications of hypoxical, hypo- and hypercapnical conditions are elaborated. They take into account the ecological factors in the development of various kinds of exogenic hypoxia, hypercapnia. For the first time the positive sides of physiological hypoxia and hypercapnia are brought in. In all classification til the last days hypoxia was considered as pathological process only. However hypoxia can be met in different physiologic conditions of organism: internal period of fetus development, hard physical work, increased sportsmen activity, hypoxia after hearty meal, hypoxia of aged organism. The same it is possible to say about the hypo- and hypercapnical conditions.


Effects of replacing the habitual consumption of sugar-sweetened beverages with milk in Chilean children.
During the nutrition transition in Chile, dietary changes were marked by increased consumption of high-energy, nutrient-poor products, including sugar-sweetened beverages (SSBs). Obesity is now the primary nutritional problem in posttransitional Chile. We conducted a randomized controlled trial to examine the effects on body composition of delivering milk beverages to the homes of overweight and obese children to displace SSBs. We randomly assigned 98 children aged 8-10 y who regularly consumed SSBs to intervention and control groups. During a 16-wk intervention, children were instructed to drink 3 servings/d (approximately 200 g per serving) of the milk delivered to their homes and to not consume SSBs. Body composition was measured by dual-energy X-ray absorptiometry. Data were analyzed by multiple regression analysis according to the intention-to-treat principle. For the intervention group, milk consumption increased by a mean (+/- SEM) of 452.5 +/- 37.7 g/d (P < 0.0001), and consumption of SSBs decreased by -711.0 +/- 33.7 g/d (P < 0.0001). For the control group, milk consumption did not change, and consumption of SSBs increased by 71.9 +/- 33.6 g/d (P = 0.04). Changes in percentage body fat, the primary endpoint, did not differ between groups. Nevertheless, the mean (+/- SE) accretion of lean body mass was greater (P = 0.04) in the intervention (0.92 +/- 0.10 kg) than in the control (0.62 +/- 0.11 kg) group. The increase in height was also greater (P = 0.01) in the intervention group (2.50 +/- 0.21 cm) than in the control group (1.77 +/- 0.20 cm) for boys but not for girls. Replacing habitual consumption of SSBs with milk may have beneficial effects on lean body mass and growth in children, despite no changes in percentage body fat. This trial was registered at clinicaltrials.gov as NCT00149695.


Synthesis of retinoic acid by rat ovarian cells that express cellular retinoic acid-binding protein-II.
The induction of pseudopregnancy by the injection of eCG in rats results in the appearance of cellular retinoic acid-binding protein type II (CRABP[II]) in the granulosa cells of the ovary and the lining epithelium of the uterus within 48 h. This expression pattern is also seen in the normal mature female rat, in which CRABP(II) is expressed in the uterine epithelium during estrus (but not diestrus) and in the granulosa and luteal cells of the ovary. We have previously demonstrated that the uterine epithelial cells from the pseudopregnant rat have gained the ability to synthesize retinoic acid from retinol, in correlation with the induced expression of CRABP(II). If this is true for other sites of CRABP(II) expression, then local production of retinoic acid is intimately connected with various stages of reproduction in the female. Here we report that granulosa cells from the ovary of the eCG-treated immature rat and luteal cells from the ovary of the eCG/hCG-treated immature rat (both of which express CRABP[II]) synthesized markedly higher amounts of retinoic acid when cultured, compared to granulosa cells cultured from the ovary of the prepubertal rat treated with control vehicle. Culturing the granulosa cells from either control or eCG-treated animals had no effect on the expression of CRABP(II) cells. These data are consistent with our hypothesis that CRABP(II) expression is associated with retinoic acid synthesis and strengthen the case that local generation of retinoic acid plays an important role in reproduction.


Microglia morphotyping in the adult mouse CNS using hierarchical clustering on principal components reveals regional heterogeneity but no sexual dimorphism.
Microglia are the resident macrophages of the central nervous system (CNS) and play a pivotal role in immune surveillance and CNS homeostasis. Morphological transitions in microglia are indicative for local changes in the CNS microenvironment and serve as a proxy for the detection of alterations in the CNS, both in health and disease. Current strategies to 'measure' microglia combine advanced morphometrics with clustering approaches to identify and categorize microglia morphologies. However, these studies are labor intensive and clustering approaches are often subject to relevant feature selection bias. Here, we provide a morphometrics pipeline with user-friendly computational tools for image segmentation, automated feature extraction and morphological categorization of microglia by means of hierarchical clustering on principal components (HCPC) without the need for feature inclusion criteria. With this pipeline we provide new and detailed insights in the distribution of microglia morphotypes across sixteen CNS regions along the rostro-caudal axis of the adult C57BL/6J mouse CNS. Although regional variations in microglia morphologies were evident, we found no evidence for male-female dimorphism at any CNS region investigated, indicating that - by and large - microglia in adult male and female mice are morphometrically indistinguishable. Taken together, our newly developed pipeline provides valuable tools for objective and unbiased identification and categorization of microglia morphotypes and can be applied to any CNS (disease) model.


[Effect of Cu++ ions on the activity of trypsin on natural substance].
In vitro experiments were carried out in order to investigate the influence of Cu++-ions on the tryptic hydrolysis of casein and soybean protein. The admixture of 10(-3) to 10(-2) Mol Cu++/l to the reaction preparations results in the activation of trypsin in both substrates. The further increase of the Cu++-concentration results in a decrease of the trypsin activity and, with casein as substrate, in trypsin inhibition. The effects are similar with the synthetic substrate N alpha-benzoyl-L-arginine-p-nitroamilide (L-BAPA), however, trypsin is already activated after the admixture of approximately 5 x 10(-6) Mol Cu++/l. Since the admixture of Cu++-ions in experiments with pepsin in similar concentrations as with trypsin also results in an activation, the question is being discussed whether the improved protein digestibility and the higher weight increase of pigs which received 250 ppm copper can be traced back to these effects.


Mouse macrophages carrying both subunits of the human interferon-gamma (IFN-gamma) receptor respond to human IFN-gamma but do not acquire full protection against viral cytopathic effect.
Studies of hamster-human and mouse-human somatic fibroblast hybrids and transfected mouse fibroblasts have demonstrated that signaling through the human interferon-gamma receptor (hu-IFN-gammaR) requires the formation of a complex consisting of ligand (IFN-gamma), a ligand binding receptor chain (IFN-gammaR1), and a signal transducing receptor chain (IFN-gammaR2). To date, the ability of this receptor complex to transduce the full repertoire of biological signals has been difficult to assess due to the limited number of activities that IFN-gamma can exert on fibroblasts. The current report assesses the ability of hu-IFN-gammaR chains to transduce signals in the absence of background human gene products by expressing hu-IFN-gammaR2 in a transformed macrophage cell line (F10/96) derived from a hu-IFN-gammaR1 transgenic mouse. Our results indicate that F10/96 clones expressing both human receptor proteins bind hu-IFN-gamma with an affinity comparable to that of human cells. Binding of either human or mouse IFN-gamma to its respective receptor elicits classic IFN-gamma responses such as up-regulation of major histocompatibility complex antigens, enhanced expression of IRF-1, and increased production of NO2- radicals, interleukin-6, tumor necrosis factor-alpha, and granulocyte macrophage-colony stimulating factor. However, hu-IFN-gamma could not fully protect the clones from cytopathic effects of encephalomyocarditis virus and vesicular stomatitis virus while mo-IFN-gamma could. These results demonstrate that while co-expression of hu-IFN-gammaR1 and hu-IFN-gammaR2 is necessary and sufficient for most IFN-gamma-induced responses, it is not sufficient to confer a generalized antiviral state. These findings further suggest that additional species-specific accessory factor(s) are necessary for full signaling potential through the IFN-gamma receptor complex. The nature and potential role of such factors in IFN-gammaR signaling is discussed.


Important psychosocial factors to target in nutrition interventions to improve diet in Inuvialuit communities in the Canadian Arctic.
With increasing chronic disease amongst Inuvialuit in the Canadian Arctic, research on dietary behaviours and their determinants in this population is needed to develop nutritional behaviour change intervention strategies. The present study aimed to assess the knowledge, self-efficacy and intentions towards healthy eating and healthy eating behaviours of Inuvialuit adults in the Northwest Territories (NWT), Canada. The Adult Impact Questionnaire was developed from behavioural theories and workshops held in the communities. It was conducted with adult Inuvialuit (≥19 years) from randomly selected households in three NWT communities to collect data on the psychosocial constructs of healthy food knowledge, self-efficacy and intentions, and the dietary behaviours of healthy and unhealthy food acquisition and preparation. Associations between demographic, socioeconomic, psychosocial constructs and behaviours were analysed using multivariate linear regression. The 228 participants [mean (SD) age 43.4 (13.6) years; response rates 65-85%] acquired non-nutrient-dense foods a mean (SD) of 2.7 (3.0) times more frequently than nutrient-dense, low sugar and low fat foods. Increased intention was associated with a greater frequency of acquiring healthy foods (β=0.17, P=0.012) and a lower frequency of acquiring unhealthy foods (β=-0.18, P=0.008). Overall, participants reported using food preparation methods that reduce fat content slightly more than methods that add fat [mean (SD) score 0.3 (1.9)]. Use of healthier food preparation methods was associated with higher levels of healthy food knowledge (β=0.26, P<0.001), self-efficacy (β=0.29, P<0.001) and intentions (β=0.22, P=0.001). Healthy food intention was the construct most significantly associated with all three healthier dietary behaviours. Interventions that target intentions to change food choice and preparation may be effective strategies to improve dietary intake in Inuvialuit populations.


