Analyses of cDNAs from growth and slug stages of Dictyostelium discoideum.
Dictyostelium is a favored model for studying problems in cell and developmental biology. To comprehend the genetic potential and networks that direct growth and multicellular development, we are performing a large-scale analysis of Dictyostelium cDNAs. Here, we newly determine 7720 nucleotide sequences of cDNAs from the multicellular, slug stage (S) and 10 439 from the unicellular, vegetative stage (V). The combined 26 954 redundant ESTs were computer assembled using the PHRAP program to yield 5381 independent sequences. These 5381 predicted genes represent about half of the estimated coding potential of the organism. One-third of them were classified into 12 functional categories. Although the overall classification patterns of the V and S libraries were very similar, stage-specific genes exist in every category. The majority of V-specific genes function in some aspect of protein translation, while such genes are in a minority in the S-specific and common populations. Instead, genes for signal transduction and multicellular organization are enriched in the population of S-specific genes. Genes encoding the enzymes of basic metabolism are mainly found in the common gene population. These results therefore suggest major differences between growing and developing Dictyostelium cells in the nature of the genes transcribed.


Modeling of the electromagnetic field and level populations in a waveguide amplifier: a multi-scale time problem.
A new algorithm based on auxiliary differential equation and finite difference time domain method (ADE-FDTD method) is presented to model a waveguide whose active layer is constituted of a silica matrix doped with rare-earth and silicon nanograins. The typical lifetime of rare-earth can be as large as some ms, whereas the electromagnetic field in a visible range and near-infrared is characterized by a period of the order of fs. Due to the large difference between these two characteristic times, the conventional ADE-FDTD method is not suited to treat such systems. A new algorithm is presented so that the steady state of rare earth and silicon nanograins electronic levels populations along with the electromagnetic field can be fully described. This algorithm is stable and applicable to a wide range of optical gain materials in which large differences of characteristic lifetimes are present.


Soft tissue management around implants in the esthetic zone.
The concept of overbuilding the implant site in the esthetic zone is paramount in creating the inconspicuous implant restoration. If teeth are congenitally missing, the site may be underdeveloped. Tooth extraction and trauma may lead to ridge deformities. The goal is to create an enhanced site for the restorative clinician. This site can then be molded to an ideal gingival framework. Cases are used to illustrate surgical and orthodontic techniques for preserving and overbuilding the implant site in the esthetic zone.


The voiding efficiency in rat models with dopaminergic brain lesions induced through unilateral and bilateral intrastriatal injections.
Bladder dysfunction is a common phenomenon in Parkinson's disease (PD) patients. A research attempt was made to analyze the voiding efficiency (VE) and bladder functions in rats with PD induced by unilateral or bilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. PD rats were divided into unilateral- and bilateral-injected groups and subjected to rotation and beam walking tests. Further, the experimental rats underwent cystometric measurements for analyses of bladder dysfunction and VE. Immunohistochemical analysis was performed to analyze the dopaminergic neuron depletion on the target area. Outcomes of the rotation and beam walking tests revealed the extent of parkinsonism in the experimental rats. Urodynamic observations denoted that rats with unilateral PD exhibited a significantly decreased VE (from 68.3±3.5% to 32.7±5.8%), while rats with bilateral PD displayed a much-reduced and substantially lower level of VE of 18.3±5.1% compared to the control value and to that of rats with unilateral PD. Rats with bilateral PD showed more-extensive behavioral deficits and urodynamic changes than did rats with unilateral PD. These significant changes in motor, behavioral, bladder function and VE were due to an extensive degeneration of dopaminergic neurons in the substantia nigra region on both sides of the brain. The obtained results were substantiated with appropriate immunohistochemical results.


Cost-effectiveness of breech version by acupuncture-type interventions on BL 67, including moxibustion, for women with a breech foetus at 33 weeks gestation: a modelling approach.
To assess, using a modelling approach, the effectiveness and costs of breech version with acupuncture-type interventions on BL67 (BVA-T), including moxibustion, compared to expectant management for women with a foetal breech presentation at 33 weeks gestation. A decision tree was developed to predict the number of caesarean sections prevented by BVA-T compared to expectant management to rectify breech presentation. The model accounted for external cephalic versions (ECV), treatment compliance, and costs for 10,000 simulated breech presentations at 33 weeks gestational age. Event rates were taken from Dutch population data and the international literature, and the relative effectiveness of BVA-T was based on a specific meta-analysis. Sensitivity analyses were conducted to evaluate the robustness of the results. We calculated percentages of breech presentations at term, caesarean sections, and costs from the third-party payer perspective. Odds ratios (OR) and cost differences of BVA-T versus expectant management were calculated. (Probabilistic) sensitivity analysis and expected value of perfect information analysis were performed. The simulated outcomes demonstrated 32% breech presentations after BVA-T versus 53% with expectant management (OR 0.61, 95% CI 0.43, 0.83). The percentage caesarean section was 37% after BVA-T versus 50% with expectant management (OR 0.73, 95% CI 0.59, 0.88). The mean cost-savings per woman was euro 451 (95% CI euro 109, euro 775; p=0.005) using moxibustion. Sensitivity analysis showed that if 16% or more of women offered moxibustion complied, it was more effective and less costly than expectant management. To prevent one caesarean section, 7 women had to use BVA-T. The expected value of perfect information from further research was euro0.32 per woman. The results suggest that offering BVA-T to women with a breech foetus at 33 weeks gestation reduces the number of breech presentations at term, thus reducing the number of caesarean sections, and is cost-effective compared to expectant management, including external cephalic version.


Gender and cognitive-emotional factors as predictors of pre-sleep arousal and trait hyperarousal in insomnia.
Elevated pre-sleep arousal has been consistently associated with insomnia, yet the cognitive-emotional mechanisms involved in sleep-related arousal remain unclear. The purpose of this study was to identify predictors of pre-sleep arousal and trait hyperarousal from a set of variables that included self-reported affect, sleep-related cognitions, locus of control, and gender. Cross-sectional data were analyzed for 128 participants (89 females) who met criteria for psychophysiological insomnia and completed a set of questionnaires that included the beliefs and attitudes about sleep (BAS), positive and negative affect schedule (negative subscale (nPANAS) and positive subscale (pPANAS)), sleep locus of control (SLOC), Pre-Sleep Arousal Scale (PSAS), hyperarousal scale (HAS) and demographic information. Step-wise regression was conducted with a set of independent variables, with PSAS and HAS serving as separate dependent variables. Trait hyperarousal was associated with higher levels of both negative and positive emotionality, as well as negative beliefs about sleep, in both genders. Pre-sleep arousal was associated with greater negative emotionality and internal sleep locus of control, varying by gender. Among women, high pre-sleep arousal was associated with negative emotionality, while in men greater pre-sleep arousal was associated with an internal sleep locus of control. These findings have clinical implications, suggesting that men and women may require different cognitive targets when addressing pre-sleep arousal.


Maternal dietary docosahexaenoic acid supplementation attenuates fetal growth restriction and enhances pulmonary function in a newborn mouse model of perinatal inflammation.
The preterm infant is often exposed to maternal and neonatal inflammatory stimuli and is born with immature lungs, resulting in a need for oxygen therapy. Nutritional intervention with docosahexaenoic acid (DHA; 6.3 g/kg of diet) has been shown to attenuate inflammation in various human diseases. Previous studies demonstrated that maternal DHA supplementation during late gestation and lactation attenuated hyperoxic lung injury in newborn mouse pups. In the present studies, we tested the hypothesis that DHA supplementation to the dam would reduce hyperoxic lung injury and growth deficits in a more severe model of systemic maternal inflammation, including lipopolysaccharide (LPS) and neonatal hyperoxia exposure. On embryonic day 16, dams were placed on DHA (6.3 g DHA/kg diet) or control diets and injected with saline or LPS. Diets were maintained through weaning. At birth, pups were placed in room air or hyperoxia for 14 d. Improvements in birth weight (P < 0.01), alveolarization (P ≤ 0.01), and pulmonary function (P ≤ 0.03) at 2 and 8 wk of age were observed in pups exposed to perinatal inflammation and born to DHA-supplemented dams compared with control diet-exposed pups. These improvements were associated with decreases in tissue macrophage numbers (P < 0.01), monocyte chemoattractant protein-1 expression (P ≤ 0.05), and decreases in soluble receptor for advanced glycation end products concentrations (P < 0.01) at 2 and 8 wk. Furthermore, DHA supplementation attenuated pulmonary fibrosis, which was associated with the reduction of matrix metalloproteinases 2, 3, and 8 (P ≤ 0.03) and collagen mRNA (P ≤ 0.05), and decreased collagen (P < 0.01) and vimentin (P ≤ 0.03) protein concentrations. In a model of severe inflammation, maternal DHA supplementation lessened inflammation and improved lung growth in the offspring. Maternal supplementation with DHA may be a therapeutic strategy to reduce neonatal inflammation.


Suicidal thoughts and emotion competence.
During deployment and upon returning home, veterans experience emotional challenges that test their social and psychological adaptation and place them at risk for suicidal thinking. Individual variability in skill-based capacity to adaptively perceive, understand, correctly use, and manage emotions (called emotional competence) may play a role in the development of psychological suffering and suicidal thinking. Based on research in healthy and clinical samples, poor emotional competence was predicted to be associated with suicidal thinking among returning veterans. Participants were selected from the W. F. Caveness Vietnam Head Injury Study (VHIS) registry, which in the late 1960s began prospectively assessing 1221 veterans). The study sample was composed of veterans examined between 2003 and 2006 and included 185 participants who at the time of assessment with the Beck Depression Inventory (BDI) did (N= 46) or did not endorse (N= 139) suicidal thinking then or during the previous two weeks and received performance-based measures of emotional competence (Mayer-Salovey-Caruso Emotional Intelligence Test; MSCEIT, Version 2.0) and theory of mind. MSCEIT subtests and theory of mind tasks were condensed via principal component analysis: Component 1 (Emotion Processing) included use, understand, and manage emotions tasks, and Component 2 (Emotion Perception) included perceive emotions. Veterans endorsing suicidal thoughts showed poorer emotion processing whereas emotion perception and theory of mind tasks did not show significant group effects. In addition, veterans who endorsed thoughts of suicide were deployed at a younger age, had lower education, and tended to report more negative experiences in social interactions upon return to the United States. The capacity to understand, use, and manage emotionally charged stimuli and situations may represent risk factors for suicidal thinking among veterans.


