Ubiquitin specific peptidase 5 mediates Histidine-rich protein Hpn induced cell apoptosis in hepatocellular carcinoma through P14-P53 signaling.
Hpn is a small histidine-rich cytoplasmic protein from Helicobacter pylori and has been recognized as a high-risk factor for several cancers including gastric cancer, colorectal cancer, and MALT lymphoma. However, the relationship between Hpn and cancers remains elusive. In this study, we discovered that Hpn protein effectively suppressed cell growth and induced apoptosis in hepatocellular carcinoma (HCC). A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics was performed to find the molecular targets of Hpn in HCC cells. It was identified that twelve proteins were differentially expressed, with USP5 being one of the most significantly downregulated protein. The P14ARF -P53 signaling was activated by USP5 knockdown in HCC cells. Furthermore, USP5 overexpression significantly rescued the suppressive effect of Hpn on the viability of HCC cells. In conclusion, our study suggests that Hpn plays apoptosis-inducing roles through suppressing USP5 expression and activating the P14ARF -P53 signaling. Therefore, Hpn may be a potential candidate for developing novel anti-HCC drugs.


Proprioceptive input from the jaw muscles and its influence on lapping, chewing, and posture.
Experiments are described which define criteria for identifying fusimotor axons discharging in filaments of the masseter nerve in lightly anaesthetized cats. During reflex movements of the jaw two patterns of discharge were observed in different fusimotor fibres. One type, called "sustained," fired at a fairly constant increased rate. The other, called "modulated," fired at high frequencies during the extrafusal muscle contraction. Evidence from spindle primary and secondary recordings in similar experiments strongly suggests that the "sustained" type were dynamic fusimotor fibres and the "modulated" type were static fusimotor fibres. New spindle recordings in normal unanaesthetized cats indicate that the modulated pattern of static fusimotor discharge also occurs in these conditions. Its effect is to reduce the tendency for spindle afferents to become silent during muscle shortening. A proposal is made that the static fusimotor discharge in cyclic movements may represent a temporal "template" for the intended movement as directed by the central pattern generator.


Generalized optimal risk allocation: foraging and antipredator behavior in a fluctuating environment.
Animals live in complex environments in which predation risk and food availability change over time. To deal with this variability and maximize their survival, animals should take into account how long current conditions may persist and the possible future conditions they may encounter. This should affect their foraging activity, and with it their vulnerability to predation across periods of good and bad conditions. Here we develop a comprehensive theory of optimal risk allocation that allows for environmental persistence and for fluctuations in food availability as well as predation risk. We show that it is the duration of good and bad periods, independent of each other, rather than the overall proportion of time exposed to each that is the most important factor affecting behavior. Risk allocation is most pronounced when conditions change frequently, and optimal foraging activity can either increase or decrease with increasing exposure to bad conditions. When food availability fluctuates rapidly, animals should forage more when food is abundant, whereas when food availability fluctuates slowly, they should forage more when food is scarce. We also show that survival can increase as variability in predation risk increases. Our work reveals that environmental persistence should profoundly influence behavior. Empirical studies of risk allocation should therefore carefully control the duration of both good and bad periods and consider manipulating food availability as well as predation risk.


Protein tyrosine kinase activation is required for lipopolysaccharide induction of cytokines in human blood monocytes.
Bacterial LPS induce production of cytokines such as IL-1, IL-6, and TNF in mononuclear phagocytes, and this represents a central component in the pathogenesis of septic shock syndrome. However, the mechanisms by which LPS activates these cells to express cytokines are not completely characterized. The present study addressed the role of different protein kinases in the LPS induction of cytokines. It is shown that LPS induced a 12- to 16-fold increase in IL-1 beta, IL-6, and TNF-alpha mRNA levels, and this was completely or more than 80% blocked by the protein tyrosine kinase specific inhibitors herbimycin A and genistein at the concentrations of 1.7 and 37 microM, respectively. Protein kinase C inhibition by staurosporine reduced LPS induction of TNF-alpha, whereas it had no effects on IL-6 and IL-1 beta. Inhibition of protein kinase A by H89 reduced IL-6 mRNA levels but did not detectably change IL-1 beta or TNF-alpha mRNA levels. In contrast, LPS did not increase leukemia inhibitory factor mRNA, which was constitutively expressed and not significantly reduced by these inhibitors. In addition to cytokine mRNA levels, LPS-induced IL-6 protein synthesis and IL-6 bioactivity were also reduced to baseline levels by the PTK inhibitors herbimycin A and genistein. Both PTK inhibitors also reduced the LPS activation of nuclear factor-kappa B (NF-kappa B), which is a transcription factor involved in the expression of cytokine genes such as IL-6 and TNF-alpha. The activation of NF-kappa B was also reduced by H89, whereas staurosporine had no effect on this response. In summary, these findings suggest that protein kinase C and protein kinase A appear to have selective effects in the LPS induction of cytokines, whereas PTK is required for LPS induction of a broad spectrum of cytokines and NF-kappa B activation in monocytes.