Peripheral vascular dysfunction in migraine: a review.
Numerous studies have indicated an increased risk of vascular disease among migraineurs. Alterations in endothelial and arterial function, which predispose to atherosclerosis and cardiovascular diseases, have been suggested as an important link between migraine and vascular disease. However, the available evidence is inconsistent. We aimed to review and summarize the published evidence about the peripheral vascular dysfunction of migraineurs.We systematically searched in BIOSIS, the Cochrane database, Embase, Google scholar, ISI Web of Science, and Medline to identify articles, published up to April 2013, evaluating the endothelial and arterial function of migraineurs.Several lines of evidence for vascular dysfunction were reported in migraineurs. Findings regarding endothelial function are particularly controversial since studies variously indicated the presence of endothelial dysfunction in migraineurs, the absence of any difference in endothelial function between migraineurs and non-migraineurs, and even an enhanced endothelial function in migraineurs. Reports on arterial function are more consistent and suggest that functional properties of large arteries are altered in migraineurs.Peripheral vascular function, particularly arterial function, is a promising non-invasive indicator of the vascular health of subjects with migraine. However, further targeted research is needed to understand whether altered arterial function explains the increased risk of vascular disease among patients with migraine.


Phenotypic and state-dependent expression of the electrical and morphological properties of oxytocin and vasopressin neurones.
Oxytocin and vasopressin secreting neurones of the hypothalamic supraoptic nucleus share many membrane characteristics and a roughly similar morphology. However, these two neurone types differ in the relative expression of some intrinsic and synaptic currents, and in the extent of their respective dendritic arbors. Spike depolarizing afterpotentials are present in both types, but more frequently give rise to prolonged burst discharges in vasopressin neurones. Oxytocin, but not vasopressin neurones, are characterized by a depolarization-activated, sustained outward rectifier which turns on near spike threshold, and which can produce prolonged spike frequency adaptation. When this sustained current is deactivated by small hyperpolarizing pulses, a rebound depolarization sufficient to evoke short spike trains follows the offset of these pulses. Both oxytocin and vasopressin neurones exhibit a transient outward rectification underlain by an Ia-type current. This transient rectifier delays spiking to depolarizing stimuli from a relatively hyperpolarized baseline, and is more prominent in vasopressin neurones. As a result, oxytocin neurones may be more reactive to depolarizing inputs. Both cell types receive glutamatergic, excitatory synaptic inputs and both possess R,S- alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor subtypes. The AMPA receptor channel on both cell types is characterized by a relatively high calcium permeability and voltage-dependent rectification, characteristic of a diminished presence of the GluR2 AMPA subunit. However, AMPA-mediated synaptic transients are larger, and decay faster, in oxytocin compared with vasopressin neurones, suggesting a potential difference for synaptic integration. The characteristics of NMDA-mediated synaptic transients are similar in oxytocin and vasopressin neurones, but some data suggest NMDA receptors may be less involved in the glutamatergic activation of oxytocin neurones. In both cell types, synaptic release of glutamate often coactivates AMPA and NMDA receptors. The dendritic morphology of oxytocin and vasopressin neurones in female rats differs from one another and exhibits considerable plasticity as a function of endocrine state. In virgin rats, oxytocin neurones have more dendritic branches and a greater total dendritic length compared with lactation, when the arbor is much less extensive. A complementary change occurs in vasopressin dendrites, which are more extensive during lactation. This reorganization suggests that oxytocin neurones may be more electronically compact during lactation. In addition, such dramatic shifts in overall dendritic length imply that significant gains and losses in either the total number of synapses, or in synaptic density, are incurred by both cell types as a function of reproductive state.


Conversion formulas between automated-perimetry indexes as measured by two different types of instrument.
Comparison between the results of measurements made using different types of automated-perimetry equipment is difficult, because of the lack of standardisation. The purpose of the study was to compare the two main indexes, mean deviation or mean defect (MD) and pattern standard deviation (PSD), as measured by two widely used instruments (Interzeag Octopus 500EZ and Humphrey Field Analyser 740) in the same group of patients. Thirty eyes of 17 patients with different stages of primary open-angle glaucoma were tested, and for 25 eyes the indexes measured using program G1 of the Octopus perimetry instrument were compared with those from program C30-2 of the Humphrey Field Analyser. Using the one-tailed Student t test, a significant difference was found between the MD and the PSD values of the Humphrey and of the Octopus perimetry equipments. However, subsequent use of the conversion formulas to adjust the measurements then indicated a good correlation between the two instruments (MD: r = 0.91; PSD: r = 0.79). MD and PSD values measured by the Octopus and Humphrey perimetry instruments are based on measurements made under significantly different conditions, so the direct comparison of the indexes is not reliable. Nonetheless, empirically valid conversion formulas exist and can be used to compare the perimetric results for a patient tested with the two types of instrument.


Wild primate microbiomes prevent weight gain in germ-free mice.
The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets low in dietary fiber have been shown to cause loss of gut microbial diversity. However, the link between microbiome composition, loss of dietary fiber, and obesity has not been well defined. To study the interactions between gut microbiota, dietary fiber, and weight gain, we transplanted captive and wild douc gut microbiota into germ-free mice and then exposed them to either a high- or low-fiber diet. The group receiving captive douc microbiota gained significantly more weight, regardless of diet, while mice receiving a high-fiber diet and wild douc microbiota remained lean. In the presence of a low-fiber diet, the wild douc microbiota partially prevented weight gain. Using 16S rRNA gene amplicon sequencing we identified key bacterial taxa in each group, specifically a high relative abundance of Bacteroides and Akkermansia in captive douc FMT mice and a higher relative abundance of Lactobacillus and Clostridium in the wild douc FMT mice. In the context of our germ-free mouse experiment, wild douc microbiota could serve as a reservoir for microbes for cross-species transplants. Our results suggest that wild douc microbiota are tailored to diverse fiber diets and can prevent weight gain when exposed to a native diet.


Home health care services: management and effectiveness in changing times.
New York City has the largest Medicaid personal care program (a form of home health care which includes many of the activities of daily living) in the country with approximately 45,000 clients and an annual budget of $1.5 billion. During the late 1980s and into the 1990s, New York State was experiencing budget difficulties, and established savings targets for local governments providing personal care services. In response, New York City, through its Home Attendant Program, began using different means of assessing clients' service needs to produce these savings. This article examines Task Based Assessment (a new service assessment methodology), and determines the degree to which it was successful, organizational issues that were faced by New York City and the 60 nonprofit and profit making companies contracted to deliver the service, legal challenges that were raised by advocacy groups and another alternative to the delivery of personal care services, a capitated long term care program. Task Based Assessment did not achieve its goals and the authors suggest, based on the positive experience from the capitated long term care program in controlling personal care hours, that it is more effective to expand these capitated programs than to seek to achieve further cost savings through the Home Attendant Program.


Evidence that capillary perfusion heterogeneity is not controlled in striated muscle.
We tested the hypothesis that the heterogeneity of capillary blood flow distribution in striated muscle is inversely proportional to tissue blood flow by examining the patterns of red blood cell flow in the capillaries of hamster tibialis anterior muscles. Capillary red blood cell velocities and capillary red blood cell fluxes were measured as indexes of blood flow and red blood cell distribution in vasoconstricted and vasodilated vascular beds of resting and working striated muscle. Standard statistical parameters describing dispersion of data (standard deviation and coefficient of variation) in addition to measured and normalized histograms were compared across treatments. With vasodilation the standard deviations of both variables increased linearly with the means, and measured distributions became broader. The coefficients of variation and normalized distributions of both variables did not differ across treatments. These observations do not support the idea that the heterogeneity of capillary perfusion is controlled. Rather they suggest that fractional flow dispersion among capillaries is constant and independent of muscle blood flow and/or O2 demand.


Analysis of clinical features of 7 cases of primary pleomorphic adenoma of lower respiratory tract and review of literature.
To investigate the clinical characteristics of patients with primary pleomorphic adenoma of the lower respiratory tract. The clinical manifestations, laboratory results, pathological and imaging, treatment and prognosis of 7 patients with primary pleomorphic adenoma of the lower respiratory tract who were treated in Hunan Provincial People's Hospital from December 2015 to May 2020 were analyzed. Among the 7 patients, 5 patients had cough and expectoration as the main clinical manifestations, and the other 2 patients had no symptoms. Pleomorphic adenomas of the lower respiratory tract are mostly located in the trachea or bronchus, and the chest computed tomography findings are circular or ellipsoid masses, or flake high-density shadows and local thickening of the tracheobronchial wall. Tumor histological features and immunohistochemistry can diagnose pleomorphic adenoma and its origin. In this study, 2 asymptomatic patients refused further treatment, 1 survived for more than 3 years, and the other was lost to follow-up during follow-up. One patient with surgical resection was followed up for 5 years after surgery and had a good survival status. The other 4 patients with respiratory symptoms who could not undergo surgery were mainly treated with bronchoscopic interventional therapy on demand, and the survival time up to now was 2 to 5 years. Primary pleomorphic adenoma of the lower respiratory tract is rare in clinic. Its clinical symptoms are related to the location and size of the tumor. Both surgical resection and bronchoscopic intervention have a good clinical prognosis. The cause of death of patients with such diseases is mostly dyspnea caused by tumors in the airway. Early diagnosis, timely intervention and regular follow-up can make patients obtain better curative effect.