Occupational trichloroethylene exposure and kidney cancer risk: a meta-analysis.
Inconsistent epidemiological findings, debate over interpretation, and extrapolation of findings from animal studies to humans have produced uncertainty surrounding the carcinogenicity of trichloroethylene (TCE) exposure in occupational settings. We updated meta-analyses of published case-control and cohort studies exploring occupational TCE exposure and kidney cancer risk, incorporating new analytical results from three recently published cohort studies and a case-control study. PubMed MEDLINE was searched for studies published from 1950 to 2011 assessing occupational exposure to chlorinated solvents, degreasers or TCE. All cohort (N=15) and case-control (N=13) studies included in analyses were stratified by assessment of occupational exposure to TCE specifically and to any chlorinated solvent. Significantly elevated summary estimates were observed for cohort studies (relative risk (RR) 1.26, 95% CI 1.02 to 1.56; p heterogeneity=0.65), case-control studies (OR 1.35, 95% CI 1.17 to 1.57; p heterogeneity=0.41), and cohort and case-control studies combined (RR 1.32, 95% CI 1.17 to 1.50, p heterogeneity=0.63) that specifically assessed TCE exposure after excluding outlier studies that contributed to heterogeneity. Non-significantly elevated summary estimates were generally observed for studies of workers exposed to chlorinated solvents but who were not assessed for TCE specifically. Regardless of study design, significant and stronger estimates were only observed in studies specifically assessing occupational exposure to TCE. Estimates were lower in studies assessing occupational exposure to chlorinated solvents. This updated meta-analysis supports an association between occupational TCE exposure and kidney cancer and provides evidence that exposure misclassification may weaken estimates assessing exposure to the broader class of chlorinated solvents.


Evaluation of the efficacy and safety of bi-daily combination therapy with pyridoxine and doxylamine for nausea and vomiting of pregnancy.
Diclectin (pyridoxine 10 mg and doxylamine 10 mg) has traditionally been used to treat nausea and vomiting of pregnancy (NVP); however, this drug is unavailable in many countries. To evaluate the efficacy and safety of a simple bi-daily treatment regimen with the combination of pyridoxine (50 mg twice daily) and doxylamine (25-50 mg) as an alternative treatment for NVP. A prospective case-controlled observational study of mother-infant pairs was conducted between February 2008 and December 2010. All women who contacted the Beilinson Teratology Information Service (BELTIS) regarding treatment of NVP were eligible for inclusion. Using data on NVP severity, treatment efficacy and outcomes, we compared the two groups of women: those treated with the combination of pyridoxine and doxylamine (treatment group, n=29) and those treated with metoclopramide (control group, n=29). Moderate to severe symptoms were present in 97% of the treatment group women vs. 69% of control group women (P < 0.01). Despite increased symptom severity in the treatment group, the combination regimen was efficacious: 20/29 (69%) vs. 18/25 (72%) in the treatment vs. control women respectively (P = 0.65). There were no congenital anomalies in the treatment group. Follow-up was normal for all infants. Bi-daily combination therapy with pyridoxine and doxylamine for NVP is safe, has comparable efficacy to metoclopramide, and is a treatment alternative in countries where Diclectin is not available. Despite symptoms warranting counseling by a teratology information service, more than a third of women do not take the suggested treatment.


Safety of carotid endarterectomy while on clopidogrel (Plavix). Clinical article.
Many patients undergoing carotid endarterectomy (CEA) regularly take clopidogrel, a permanent platelet inhibitor. The authors sought to determine whether taking clopidogrel in the period before CEA leads to more bleeding or other complications. The authors performed a retrospective, institutional review board–approved review of 182 consecutive patients who underwent CEA. Clinical, radiographic, and surgical data were gleaned from hospital and clinic records. Analysis was based on the presence or absence of clopidogrel in patients undergoing CEA and was performed twice by considering clopidogrel use within 8 days and within 5 days of surgery to define the groups. Taking clopidogrel within 8 days before surgery resulted in no statistical increase in any measure of morbidity or death. Taking clopidogrel within 5 days was associated with a small but significant increase in operative blood loss and conservatively managed postoperative neck swelling. No measure of permanent morbidity or death was increased in either clopidogrel group. Findings in this study support the safety of preoperative clopidogrel in patients undergoing CEA.


Functional gastrointestinal disorders: advances in understanding and management.
Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled as having a functional gastrointestinal disorder, such as irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, and two-thirds of these people will have chronic, fluctuating symptoms. The pathophysiology of functional gastrointestinal disorders is complex, but involves bidirectional dysregulation of gut-brain interaction (via the gut-brain axis), as well as microbial dysbiosis within the gut, altered mucosal immune function, visceral hypersensitivity, and abnormal gastrointestinal motility. Hence, nomenclature refers to the conditions as disorders of gut-brain interaction. Psychological comorbidity is common; however, whether or not this predates, or is driven by, symptoms is not clear. Patients with functional gastrointestinal disorders can feel stigmatised, and often this diagnosis is not communicated effectively by physicians, nor is education provided. Prompt identification and treatment of these conditions is crucial as they have a considerable impact on health-care systems and society as a whole because of repeated consultations, unnecessary investigations and surgeries, prescriptions and over-the-counter medicine use, and impaired health-related quality of life and ability to work. Symptom-based criteria are used to make a diagnosis, with judicious use of limited investigations in some patients. The general principles of treatment are based on a biopsychosocial understanding and involve management of physical symptoms and, if present, psychological comorbidity. In the future, treatment approaches to functional gastrointestinal disorders are likely to become more personalised, based not only on symptoms but also underlying pathophysiology and psychology.


From spiking neuron models to linear-nonlinear models.
Neurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN) cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF), exponential integrate-and-fire (EIF) and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates.


Conservation of flexible residue clusters among structural and functional enzyme homologues.
Conformational flexibility between structural ensembles is an essential component of enzyme function. Although the broad dynamical landscape of proteins is known to promote a number of functional events on multiple time scales, it is yet unknown whether structural and functional enzyme homologues rely on the same concerted residue motions to perform their catalytic function. It is hypothesized that networks of contiguous and flexible residue motions occurring on the biologically relevant millisecond time scale evolved to promote and/or preserve optimal enzyme catalysis. In this study, we use a combination of NMR relaxation dispersion, model-free analysis, and ligand titration experiments to successfully capture and compare the role of conformational flexibility between two structural homologues of the pancreatic ribonuclease family: RNase A and eosinophil cationic protein (or RNase 3). In addition to conserving the same catalytic residues and structural fold, both homologues show similar yet functionally distinct clusters of millisecond dynamics, suggesting that conformational flexibility can be conserved among analogous protein folds displaying low sequence identity. Our work shows that the reduced conformational flexibility of eosinophil cationic protein can be dynamically and functionally reproduced in the RNase A scaffold upon creation of a chimeric hybrid between the two proteins. These results support the hypothesis that conformational flexibility is partly required for catalytic function in homologous enzyme folds, further highlighting the importance of dynamic residue sectors in the structural organization of proteins.


Aphid protected from pathogen by endosymbiont.
Aphids are associated with several facultative bacterial endosymbionts that may influence their interactions with other organisms. We show here that one of the three most common facultative symbionts of pea aphid (Acyrthosiphon pisum), the bacterium Regiella insecticola, has a major effect on host resistance to a fungal pathogen. Experimental establishment of the bacterium in uninfected aphid clones led to higher survival after fungal attack. The bacteria also increased the aphid's inclusive fitness, because the presence of the symbiont reduced the probability of fungal sporulation on aphid cadavers, hence lowering the rate of transmission of the disease to nearby related aphids.


HIV and mature dendritic cells: Trojan exosomes riding the Trojan horse?
Exosomes are secreted cellular vesicles that can induce specific CD4(+) T cell responses in vivo when they interact with competent antigen-presenting cells like mature dendritic cells (mDCs). The Trojan exosome hypothesis proposes that retroviruses can take advantage of the cell-encoded intercellular vesicle traffic and exosome exchange pathway, moving between cells in the absence of fusion events in search of adequate target cells. Here, we discuss recent data supporting this hypothesis, which further explains how DCs can capture and internalize retroviruses like HIV-1 in the absence of fusion events, leading to the productive infection of interacting CD4(+) T cells and contributing to viral spread through a mechanism known as trans-infection. We suggest that HIV-1 can exploit an exosome antigen-dissemination pathway intrinsic to mDCs, allowing viral internalization and final trans-infection of CD4(+) T cells. In contrast to previous reports that focus on the ability of immature DCs to capture HIV in the mucosa, this review emphasizes the outstanding role that mature DCs could have promoting trans-infection in the lymph node, underscoring a new potential viral dissemination pathway.