Nitric oxide-dependent soluble guanylate cyclase activity is decreased in platelets from male NIDDM patients.
To elucidate the underlying mechanisms of platelet dysfunction in diabetes mellitus, we examined the activity of soluble guanylate cyclase (sGC), a key enzyme in the nitric oxide (NO)-related signalling pathway, in platelets from NIDDM (non-insulin dependent diabetes mellitus) patients. The sGC activity was determined by measuring the amount of cyclic GMP produced in platelet cytosol. In the first study, we investigated the platelet sGC activity in untreated NIDDM patients without diabetic complications. In the male NIDDM patients, sodium nitroprusside (SNP) caused a significantly lower sGC response than that in age-matched control male subjects, while the enzyme activity of female diabetics did not differ from that in the controls. Secondly, we investigated effects of diabetic-associated factors on the enzyme activity in the male NIDDM patients. There was no difference in the SNP-stimulated sGC activity in platelets from male diabetics between with and without retinopathy. In the male diabetic patients with retinopathy, however, the platelet sGC activity was slightly increased by treatment with insulin. Interestingly, the changes in enzyme activity did not correlate with plasma glycosylated hemoglobin A1c levels in diabetic patients. The impairment of the NO-related signalling pathway may contribute to the platelet dysfunction observed in patients with diabetes mellitus.


[Experimental toxocariasis in rabbits: immunological markers of ocular infections].
Rabbits were infected with an oral dose of 50 000 eggs of Toxocara canis or with an intracarotid injection of the second stage larvae of the parasite in order to develop ocular toxocariasis. Serum and ocular fluid samples were collected from the rabbits after 1, 3 and 6 months after infection and examined for specific toxocaral antibodies and circulating parasite antigen. Furthermore, an ophthalmoscopic examination was performed at the time of sampling. None of the infected animals showed the signs of ocular involvement, however, toxocaral IgG antibodies and circulating parasite antigen were present in the anterior chamber fluid samples.


The Men's Shed: providing biopsychosocial and spiritual support.
Community Men's Sheds (CMS) have been a unique approach within Australia for addressing and promoting men's health and well-being issues by providing biopsychosocial support. Given the decline of traditional religious influence, and the contemporary understanding of 'spirituality', it can be argued that CMS may also develop and demonstrate characteristics of a communal spirituality. This research aimed to explore the individual and community contribution of CMS in terms of men's health and well-being and subsequently whether CMS programmes satisfied the contemporary and consensus understanding of spirituality. A qualitative case study was undertaken combining both participant observation over a 6-month period and semi-structured in-depth interviews with 21 men of varying ages and occupations attending a Melbourne suburban CMS (Victoria, Australia). Thematic analysis indicated that the CMS provided a number of health and well-being benefits at individual, family, community and public health levels. These included increased self-esteem and empowerment, respite from families, a sense of belonging in the community and the opportunity to exchange ideas relating to personal, family, communal and public health issues. It is concluded that CMS, through the provision of an appropriate spatial context and organizational activities, encourage intra-personal and inter-personal reflection and interaction that subsequently results in men meaningfully, purposefully and significantly connecting with the moment, to self, to others and to their environment-and thus, CMS not only provides biopsychosocial support but can also deliver spiritual support.


Tracking an object through feature space.
Visual attention allows an observer to select certain visual information for specialized processing. Selection is readily apparent in 'tracking' tasks where even with the eyes fixed, observers can track a target as it moves among identical distractor items. In such a case, a target is distinguished by its spatial trajectory. Here we show that one can keep track of a stationary item solely on the basis of its changing appearance--specified by its trajectory along colour, orientation, and spatial frequency dimensions--even when a distractor shares the same spatial location. This ability to track through feature space bears directly on competing theories of attention, that is, on whether attention can select locations in space, features such as colour or shape, or particular visual objects composed of constellations of visual features. Our results affirm, consistent with a growing body of psychophysical and neurophysiological evidence, that attention can indeed select specific visual objects. Furthermore, feature-space tracking extends the definition of visual object to include not only items with well defined spatio-temporal trajectories, but also those with well defined featuro-temporal trajectories.


Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway.
HIF-1alpha (hypoxia-inducible factor 1alpha) is a basic-helix-loop-helix PAS (Per/Arnt/Sim) transcription factor that, under hypoxic conditions, dimerizes with a partner factor, the basic-helix-loop-helix/PAS protein Arnt, to recognize hypoxia-responsive elements of target genes. It has recently been demonstrated that HIF-1alpha protein but not mRNA levels are dramatically up-regulated in response to hypoxia. Here we show that inhibitors of 26 S proteasome activity produced a dramatic accumulation of endogenous as well as transfected HIF-1alpha protein under normoxic conditions, whereas the levels of Arnt protein were not affected. HIF-1alpha was polyubiquitinated in vivo under normoxic conditions, indicating rapid degradation via the ubiquitin-proteasome pathway. This degradation process appeared to target a region within the C terminus of HIF-1alpha. Importantly, HIF-1alpha ubiquitination was drastically decreased under hypoxic conditions. Up-regulation of HIF-1alpha protein by proteasome inhibitors did not result in transcriptional activation of reporter genes, indicating either the requirement of additional regulatory steps to induce functional activity of HIF-1alpha or the inability of polyubiquitinated forms of HIF-1alpha to mediate hypoxic signal transduction. In support of both these notions, we demonstrate that HIF-1alpha showed hypoxia-dependent translocation from the cytoplasm to the nucleus and that this regulatory mechanism was severely impaired in the presence of proteasome inhibitors. Taken together, these data demonstrate that the mechanism of hypoxia-dependent activation of HIF-1alpha is a complex multistep process and that stabilization of HIF-1alpha protein levels is not sufficient to generate a functional form.


Effect and putative mechanism of action of ginseng on the formation of glycated hemoglobin in vitro.
As a non-enzymatic, covalent binding between glucose and protein, glycation is a well-known cause of various forms of diabetic complications. This study was undertaken to determine the effect and mechanism of action of ginseng on the formation of glycated protein. A solution containing hemoglobin and glucose was incubated for 5 days by adding ginseng extract or glutathione. The quantitative measurement of glycated hemoglobin was determined using the ion capture component set. The anti-oxidative effect of ginseng and quercetin was determined through the TBA method. The amount of glycated hemoglobin (%GHb) significantly increased with the addition of glucose (27.8 mM) compared to the non-addition group. Nonetheless, this significantly decreased when ginseng extract (2 g/dl) was added and further dropped when glutathione (50 mM) was added. The amount of hemoglobin A1c (%HbA1c), a sub-fraction of glycated hemoglobin, was lower than that of glycated hemoglobin, but it showed a similar tendency. Compared to a non-addition group, the optical density of the organic layer that was separated through the addition of chloroform in oxidized linoleic acid significantly and dose-dependently decreased when ginseng extract or quercetin was added. These results suggest that the inhibitory effect of ginseng on the formation of glycated hemoglobin could be attributed to the anti-oxidative activity of ginseng.


Multiple perspectives on diagnosis delay for tuberculosis from key stakeholders in poor rural China: case study in four provinces.
This study aims to understand the contextual barriers to accessing timely TB diagnosis after first seeking care, especially among the poor and vulnerable in rural China. Both quantitative and qualitative methods were used to elicit the experiences and perspectives of TB patients and suspected TB patients, community residents, health providers and policy makers in poor, rural areas of four provinces. Between 30 and 60% of patients across the four provinces experienced a delay in receiving a diagnosis after first seeking care. Most patients had to visit health facilities more than once before diagnosis, with 17-30% patients making more than 6 visits. These delays and multiple visits mainly occurred because of the limited capacity of health providers to recognize TB, and financial disincentives to refer patients to TB dispensaries, due to the pressures of the cost recovery system. Poverty and socio-economic disadvantage amongst patients also influenced their capability to seek further care to obtain a reliable diagnosis. Qualitative data showed that women and the elderly patients were likely to experience more 'system' delay, and these findings were to some extent supported by the survey. The study concludes that 'system' delay is a serious problem, which is influenced by the financing mechanisms for both TB control and general health services as well as poverty and disadvantage amongst patients. This requires a comprehensive strategy to shorten 'system' delay in order to enable successful DOTS expansion, including developing appropriate financing mechanisms to improve general provider capacity and encourage referral, as well as measures to improve financial and social access to services for potential TB patients.


Reaginic bronchial allergy and the occurrence of reagins against mites in a representative sample of a local Swedish population.
This study involves an investigation of 185 subjects, aged 35--54 years, a representative sample of persons with chronic obstructive lung disease in a local Swedish population. Bronchial asthma was diagnosed in 86 persons, chronic bronchitis in 69 and a combination of bronchial asthma and chronic bronchitis in 30. Reaginic bronchial allergy as a provoking factor was considered as definite when the case history, an intracutaneous test, a bronchial provocation test and a radioallergosorbent test were all positive with regard to one and the same allergen. This was found in 28% of the asthmatics. In 16% of the asthmatics, the diagnosis of reaginic bronchial allergy was not supported by all the four diagnostic criteria used but was considered as probable since the case history or the bronchial provocation test was positive in association with a positive RAST or intracutaneous test with the same allergen. Reaginic (IgE) antibodies in serum to mites (Dermatophagoides pteronyssinus) were found in 20 subjects, 18 of whom also had a positive intracutaneous test for house dust. Four of these 20 subjects had definite and 12 had probable reaginic bronchial allergy. One of the remaining four subjects had chronic bronchitis without asthma. The percentage of definite reaginic bronchial allergy may possibly be increased when reliable bronchial provocations with mite allergen can be performed. Increased IgE levels in serum were found in only eight of the 51 asthmatics with reaginic bronchial allergy and in two of the 65 other asthmatics.