Breastfeeding at 6 months and effects on infections.
To examine the pattern of and the influence of some socio-demographic factors on infant milk feedings, and the protective role of breastfeeding against infections. Mothers who breastfed their infants (exclusively or partially) at 6 weeks postpartum, and who had singleton pregnancies and healthy infants at birth, were interviewed when their infants had reached 6 months of age. Of the 234 mothers studied, only 31 (13%) mothers were practising exclusive breastfeeding (EBF) and 133 (57%) mothers were using exclusive infant formula feeding (EIF). Solid and semi-solid foods were introduced between 4 to 6 months of life in 89% of the infants. On logistic regression analysis, mothers who were in paid employment [OR 0.25, 95% CI 0.15, 0.42] and not breast feeding at 6 weeks [OR 0.32, 95% CI 0.19, 0.54] had decreased odds of EBF. Antenatal plans to breastfeed, breast-feeding difficulties, ethnicity, level of parental education, parental ages, fathers' income, primigravida status and infants' gender were not significant co-variates. In comparison, EIF was more likely in mothers who worked, practised mixed feedings at 6 weeks and of Chinese descent. There were no significant differences in the rates of upper respiratory tract infections (URTI) or diarrhoeal illnesses between the infants who were or were not being breast-fed. Most mothers were unable to breastfeed their infants exclusively in the recommended first 4 to 6 months of life. Complementary changes outside the hospital and maternity services are essential in improving breastfeeding rates. Breastfeeding does not appear to confer significant protection to either URTI or gastrointestinal tract infections.


Observation of pH-Induced Protein Reorientation at the Water Surface.
Hydrophobins are surface-active proteins that form a hydrophobic, water-repelling film around aerial fungal structures. They have a compact, particle-like structure, in which hydrophilic and hydrophobic regions are spatially separated. This surface property renders them amphiphilic and is reminiscent of synthetic Janus particles. Here we report surface-specific chiral and nonchiral vibrational sum-frequency generation spectroscopy (VSFG) measurements of hydrophobins adsorbed to their natural place of action, the air-water interface. We observe that hydrophobin molecules undergo a reversible change in orientation (tilt) at the interface when the pH is varied. We explain this local orientation toggle from the modification of the interprotein interactions and the interaction of hydrophobin with the water solvent, following the pH-induced change of the charge state of particular amino acids.


Ornithine decarboxylase modification and polyamine-stimulated enzyme inactivation in HTC cells.
Ornithine decarboxylase isolated from HTC cells was separated into two distinct charged states by salt-gradient elution from DEAE-Sepharose columns. This charge difference between the enzyme forms was maintained in partially purified preparations, but enzyme form II was observed to change to form I in a time-dependent polyamine-stimulated fashion in crude cell homogenates. The enzyme modification that produces this charge diversity between the alternative enzyme states was further investigated for its role in enzyme activity induction, protein stability and rapid turnover. Inhibition of new protein synthesis by cycloheximide resulted in a much more rapid loss of form I enzyme than of form II, suggesting that during normal enzyme turnover the latter enzyme state may be derived from the former. Culture conditions that favour the stabilization of this usually labile enzyme generally induced an increased proportion of the enzyme in the form II charge state. In particular, inhibitors of synthesis of spermidine and spermine induced the stabilization of cellular ornithine decarboxylase and promoted a marked accumulation in form II. Conversely, polyamines added to the cells in culture induced a very rapid loss in both forms of the enzyme, an effect that could not be attributed merely to an inhibition of new enzyme synthesis. It appears that the polyamines, but not putrescine, may be an essential part of the rapid ornithine decarboxylase inactivation process and that they may function in part by stimulating the conversion of the more stable enzyme form II into the less stable enzyme state, form I.


Domain analysis of human transmembrane guanylyl cyclase receptors: implications for regulation.
In the human genome, sequence analysis indicates there are five functional transmembrane guanylyl cyclases, enzymes that synthesize the intracellular second messenger, cGMP. Two, GC-A and GC-B or NPR-A and NPR-B, are widely distributed receptors for atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide, more commonly known as ANP, BNP and CNP, respectively. One cyclase, GC-C or StaR, is predominantly found in the intestinal epithelium and is the receptor for guanylin and uroguanylin, as well as for the bacterial pathogen, heat-stable enterotoxin (Sta). The remaining two cyclases, GC-E and GC-F or RetGC-1 and RetGC-2, are expressed in the retina and regulate the dark cycle of phototransduction. Unlike the other family members, GC-E and GC-F have no known extracellular ligands. Instead, they are activated under low calcium conditions by guanylyl cyclase activating proteins called GCAPs. All five members consist of an extracellular ligand binding domain, single transmembrane spanning domain, and intracellular kinase homology, dimerization and guanylyl cyclase catalytic domains. In the first part of this review, the tissue expression, ligands and "knockout" phenotypes of each receptor are summarized and individual domains are compared. In the second part, regulation by ATP, calcium, protein kinase C and phosphorylation is discussed.


First aid provision in nightclubs and other entertainment venues.
This article discusses the role and responsibilities of the registered nurse in providing first aid in challenging environments, such as crowded nightclubs. Basic assistance for common emergencies, including substance misuse, wounds, choking and anaphylaxis, are discussed. This article emphasises the importance of risk assessment and reminds readers of the need to maintain personal safety.


Translocation of outer membrane vesicles from enterohemorrhagic Escherichia coli O157 across the intestinal epithelial barrier.
Outer membrane vesicles (OMVs) carrying virulence factors of enterohemorrhagic Escherichia coli (EHEC) are assumed to play a role in the pathogenesis of life-threatening hemolytic uremic syndrome (HUS). However, it is unknown if and how OMVs, which are produced in the intestinal lumen, cross the intestinal epithelial barrier (IEB) to reach the renal glomerular endothelium, the major target in HUS. We investigated the ability of EHEC O157 OMVs to translocate across the IEB using a model of polarized Caco-2 cells grown on Transwell inserts and characterized important aspects of this process. Using unlabeled or fluorescently labeled OMVs, tests of the intestinal barrier integrity, inhibitors of endocytosis, cell viability assay, and microscopic techniques, we demonstrated that EHEC O157 OMVs translocated across the IEB. OMV translocation involved both paracellular and transcellular pathways and was significantly increased under simulated inflammatory conditions. In addition, translocation was not dependent on OMV-associated virulence factors and did not affect viability of intestinal epithelial cells. Importantly, translocation of EHEC O157 OMVs was confirmed in human colonoids thereby supporting physiological relevance of OMVs in the pathogenesis of HUS.


Spatial analysis of air pollution and cancer incidence rates in Haifa Bay, Israel.
The Israel National Cancer Registry reported in 2001 that cancer incidence rates in the Haifa area are roughly 20% above the national average. Since Haifa has been the major industrial center in Israel since 1930, concern has been raised that the elevated cancer rates may be associated with historically high air pollution levels. This work tests whether persistent spatial patterns of metrics of chronic exposure to air pollutants are associated with the observed patterns of cancer incidence rates. Risk metrics of chronic exposure to PM(10), emitted both by industry and traffic, and to SO(2), a marker of industrial emissions, was developed. Ward-based maps of standardized incidence rates of three prevalent cancers: Non-Hodgkin's lymphoma, lung cancer and bladder cancer were also produced. Global clustering tests were employed to filter out those cancers that show sufficiently random spatial distribution to have a nil probability of being related to the spatial non-random risk maps. A Bayesian method was employed to assess possible associations between the morbidity and risk patterns, accounting for the ward-based socioeconomic status ranking. Lung cancer in males and bladder cancer in both genders showed non-random spatial patterns. No significant associations between the SO(2)-based risk maps and any of the cancers were found. Lung cancer in males was found to be associated with PM(10), with the relative risk associated with an increase of 1 microg/m(3) of PM(10) being 12%. Special consideration of wards with expected rates <1 improved the results by decreasing the variance of the spatially correlated residual log-relative risk.


Personal monitoring instrument for the selective measurement of multiple organic vapors.
Development and laboratory testing of a small instrument capable of recognizing and quantifying multiple organic vapors at low- and sub-ppm concentrations is described. The instrument is slightly larger than a standard personal sampling pump and employs an array of three polymer-coated surface-acoustic-wave microsensors for vapor detection. Vapors are first trapped on a miniature adsorbent preconcentrator housed within the instrument and then thermally desorbed for analysis by the microsensor array. Each measurement cycle requires 5.5 min. The collective responses from the array are stored and then analyzed using pattern recognition methods to yield the identities and concentrations of collected vapors and vapor mixture components. Following initial optimization of instrument operating parameters, calibrations were performed with 16 organic solvent vapors and selected mixtures to establish a response library for each of two identical instruments. Limits of detection < or = 0.1 x threshold limit value were obtained for most vapors. In a series of 90 subsequent exposure tests, vapors were recognized with an error of < 6% (individual vapor challenges) and < 16% (binary mixture challenges) and quantified with an average error of < 10%. Monte Carlo simulations were coupled with pattern recognition analyses to predict the performance for many possible vapor mixtures and sensor combinations. Predicted recognition errors ranged from < 1 to 24%. Performance is shown to depend significantly on the interfacial polymer layers deposited on the sensors in the array and the nature and complexity of the vapor mixtures being analyzed. Results establish the capability of this technology to provide selective multivapor monitoring of personal exposures in workplace environments.


Evolution and refinement of magnetically guided sentinel lymph node detection in breast cancer: meta-analysis.
Superparamagnetic iron oxide nanoparticles (SPIO) have been used as a tracer for sentinel lymph node (SLN) localization in breast cancer, demonstrating comparable performance to the combination of radioisotope (RI) and blue dye (BD). A systematic literature search and meta-analysis with subgroup and meta-regression analysis were undertaken to update the available evidence, assess technique evolution, and define knowledge gaps. Recommendations were made using the GRADE approach. In 20 comparative studies, the detection rate was 97.5 per cent for SPIO and 96.5 per cent for RI ± BD (risk ratio 1.006, 95 per cent c.i. 0.992 to 1.019; P = 0.376, high-certainty evidence). Neoadjuvant therapy, injection site, injection volume or nodal metastasis burden did not affect the detection rate, but injection over 24 h before surgery increased the detection rate on meta-regression. Concordance was 99.0 per cent and reverse concordance 97.1 per cent (rate difference 0.003, 95 per cent c.i. -0.009 to 0.015; P = 0.656, high-certainty evidence). Use of SPIO led to retrieval of slightly more SLNs (pooled mean 1.96 versus 1.89) with a higher nodal detection rate (94.1 versus 83.5 per cent; RR 1.098, 1.058 to 1.140; P < 0.001; low-certainty evidence). In meta-regression, injection over 24 h before surgery increased the SPIO nodal yield over that of RI ± BD. The skin-staining rate was 30.8 per cent (very low-certainty evidence), and possibly prevented with use of smaller doses and peritumoral injection. The performance of SPIO is comparable to that of RI ± BD. Preoperative injection increases the detection rate and nodal yield, without affecting concordance. Whether skin staining and MRI artefacts are reduced by lower dose and peritumoral injection needs to be investigated.