Sex estimation of the tibia in modern Turkish: A computed tomography study.
The utilization of computed tomography is beneficial for the analysis of skeletal remains and it has important advantages for anthropometric studies. The present study investigated morphometry of left tibia using CT images of a contemporary Turkish population. Seven parameters were measured on 203 individuals (124 males and 79 females) within the 19-92-years age group. The first objective of this study was to provide population-specific sex estimation equations for the contemporary Turkish population based on CT images. A second objective was to test the sex estimation formulae on Southern Europeans by Kranioti and Apostol (2015). Univariate discriminant functions resulted in classification accuracy that ranged from 66 to 86%. The best single variable was found to be upper epiphyseal breadth (86%) followed by lower epiphyseal breadth (85%). Multivariate discriminant functions resulted in classification accuracy for cross-validated data ranged from 79 to 86%. Applying the multivariate sex estimation formulae on Southern Europeans (SE) by Kranioti and Apostol in our sample resulted in very high classification accuracy ranging from 81 to 88%. In addition, 35.5-47% of the total Turkish sample is correctly classified with over 95% posterior probability, which is actually higher than the one reported for the original sample (25-43%). We conclude that the tibia is a very useful bone for sex estimation in the contemporary Turkish population. Moreover, our test results support the hypothesis that the SE formulae are sufficient for the contemporary Turkish population and they can be used safely for criminal investigations when posterior probabilities are over 95%.


Long non-coding RNA-guided regulation in organisms.
It is clear that RNA is more than just a messenger between gene and protein. The mammalian genome is pervasively transcribed, giving rise to tens of thousands of non-coding transcripts. Whether all of these transcripts are functional remains to be elucidated, but it is evident that there are many functional long non-coding RNAs (lncRNAs). Recent studies have set out to decode the regulatory role and functional diversity of lncRNAs. Here we organize these studies to highlight the significant involvements of lncRNAs in regulation of gene expression and human physiological and pathological processes, which are achieved by their interaction with DNA, RNA or protein.


Calcium homeostasis alterations in a mouse model of the Dynamin 2-related centronuclear myopathy.
Autosomal dominant centronuclear myopathy (CNM) is a rare congenital myopathy characterized by centrally located nuclei in muscle fibers. CNM results from mutations in the gene encoding dynamin 2 (DNM2), a large GTPase involved in endocytosis, intracellular membrane trafficking, and cytoskeleton regulation. We developed a knock-in mouse model expressing the most frequent DNM2-CNM mutation; i.e. the KI-Dnm2R465W model. Heterozygous (HTZ) KI-Dnm2 mice progressively develop muscle atrophy, impairment of contractile properties, histopathological abnormalities, and elevated cytosolic calcium concentration. Here, we aim at better characterizing the calcium homeostasis impairment in extensor digitorum longus (EDL) and soleus muscles from adult HTZ KI-Dnm2 mice. We demonstrate abnormal contractile properties and cytosolic Ca2+ concentration in EDL but not soleus muscles showing that calcium impairment is correlated with muscle weakness and might be a determinant factor of the spatial muscle involvement. In addition, the elevated cytosolic Ca2+ concentration in EDL muscles is associated with an increased sarcolemmal permeability to Ca2+ and releasable Ca2+ content from the sarcoplasmic reticulum. However, amplitude and kinetics characteristics of the calcium transient appear unchanged. This suggests that calcium defect is probably not a primary cause of decreased force generation by compromised sarcomere shortening but may be involved in long-term deleterious consequences on muscle physiology. Our results highlight the first pathomechanism which may explain the spatial muscle involvement occurring in DNM2-related CNM and open the way toward development of a therapeutic approach to normalize calcium content.


Evidence that bradykinin stimulates renal prostaglandin synthesis by a mechanism distinct from that of other vasoactive substances.
Arginine-vasopressin (AVP), angiotensin II (AII), and norepinephrine (NE) are known to stimulate prostaglandin (PG) synthesis in the intact rat kidney perfused with Tyrode's solution by a mechanism that requires intracellular Ca2+, while PG synthesis elicited by bradykinin (BK) is independent of Ca2+. To elucidate further the differences in the mechanism of action of BK and other vasoactive agents, in this preparation we have investigated the effect of caffeine, an agent known to interfere with the uptake and storage of Ca2+ in intracellular sites, on renal output of PGE2 and 6-keto-PGF1 alpha elicited by AVP, AII, NE, and BK; various combinations of the maximal doses of BK, AII, AVP, and NE on renal PG synthesis; and RHC 80267, an inhibitor of diglyceride and monoglyceride lipase, on the output of PGs produced by these vasoactive agents. Infusion of 1 mM caffeine inhibited PG output elicited by AVP, AII, and NE but not that caused by BK in the absence of extracellular Ca2+. Combined administration of maximal doses of BK (2.8 nmol) with that of AII (0.28 nmol), AVP (0.27 nmol), or NE (3.2 nmol) but not AVP and AII, NE and AVP, or NE and AII produced an additive effect on renal PG output in the presence or absence of Ca2+. The renal vasoconstrictor effect of AVP, AII, and NE produced in the presence of Ca2+ was not additive and remained unaltered when given together with BK.(ABSTRACT TRUNCATED AT 250 WORDS)


Physico-chemical changes in Ca, Sr and Al-doped La-Mn-O perovskites upon thermochemical splitting of CO2 via redox cycling.
Thermochemical CO2-splitting via redox cycling of Ca, Sr and Al-doped La-Mn perovskites induces irreversible changes in the texture and chemical composition of these oxides. Though the crystal structure is mostly preserved after high-temperature redox cycling, the chemical stability is detrimentally affected by sintering and by the formation and eventual segregation of a carbonate phase during oxidation by CO2. Carbonation of the Ca and Sr phase was diminished by Al-substitution of the Mn-cation in the B-position.


Characterization of proteins associating with 5' terminus of PGHS-1 mRNA.
Induction of Prostaglandin Endoperoxide H Synthase-1 (PGHS-1) gene has been previously documented in a few studies during events such as development and cellular differentiation. However, molecular mechanisms governing the regulation of PGHS-1 gene expression and contributing to changes in protein levels are poorly understood. Using the MEG-01 cell model of PGHS-1 gene induction, our laboratory has previously demonstrated that the 5'UTR and the first two exons of PGHS-1 mRNA had a significant impact on decreasing the translational efficiency of a reporter gene and suggested that the presence of a secondary structure is required for conservation of this activity. This 5'end of PGHS-1 mRNA sequence has also been shown to associate with nucleolin protein. In the current study, we set to investigate the protein composition of the mRNP (messenger ribonucleoprotein) associating with the 5'end of PGHS-1 mRNA and to identify its protein members. RNA/protein binding assays coupled with LC-MS analysis identified serpin B1 and NF45 (nuclear factor 45) proteins as potential members of PGHS-1 mRNP complex. Immunoprecipitation experiments using MEG-01 protein extracts validated mass spectrometry data and confirmed binding of nucleolin, serpin B1, NF45 and NF90. The RNA fraction was extracted from immunoprecipitated mRNP complexes and association of RNA binding proteins, serpin B1, NF45 and NF90, to PGHS-1 mRNA target sequence was confirmed by RT-PCR. Together these data suggest that serpin B1, NF45 and NF90 associate with PGHS-1 mRNA and can potentially participate in the formation a single or a number of PGHS-1 ribonucleoprotein complexes, through nucleolin that possibly serves as a docking base for other protein complex members.


Household dietary exposure to aflatoxins from maize and maize products in Kenya.
Aflatoxicosis has repeatedly affected Kenyans, particularly in the eastern region, due to consumption of contaminated maize. However, save for the cases of acute toxicity, the levels of sub-lethal exposure have not been adequately assessed. It is believed that this type of exposure does exist even during the seasons when acute toxicity does not occur. This study, therefore, was designed to assess the exposure of households to aflatoxins through consumption of maize and maize products. Twenty samples each of maize kernels, muthokoi and maize meal were randomly sampled from households in Kibwezi District of Makueni County in Eastern Kenya and analysed for aflatoxin contamination. The samples were quantitatively analysed for aflatoxin contamination using HPLC. The uncertainty and variability in dietary exposure was quantitatively modelled in Ms Excel using Monte Carlo simulation in @Risk software. Aflatoxins were found in 45% of maize kernels at between 18 and 480 μg kg⁻¹, 20% of muthokoi at between 12 and 123 μg kg⁻¹, and 35% of maize meal at between 6 and 30 μg kg⁻¹. The mean dietary exposure to aflatoxin in maize kernels was 292 ± 1567 ng kg⁻¹ body weight day⁻¹, while the mean dietary exposure to aflatoxin in maize meal and muthokoi were 59 ± 62 and 27 ± 154 ng kg⁻¹ body weight day⁻¹ respectively. The results showed that the amount and frequency of consumption of the three foods is the more important contributing factor than the mean aflatoxin concentration levels, to the risk of dietary exposure to aflatoxins.


Shared sugars - parasite glycan homology in HIV-1 vaccine design.
Immune tolerance to self-glycans is a host mechanism to avoid autoimmunity, which is exploited by HIV-1 coating its envelope glycoproteins with glycans to evade neutralising antibodies (nAbs). Huettner et al. describe cross-reactivity between Schistosoma mansoni glycans and HIV-1 envelope glycoprotein glycans, suggesting a strategy for induction of HIV-1 nAbs by vaccination.


Curcumin Inhibits the Proliferation, Migration, Invasion, and Apoptosis of Diffuse Large B-Cell Lymphoma Cell Line by Regulating MiR-21/VHL Axis.
Curcumin exerts its anti-cancer effects, partly by targeting special microRNAs, in human cancers. MiR-21 is a key oncomir in carcinogenesis of multiple human cancers. Here, we aimed to further explore the mechanistic insight into the link between curcumin and miR-21 on diffuse large B-cell lymphoma (DLBCL). Quantitative real-time PCR assays were performed to assess the levels of miR-21 and Von Hippel-Lindau (VHL) mRNA. In situ hybridization assay was used for miR-21 expression visualization in lymphoma tissues. Western blot was used for determination of VHL protein, Ki-67, caspase-3, and cleaved caspase-3 levels. Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to confirm the direct target of miR-21. MTT assay, flow cytometric analysis, and transwell assay were used to evaluate cell proliferation, apoptosis, and migration and invasion capacities, respectively. Curcumin repressed the proliferation, migration, and invasion abilities and promoted apoptosis in SU-DHL-8 cells. Curcumin inhibited miR-21 expression and curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis effects by miR-21 in SU-DHL-8 cells. VHL was a direct target of miR-21. Moreover, curcumin exerted its regulatory effects on SU-DHL-8 cells by VHL. Curcumin exerted its anti-proliferation, anti-migration, anti-invasion, and pro-apoptosis functions, at least partly, by repressing miR-21 and regulating VHL expression in DLBCL cell line. Our findings provided a possible molecular mechanism of curcumin-mediated anti-cancer effect.