Detecting Li Dendrites in a Two-Electrode Battery System.
The use of high-energy-density Li metal anodes in rechargeable batteries is not possible because of dendrite formation that can potentially result in a battery fire. Although so-called dendrite-free Li metal anodes have been reported in many recent publications, Li dendrite growth is still kinetically favorable and it remains a severe safety concern in mass production. Here, a detection system capable of alerting for Li dendrite formation in a two-electrode battery with no additional electrodes required is reported. When dendrites contact a red phosphorous-coated separator, dendrite growth is revealed by a significant voltage change. This can activate a signal through the battery management system, warning of the presence of Li dendrites and leading to shutdown of the battery before the dendrites become dangerous.


Identification of miR-210 and combination biomarkers as useful agents in early screening non-small cell lung cancer.
Recently, extensive researches have explored the potential biomarker roles of microRNA-210 (miR-210) in non-small cell lung cancer (NSCLC). Inconsistent results, however, have prevented its widespread use in diagnosis. In the present study, we aimed to clarify the biomarker roles of miR-210 in NSCLC through a comprehensive meta-analysis and an integrative bioinformatics analysis. Relevant studies were searched from several literature databases and included for qualitative synthesis based on the bivariate random-effects meta-analysis model. At the same time, we combined several bioinformatics analysis methods for exploring the potential mechanism of miR-210 involved in NSCLC. Overall, miR-210 yieled the area under curve (AUC) of 0.80 (95%CI: 0.76-0.83) with sensitivity of 0.66 (0.59-0.73) and specificity of 0.79 0.74-0.84) for being applied to discriminate NSCLC cases from normal individuals. Besides, the combination biomarkers based on miR-210 had a higher diagnostic value accuracy than individual miR-210, with the sensitivity of 0.76 (0.72-0.79), specificity of 0.88 (0.86-0.90) and AUC of 0.91 (0.88-0.93). Through bioinformatics analysis including gene ontology, pathway enrichment, protein-protein interaction networks construction and analysis, crucial genes, pathways, modules and functional terms were identified, which were proved highly involved in the initiation and development of NSCLC. In summary, the current study suggests that miR-210 may function as a potential biomarker in NSCLC detection. Particularly, combination biomarkers may be more comprehensive indicators than single miR-210. However, the clinical diagnostic utilization and additional exploration still remain to be further tested and verified through more future studies.


PCP4 is highly expressed in ectoderm and particularly in neuroectoderm derivatives during mouse embryogenesis.
PCP4 (PEP-19) belongs to a family of proteins involved in calcium transduction signals and binds calmodulin via an IQ motif, in a calcium independent manner. PCP4 gene maps to murine chromosome 16 and in human to chromosome 21. Murine PCP4 expression in the brain has been detected by Northern blot analysis to be mainly post-natal and in the adult to have a neuronal pattern. To investigate if it might have a role earlier in development, we analyzed its expression during mouse embryogenesis by in situ hybridization from E7.5 post-coitum (p.c.) to E17.5 p.c., and in P0 brain. Early, at E7.5, a high expression is restricted to the extra embryonic ectoderm. Embryonic expression starts at E9.5. At E10.5, PCP4 shows a strong signal in the post-mitotic cells of the diencephalon, the metencephalon and the myelencephalon and in the dorsal and cranial ganglia. The floor plate is also densely labelled. At E17.5, PCP4 is expressed in the central nervous system, in the myenteric plexus, and in other ectoderm derivatives, for instance the lens, the hairy cells of the cochlea, the enamel organ and the hair follicles. Thus, during embryogenesis PCP4 is mainly expressed in ectoderm and neuroectoderm comprising neural crest derived cells.


Honesty, perception and population divergence in sexually selected traits.
We investigate the evolution of female preference for one and two male ornaments, to address two issues in sexual selection: (i) what factors affect the evolution of female preferences; and (ii) how do preferences diverge between isolated populations, leading to speciation? We assume that the male traits are costly indicators of male condition ('handicaps'), and that females benefit directly from a high-condition mate. We find that optimal female preference for a single male trait equals (benefit of condition) x (detectability of male trait) x (honesty of male trait)/(costliness of preference). With two male traits to choose from, females should prefer the one with greatest honesty x detectability, and ignore the second. These results highlight the role of perception in the evolution of both male ornaments and female preferences, and provide a theoretical illustration of 'sensory drive'. They confirm that a less honest male trait can displace a more honest trait if its detectability is sufficiently high. Environmental differences can drive evolutionary divergence between populations in both the male trait and female preference. Even small differences between habitats in detectability of male traits can trigger dramatic change in the female preference. Finally, populations may drift apart in arbitrary directions if choice of different male traits yields equivalent benefits to females.