Learning classification in the olfactory system of insects.
We propose a theoretical framework for odor classification in the olfactory system of insects. The classification task is accomplished in two steps. The first is a transformation from the antennal lobe to the intrinsic Kenyon cells in the mushroom body. This transformation into a higher-dimensional space is an injective function and can be implemented without any type of learning at the synaptic connections. In the second step, the encoded odors in the intrinsic Kenyon cells are linearly classified in the mushroom body lobes. The neurons that perform this linear classification are equivalent to hyperplanes whose connections are tuned by local Hebbian learning and by competition due to mutual inhibition. We calculate the range of values of activity and size of the network required to achieve efficient classification within this scheme in insect olfaction. We are able to demonstrate that biologically plausible control mechanisms can accomplish efficient classification of odors.


Psychometric analysis of the Psychopathic Personality Inventory (PPI) with female inmates.
This study evaluated the reliability, internal structure, and validity of the Psychopathic Personality Inventory (PPI; Lilienfeld & Andrews, 1996) among female inmates (n = 153) housed at a multilevel prison facility. Findings from this research suggested both strengths and weaknesses associated with PPI psychopathy assessment. Reliability of the PPI was supported by internal consistency analyses of scale and subscale item sets, and test-retest reliability was supported by findings obtained with a subsample (n = 36) retested an average of 49 days after initial test administration. Validity of the PPI total score was also supported by moderate to very high correlations with other self-report measures of psychopathy. Relative weaknesses of the PPI were evident by the low or negative associations among many of the PPI subscales, moderate associations that PPI total scores demonstrated with response set indexes, and the similarity of PPI total scores among female inmates and undergraduates. Findings from this research are considered in relation to possible sex differences in the expression of psychopathy and challenges associated with the assessment of the psychopathy construct with self-report methods.


Differential effects of age and sex on the cerebellar hemispheres and the vermis: a prospective MR study.
The purpose of this study was to determine the effects of age and sex on the size of the cerebellar hemispheres, the cerebellar vermis, and the pons in healthy adults. We estimated the volumes of the cerebellar hemispheres (excluding the vermis and the peduncles), the cross-sectional area of the vermis, and the cross-sectional area of the ventral pons from MR images obtained in 146 healthy volunteers, 18 to 77 years old. We found a mild but significant age-related reduction in the volume of the cerebellar hemispheres and in the total area of the cerebellar vermis; however, the analysis of age trends in the vermian lobules revealed differential age-related declines. The areas of lobules VI and VII and of the posterior vermian lobules (VIII-X) declined significantly with age, whereas the anterior vermis (I-V) showed no significant age-related shrinkage. The volume of the cerebellar hemispheres (especially the right) and the area of the anterior vermis were greater in men, even after adjustment for height. Neither age nor sex affected the area of the ventral pons. Normal aging of the cerebellum is associated with selective regional shrinkage. The cerebellar hemispheres and the area of the anterior vermis may be larger in men than in women regardless of differences in body size.


DTI Connectometry Analysis Reveals White Matter Changes in Cognitively Impaired World Trade Center Responders at Midlife.
More than 8% of responders who participated in the search and rescue efforts at the World Trade Center (WTC) following 9/11 developed early-onset cognitive impairment (CI). Approximately 23% were also diagnosed with chronic post-traumatic stress disorder (PTSD). To shed light on the pathophysiology of these WTC-related conditions, we examined diffusion connectometry to identify altered white matter tracts in WTC responders with CI and/or PTSD compared to unaffected responders. 99 WTC responders (mean age 56 years) consisting of CI-/PTSD- (n = 27), CI+/PTSD- (n = 25), CI-/PTSD+ (n = 24), and CI+/PTSD+ (n = 23) were matched on age, sex, occupation, race, and education. Cognitive status was determined using the Montreal Cognitive Assessment and PTSD status was determined using the DSM-IV SCID. Diffusion tensor imaging was acquired on a 3T Siemens Biograph mMR scanner. Connectometry analysis was used to examine whole-brain tract-level differences in white matter integrity as reflected by fractional anisotropy (FA) values after adjusting for confounders. Analyses identified that FA was negatively correlated with CI and PTSD status in the fornix, cingulum, forceps minor of the corpus callosum and the right uncinate fasciculus. Furthermore, FA was negatively correlated with PTSD status, regardless of CI status in the superior thalamic radiation and the cerebellum. This is the first connectometry study to examine altered white matter tracts in a sample of WTC responders with CI and/or PTSD. Results from this study suggest that WTC responders with early-onset CI may be experiencing an early neurodegenerative process characterized by decreased FA in white matter tracts.


Improving the quantification of secondary organic aerosol using a microflow reactor coupled to HPLC-MS and NMR to manufacture ad hoc calibration standards.
Secondary organic aerosol (SOA) is a key uncertainty in quantifying the impact of humans on Earth's climate. SOA is a complex mixture of oxidized organic species, and a fundamental hurdle in determining its composition is the lack of authentic standards for comparison and quantification. Organic synthesis can be used to produce pure standards, but is limited to compounds for which there is a degree of confidence in the proposed structure and can be expensive and time-consuming. In this study, a flow reactor was developed to form SOA in sufficient quantities to be collected and pure compounds subsequently isolated from the mixture using semipreparative high performance liquid chromatography. The purity and yield of each isolated compound were obtained using proton nuclear magnetic resonance ((1)H NMR), whereas molecular formulas were confirmed by high resolution Fourier transform ion cyclotron mass spectrometry (FTICR-MS). The effectiveness of the methodology has been evaluated here by using α-pinene as the precursor because it is the monoterpene with the most well characterized SOA chemistry. Eleven individual α-pinene SOA compounds were produced from α-pinene oxidation experiments and used for quantitative analysis of SOA formed during chamber experiments carried out close to ambient conditions. These compounds represented 25% of the total SOA mass, a significant improvement in mass balance compared to previous studies. This relatively simple approach may be extended to produce other SOA components not available commercially to improve quantification of aerosol sources.


EIF3H Orchestrates Hippo Pathway-Mediated Oncogenesis via Catalytic Control of YAP Stability.
EIF3H is presumed to be a critical translational initiation factor. Here, our unbiased screening for tumor invasion factors has identified an unexpected role for EIF3H as a deubiquitylating enzyme that dictates breast tumor invasion and metastasis by modulating the Hippo-YAP pathway. EIF3H catalyzed YAP for deubiquitylation, resulting in its stabilization. Structure-based molecular modeling and simulations coupled with biochemical characterization unveiled a unique catalytic mechanism for EIF3H in dissociating polyubiquitin chains from YAP through a catalytic triad consisting of Asp90, Asp91, and Gln121. Trp119 and Tyr 140 on EIF3H directly interacted with the N-terminal region of YAP1, facilitating complex formation of EIF3H and YAP1 for YAP1 deubiquitylation. Stabilization of YAP via elevated EIF3H promoted tumor invasion and metastasis. Interference of EIF3H-mediated YAP deubiquitylation blocked YAP-induced tumor progression and metastasis in breast cancer models. These findings point to a critical role for YAP regulation by EIF3H in tumor invasion and metastasis. SIGNIFICANCE: This work demonstrates that EIF3H is a novel bona fide deubiquitinase that counteracts YAP ubiquitylation and proteolysis, and stabilization of YAP by EIF3H promotes tumor invasion and metastasis.


Extracerebral collections: recognition by NMR imaging.
After head injury, nuclear magnetic resonance (NMR) scanning is, like computed tomography (CT), an effective method of distinguishing between intracerebral and extracerebral lesions. The location and shape of extracerebral collections are excellently displayed using the multiplanar facility of NMR. There are good grounds for believing that the problem of the isodense subdural hematoma encountered in CT scanning can almost certainly be overcome by the use of NMR imaging.


Mechanisms of action underlying virtual reality exposure treatment in spider phobia: Pivotal role of within-session fear reduction.
Although virtual-reality exposure treatment (VRET) for anxiety disorders is an efficient treatment option for specific phobia, mechanisms of action for immediate and sustained treatment response need to be elucidated. Towards this aim, core therapy process variables were assessed as predictors for short- and long-term VR treatment outcomes. In a bi-centric study, n = 186 patients with spider phobia completed a baseline-assessment, a one-session VRET, a post-therapy assessment, and a 6-month-follow-up assessment (ClinicalTrials.gov, ID: NCT03208400). Short- and long-term outcomes regarding self-reported symptoms in the spider phobia questionnaire (SPQ) and final patient-spider distance in the behavioral avoidance test (BAT) were predicted via logistic regression models with the corresponding baseline score, age, initial fear activation, within-session fear reduction and fear expectancy violation as predictors. To predict long-term remission status at 6-month-follow-up, dimensional short-term changes in the SPQ and BAT were additionally included. Higher within-session fear reductions predicted better treatment outcomes (long-term SPQ; short- and long-term BAT). Lower initial fear activation tended to be associated with better long-term outcomes (SPQ), while fear expectancy violation was not associated with any outcome measure. Short-term change in the SPQ predicted remission status. Findings highlight that in VRET for spider phobia, the experience of fear reduction is central for short- and long-term treatment success and should be focused by therapists.