Characterization of human organ donors testing positive for type 1 diabetes-associated autoantibodies.
In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within the Nordic Network for Islet Transplantation. One thousand and thirty organ donors have been screened in Uppsala for antibodies against glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A). The 32 non-diabetic donors that tested positive for GADA (3.3% of all non-diabetic donors) were studied in more detail, together with 32 matched controls. Mean age among the autoantibody-positive donors was 52.6 (range 21-74), family history of type 1 diabetes (T1D) was unknown, and no donor was genetically predisposed for T1D regarding the human leucocyte antigen (HLA) locus. Subjects were analysed for islet cell antibodies (ICA), insulin autoantibodies (IAA) and zinc transporter 8 antibodies (ZnT8A), and pancreas morphology and clinical data were examined. Eight non-diabetic donors tested positive for two antibodies and one donor tested positive for four antibodies. No insulitis or other signs of a diabetic process were found in any of the donors. While inflammatory cells were present in all donors, subjects with high GADA titres had significantly higher CD45 cell numbers in exocrine tissue than controls. The extent of fibrosis was more pronounced in autoantibody-positive donors, even in subjects with lower GADA titres. Notably, it is possible that events not related directly to T1D (e.g. subclinical pancreatitis) may induce autoantibodies in some cases.


Antibodies armed with photosensitizers: from chemical synthesis to photobiological applications.
Targeting photosensitizers to cancer cells by conjugating them with specific antibodies, able to recognize and bind to tumor-associated antigens, is today one of the most attractive strategies in photodynamic therapy (PDT). This comprehensive review updates on chemical routes available for the preparation of photo-immunoconjugates (PICs), which show dual chemical and biological functionalities: photo-properties of the photosensitizer and the immunoreactivity of the antibody. Moreover, photobiological results obtained with such photo-immunoconjugates using in vitro and in vivo cancer models are also discussed.


Behavior of mesenchymal stem cells in the chemical microenvironment of the intervertebral disc.
Responses of mesenchymal stem cells (MSCs) from 2 age groups was analyzed under chemical conditions representative of the intervertebral disc (IVD) (low glucose levels, acidic pH, high osmolarity, and combined conditions). OBJECTIVE.: To determine the microenvironmental conditions of the IVD that are critical for MSC-based tissue repair and to determine whether MSCs from different age groups respond differently. MSCs offer promise for IVD repair, but their potential is limited by the harsh chemical microenvironment in which they must survive. MSCs were isolated from bone marrow from mature (4-5 month old) and young (1 month old) rats and cultured in monolayer under IVD-like glucose, osmolarity, and pH conditions as well as under a combination of these conditions and under standard media conditions for 2 weeks. The response of MSCs was examined by measuring gene expression (real-time RT-PCR), proliferation (MTT assay), and viability (fluorescence staining). Culturing under IVD-like glucose conditions (1.0 mg/mL glucose) stimulated aggrecan and collagen-1 expression and caused a small increase in proliferation. In contrast, IVD-like osmolarity (485 mOsm) and pH (pH = 6.8) conditions strongly decreased proliferation and expression of matrix proteins, with more pronounced effects for osmolarity. Combining these 3 conditions also resulted in decreased proliferation, and gene expression of matrix proteins, demonstrating that osmolarity and pH dominated the effects of glucose. Both age groups showed a similar response pattern to the disc microenvironment. IVD repair using MSCs requires increased knowledge of MSC response to the chemical microenvironment. IVD-like low glucose enhanced matrix biosynthesis and maintained cell proliferation whereas IVD-like high osmolarity and low pH conditions were critical factors that reduced biosynthesis and proliferation of young and mature MSCs. Since osmolarity decreases and acidity increases during degeneration, we speculate that pH may be the major limitation for MSC-based IVD repair.


Gibel carp Carassius auratus gut microbiota after oral administration of trimethoprim/ sulfamethoxazole.
Trimethoprim/sulfamethoxazole is widely used in the treatment of infectious diseases caused by bacterial pathogens in aquaculture. However, the practice of antibiotic administration can promote the emergence of resistant strains of bacteria and result in a wane in efficacy over time. The objective of this study was to assess the effect of oral treatment with trimethoprim/sulfamethoxazole on the gastrointestinal (GI) microbiota of healthy gibel carp and those affected with bacterial enteritis. By using denaturing gradient gel electrophoresis (DGGE), the changes in the predominant bacterial communities were directly depicted for the first time. The main findings were (1) Actinobacteria, Firmicutes and Proteobacteria were the predominant phyla in the healthy gibel carp intestine; (2) administration of antibiotics had a more profound impact on the intestinal microflora of healthy fish than of the diseased ones; and (3) Enterobacteriaceae might be one of the major drug-resistant bacteria in the gibel carp intestine. This study provides an insight into the effect of antibiotic treatment on the establishment and colonization of fish GI microbiota and speculates on some possible drug-resistant bacteria.


A SEARCH FOR VIRUS-INACTIVATING SUBSTANCES AMONG MICROORGANISMS.
One hundred and fifty organisms, comprising bacteria, fungi and actinomycetes, were isolated from straw-compost, manure, soil, drainage material and soil enriched with virus concentrates, and were tested for antiviral activity in vitro. Three of these organisms gave indications of possible inactivation of some of the fowl pox virus, and, in one case, of the laryngotracheitis virus. The active principle of one of these organisms was actinomycin A, an antibacterial substance known to be highly toxic to animals. The other two organisms were less extensively studied, and no claims regarding their antiviral potentialities can be made at present.


Oscillatory integration windows in neurons.
Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking.


Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies.
In the United States, more than half of all new invasive cancers diagnosed are non-small cell lung cancer, with a significant number of these cases presenting at locally advanced stages, resulting in about one-third of all cancer deaths. While the advent of stereotactic ablative radiation therapy (SABR, also known as stereotactic body radiotherapy, or SBRT) for early-staged patients has improved local tumor control to >90%, survival results for locally advanced stage lung cancer remain grim. Significant challenges exist in lung cancer radiation therapy including tumor motion, accurate dose calculation in low density media, limiting dose to nearby organs at risk, and changing anatomy over the treatment course. However, many recent technological advancements have been introduced that can meet these challenges, including four-dimensional computed tomography (4DCT) and volumetric cone-beam computed tomography (CBCT) to enable more accurate target definition and precise tumor localization during radiation, respectively. In addition, advances in dose calculation algorithms have allowed for more accurate dosimetry in heterogeneous media, and intensity modulated and arc delivery techniques can help spare organs at risk. New delivery approaches, such as tumor tracking and gating, offer additional potential for further reducing target margins. Image-guided adaptive radiation therapy (IGART) introduces the potential for individualized plan adaptation based on imaging feedback, including bulky residual disease, tumor progression, and physiological changes that occur during the treatment course. This review provides an overview of the current state of the art technology for lung cancer volume definition, treatment planning, localization, and treatment plan adaptation.


The BACH classification of long bone osteomyelitis.
The aim of this study was to assess the clinical application of, and optimize the variables used in, the BACH classification of long-bone osteomyelitis. A total of 30 clinicians from a variety of specialities classified 20 anonymized cases of long-bone osteomyelitis using BACH. Cases were derived from patients who presented to specialist centres in the United Kingdom between October 2016 and April 2017. Accuracy and Fleiss' kappa (Fκ) were calculated for each variable. Bone involvement (B-variable) was assessed further by nine clinicians who classified ten additional cases of long bone osteomyelitis using a 3D clinical imaging package. Thresholds for defining multidrug-resistant (MDR) isolates were optimized using results from a further analysis of 253 long bone osteomyelitis cases. The B-variable had a classification accuracy of 77.0%, which improved to 95.7% when using a 3D clinical imaging package (p < 0.01). The A-variable demonstrated difficulty in the accuracy of classification for increasingly resistant isolates (A1 (non-resistant), 94.4%; A2 (MDR), 46.7%; A3 (extensively or pan-drug-resistant), 10.0%). Further analysis demonstrated that isolates with four or more resistant test results or less than 80% sensitive susceptibility test results had a 98.1% (95% confidence interval (CI) 96.6 to 99.6) and 98.8% (95% CI 98.1 to 100.0) correlation with MDR status, respectively. The coverage of the soft tissues (C-variable) and the host status (H-variable) both had a substantial agreement between users and a classification accuracy of 92.5% and 91.2%, respectively. The BACH classification system can be applied accurately by users with a variety of clinical backgrounds. Accuracy of B-classification was improved using 3D imaging. The use of the A-variable has been optimized based on susceptibility testing results.Cite this article: A. J. Hotchen, M. Dudareva, J. Y. Ferguson, P. Sendi, M. A. McNally. The BACH classification of long bone osteomyelitis. Bone Joint Res 2019;8:459-468. DOI: 10.1302/2046-3758.810.BJR-2019-0050.R1.