Growth hormone response to growth hormone-releasing hormone is reduced in adult asthmatic patients receiving long-term inhaled corticosteroid treatment.
Some studies have demonstrated that the function of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis is significantly impaired in patients with oral corticosteroid (CS)-induced osteoporosis. The aim of study was to investigate the effects of long-term therapy with inhaled CSs (ICSs) on the hypothalamic-pituitary-GH axis by the GH response to GH-releasing hormone (GHRH), as well as bone turnover, in adult asthmatic patients. Cross-sectional study. Twenty-seven adult subjects with mild-to-moderate persistent asthma (long-term ICS therapy [ie, > 1 year], 20 patients; naive to ICS treatment, 7 patients) and 10 control subjects. Each subject underwent testing with an IV bolus (1 mug/kg) injection of human GHRH, and samples of GH were taken 15 min before the GHRH injection, at 0 min (ie, at the time of GHRH injection), and at 15, 30, 45, 60, and 90 min after injection to obtain values for peak GH and DeltaGH. At baseline, samples of serum IGF-1 and blood-urine were collected for bone turnover markers. The GH response to GHRH was significantly reduced in asthmatic patients receiving ICSs (peak GH, p < 0.05; and DeltaGH, p < 0.01) in comparison with control subjects and asthmatic patients who were naive to ICS therapy (peak GH and DeltaGH, p < 0.01). Baseline IGF-1 levels were similar in the three groups. Serum osteocalcin, a marker of bone formation, was significantly reduced (p < 0.01) and correlated with GH peak (r(2) = 0.34; p = 0.007) in asthmatic patients who were treated with ICSs. We conclude that GH secretion in response to GHRH is significantly reduced in adult asthmatic patients receiving therapy with ICS and that such inhibition could play a negative role in bone metabolism.


Comparative performance of heterogeneity variance estimators in meta-analysis: a review of simulation studies.
Random-effects meta-analysis methods include an estimate of between-study heterogeneity variance. We present a systematic review of simulation studies comparing the performance of different estimation methods for this parameter. We summarise the performance of methods in relation to estimation of heterogeneity and of the overall effect estimate, and of confidence intervals for the latter. Among the twelve included simulation studies, the DerSimonian and Laird method was most commonly evaluated. This estimate is negatively biased when heterogeneity is moderate to high and therefore most studies recommended alternatives. The Paule-Mandel method was recommended by three studies: it is simple to implement, is less biased than DerSimonian and Laird and performs well in meta-analyses with dichotomous and continuous outcomes. In many of the included simulation studies, results were based on data that do not represent meta-analyses observed in practice, and only small selections of methods were compared. Furthermore, potential conflicts of interest were present when authors of novel methods interpreted their results. On the basis of current evidence, we provisionally recommend the Paule-Mandel method for estimating the heterogeneity variance, and using this estimate to calculate the mean effect and its 95% confidence interval. However, further simulation studies are required to draw firm conclusions. Copyright © 2016 John Wiley & Sons, Ltd.


Assessment of AMPK-Stimulated Cellular Long-Chain Fatty Acid and Glucose Uptake.
Here we describe an assay for simultaneous measurement of cellular uptake rates of long-chain fatty acids (LCFA) and glucose that can be applied to cells in suspension. The uptake assay includes the use of radiolabeled substrates at such concentrations and incubation periods that exact information is provided about unidirectional uptakes rates. Cellular uptake of both substrates is under regulation of AMPK. The underlying mechanism includes the translocation of LCFA and glucose transporters from intracellular membrane compartments to the cell surface, leading to an increase in substrate uptake. In this chapter, we explain the principles of the uptake assay before detailing the exact procedure. We also provide information of the specific LCFA and glucose transporters subject to AMPK-mediated subcellular translocation. Finally, we discuss the application of AMPK inhibitors and activators in combination with cellular substrate uptake assays.


Proteomics and the Trypanosoma brucei cytoskeleton: advances and opportunities.
Trypanosoma brucei is the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan Africa. The pathogenicity and growth of the parasite are intimately linked to its shape and form. This is in turn derived from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage directly beneath the pellicular membrane and numerous other cytoskeletal structures such as the flagellum. The parasite undergoes extreme changes in cellular morphology during its life cycle and cell cycles which require a high level of integration and coordination of cytoskeletal processes. In this review we will discuss the role that proteomics techniques have had in advancing our understanding of the molecular composition of the cytoskeleton and its functions. We then consider future opportunities for the application of these techniques in terms of addressing some of the unanswered questions of trypanosome cytoskeletal cell biology with particular focus on the differences in the composition and organisation of the cytoskeleton through the trypanosome life-cycle.