Oestrogen dependence of lactate dehydrogenase and peroxidase in cell subpopulations of 7,12-dimethylbenz[alpha]anthracene-induced mammary tumours in the rat.
Recent investigations of certain enzymes as markers for predicting the response of breast tumours to hormonal therapy have neglected the possible differential contribution of cell subpopulation(s) within a solid tumour to enzyme activity. In this investigation, lactate dehydrogenase (LDH) and peroxidase activities in density-defined cell subpopulations from autotransplanted 7,12-dimethylbenz[alpha]anthracene-induced mammary tumours were determined. The effects of ovariectomy and subsequent oestrogen administration on the activity of these enzymes were also examined. Five cell subpopulations (cell bands) were routinely obtained from each mammary tumour. The highest LDH activity was found in cell band 4. The highest level of peroxidase activity was found in cell band 5. These two cell bands with high levels of enzyme activity consisted mainly of poorly differentiated cells. After bilateral ovariectomy, a significant (P less than 0.001) decrease in the level of LDH activity in cell bands 3, 4 and 5 was observed. The enzyme activity was reduced to 20, 2.1 and 12% of the preovariectomy levels respectively. Significant (P less than 0.05) decreases between baseline and postovariectomy peroxidase values were evident in each cell band. In the presence of oestradiol-17 beta, significant increases in the LDH activity of band 4 (P less than 0.001) and the peroxidase activity of band 5 (P less than 0.05) were observed. Our data suggest that, given the existence of multiple cell types in hormone-responsive tumour tissue, the actual cell subpopulation(s) responsible for any enzyme response may be a more precise indicator of hormone dependence.


Malaria control reinvented: health sector reform and strategy development in Colombia.
The consequences of health sector reforms on control of malaria were analysed using Colombia as an example. One of the most complex health sector reform programmes in Latin America took place in the 1990s; it included transferring the vertical vector-borne disease control (VBDC) programme into health systems at state and district levels. A series of studies was undertaken in 1998-2000 at the national level (Ministry of Health Study), at the state level (Departamento Study) and at the health district level (District Study) using formal and informal interviews among control staff and document analysis as data collection tools. A government-financed national training programme for VBDC staff - which included direct observation of control operations - was also used to analyse health workers' performance in the postreform period (longitudinal study). The results showed that some shortcomings of the old vertical system, such as the negative aspects of trade union activity, have not been overcome while some positive aspects of the old system, such as capacity building, operational planning and supervision have been lost. This has contributed to a decrease in control activity which, in turn, has been associated with more malaria cases. Malaria control had to be reinvented at a much larger scale than anticipated by the reformers caused by a whole series of problems: complex financing of public health interventions in the new system, massive staff reductions, the difficulty of gaining access to district and state budgets, redefining entire organizations and - in addition to the reforms - introducing alternative strategies based on insecticide-treated materials and the growth of areas of general insecurity in many parts of Colombia itself. However, positive signs in the transformed system include: the strengthening of central control staff (albeit insufficient in numbers) when transferred from the Ministry of Health to the National Institute of Health, the opportunities offered by the Basic Health Plan (PAB) for new planning initiatives and intersectoral co-operation and the integration of malaria diagnosis and treatment into the general health services (associated with a decrease of malaria mortality). The potentials of the new system have not yet been fully exploited: capacity building, communication and management skills need to be improved and it require guidance from the national level.


Protein kinase C activator PMA reduces the Ca(2+) response to antigen stimulation of adherent RBL-2H3 mucosal mast cells by inhibiting depletion of intracellular Ca(2+) stores.
Activation of protein kinase C has been shown to reduce the Ca(2+) responses of a variety of cell types. In most cases, the reduction is due to inhibition of Ca(2+) influx, but acceleration of Ca(2+) efflux and inhibition of Ca(2+) store depletion by protein kinase C activation have also been described. For adherent RBL-2H3 mucosal mast cells, results from whole-cell patch clamp experiments suggest that protein kinase C activation reduces Ca(2+) influx, while experiments with intact, fura-2-loaded cells suggest that Ca(2+) influx is not affected. Here we present single-cell data from Ca(2+) imaging experiments with adherent RBL-2H3 cells, showing that antigen-stimulated Ca(2+) responses of phorbol 12-myristate 13-acetate (PMA)-treated cells are more transient than those of control cells. PMA also reduced the response to antigen in the absence of extracellular Ca(2+), indicating that depletion of intracellular Ca(2+) stores is inhibited. If PMA was added after stores had been depleted by thapsigargin, a small decrease in [Ca(2+)](i) was observed, consistent with a slight inhibition of Ca(2+) influx. However, the major effect of PMA on the antigen-stimulated Ca(2+) response is to inhibit depletion of intracellular Ca(2+) stores. We also show that inhibition of protein kinase C did not enhance the Ca(2+) response to antigen, suggesting that inhibition of the Ca(2+) response by activation of protein kinase C does not contribute to the physiological response to antigen.


Fixed Low-Dose Triple Combination Antihypertensive Medication vs Usual Care for Blood Pressure Control in Patients With Mild to Moderate Hypertension in Sri Lanka: A Randomized Clinical Trial.
Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies. To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care. Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. A once-daily fixed-dose triple combination pill (20 mg of telmisartan, 2.5 mg of amlodipine, and 12.5 mg of chlorthalidone) therapy (n = 349) or usual care (n = 351). The primary outcome was the proportion achieving target systolic/diastolic BP (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6 months. Secondary outcomes included mean systolic/diastolic BP difference during follow-up and withdrawal of BP medications due to an adverse event. Among 700 randomized patients (mean age, 56 years; 58% women; 29% had diabetes; mean baseline systolic/diastolic BP, 154/90 mm Hg), 675 (96%) completed the trial. The triple combination pill increased the proportion achieving target BP vs usual care at 6 months (70% vs 55%, respectively; risk difference, 12.7% [95% CI, 3.2% to 22.0%]; P < .001). Mean systolic/diastolic BP at 6 months was 125/76 mm Hg for the triple combination pill vs 134/81 mm Hg for usual care (adjusted difference in postrandomization BP over the entire follow-up: systolic BP, -9.8 [95% CI, -7.9 to -11.6] mm Hg; diastolic BP, -5.0 [95% CI, -3.9 to -6.1] mm Hg; P < .001 for both comparisons). Overall, 419 adverse events were reported in 255 patients (38.1% for triple combination pill vs 34.8% for usual care) with the most common being musculoskeletal pain (6.0% and 8.0%, respectively) and dizziness, presyncope, or syncope (5.2% and 2.8%). There were no significant between-group differences in the proportion of patient withdrawal from BP-lowering therapy due to adverse events (6.6% for triple combination pill vs 6.8% for usual care). Among patients with mild to moderate hypertension, treatment with a pill containing low doses of 3 antihypertensive drugs led to an increased proportion of patients achieving their target BP goal vs usual care. Use of such medication as initial therapy or to replace monotherapy may be an effective way to improve BP control. anzctr.org.au Identifier: ACTRN12612001120864; slctr.lk Identifier: SLCTR/2015/020.


Evaluation of Biochemical Assays and Optimization of LC-MS/MS Analysis for the Detection of Synthetic Urine.
Ensuring specimen validity is an essential aspect of toxicological laboratories. In recent years, substituting authentic urine specimens for synthetic urine has become increasingly popular. Such synthetic urine products consist of components expected in normal urine and show physiological values for specific gravity and pH. Thus, standard specimen validity testing may fail in revealing adulteration by synthetic urine. The present study investigated three methods to distinguish authentic and synthetic urine specimens: enzymatic detection of uric acid, the commercially available Axiom Test True Synthetic Urine, and LC-MS/MS analysis of 10 endogenous biomolecules. Additionally, novel direct markers of synthetic urine were investigated. Two specimen sets were analyzed by each method. Specimen set A consisted of 8 synthetic urine products purchased from the Austrian/German market and 43 urine specimens from volunteers of known authenticity, which underwent double-blind analysis. Specimen set B consisted of 137 real urine specimens submitted for drug testing, which were selected due to initial suspicious test results in adulteration testing and reanalyzed by all three methods. Uric acid and LC-MS/MS-based endogenous biomolecule testing showed 100% sensitivity and specificity for set A. The commercial test had 87.5% sensitivity and 97.7% specificity for set A. For set B, uric acid and LC-MS/MS analysis showed almost similar results, even if uric acid was missing one presumptive authentic urine specimen according to LC-MS/MS findings. Nearly half of the synthetic urine assignments for the commercial test were presumptive false positives. New synthetic urine markers were observed for synthetic urine products from the Austrian/German market. One specimen in set B had both endogenous biomolecule pattern and synthetic urine markers suggesting urine dilution with synthetic urine. In conclusion, several analytes or methods should be used rather than one, and the most reliable results are achieved if both indirect and direct markers of urine substitution are analyzed.


Defect-induced magnetic structure in (Ga(1)-(x)Mn(x))As.
We show that magnetic structures involving partial disorder of local magnetic moments on the Mn atoms in (Ga(1)-(x)Mn(x))As lower the total energy, compared to the case of perfect ferromagnetic ordering, when As defects on the Ga sublattice are present. Such magnetic structures are found to be stable for a range of concentrations of As antisites, and this result accounts for the observed magnetic moments and critical temperatures in (Ga(1)-(x)Mn(x))As. We propose an explanation for the stabilization of the partially disordered magnetic structures and conclude that the magnetization and critical temperatures should increase substantially by reducing the number of As antisite defects.


Pregnancy after solid organ transplantation.
For women with end-stage organ failure, transplantation is an established therapeutic option. Pregnancy after solid organ transplantation is no longer uncommon, especially with the recent advances in transplantation surgery and the availability of newer immunosuppressants. This article will review preconceptional counseling, common pregnancy complications, prenatal and intrapartum considerations, outcome by organ, immunosuppressant therapies, and neonatal outcomes based on data available from case series and voluntary registries. Some recommendations are provided to assist in the management of pregnancies after solid organ transplantation.