Theoretical Description of R-X⋯NH3 Halogen Bond Complexes: Effect of the R Group on the Complex Stability and Sigma-Hole Electron Depletion.
In the present work, a number of R-X⋯NH3 (X = Cl, Br, and I) halogen bonded systems were theoretical studied by means of DFT calculations performed at the ωB97XD/6-31+G(d,p) level of theory in order to get insights on the effect of the electron-donating or electron-withdrawing character of the different R substituent groups (R = halogen, methyl, partially fluorinated methyl, perfluoro-methyl, ethyl, vinyl, and acetyl) on the stability of the halogen bond. The results indicate that the relative stability of the halogen bond follows the Cl < Br < I trend considering the same R substituent whereas the more electron-withdrawing character of the R substituent the more stable the halogen bond. Refinement of the latter results, performed at the MP2/6-31+G(d,p) level showed that the DFT and the MP2 binding energies correlate remarkably well, suggesting that the Grimme's type dispersion-corrected functional produces reasonable structural and energetic features of halogen bond systems. DFT results were also observed to agree with more refined calculations performed at the CCSD(T) level. In a further stage, a more thorough analysis of the R-Br⋯NH3 complexes was performed by means of a novel electron localization/delocalization tool, defined in terms of an Information Theory, IT, based quantity obtained from the conditional pair density. For the latter, our in-house developed C++/CUDA program, called KLD (acronym of Kullback-Leibler divergence), was employed. KLD results mapped onto the one-electron density plotted at a 0.04 a.u. isovalue, showed that (i) as expected, the localized electron depletion of the Br sigma-hole is largely affected by the electron-withdrawing character of the R substituent group and (ii) the R-X bond is significantly polarized due to the presence of the NH3 molecule in the complexes. The afore-mentioned constitutes a clear indication of the dominant character of electrostatics on the stabilization of halogen bonds in agreement with a number of studies reported in the main literature. Finally, the cooperative effects on the [Br-CN]n system (n = 1-8) was evaluated at the MP2/6-31+G(d,p) level, where it was observed that an increase of about ~14.2% on the complex stability is obtained when going from n = 2 to n = 8. The latter results were corroborated by the analysis of the changes on the Fermi-hole localization pattern on the halogen bond zones, which suggests an also important contribution of the electron correlation in the stabilization of these systems.


Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract.
Food allergy may be life-threatening, and patients affected need to receive accurate diagnoses and treatment. Hazelnut has often been implicated as responsible for allergic reactions, and trace quantities can induce systemic reactions. The aim of this study was to evaluate the efficacy and tolerance of sublingual immunotherapy with a standardized hazelnut extract in patients allergic to hazelnut. This was a randomized, double-blind, placebo-controlled study. Inclusion criteria were a history of hazelnut allergy and positive skin prick test and double-blind placebo-controlled food challenge results. Patients were then randomly assigned into 2 treatment groups (hazelnut immunotherapy or placebo). Efficacy was assessed by double-blind, placebo-controlled food challenge after 8 to 12 weeks of treatment. Blood samples were drawn for measurement of specific IgE, IgG(4), and serum cytokines before and after treatment. Twenty-three patients were enrolled and divided into 2 treatment groups. Twenty-two patients reached the planned maximum dose at 4 days. Systemic reactions were observed in only 0.2% of the total doses administered. Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to 11.56 g (P = .02; active group) versus 3.49 g to 4.14 g (placebo; NS). Moreover, almost 50% of patients who underwent active treatment reached the highest dose (20 g), but only 9% in the placebo. Laboratory data showed an increase in IgG(4) and IL-10 levels after immunotherapy in only the active group. Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy as assessed by double-blind, placebo-controlled food challenge, and good tolerance to this treatment.


The ongoing cut-down of the Amazon rainforest threatens the climate and requires global tree planting projects: A short review.
The Amazon rainforest has sustained human existence for more than 10,000 years. Part of this has been the way that the forest controls regional climate including precipitation important for the ecosystem as well as agroforestry and farming. In addition, the Amazon also affects the global weather systems, so cutting down the rainforest significantly increases the effects of climate change, threatening the world's biodiversity and causing local desertification and soil erosion. The current fire activities and deforestation in the Amazon rainforest therefore have consequences for global sustainability. In the light of this, the current decisions made in Brazil regarding an increase in Amazon deforestation require policy changes if the global ecosystems and biodiversity are not to be set to collapse. There is only one way to move forward and that is to increase efforts in sustainable development of the region including limitation in deforestation and to continuously measure and monitor the development. The G7 countries have offered Brazil financial support for at least 20 million euros for fighting the forest fires but the president denies receiving such financial support and says that it is more relevant to raise new forests in Europe. In fact, this is exactly what is happening in Denmark and China in order to reduce climate change. Such activities should be global and include South America, Europe, Africa and Asia where deforestation is important issue. Forest restoration reduces climate change, desertification, and preserves both the regional tropical and global environment if the wood is not burned at a later stage but instead used in e.g. roads as filling material. Changes are therefore needed through improved international understanding and agreements to better avoid the global climate changes, from cutting down the precious rainforest before it is too late as rainforest cannot be re-planted.


Assessing the impact of copy number variants on miRNA genes in autism by Monte Carlo simulation.
Autism Spectrum Disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies have investigated the role of de novo Copy Number Variants (CNVs) and microRNAs as important but distinct etiological factors in ASD. We developed a novel computational procedure to assess the potential pathogenic role of microRNA genes overlapping de novo CNVs in ASD patients. Here we show that for chromosomes # 1, 2 and 22 the actual number of miRNA loci affected by de novo CNVs in patients was found significantly higher than that estimated by Monte Carlo simulation of random CNV events. Out of 24 miRNA genes over-represented in CNVs from these three chromosomes only hsa-mir-4436b-1 and hsa-mir-4436b-2 have not been detected in CNVs from non-autistic subjects as reported in the Database of Genomic Variants. Altogether the results reported in this study represent a first step towards a full understanding of how a dysregulated expression of the 24 miRNAs genes affect neurodevelopment in autism. We also propose that the procedure used in this study can be effectively applied to CNVs/miRNA genes association data in other genomic disorders beyond autism.


Alpha-Linolenic Acid-Enriched Butter Promotes Fatty Acid Remodeling and Thermogenic Activation in the Brown Adipose Tissue.
Supplementation with n-3 long-chain (LC) polyunsaturated fatty acids (PUFA) is known to promote thermogenesis via the activation of brown adipose tissue (BAT). Agricultural products that are biofortified with α-linolenic acid (ALA), the precursor of n-3 LC PUFA, have been launched to the market, but their impact on BAT function is unknown. This study aimed to evaluate the effects of ALA-biofortified butter on lipid metabolism and thermogenic functions in the BAT. C57BL/6 mice were fed a high-fat diet containing ALA-biofortified butter (n3Bu, 45% calorie from fat) for ten weeks in comparison with the isocaloric high-fat diets prepared from conventional butter or margarine. The intake of n3Bu significantly reduced the whitening of BAT and increased the thermogenesis in response to acute-cold treatment. Also, n3Bu supplementation is linked with the remodeling of BAT by promoting bioconversion into n-3 LC PUFA, FA elongation and desaturation, and mitochondrial biogenesis. Taken together, our results support that ALA-biofortified butter is a novel source of n-3 PUFA, which potentiates the BAT thermogenic function.


P-Rex1 is required for efficient melanoblast migration and melanoma metastasis.
Metastases are the major cause of death from melanoma, a skin cancer that has the fastest rising incidence of any malignancy in the Western world. Molecular pathways that drive melanoblast migration in development are believed to underpin the movement and ultimately the metastasis of melanoma. Here we show that mice lacking P-Rex1, a Rac-specific Rho GTPase guanine nucleotide exchange factor, have a melanoblast migration defect during development evidenced by a white belly. Moreover, these P-Rex1(-/-) mice are resistant to metastasis when crossed to a murine model of melanoma. Mechanistically, this is associated with P-Rex1 driving invasion in a Rac-dependent manner. P-Rex1 is elevated in the majority of human melanoma cell lines and tumour tissue. We conclude that P-Rex1 has an important role in melanoblast migration and cancer progression to metastasis in mice and humans.


National practice in antibiotic prophylaxis in breast cancer surgery.
Although breast cancer surgery is regarded as a "clean" surgery, surgical site infection (SSI) rates are higher than expected. There is no consensus regarding the use of antibiotic prophylaxis in elective breast surgery. The nationwide survey was conducted to determine the trend of antibiotic prophylaxis in breast cancer among Turkish surgeons. The survey was sent to surgeons who are member of Turkish Surgical Association (TSA) via e-mail from TSA web address. A 15 item web-based survey consisted of surgeon demographics and the use of prophylactic antibiotic in patients with risk factors related to SSI. The number of completed questionnaires was 245. The most common antibiotic used was first generation of cephalosporins. A majority of respondents indicated that prophylaxis was preferred in patients with high risk of SSI including preoperative chemotherapy or radiotherapy, older age, diabetes mellitus, immunodeficiency, immediate reconstruction (P < 0.05). However, the use of drain did not significantly influence antibiotic prophylaxis (P = 0.091). The use of prophylactic antibiotic was strongly dependent on the presence of some risk factors; however, the variation in current practice regarding antibiotic prophylaxis demonstrated a lack of its effect on preventing SSI after breast cancer surgery.


Dietary behaviour and socioeconomic position: the role of physical activity patterns.
The positive association between education level and health outcomes can be partly explained by dietary behaviour. We investigated the associations between education and several indices of food intake and potential influencing factors, placing special emphasis on physical-activity patterns, using a representative sample of the German adult population. The German National Health Interview and Examination Survey 1998 (GNHIES98) involved 7,124 participants aged between 18 and 79. Complete information on the exposure (education) and outcome (nutrition) variables was available for 6,767 persons. The associations between 'education' and indices of 'sugar-rich food', 'fat-rich food', 'fruit-and-vegetable' and 'alcohol' intake were analysed separately for men and women using multivariate logistic regression analysis. Odds ratios (OR) of education level on nutrition outcomes were calculated and adjusted for age, region (former East/West Germany), occupation, income and other influencing factors such as physical activity indicators. Men and women with only a primary education had a more frequent intake of sugar-rich and fat-rich foods and a less frequent intake of fruit and vegetables and alcohol than people with a tertiary education. 'Physical work activity' partly explained the associations between education and sugar-rich food intake. The interference with physical work activity was stronger among men than women. No significant associations between education and energy-dense food intake were observed in the retirement-age group of persons aged 65+ and among persons with low energy expenditure. In Germany, adults with a low level of education report that they consume energy-dense foods more frequently - and fruit and vegetables and alcohol less frequently - than adults with a high education level. High levels of physical work activity among adults with a low education level may partly explain why they consume more energy-dense foods.