Core and surface mutations affect folding kinetics, stability and cooperativity in IL-1 beta: does alteration in buried water play a role?
Interleukin-1 beta (IL-1 beta) is a cytokine and a member of the beta-trefoil superfamily of protein structures. An interesting feature in the folding of IL-1 beta, shared with some other members of the same topological family, is the existence of a slow step in folding to the native conformation from a discrete intermediate. Wanting to probe the nature of this slow step in the folding of WT IL-1 beta (tau(1)=45 seconds), we made ten sequence variants of IL-1 beta (L10A, T9Q, T9G, C8S, C8A, N7G, N7D, L6A, R4P, and R4Q), where all mutations are located along strand 1. This strand is not protected from hydrogen exchange until late in folding. Most of the mutations showed little effect on the kinetics of folding for IL-1 beta. However, C8 is clearly involved in both the late and the early steps in folding, while sequence variants at L10 and L6 affect only late events in folding. The value of the slowest relaxation time, tau(1), which is associated with the rate of native protein formation, increased for the refolding of C8S, while C8A, L6A, and L10A showed smaller but systematic increases in the value of tau(1.)For both C8S and C8A, the value of the step associated with formation of the intermediate, tau(2), was independent of denaturant concentration. In addition, mutations in the hydrophobic core (L10A, C8A, C8S, and L6A) and, surprisingly, along the surface (T9G, T9Q, and N7G) alter the stability. The most destabilizing mutations show changes in equilibrium unfolding cooperativity, which is atypical for destabilizing mutations in IL-1 beta. Crystallographic studies indicate that mutations along strand 1 may alter the number of ordered water molecules within the core. Thus, side-chain replacement in this region can disrupt essential main-chain interactions mediated by ordered water contacts in a highly cooperative network of hydrogen bonding.


Renal cell carcinoma with a fatty component mimicking angiomyolipoma on CT.
A very unusual CT appearance of renal cel carcinoma is presented, in which the fatty density mimicked a benign angiomyolipoma.


Note on the relationships among job satisfaction, organizational commitment, and organizational citizenship behavior.
Previous research which has established a relationship between organizational citizenship behavior and job satisfaction has involved primarily white collar workers. This study extends the prior research to a different sample--blue collar workers--and investigates the relations of organizational citizenship behavior to the various facets of job satisfaction as measured by the Job Descriptive Index. We also examine the relative effects of organizational commitment and job satisfaction on citizenship behaviors. Analysis of responses from a sample of 91 machine operators employed by a clothing manufacturer in the southeastern United States indicates that citizenship behaviors of blue collar workers are related to satisfaction with coworkers, satisfaction with supervision, and satisfaction with pay, but not satisfaction with opportunities for advancement, satisfaction with the work itself, or organizational commitment.


Host-cell invasion by malaria parasites: insights from Plasmodium and Toxoplasma.
Recent years have seen tremendous progress in our understanding of malaria parasite molecular biology. To a large extent, this progress follows significant developments in genetic, molecular and chemical tools available to study the malaria parasites and related Apicomplexa, in particular Toxoplasma gondii. One area of major advancement has been in understanding parasite host-cell invasion, a process that utilizes several essential molecular mechanisms that are conserved across the different lifecycle stages. Here, we summarize some of the most recent experimental data that shed light on the events underlying preparation and execution of malaria parasite invasion and how these insights might relate to the development of new antimalarial drugs.


On-line monitoring of the methanol concentration in Pichia pastoris cultures producing an heterologous lipase by sequential injection analysis.
An automated sequential injection analysis (SIA) system using stop-flow technique was developed to determine methanol concentration by means of the enzymatic reactions of alcohol oxidase and peroxidase. Its application as an on-line device for monitoring Pichia pastoris fermentations producing an heterologous protein was demonstrated. Linear response, observed up to 2 g l(-1), was reached by including a dilution chamber in the SIA manifold. The sampling frequency was 7 analyses per hour with a relative standard deviation lower than 4%.