What does physical rotation reveal about mental rotation?
In a classic psychological science experiment, Shepard and Metzler (1971) discovered that the time participants took to judge whether two rotated abstract block figures were identical increased monotonically with the figures' relative angular disparity. They posited that participants rotate mental images to achieve a match and that mental rotation recruits motor processes. This interpretation has become central in the literature, but until now, surprisingly few researchers have compared mental and physical rotation. We had participants rotate virtual Shepard and Metzler figures mentally and physically; response time, accuracy, and real-time rotation data were collected. Results suggest that mental and physical rotation processes overlap and also reveal novel conclusions about physical rotation that have implications for mental rotation. Notably, participants did not rotate figures to achieve a match, but rather until they reached an off-axis canonical difference, and rotational strategies markedly differed for judgments of whether the figures were the same or different.


[Changes in the indices of lipid metabolism in patients with ischemic heart disease occupied in natural gas fields].
The influence of adaptation to periodic pressure-chamber hypoxia produced on the condition of the lipid spectrum of blood serum before and after adaptation as well as in 3, 6 and 10 months after hypoxic training was studied in 46 patients with ischemic heart disease working at a enterprise specializing in winning and processing the hydrogen-sulfide-containing gas-condensate. The adaptation therapy was found to result in a reliable reduction of the total cholesterol level, of the level of cholesterol of lipoproteins of the low and extra low densities and of triglycerides; it also contributed to the increase of cholesterol of lipoproteins of the high density in blood serum, which, in the end, ensures a reduced atherogenic coefficient. The positive-for-organism changes in the lipid spectrum of blood serum hold on in patients with coronary heart disease for as long as 6 months after the adaptation therapy. The nature and degree of blood lipids' changes depend on an initial level of the atherogenic index; they were maximally pronounced in persons with the index exceeding 3, and virtually absent in IHD patients with the atherogenicity coefficient being below the mentioned figure.


Field-based stable isotope probing reveals the identities of benzoic acid-metabolizing microorganisms and their in situ growth in agricultural soil.
We used a combination of stable isotope probing (SIP), gas chromatography-mass spectrometry-based respiration, isolation/cultivation, and quantitative PCR procedures to discover the identity and in situ growth of soil microorganisms that metabolize benzoic acid. We added [(13)C]benzoic acid or [(12)C]benzoic acid (100 microg) once, four times, or five times at 2-day intervals to agricultural field plots. After monitoring (13)CO(2) evolution from the benzoic acid-dosed soil, field soils were harvested and used for nucleic acid extraction and for cultivation of benzoate-degrading bacteria. Exposure of soil to benzoate increased the number of culturable benzoate degraders compared to unamended soil, and exposure to benzoate shifted the dominant culturable benzoate degraders from Pseudomonas species to Burkholderia species. Isopycnic separation of heavy [(13)C]DNA from the unlabeled fraction allowed terminal restriction fragment length polymorphism (T-RFLP) analyses to confirm that distinct 16S rRNA genes were localized in the heavy fraction. Phylogenetic analysis of sequenced 16S rRNA genes revealed a predominance (15 of 58 clones) of Burkholderia species in the heavy fraction. Burkholderia sp. strain EBA09 shared 99.5% 16S rRNA sequence similarity with a group of clones representing the dominant RFLP pattern, and the T-RFLP fragment for strain EBA09 and a clone from that cluster matched the fragment enriched in the [(13)C]DNA fraction. Growth of the population represented by EBA09 during the field-dosing experiment was demonstrated by using most-probable-number-PCR and primers targeting EBA09 and the closely related species Burkholderia hospita. Thus, the target population identified by SIP not only actively metabolized benzoic acid but reproduced in the field upon the addition of the substrate.


The HpSGNi system: A compact approach for genetic suppression without sequence limitation in Escherichia coli.
Targeted gene regulation is indispensable for exploring gene functions in microbes and the development of microbial cell factories. While most loci can be regulated by CRISPRi, it cannot be used for targets lacking protospacer adjacent motifs (PAM) or protospacer flanking sequences (PFS). Here, we characterized a genetic suppression approach named the hpDNA-assisted structure-guided nuclease mediating interference system (HpSGNi). It was composed of a flap endonuclease 1 (FEN1) and mis-hairpin DNA probes (mis-hpDNA) to suppress the expression of target genes simply and efficiently in microbe without sequence restrictions. By inhibiting the initiation and elongation of the transcription, HpSGNi successfully silenced the transcription of exogenous fluorescent protein genes, ampicillin resistance gene and endogenous folP/sulA genes in Escherichia coli BL21(DE3) and K-12 MG1655. Meanwhile, aiming at optimizing the mis-hpDNA, we displayed the characteristics by detecting the tolerance to the single base mismatch and length of the guide sequence. This DNA-guided recognition platform provides a simple approach for selectively inhibiting gene expression.


A comparison of two diagnostic methods. Clinical ICD diagnoses vs DSM-III and Research Diagnostic Criteria using the Diagnostic Interview Schedule (version 2).
In the context of a seven-year follow-up study, 171 former psychiatric inpatients and 158 subjects from the general population were interviewed twice, first with the German version of the Diagnostic Interview Schedule (DIS) (version 2), and second with a clinical interview using the Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie (AMDP) checklist to assign a clinical International Classification of Diseases (eighth revision) (ICD-8) diagnosis, independent of the DIS. With the clinicians' ICD-8 diagnosis as a measure of the quality of the DIS, the results indicate a sufficiently high overall specificity and sensitivity of the DIS as a case-finding instrument in a general population survey, and a surprisingly high concordance of most DIS diagnostic classes with comparable ICD diagnoses. Only for panic disorders (possibly due to different symptom and time criteria) and schizophrenia (possibly due to the strict probe system, the dependence on self-reports, and time criteria) was low sensitivity found. Because there is no DIS diagnostic category comparable with ICD-8 unipolar affective psychosis, a meaningful comparison of this ICD category with Research Diagnostic Criteria and DSM-III was not possible.


Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-II (TRACE II): rationale and design.
Tenecteplase (TNK) is a promising agent for treatment of acute ischaemic stroke (AIS). We hypothesised that recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) is non-inferior to rt-PA in achieving excellent functional outcome at 90 days, when administered within 4.5 hours of ischaemic stroke onset. Tenecteplase Reperfusion therapy in Acute ischemic Cerebrovascular Events (TRACE) is a phase III, multicentre, prospective, randomised, open-label, blinded-end point non-inferiority study. Patients eligible for intravenous thrombolysis therapy are randomised to rhTNK-tPA 0.25 mg/kg (single bolus) to a maximum of 25 mg or rt-PA 0.9 mg/kg (10% bolus+90% infusion/1 hour) to a maximum of 90 mg. Medications considered necessary for the patient's health may be given at the discretion of the investigator during 90-day follow-up. The primary study outcome is excellent functional outcome defined as modified Rankin Scale (mRS) 0-1 at 90 days. Secondary efficacy outcomes include favourable functional outcome defined as mRS ≤2 at 90 days, ordinal distribution of mRS and major neurological improvement on the National Institutes of Health Stroke Scale. Safety outcomes are symptomatic intracranial haemorrhage within 36 hours and death from any cause. There is no completed registration study of TNK in AIS worldwide. TRACE II strives to provide evidence for a new drug application for rhTNK-tPA in AIS within 4.5 hours through a well-designed and rigorously executed randomised trial in China. NCT04797013.


"Subclinical" pacemaker syndrome: a randomised study of symptom free patients with ventricular demand (VVI) pacemakers upgraded to dual chamber devices.
To determine whether symptom free patients with single chamber pacemakers benefit from dual chamber pacing. A randomised double blind crossover comparison of ventricular demand (VVI), dual chamber demand (DDI), and dual chamber universal (DDD) modes after upgrading from a VVI device. Cardiology outpatient department. Sixteen patients aged 41-84 years who were symptom free during VVI mode pacing for three or more years. Pacemaker upgrade during routine generator change. Change in subjective (general health perception, symptoms) and objective (clinical assessment, treadmill exercise, and radiological and echocardiographic indices) results between pacing modes before and after upgrading. 75% preferred DDD, 68% found VVI least acceptable with 12% expressing no preference. Perceived general well-being and exercise capacity (p less than 0.01) and treadmill times (p less than 0.05) were improved in DDD mode but VVI and DDI modes were similar. Clinical, echocardiographic, radiological, and electrophysiological indices confirmed the absence of overt pacemaker syndrome, although mitral and tricuspid regurgitation was greatest in VVI mode (p less than 0.01). Most patients who were satisfied with long term pacing in VVI mode benefited from upgrading to DDD mode pacing suggesting the existence of "subclinical" pacemaker syndrome in up to 75% of such patients. The DDI mode offered little subjective or objective benefit over VVI mode in this population and should be reserved for patients with paroxysmal atrial arrhythmias. VVI mode pacing should be used only for patients with very intermittent symptomatic bradycardia or atrial fibrillation with a good chronotropic response during exercise.


Viruses in Horses with Neurologic and Respiratory Diseases.
Metagenomics was used to identify viral sequences in the plasma and CSF (cerobrospinal fluid) of 13 horses with unexplained neurological signs and in the plasma and respiratory swabs of 14 horses with unexplained respiratory signs. Equine hepacivirus and two copiparvoviruses (horse parvovirus-CSF and a novel parvovirus) were detected in plasma from neurological cases. Plasma from horses with respiratory signs contained the same two copiparvoviruses plus equine pegivirus D and respiratory swabs contained equine herpes virus 2 and 5. Based on genetic distances the novel copiparvovirus qualified as a member of a new parvovirus species we named Eqcopivirus. These samples plus another 41 plasma samples from healthy horses were tested by real-time PCRs for multiple equine parvoviruses and hepacivirus. Over half the samples tested were positive for one to three viruses with eqcopivirus DNA detected in 20.5%, equine hepacivirus RNA and equine parvovirus-H DNA in 16% each, and horse parvovirus-CSF DNA in 12% of horses. Comparing viral prevalence in plasma none of the now three genetically characterized equine parvoviruses (all in the copiparvovirus genus) was significantly associated with neurological and respiratory signs in this limited sampling.