Analysis of cubitus interruptus regulation in Drosophila embryos and imaginal disks.
The cubitus interruptus (ci) gene of Drosophila is expressed in all anterior compartment cells in both embryos and imaginal disks where it encodes a putative zinc-finger protein related to the vertebrate Gli and C. elegans Tra-1 proteins. Using ci/lacZ fusions, we located regulatory sequences responsible for the normal pattern of ci expression, and obtained evidence that separate elements regulate its expression in embryos and imaginal disks. Mutants that delete a portion of this regulatory region express ci ectopically in the posterior compartments of their wing imaginal disks and have wings with malformed posterior compartments. Similar deletions of ci/lacZ fusion constructs also result in ectopic posterior compartment expression. Evidence that the engrailed protein normally represses ci in posterior compartments includes the expansion of ci expression into posterior compartment cells that lack engrailed function, diminution of ci expression upon overexpression of engrailed protein in anterior compartment cells, and the ability of engrailed protein to bind to the ci regulatory region in vivo and in vitro. We suggest that engrailed protein directly represses ci expression in posterior compartment cells.


Calcium Enhances Bile Salt-Dependent Virulence Activation in Vibrio cholerae.
Vibrio cholerae is the causative bacteria of the diarrheal disease cholera, but it also persists in aquatic environments, where it displays an expression profile that is distinct from that during infection. Upon entry into the host, a tightly regulated circuit coordinates the induction of two major virulence factors: cholera toxin and a toxin-coregulated pilus (TCP). It has been shown that a set of bile salts, including taurocholate, serve as host signals to activate V. cholerae virulence through inducing the activity of the transmembrane virulence regulator TcpP. In this study, we investigated the role of calcium, an abundant mental ion in the gut, in the regulation of virulence. We show that whereas Ca2+ alone does not affect virulence, Ca2+ enhances bile salt-dependent virulence activation for V. cholerae The induction of TCP by murine intestinal contents is counteracted when Ca2+ is depleted by the high-affinity calcium chelator EGTA, suggesting that the calcium present in the gut is a relevant signal for V. cholerae virulence induction in vivo We further show that Ca2+ enhances virulence by promoting bile salt-induced TcpP-TcpP interaction. Moreover, fluorescence recovery after photobleaching (FRAP) analysis demonstrated that exposure to bile salts and Ca2+ together decreases the recovery rate for fluorescently labeled TcpP, but not for another inner membrane protein (TatA). Together, these data support a model in which physiological levels of Ca2+ may result in altered bile salt-induced TcpP protein movement and activity, ultimately leading to an increased expression of virulence.


Effects of basal insulin analog and metformin on glycaemia control and weight as risk factors for endothelial dysfunction.
Obese patients with type 2 diabetes and impaired glucose tolerance are at increased risk of development of cardiovascular diseases. Endothelial dysfunction may be a reason for development of atherosclerosis and cardiovascular diseases. Lifestyle modification, increased physical activity, weight reduction, energy restricted diet and good glycaemia control can be useful for the endothelial function improvement and may decrease the risk of cardiovascular diseases. The aim of this study was to evaluate the effects of basal insulin analog and metformin on glycaemia control and weight as risk factors of endothelial dysfunction. Total of 15 patients (9 male and 6 female) with type 2 diabetes were studied. The patients were monitored over six months period. Glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body mass index (BMI) were observed. Mean age of the subjects was 53,4 +/- 6,27 years. Mean diabetes duration was 3,71 +/- 1,89 years. At the end of the study mean body mass index decreased from 27,5 +/- 1,45 kg/m2 to 25,7 +/-1,22 kg/m2. In this study we included diabetic patients with fasting glycaemia over 7 mmol/dm3, postmeal glycaemia over 7,8 mmol/dm3 and glycated hemoglobin over 7%. Prior to the study, the patients were treated with premix insulin divided in two daily doses and metformin after the lunch, which did not result in sufficient regulation of glycaemia. We started treatment with one daily insulin basal analog and three daily doses of metformin and monitored the above mentioned parameters. We advised patients to change their lifestyle, to practice energy restricted diet and to increase their daily physical activity. Insulin doses were titrated separately for each patient (0,7-1 IU/kg). Weight reduction was recorded after the study. Mean fasting glycaemia decreased from 8,6+/-0,49 mmol/dm3 to 7,04+/-0,19 mmol/dm3 (p < 0,05). Mean postmeal glycaemia decreased from 9,74 +/- 0,79 mmol/dm3 to 7,6 +/- 0,43 mmol/dm3 (p<0,05). Mean HbA1c decreased from 8,80 +/- 0,59 % to 7,11 +/- 0,22 % (p<0,05). Treatment with one daily doses of basal insulin analog and three daily doses of metformin with lifestyle modification and weight reduction, in obese patients with type 2 diabetes can be useful for the endothelial function improvement and may decrease the risk of cardiovascular diseases.


Consuming organic versus conventional vegetables: the effect on nutrient and contaminant intakes.
The health benefits of consuming organic compared to conventional foods are unclear. This study aimed at evaluating the nutrient and contaminant intake of adults through consumption of organic versus conventional vegetables, namely carrots, tomatoes, lettuce, spinach and potatoes. A probabilistic simulation approach was used for the intake assessment in two adult populations: (1) a representative sample of Belgians (n=3245) and (2) a sample of Flemish organic and conventional consumers (n=522). Although significant differences in nutrient and contaminant contents were previously found between organic and conventional vegetables, they were inconsistent for a component and/or vegetable. These findings were translated here into inconsistent intake assessments. This means that the intake of specific nutrients and contaminants can be higher or lower for organic versus conventional vegetables. However, when considering the consumption pattern of organic consumers, an increase in intake of a selected set of nutrients and contaminants is observed, which are explained by the general higher vegetable consumption of this consumer group. In public health terms, there is insufficient evidence to recommend organic over conventional vegetables. The general higher vegetable consumption of organic compared to conventional consumers outweighs usually the role of differences in nutrient and contaminant concentrations between organic and conventional vegetables.


Mislocalization of the cell polarity protein scribble promotes mammary tumorigenesis and is associated with basal breast cancer.
Scribble (SCRIB) localizes to cell-cell junctions and regulates establishment of epithelial cell polarity. Loss of expression of SCRIB functions as a tumor suppressor in Drosophila and mammals; conversely, overexpression of SCRIB promotes epithelial differentiation in mammals. Here, we report that SCRIB is frequently amplified, mRNA overexpressed, and protein is mislocalized from cell-cell junctions in human breast cancers. High levels of SCRIB mRNA are associated with poor clinical prognosis, identifying an unexpected role for SCRIB in breast cancer. We find that transgenic mice expressing a SCRIB mutant [Pro 305 to Leu (P305L)] that fails to localize to cell-cell junctions, under the control of the mouse mammary tumor virus long terminal repeat promoter, develop multifocal hyperplasia that progresses to highly pleomorphic and poorly differentiated tumors with basal characteristics. SCRIB interacts with phosphatase and tensin homolog (PTEN) and the expression of P305L, but not wild-type SCRIB, promotes an increase in PTEN levels in the cytosol. Overexpression of P305L, but not wild-type SCRIB, activates the Akt/mTOR/S6K signaling pathway. Human breast tumors overexpressing SCRIB have high levels of S6K but do not harbor mutations in PTEN or PIK3CA, identifying SCRIB amplification as a mechanism of activating PI3K signaling in tumors without mutations in PIK3CA or PTEN. Thus, we demonstrate that high levels of mislocalized SCRIB functions as a neomorph to promote mammary tumorigenesis by affecting subcellular localization of PTEN and activating an Akt/mTOR/S6kinase signaling pathway.


Graphene-based plasmonic switches at near infrared frequencies.
The concept, analysis, and design of series switches for graphene-strip plasmonic waveguides at near infrared frequencies are presented. Switching is achieved by using graphene's field effect to selectively enable or forbid propagation on a section of the graphene strip waveguide, thereby allowing good transmission or high isolation, respectively. The electromagnetic modeling of the proposed structure is performed using full-wave simulations and a transmission line model combined with a matrix-transfer approach, which takes into account the characteristics of the plasmons supported by the different graphene-strip waveguide sections of the device. The performance of the switch is evaluated versus different parameters of the structure, including surrounding dielectric media, electrostatic gating and waveguide dimensions.


[Maternal and child health indicators in Belo Horizonte, Minas Gerais State, Brazil, 2001: an analysis of intra-urban differences].
Spatial analysis of health indicators is as an important methodology for detection of intra-urban differences. This study aimed to examine the spatial distribution of all live births in Belo Horizonte, analyzing the presence of spatial clusters of health indicators for newborns and their mothers, using data from the Information System on Live Births. For each area covered by a Primary Health Care Unit, we calculated the indicators using empirical Bayesian methods. For spatial analysis, the indicators obtained from the global Moran (I) index and Local Indicators of Spatial Association (LISA) were used. Analysis using LISA showed the presence of relevant spatial clusters for adolescent mothers and those with low schooling, stillbirths in previous pregnancies, cesarean sections, and low attendance at prenatal care, especially in areas with low socio-demographic characteristics. The methodology adopted was configured as a key instrument for detecting risk areas where clustering occurs. The method can easily be incorporated into health surveillance systems as a mechanism for controlling events related to births in a given area.