The effect of extracellular Ca2+ on responses to purinoceptor agonists in cultured swine tracheal smooth muscle cells.
The effects of extracellular Ca2+ ions on purinergic responses were examined in swine tracheal smooth muscle cells (TSMCs) in primary culture. ATP (1 microM to 1 mM) and alpha, beta-methylene adenosine 5' triphosphate (alpha, beta-Me ATP) (100 microM and 1 mM) concentration-dependently increased [Ca2+]i in the presence and the absence of extracellular Ca2+. Responses to ATP (10 microM to 1 mM) in the presence of extracellular Ca2+ were significantly larger than those in its absence (n=8), whereas those to alpha, beta-Me ATP were not significantly different between the presence (n=7) and the absence (n=8) of extracellular Ca2+. Responses to ATP (1 mM) at extracellular Ca2+ concentration ([Ca2+]o) of 10 and 5 mM were significantly larger than that at extracellular EGTA concentration ([EGTA]o) of 1 mM (p< 0.01, n=5), whereas the responses to alpha, beta-Me ATP (1 mM) at 10 and 5 mM [Ca2+]o were significantly smaller than that at [EGTA]o of 1 mM (p<0.05, n=5). Increasing [Ca2+]o to 5 mM after the application of either 1 mM ATP (n=4) or 1 mM alpha, beta-Me ATP (n=4) in the absence of extracellular Ca2+ (1 mM [EGTA]o) further increased [Ca2+]i, though the increases in [Ca2+]i by agonists in 1 mM [EGTA]o had been already maximal. Incubating cells for 300 s in 5 mM [Ca2+]o before the application of ATP (1 mM) significantly increased the response to the drug than that obtained by incubating cells for 6 sec in 5 mM [Ca2+]o before the drug application (p< 0.01, n=4). However, alpha, beta-Me ATP (1 mM) induced similar responses by incubating cells for 30 or 300 s in 5 mM [Ca2+]o to that by incubating them for 6 s. These results suggest that the effect of alpha, beta-Me ATP in swine TSMCs in primary culture is mainly through Ca2+ release and that its effect on Ca2+ entry is smaller than other nucleotides.


Effects of protein undernutrition on the dentate gyrus in rats of three age groups.
The effect of an 8% casein and a control 25% casein diet on the granule cells in the dorsal blade of the dentate gyrus of the rat hippocampal formation was studied at 30, 90 and 220 days of age. Female rats were fed either an 8% or 25% casein diet 5 weeks prior to conception and the litters were maintained on these respective diets until killed. In rapid-Golgi-impregnated cells, we measured major and minor axes of the soma of the dentate granule neurons, the number of spines on 50-microns segments of proximal, middle and terminal regions of the largest dendrite per granule cell and the number of dendrites intersecting 8 concentric rings 38 microns apart. At all 3 ages studied undernourished rats showed, when compared to controls, significant reductions of the major and minor axes of the somata and significant reductions in the number of spines on dendrites in the middle and terminal dendritic segments. Dendritic branching was significantly reduced in undernourished rats compared to controls in all but the 4th concentric rings, with the greatest effect being seen on the outer 3 concentric rings at 90 and 220 days of age. The location of the deficit in dendritic synaptic spines and the greatest deficit in dendritic branching correspond to the sites of termination of the lateral and medial perforant pathway projection to the dentate gyrus on the terminal and middle dendritic segments of the granule cells. The deficits noted in the granule cells of the dentate gyrus in this study were more severe than those found in our previous studies on the effect of the low protein diet in these same rats on visual cortical pyramidal cells and on the 3 cell types in the nucleus raphe dorsalis and nucleus locus coeruleus.


"Am I Going to Be in Trouble for What I'm Doing?": Providing Contraceptive Care in Religious Health Care Systems.
Catholic systems control a growing share of health care in the United States. Because patients seeking contraceptives in Catholic facilities face doctrinal restrictions that may affect access to and quality of care, it is important to understand whether and how providers work within and around institutional policies regarding contraception. In 2016-2018, in-depth interviews were conducted in Illinois with 28 key informants-including providers (obstetrician-gynecologists, other physicians, nurse-midwives) and nonclinical professionals (ethicists, administrators, chaplains)-who had experience in secular, Protestant or Catholic health care systems. Interviews addressed multiple aspects of reproductive care and hospital and system policy. A thematic content approach was used to identify themes related to participants' experiences with and perspectives on contraceptive care. While respondents working in secular and Protestant systems reported few limitations on contraceptive care, those working in Catholic systems reported multiple barriers. Providers who had worked in Catholic systems described variable institutional policies and enforcement practices, ranging from verbal admonishments to lease agreements prohibiting contraceptive provision in secular clinics on church-owned land. Despite these restrictions, patients' needs motivated many providers to utilize work-arounds; some providers reported having been pressured or directly instructed to document false diagnoses in patients' medical records. Interviewees described how these obstacles burdened patients, especially those with social and financial constraints, and resulted in delayed or lower quality care. Providers working in Catholic hospitals are limited in their ability to serve women of reproductive age. Work-arounds intended to circumvent restrictions may inadvertently stigmatize contraception and negatively affect patient care.