Porous titanium obtained by a new powder metallurgy technique: Preliminary results of human osteoblast adhesion on surface polished substrates.
This study concerns a novel powder metallurgy method for producing porous titanium (pTi) exhibiting high mechanical properties. The preparation procedure consisted of the following stages: first, the preparation of Ti and titanium hydride (TiH2) powder mixtures and their consolidation with a cold isostatic press, followed by a sintering of the green bodies performed with hot isostatic press (HIP) equipment. Thermal decomposition in controlled environment of the TiH2 phase results in the foam structure. The resulting porosity percolates with a volume fraction of approximately 20%. The final material exhibits interesting mechanical properties, comparable to those of full density titanium (between grade 2 and grade 3), with the advantage of a minor density. The samples produced were tested to verify their biological response by studying the effectiveness of osteoblast adhesion and growth. In this preliminary study, osteoblastic cell morphology was investigated and compared to that observed on fully dense commercially pure titanium (Ti-cp) (ASTM, grade 3). The preliminary results were promising regarding cellular adhesion and spreading. (Journal of Applied Biomaterials & Biomechanics 2003; 1: 172-7).


Heart failure and depression: an association with clinical importance.
Major depression is found in one fifth of heart failure patients, and clinically significant depressive symptoms in almost half. The association of depression and heart failure appears to be related both to the psychological aspects of severe heart disease, and to pathophysiological and psychosocial mechanisms. The presence of depression is associated with a worsening of the prognosis, and increased risk of death, rehospitalization, and functional decline. Detection and treatment of depression should be part of a comprehensive approach to heart failure patients by cardiologists and family doctors. Good quality cardiac care should include psychosocial assessment, strengthening of the doctor-patient relationship and of family and social bonds, and, when appropriate, antidepressants and psychotherapy. Selective serotonin reuptake inhibitors are effective and safe antidepressants in cardiac patients. They should be prescribed in therapeutic doses until sustained remission is obtained. Collaboration between psychiatrists and other specialists at primary and secondary care levels is recommended and contributes to better quality care.


Anthropological cybernetic model of demography of the island of Hvar.
Intentions of the present investigation were to apply a cybernetic model in description of demography on the island of Hvar for a time period from year 1800 till now. The basic idea of the model applied in this anthropological study (LOPI) is that the rate of reproduction is given by the non-linear controller: Y2/Te(1-(Y3/G)). Constant G represents an environmental carrying capacity of a community with respect to the cohort of older people (no longer a part of the pool of reproductive inhabitants; Y3) sharing limited survival resources. The proportional constant 1/Te connected with the pool of reproductive inhabitants (Y2) correspond to the reproduction maximum. The consistency of the model is evaluated through comparison between model data and census. The LOPI model describes incredibly well the demography of the island of Hvar from the year 1800 till 1940. After year 1950 there were more inhabitants on the island then the model would predict. This fact is connected with changes in the migration or also in the increased carrying capacity (G). On the basis LOPI model, population dynamic oscillates in its development. The example of the island of Hvar has proved that population reaches a maximal number of inhabitants every 200 years. The oscillation of population dynamics is influenced by the migration processes. The mere fact that oscillating population size is connected to population genetics and probably also to sociocultural factors suggests that a cybernetics demographic model can be a guide in the holistic anthropological approach.


Cross Validation of Two Partitioning-Based Sampling Approaches in Mesocosms Containing PCB Contaminated Field Sediment, Biota, and Activated Carbon Amendment.
The Gold Standard for determining freely dissolved concentrations (Cfree) of hydrophobic organic compounds in sediment interstitial water would be in situ deployment combined with equilibrium sampling, which is generally difficult to achieve. In the present study, ex situ equilibrium sampling with multiple thicknesses of silicone and in situ pre-equilibrium sampling with low density polyethylene (LDPE) loaded with performance reference compounds were applied independently to measure polychlorinated biphenyls (PCBs) in mesocosms with (1) New Bedford Harbor sediment (MA, U.S.A.), (2) sediment and biota, and (3) activated carbon amended sediment and biota. The aim was to cross validate the two different sampling approaches. Around 100 PCB congeners were quantified in the two sampling polymers, and the results confirmed the good precision of both methods and were in overall good agreement with recently published LDPE to silicone partition ratios. Further, the methods yielded Cfree in good agreement for all three experiments. The average ratio between Cfree determined by the two methods was factor 1.4 ± 0.3 (range: 0.6-2.0), and the results thus cross-validated the two sampling approaches. For future investigations, specific aims and requirements in terms of application, data treatment, and data quality requirements should dictate the selection of the most appropriate partitioning-based sampling approach.


Does single use of an autologous transfusion system in TKA reduce the need for allogenic blood?: a prospective randomized trial.
Mechanical autotransfusion systems for washed shed blood (WSB) were introduced to reduce the need for postoperative allogenic blood transfusions (ABTs). Although some authors have postulated decreased requirements for ABT by using autologous retransfusion devices, other trials, mostly evaluating retransfusion devices for unwashed shed blood (USB), verified a small or no benefit in reducing the need for postoperative ABT. Because of these contradictory findings it is still unclear whether autologous retransfusion systems for WSB can reduce transfusion requirements. We therefore asked whether one such autologous transfusion system for WSB can reduce the requirements for postoperative ABT. In a prospective, randomized, controlled study, we enrolled 151 patients undergoing TKA. In Group A (n=76 patients), the autotransfusion system was used for a total of 6 hours (intraoperatively and postoperatively) and the WSB was retransfused after processing. In Control Group B (n=75 patients), a regular drain without suction was used. We used signs of anemia and/or a hemoglobin value less than 8 g/dL as indications for transfusion. If necessary, we administered one or two units of allogenic blood. Twenty-three patients (33%) in Group A, who received an average of 283 mL (range, 160-406 mL) of salvaged blood, needed a mean of 2.1 units of allogenic blood, compared with 23 patients (33%) in Control Group B who needed a mean of 2.1 units of allogenic blood. We found the use of an autotransfusion system did not reduce the rate of postoperative ABTs. Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


Tuning resistive switching characteristics of tantalum oxide memristors through Si doping.
An oxide memristor device changes its internal state according to the history of the applied voltage and current. The principle of resistive switching (RS) is based on ion transport (e.g., oxygen vacancy redistribution). To date, devices with bi-, triple-, or even quadruple-layered structures have been studied to achieve the desired switching behavior through device structure optimization. In contrast, the device performance can also be tuned through fundamental atomic-level design of the switching materials, which can directly affect the dynamic transport of ions and lead to optimized switching characteristics. Here, we show that doping tantalum oxide memristors with silicon atoms can facilitate oxygen vacancy formation and transport in the switching layer with adjustable ion hopping distance and drift velocity. The devices show larger dynamic ranges with easier access to the intermediate states while maintaining the extremely high cycling endurance (>10(10) set and reset) and are well-suited for neuromorphic computing applications. As an example, we demonstrate different flavors of spike-timing-dependent plasticity in this memristor system. We further provide a characterization methodology to quantitatively estimate the effective hopping distance of the oxygen vacancies. The experimental results are confirmed through detailed ab initio calculations which reveal the roles of dopants and provide design methodology for further optimization of the RS behavior.


Reverse micellar extraction of lectin from black turtle bean (Phaseolus vulgaris): optimisation of extraction conditions by response surface methodology.
Lectin from black turtle bean (Phaseolus vulgaris) was extracted and purified by reverse micellar extraction (RME) method. Response surface methodology (RSM) was used to optimise the processing parameters for both forward and backward extraction. Hemagglutinating activity analysis, SDS-PAGE, RP-HPLC and FTIR techniques were used to characterise the lectin. The optimum extraction conditions were determined as 77.59 mM NaCl, pH 5.65, AOT 127.44 mM sodium bis (2-ethylhexyl) sulfosuccinate (AOT) for the forward extraction; and 592.97 mM KCl, pH 8.01 for the backward extraction. The yield was 63.21 ± 2.35 mg protein/g bean meal with a purification factor of 8.81 ± 0.17. The efficiency of RME was confirmed by SDS-PAGE and RP-HPLC, respectively. FTIR analysis indicated there were no significant changes in the secondary protein structure. Comparison with conventional chromatographic method confirmed that the RME method could be used for the purification of lectin from the crude extract.


Small-intestinal endoscopy.
A small imaging capsule without cables, wires, or external connections has been developed for exploration of the small bowel. This swallowable device is propelled by peristalsis through the intestinal tract, and transmits data to a nearby receiver that captures video images on a regular basis. This technology will soon be available throughout the world, and it promises to revolutionize deep endoscopy of the small bowel. Sonde enteroscopy will be laid to rest forever. There continues to be considerable interest in the use of push enteroscopy in the investigation of obscure gastrointestinal bleeding. Physicians are beginning to rely more on intraoperative enteroscopy, because of its high degree of accuracy and its ability to provide visualization of the entire small bowel in selected patients in whom the bleeding source cannot be diagnosed, but who require blood transfusions.