Dendrimer-Fullerenol Soft-Condensed Nanoassembly.
Nanoscale assembly is an area of research that has vast implications for molecular design, sensing, nanofabrication, supramolecular chemistry, catalysis, and environmental remediation. Here we show that poly(amidoamine) (PAMAM) dendrimers of both generations 1 (G1) and 4 (G4) can host 1 fullerenol per 2 dendrimer primary amines as evidenced by isothermal titration calorimetry, dynamic light scattering and spectrofluorometry. Thermodynamically, the interactions were similarly spontaneous between both generations of dendrimers and fullerenols, however, G4 formed stronger complexes with fullerenols resulting from their higher surface charge density and more internal voids, as demonstrated by spectrofluorometry. In addition to hydrogen bonding that existed between the dendrimer primary amines and the fullerenol oxygens, hydrophobic and electrostatic interactions also contributed to complex formation and dynamics. Such hybrid of soft and condensed nanoassembly may have implications for environmental remediation of discharged nanomaterials and entail new applications in drug delivery.


Modulation of delayed rectifier potassium current, iK, by isoprenaline in rabbit isolated pacemaker cells.
Permeabilized patch whole-cell voltage clamp methods were used to investigate the effects of isoprenaline (ISO) on total delayed rectifier potassium current, iK, in rabbit sino-atrial (SA) node pacemaker cells; total iK is composed of the rapidly activating iKr and the slowly activating iKs, but predominantly iKr in this species. ISO (20 nM) increased the amplitude of total iK and caused a negative shift of approximately 10 mV in the activation curve for iK, both in the absence and in the presence of 300 nM nisoldipine to block the L-type Ca2+ current, iCa,L. The same concentration (20 nM) of ISO increased the spontaneous pacemaker rate of SA node pacemaker cells by 16%. In addition to increasing the amplitude of iK, ISO (20-50 nM) also increased the rate of deactivation of this current. The stimulation of iK by ISO was reversed by 10 microM H-89, a selective protein kinase A inhibitor, but not by 200 nM bisindolymaleimide I, a selective protein kinase C inhibitor. It therefore appears that the mechanisms by which -adrenoceptor agonists increase pacemaking rate in sinoatrial node pacemaker cells include an increase in the rate of deactivation of iK in addition to the well-documented augmentation of iCa,L and the positive shift of the activation curve for the hyperpolarization-activated inward current, if. The observations are also consistent with a role for protein kinase A in the stimulation of iK by ISO in SA node cells.


Dark current and noise analyses of quantum dot infrared photodetectors.
Because the dark current and the noise of quantum dot infrared photodetectors (QDIPs) can bring about a degradation in their performance, they have attracted more and more attention in recent years. In this paper, an algorithm used to evaluate the dark current of the QDIP is proposed, which is based on the algorithm including the common contribution of the microscale and the nanoscale electron transport. Namely, by accounting for the dependence of the drift velocity on the applied electric field, we greatly enhance the accuracy of the dark current calculation compared with that in the previous algorithm. This proposed algorithm is further used to estimate the noise current of QDIP, and the calculated results show a good agreement with the published data.


Strengthening and updating supervising staff nurses in educational workshops--an international partnership project.
As part of a collaborative project involving Tanzania and Sweden, workshops were arranged for staff nurses in order to develop a forum for discussing the raised demands for supervision of nursing students during their clinical education. The aim was to meet nurses in educational workshops to initiate a dialogue on their views and experiences of supporting and supervising nursing students in their clinical studies. Their experiences of the workshops were also requested. Two groups of nurses in Tanzania (n=30), and six groups in Sweden (n=60) participated. The content, which was agreed between the project leaders in Tanzania and Sweden was carried out either on a whole day workshops or divided at three different occasions. Questionnaires were given before and about two months after, and workshops were also evaluated with an open-ended question immediately after. The nurses both in Tanzania and in Sweden appreciated the workshops as a possibility to create a dialogue and to discuss challenges in the supervision of students. Their views and experiences of the supervision role showed awareness of staff nurses as role models and teachers. Accomplishment of this partnership co-operation through arranging workshops has shown to be an easy and simple way of giving support to staff nurses for the supervision task.


Challenges and opportunities for nutrition education and training in the health care professions: intraprofessional and interprofessional call to action.
Understanding and applying nutrition knowledge and skills to all aspects of health care are extremely important, and all health care professions need basic training to effectively assess dietary intake and provide appropriate guidance, counseling, and treatment to their patients. With obesity rates at an all-time high and the increasing prevalence of diabetes projected to cost the Federal government billions of dollars, the need for interprofessional nutrition education is paramount. Physicians, physician assistants, nurses, nurse practitioners, pharmacists, dentists, dental hygienists, occupational therapists, physical therapists, speech and language pathologists, and others can positively affect patient care by synchronizing and reinforcing the importance of nutrition across all specialty areas. Although nutrition is a critical component of acute and chronic disease management, as well as health and wellness across the health care professions, each profession must reevaluate its individual nutrition-related professional competencies before the establishment of meaningful interprofessional collaborative nutrition competencies. This article discusses gaps in nutrition education and training within individual health professions (ie, nursing, pharmacy, dentistry, and dietetics) and offers suggestions for educators, clinicians, researchers, and key stakeholders on how to build further capacity within the individual professions for basic and applied nutrition education. This "gaps methodology" can be applied to all health professions, including physician assistants, physical therapists, speech and language pathologists, and occupational therapists.


Anti-dengue activity of Andrographis paniculata extracts and quantification of dengue viral inhibition by SYBR green reverse transcription polymerase chain reaction.
Dengue virus is a leading cause of illness and death in the tropics and subtropics. As many as 400 million people are infected yearly. Dengue is caused by any one of four related viruses transmitted by mosquitoes. Currently, there is no vaccine to prevent infection with dengue virus and the most effective protective measures are those that avoid mosquito bites. When infected, early recognition and prompt supportive treatment can substantially lower the risk of medical complications and death. Nowadays, the search for natural plant products to fight against viral diseases has been increasing. To test the anti-dengu viral activity of both ethanolic & aqueous extract of Andrographis paniculata. In vitro antiviral activity were performed against dengue virus by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and SYBR green quantitative real-time polymerase chain reaction (PCR) method. Cytotoxicity was also evaluated by MTT. The dengue viral load (VL) inhibition in plant extracts was characterized by reverse transcription PCR (RT-PCR) analysis. In this study, the maximum nontoxic dose (MNTD) of A. paniculata plant was determined by testing the ethanolic extracts against Vero cells in vitro. Antiviral assay based on cytopathic effects denoted by degree of inhibition upon treating DENV 1-4-infected Vero cells with MNTD of A. paniculata has the most antiviral inhibitory effects. These results were further verified with an in vitro inhibition assay using MTT and RT-PCR, in which 55%-97% of cell viability were recorded in DENV-1-4-infected cells in different duration. Ethanolic extracts treated with dengue VLs also showed a significant changes which were reflected in RT PCR assay.


Plasma nitrogen oxides and blood lactate concentrations in Ghanaian children with malaria.
Nitric oxide is an important host defence molecule as well as being a mediator in many pathophysiological processes. To investigate its role in severe malaria, we measured plasma nitrate and nitrite concentrations in 70 children with malaria (54 with severe malaria) and 48 control subjects (33 with medical conditions and 15 surgical patients). We related these measurements to plasma lactate concentrations, an established marker of disease severity in malaria. Plasma lactate levels were significantly elevated in patients with deep coma (P = 0.0007) and those with a fatal outcome, but mean nitrogen oxide concentrations were not significantly different in the 2 outcome categories and were not related to depth of coma (P > 0.5). In patients whose cerebrospinal fluid (CSF) was examined, lactate concentrations were elevated in fatal cases (geometric mean 8.2 mmol/L, n = 5) compared with survivors (3.4 mmol/L, n = 13; P = 0.032); corresponding CSF nitrogen oxide concentrations were 10.7 microM in fatal cases compared with 12.5 microM in survivors (P = 0.5). Plasma nitrogen oxide concentrations were negatively correlated with admission parasitaemia (r = -0.41, n = 70; P < 0.0001). In our population, elevations of plasma lactate, but not nitrite or nitrate, reflected disease severity in malaria.


EFAD transgenic mice as a human APOE relevant preclinical model of Alzheimer's disease.
Identified in 1993, APOE4 is the greatest genetic risk factor for sporadic Alzheimer's disease (AD), increasing risk up to 15-fold compared with APOE3, with APOE2 decreasing AD risk. However, the functional effects of APOE4 on AD pathology remain unclear and, in some cases, controversial. In vivo progress to understand how the human (h)-APOE genotypes affect AD pathology has been limited by the lack of a tractable familial AD-transgenic (FAD-Tg) mouse model expressing h-APOE rather than mouse (m)-APOE. The disparity between m- and h-apoE is relevant for virtually every AD-relevant pathway, including amyloid-β (Aβ) deposition and clearance, neuroinflammation, tau pathology, neural plasticity and cerebrovascular deficits. EFAD mice were designed as a temporally useful preclinical FAD-Tg-mouse model expressing the h-APOE genotypes for identifying mechanisms underlying APOE-modulated symptoms of AD pathology. From their first description in 2012, EFAD mice have enabled critical basic and therapeutic research. Here we review insights gleaned from the EFAD mice and summarize future directions.


The contribution of scene context on change detection performance.
The gist of a visual scene is perceived in a fraction of a second but in change detection tasks subjects typically need several seconds to find the changing object in a visual scene. Here, we report influences of scene context on change detection performance. Scene context manipulations consisted of scene inversion, scene jumbling, where the images were cut into 24 pieces and randomly recombined, and scene configuration scrambling, where the arrangement of the objects in the scene was randomized. Reaction times, where significantly lower in images with normal scene context. We conclude that scene context structures scene perception.


Time trends in the prevalence of cancer and non-cancer diseases among older U.S. adults: Medicare-based analysis.
Longer lifespan is accompanied by a larger number of chronic diseases among older adults. Because of a growing proportion of older adults in the U.S., this brings the problem of age-related morbidity to the forefront as a major contributor to rising medical expenditures. We evaluated 15-year time trends (from 1998 to 2013) in the prevalence of 48 acute and chronic non-cancer diseases and cancers in older U.S. adults aged 65+ and estimated the annual percentage changes of these prevalence trends using SEER-Medicare and HRS-Medicare data. We found that age-adjusted prevalence of cancers of kidney, pancreas, and melanoma, as well as diabetes, renal disease, limb fracture, depression, anemia, weight deficiency, dementia/Alzheimer's disease, drug/medications abuse and several other diseases/conditions increased over time. Conversely, prevalence of myocardial infarction, heart failure, cardiomyopathy, pneumonia/influenza, peptic ulcer, and gastrointestinal bleeding, among others, decreased over time. There are also diseases whose prevalence did not change substantially over time, e.g., a group of fast progressing cancers and rheumatoid arthritis. Analysis of trends of multiple diseases performed simultaneously within one study design with focus on the same time interval and the same population for all diseases allowed us to provide insight into the epidemiology of these conditions and identify the most alarming and/or unexpected trends and trade-offs. The obtained results can be used for health expenditures planning for growing sector of older adults in the U.S.


Interconnected network motifs control podocyte morphology and kidney function.
Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3',5'-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element-binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor-driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease.


Effect of a commercial alcohol ethoxylate surfactant (C11-15E7) on biodegradation of phenanthrene in a saline water medium by Neptunomonas naphthovorans.
Biodegradation of poorly soluble polycyclic aromatic hydrocarbons (PAHs) has been a challenge in bioremediation. In recent years, surfactant-enhanced bioremediation of PAH contaminants has attracted great attention in research. In this study, biodegradation of phenanthrene as a model PAHs solubilized in saline micellar solutions of a biodegradable commercial alcohol ethoxylate nonionic surfactant was investigated. The critical micelle concentration (CMC) of the surfactant and its solubilization capacity for phenanthrene were examined in an artificial saline water medium, and a type of marine bacteria, Neptunomonas naphthovorans, was studied for the biodegradation of phenanthrene solubilized in the surfactant micellar solutions of the saline medium. It is found that the solubility of phenanthrene in the surfactant micellar solutions increased linearly with the surfactant concentrations, but, at a fixed phenanthrene concentration, the biodegradability of phenanthrene in the micellar solutions decreased with the increase of the surfactant concentrations. This was attributed to the reduced bioavailability of phenanthrene, due to its increased solubilization extent in the micellar phase and possibly lowered mass transfer rate from the micellar phase into the aqueous phase or into the bacterial cells. In addition, an inhibitory effect of the surfactant on the bacterial growth at high surfactant concentrations may also play a role. It is concluded that the surfactant largely enhanced the solubilization of phenanthrene in the saline water medium, but excess existence of the surfactant in the medium should be minimized or avoided for the biodegradation of phenanthrene by Neptunomonas naphthovorans.


Androgen receptor remains critical for cell-cycle progression in androgen-independent CWR22 prostate cancer cells.
The majority of prostate cancers (PCa) that relapse after androgen deprivation therapy (androgen-independent PCa) continue to express androgen receptor (AR). To study the functional importance of AR in these tumors, we derived androgen-independent CWR22 PCa xenografts in castrated mice and generated a cell line from one of these xenografts (CWR22R3). Similarly to androgen-independent PCa in patients, the relapsed xenografts and cell line expressed AR and were resistant to treatment with bicalutamide. However, expression of the AR-regulated PSA gene in the CWR22R3 cell line was markedly decreased compared to the relapsed xenografts in vivo. Transfections with androgen-regulated reporter genes further indicated that the cells lacked androgen-independent AR transcriptional activity and were not hypersensitive to low androgen concentrations despite constitutive activation of the Erk/MAP kinases. Nonetheless, AR remained essential for androgen-independent growth because retroviral shRNA-mediated AR down-regulation resulted in marked long-term growth suppression. This was associated with increased levels of p27(kip1) and hypophosphorylation of retinoblastoma protein but not with decreases in D-type cyclin levels or MAP kinase activation. These results reveal a potentially critical function of AR in androgen-independent PCa that is distinct from its previously described transcriptional or nontranscriptional functions.


Effect of changing female stimulus on intensive semen collection in young Murciano-granadina male goats.
The aim of this research was to study the effect of changing female stimulus on libido and semen characteristics from young Murciano-granadina male goats submitted to intensive semen collection using females not in estrus as teasers. Males were submitted to two different sexual stimulation procedures. In the first procedure, the same doe was used as the female stimulus for three consecutive presentations. In the second, the doe was replaced after the second presentation by a new female. Semen volume, concentration, forward progressive motility, and live spermatozoa were scored. To analyze reaction time (RT), three types of analysis were performed. In the first one, RT was analyzed by multifactor ANOVA, taking as a missing value 300 s when a buck did not ejaculate. In the second, RT also was analyzed by multifactor ANOVA, but data from males that did not ejaculate were removed. In the third, a Cox Survival analysis was carried out by censoring data when a buck did not ejaculate within 5 min of entering the test arena. A decrease in semen volume and sperm concentration in the successive ejaculations was observed, being highly marked in the third ejaculation independent of the stimulation procedure (0.62 vs. 0.38 and 0.43 mL, and 2,828 vs. 2,183 and 2,223 million spermatozoa/mL to the first and third ejaculation respectively; P < 0.05). No significant differences were observed either in forward progressive motility or live sperm rate. Changing the female stimulus in the third presentation had no significant effect on any seminal characteristic. Regarding libido and mounting behavior variables, there was a substantial decrease in RT in the third service when the female was changed (with both types of ANOVA). When censored data were taken into account, the relative risk showed that the probability of a male ejaculating in the third presentation increased almost fourfold when the female was replaced than when the female was the same in all services (P < 0.05). In conclusion, young Murciano-granadina bucks can be used as semen donors because none of the most important semen variables used to reject or accept an ejaculate before freezing process decreased after intensive semen collection. We also recommend changing the female stimulus to make the semen collection procedure more efficient and using survival analysis methodology to analyze time data, mainly when a high rate of censored data are scored.


The Effect of DPT-1 Intravenous Insulin Infusion and Daily Subcutaneous Insulin on Endogenous Insulin Secretion and Postprandial Glucose Tolerance.
To investigate the effect of parenteral insulin therapy on endogenous insulin secretion in the Diabetes Prevention Trial-Type 1 (DPT-1). In the parenteral insulin arm of DPT-1, subjects without diabetes at high risk of future type 1 diabetes randomized to active treatment received a yearly 4-day intravenous insulin infusion (IV-I) and daily subcutaneous insulin (SC-I). To examine the effects of these insulin therapies on endogenous insulin secretion, C-peptide and glucose levels were compared during oral glucose tolerance tests (OGTTs) performed on and off IV-I and SC-I. Forty-six paired OGTTs were performed in 30 subjects from DPT-1 to determine the effect of IV-I. Twenty paired OGTTs were performed in 15 subjects from DPT-1 to determine the effect of SC-I. IV-I suppressed fasting and OGTT-stimulated C-peptide (62% and 40%, respectively), and it significantly lowered fasting glucose (67.4 ± 4.5 mg/dL during IV-I vs. 90.9 ± 1.8 mg/dL off insulin; P < 0.05). By contrast, post-OGTT glucose levels were significantly higher during IV-I: Glucose during IV-I versus off insulin at 120 min was 203.9 ± 15.1 vs. 151.6 ± 10.2 mg/dL, respectively (P < 0.05); 49% of OGTTs became transiently diabetic (>200 mg/dL at 120 min) when receiving IV-I. Fasting glucose was significantly lower when receiving SC-I versus when off insulin (85 ± 3 vs. 94 ± 2 mg/dL, respectively; P < 0.05), but SC-I did not significantly alter fasting or OGTT-stimulated C-peptide compared with being off insulin. These data demonstrate that the IV-I used in the DPT-1 markedly suppressed endogenous insulin secretion, which was frequently associated with postprandial glucose intolerance. SC-I, however, did not.


Bacterially mediated removal of phosphorus and cycling of nitrate and sulfate in the waste stream of a "zero-discharge" recirculating mariculture system.
Simultaneous removal of nitrogen and phosphorus by microbial biofilters has been used in a variety of water treatment systems including treatment systems in aquaculture. In this study, phosphorus, nitrate and sulfate cycling in the anaerobic loop of a zero-discharge, recirculating mariculture system was investigated using detailed geochemical measurements in the sludge layer of the digestion basin. High concentrations of nitrate and sulfate, circulating in the overlying water (∼15 mM), were removed by microbial respiration in the sludge resulting in a sulfide accumulation of up to 3 mM. Modelling of the observed S and O isotopic ratios in the surface sludge suggested that, with time, major respiration processes shifted from heterotrophic nitrate and sulfate reduction to autotrophic nitrate reduction. The much higher inorganic P content of the sludge relative to the fish feces is attributed to conversion of organic P to authigenic apatite. This conclusion is supported by: (a) X-ray diffraction analyses, which pointed to an accumulation of a calcium phosphate mineral phase that was different from P phases found in the feces, (b) the calculation that the pore waters of the sludge were highly oversaturated with respect to hydroxyapatite (saturation index = 4.87) and (c) there was a decrease in phosphate (and in the Ca/Na molar ratio) in the pore waters simultaneous with an increase in ammonia showing there had to be an additional P removal process at the same time as the heterotrophic breakdown of organic matter.