Dormancy in Embryos: Insight from Hydrated Encysted Embryos of an Aquatic Invertebrate.
Numerous aquatic invertebrates remain dormant for decades in a hydrated state as encysted embryos. In search for functional pathways associated with this form of dormancy, we used label-free quantitative proteomics to compare the proteomes of hydrated encysted dormant embryos (resting eggs; RE) with nondormant embryos (amictic eggs; AM) of the rotifer Brachionus plicatilisA total of 2631 proteins were identified in rotifer eggs. About 62% proteins showed higher abundance in AM relative to RE (Fold Change>3; p = 0.05). Proteins belonging to numerous putative functional pathways showed dramatic changes during dormancy. Most striking were changes in the mitochondria indicating an impeded metabolism. A comparison between the abundance of proteins and their corresponding transcript levels, revealed higher concordance for RE than for AM. Surprisingly, numerous highly abundant dormancy related proteins show corresponding high mRNA levels in metabolically inactive RE. As these mRNAs and proteins degrade at the time of exit from dormancy they may serve as a source of nucleotides and amino acids during the exit from dormancy. Because proteome analyses point to a similarity in functional pathways of hydrated RE and desiccated life forms, REs were dried. Similar hatching and reproductive rates were found for wet and dried REs, suggesting analogous pathways for long-term survival in wet or dry forms. Analysis by KEGG pathways revealed a few general strategies for dormancy, proposing an explanation for the low transcriptional similarity among dormancies across species, despite the resemblance in physiological phenotypes.


Cervical Spine Spondylitis with an Epidural Abscess in a Patient with Brucellosis: A Case Report.
Human brucellosis, the most prevalent zoonotic disease worldwide, is a systemic infection which can involve several organs. Among musculoskeletal complaints, spondylitis is the most frequent complication of brucellosis and primarily affects the lumbar and thoracic vertebrae. The involvement of the cervical spine is infrequent. This case report concerns an unusual case of cervical spine spondylitis with an epidural abscess due to Brucella in a 43-year-old man. The diagnosis was based on the patient being domiciled in an endemic region, his symptoms and his occupation. Clinical outcomes improved following antimicrobial therapy of rifampin, doxycycline, and gentamycin, and were confirmed radiologically. Early diagnosis and treatment are crucial for these patients. The timely commencement of medical treatment can help prevent surgery.


Assessment of computational methods for predicting the effects of missense mutations in human cancers.
Recent advances in sequencing technologies have greatly increased the identification of mutations in cancer genomes. However, it remains a significant challenge to identify cancer-driving mutations, since most observed missense changes are neutral passenger mutations. Various computational methods have been developed to predict the effects of amino acid substitutions on protein function and classify mutations as deleterious or benign. These include approaches that rely on evolutionary conservation, structural constraints, or physicochemical attributes of amino acid substitutions. Here we review existing methods and further examine eight tools: SIFT, PolyPhen2, Condel, CHASM, mCluster, logRE, SNAP, and MutationAssessor, with respect to their coverage, accuracy, availability and dependence on other tools. Single nucleotide polymorphisms with high minor allele frequencies were used as a negative (neutral) set for testing, and recurrent mutations from the COSMIC database as well as novel recurrent somatic mutations identified in very recent cancer studies were used as positive (non-neutral) sets. Conservation-based methods generally had moderately high accuracy in distinguishing neutral from deleterious mutations, whereas the performance of machine learning based predictors with comprehensive feature spaces varied between assessments using different positive sets. MutationAssessor consistently provided the highest accuracies. For certain combinations metapredictors slightly improved the performance of included individual methods, but did not outperform MutationAssessor as stand-alone tool. Our independent assessment of existing tools reveals various performance disparities. Cancer-trained methods did not improve upon more general predictors. No method or combination of methods exceeds 81% accuracy, indicating there is still significant room for improvement for driver mutation prediction, and perhaps more sophisticated feature integration is needed to develop a more robust tool.


[Risk behaviors to health in Brazilian college students].
The scope of this study was to estimate the prevalence and associated factors of lower levels of leisure-time physical activities, insufficient consumption of fruit and vegetables, alcohol consumption and smoking among college students from a public university in the northeastern region of Brazil. The sample was stratified in accordance with the academic program, period of study and year of admission to the university. The negative health-related behaviors were analyzed in relation to socio-demographic and program affiliation indicators by means of Prevalence Ratios. The most prevalent negative health-related behaviors were insufficient consumption of fruit and vegetables, lowers levels of leisure-time physical activities and alcohol consumption. Insufficient consumption of fruit, smoking and alcohol consumption were more prevalent among men. Furthermore, insufficient consumption of vegetables was higher among younger, unmarried, men after three years at the university, whose fathers failed to complete elementary school. Lower levels of leisure-time physical activities were higher among older women, who evaluated relationships with colleagues negatively and whose fathers failed to complete elementary school.


[Psychosis: recognising the symptoms and disorders in children and adolescents].
Psychotic symptoms can occur during normal development, but they can also indicate the presence of or an increased risk of a psychotic disorder. By studying children who are at risk of developing a psychotic disorder we can obtain information that will help to distinguish more accurately between developmental phenomena and psychopathology. To present the current state of our knowledge about the development of psychotic symptoms and psychotic disorders and to discuss the importance of continuing research into subpopulations of children who are at risk of developing a psychotic disorder. We give an epidemiological and clinical description of psychosis in childhood and we report on recent Dutch and international studies about children with an increased risk of developing psychotic disorders. Results so far indicate that these children tend to have an increased risk of developing not only psychotic disorders but also a wide range of psychopathological conditions in later life. The degree of risk depends on the nature and number of risk factors involved. More research is needed to follow the development of children with an increased risk of psychotic disorders.


Myb26: a MYB-like protein of pea flowers with affinity for promoters of phenylpropanoid genes.
Plant Myb proteins represent a group of transcription factors which have a DNA-binding domain similar to that found in the products of the animal myb proto-oncogenes. Members of the Myb family regulate the biosynthesis of phenylpropanoids, including anthocyanin and phlobaphene pigments, in several species. In this study, PCR with degenerate primers was used to analyse the presence of myb-like genes in pea (Pisum sativum L.). A fragment representing a flower bud-expressed gene, designated myb26, was recovered, and a full length cDNA was isolated from a pea flower bud cDNA library. The predicted protein is 217 amino acids long and its Myb-domain and carboxy terminal region show extensive homology to the snap-dragon proteins Myb305 and Myb340, both of which regulate phenylpropanoid biosynthesis. Expression of myb26 is flower-specific and parallels the expression of flavonoid biosynthetic genes, increasing as the flower bud matures and intensifies in colour. However, myb26 represents neither of the two known regulatory genes for anthocyanin production in pea, nor does it complement mutants of the myb-like anthocyanin regulatory gene an2 in petunia. Myb26 was expressed in E. coli as a fusion protein. It was shown that in vitro Myb26 recognizes the c-Myb and P-box-like binding sites representing cis-elements in the promoter regions of several phenylpropanoid biosynthetic genes. The results suggest that myb26 is a previously undefined gene involved in regulation of some aspect of phenylpropanoid production in pea.


Phase II study of perioperative chemotherapy with cisplatin and pemetrexed in non-small-cell lung cancer.
Pathologic complete response (pCR) with neoadjuvant chemotherapy is associated with improved survival in many solid tumors. We evaluated pCR rate of cisplatin with pemetrexed in non-small-cell lung cancer. Patients with stages IB to IIIA non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 1 were enrolled in this single-arm phase II trial using two-stage design with 90% power to detect pCR rate of more than or equal to 10%. Pretreatment mediastinal lymph node biopsy was required. Patients received three cycles of cisplatin 75 mg/m with pemetrexed 500 mg/m (day 1 every 21 days) preoperatively and additional two cycles within 60 to 80 days after surgery. The primary end point was pCR. Polymorphisms in FPGS, GGH, SLC19A1, and TYMS genes were correlated with treatment outcomes. Thirty-eight patients were enrolled, with median age of 62.5 years. Preoperatively, 26% had squamous histology, and 34% had biopsy-proven N2 involvement. R0 resection was achieved in 94% of the 34 patients who underwent surgery, and 54% had documented N2 clearance. There was no pCR seen. Median disease-free survival (DFS) and overall survival of these patients have not yet been reached in contrast to median of 13.8 and 24.2 months, respectively, in patients with persistent N2 disease (p = 0.3241 and p = 0.1022, respectively). There was a statistically significant association between DFS and postoperative tumor, node, metastasis stage (p = 0.0429), SLC19A1 rs3788189 TT genotype (p = 0.0821), and viable tumor defined as less than or equal to 10% of resected specimen (p = 0.026). The primary end point was not met. Patients with N2 clearance, less than or equal to 10% viable tumor in the resected specimen, and SLC19A1 rs3788189 TT genotype have favorable DFS outcomes.


The Standard Days Method: an addition to the arsenal of family planning method choice in Ethiopia.
The Standard Days Method ® (SDM) is a fertility awareness-based method of family planning that helps users to identify the fertile days of the reproductive cycle (Days 8-19). To prevent pregnancy users avoid unprotected sexual intercourse during these days. A cross-sectional community-based study was conducted from December 2007 to June 2008 in four operational areas of Pathfinder International Ethiopia. A total of 184 SDM users were included in the study. Quantitative and qualitative methods of data collection were used. The aim of the study was to examine the experience of introducing the SDM at community level in Ethiopia. Of the 184 participants, 80.4% were still using the SDM at the time of the survey, with 35% having used it for between 6 and 12 months, while 42% had used it for more than a year. The majority (83%) knew that a woman is most likely to conceive halfway through her menstrual cycle, and nearly 91% correctly said that the SDM does not confer protection from sexually transmitted infections/AIDS. A substantial majority (75%) had correctly identified what each colour-coded bead represents in the CycleBeads ®, and an aggregate of 90.5% of women practised all the elements of correct use. This study demonstrates the importance of the SDM in increasing the availability and accessibility of family planning, and the potential to improve family planning method choice and method mix by expanding use of the SDM.