An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone.
The basal ganglia may contribute to extrapyramidal movement disorders, affective disturbances, and cognitive deficits in schizophrenia. Basal ganglia volumes are putatively affected by antipsychotic medications. The purpose of this study was to determine the long-term effects of risperidone treatment in a cohort of first-episode patients with schizophrenia. The subjects were 30 patients with first-episode schizophrenia, 12 patients chronically treated with typical antipsychotics, and 23 healthy comparison subjects. They were scanned by magnetic resonance imaging at baseline. The first-episode patients received 1 year of continuous risperidone treatment, after which they and the comparison subjects were rescanned. Caudate, putamen, and globus pallidus volumes were determined from coronal images. The baseline caudate, putamen, and globus pallidus volumes were significantly larger in the chronically treated patients than in the untreated first-episode subjects and comparison subjects. These volumes did not differ between the first-episode patients and healthy comparison subjects. Basal ganglia volumes were unchanged after 1 year of exposure to risperidone in the first-episode subjects. Extrapyramidal movement disorders were present in the majority of chronically treated patients and more than one-third of the never-medicated first-episode patients at baseline. This group of first-episode patients did not exhibit abnormalities of basal ganglia volumes, nor were basal ganglia volumes affected by exposure to risperidone. Movement disorders were observed in both first-episode and chronically treated patients, suggesting effects of both illness and medications.


Chondrocyte-matrix attachment complexes mediate survival and differentiation.
Integrin mediated cell-extracellular matrix interactions are required for survival and differentiation of many cell types. In this review, the cell-matrix attachment complex (CMAX) is described for chondrocytes. The evidence that integrin-mediated signal transduction is necessary for normal chondrocyte differentiation and survival in various culture conditions and in vivo are reviewed. The possible signal transduction pathways stimulated by the extracellular matrix components are discussed with a review of current data from chondrocyte experiments. In addition, the influence of parathyroid hormone and transforming growth factor beta on chondrocyte survival has been included as they may function in concert with integrin mediated signal transduction. Finally, specific changes in gene expression preceding apoptosis are discussed. The current understanding of how integrin-mediated signals prevent apoptosis and implications of anchorage-dependent survival for development and differentiation of the chondrocyte phenotype are discussed.


Effects of dietary iron and folate supplementation on the physiological changes produced in weanling rats by sodium saccharin exposure.
Exposure of rats to high dietary levels of sodium saccharin (NaSac) started in utero produce physiological effects at 30 days post-birth that are similar to those found in pups of iron-deficient dams. These similarities suggest that some of the changes due to NaSac are secondary to iron deficiency. The present experiment investigated whether the effects of 7.5% dietary NaSac in the newborn rat could be prevented by dietary iron and/or folate supplementation. The NaSac-related effects prevented by iron supplementation included anaemia, decreased serum iron and folate, increased serum cholesterol and triglyceride and increased serum vitamin E. Folate supplementation prevented NaSac-induced depression of serum folate and increase in serum vitamin E. Although bladder hyperplasia was increased by dietary iron and/or folate supplementation, the majority of the urinary chemistry changes associated with NaSac treatment were not affected. The results show that some physiological changes associated with NaSac treatment in the newborn rat may occur as a consequence of iron deficiency rather than a direct effect of NaSac treatment. These changes may be independent of the urinary and bladder effects, which are not reversed by iron supplementation.


Dynamic molecular combing: stretching the whole human genome for high-resolution studies.
DNA in amounts representative of hundreds of eukaryotic genomes was extended on silanized surfaces by dynamic molecular combing. The precise measurement of hybridized DNA probes was achieved directly without requiring normalization. This approach was validated with the high-resolution mapping of cosmid contigs on a yeast artificial chromosome (YAC) within yeast genomic DNA. It was extended to human genomic DNA for precise measurements ranging from 7 to 150 kilobases, of gaps within a contig, and of microdeletions in the tuberous sclerosis 2 gene on patients' DNA. The simplicity, reproducibility, and precision of this approach makes it a powerful tool for a variety of genomic studies.


A new concept of long-term donor heart preservation: nucleoside transport inhibition.
Myocardial ischemia results in a breakdown of adenosine triphosphate (ATP), which is associated with an accumulation of its catabolites adenosine and inosine. Adenosine is a potent but ineffective cardioprotective agent because it is rapidly transported to the endothelium and irreversibly catabolized. With the use of specific nucleoside transport inhibition (NTI), however, endogenous adenosine may accumulate at its site of production, and its further breakdown and washout on reperfusion is prevented. In this study we tested this concept and assessed the effect of NTI drug administration on 24 hours' preservation of donor hearts for transplantation. Twelve dogs were randomly allocated to two groups. In the first group (group 1, n = 6) the hearts were arrested with a cold hyperkalemic cardioplegic solution, excised and stored for 24 hours at 0.5 degrees C. After 24 hours the hearts were transplanted orthotopically. In group 2 (n = 6) the same procedure was followed, but a specific NTI agent was added to the cardioplegic solution (1 mg/L) and administered intravenously to the recipient dog before reperfusion of the transplanted heart (0.1 mg/kg). Despite maximal positive inotropic support, none of the control animals (group 1) could be weaned from cardiopulmonary bypass: within 1 hour irreversible cardiogenic shock occurred in all animals. In group 2 all hearts could be weaned from cardiopulmonary bypass and were hemodynamically stable without positive inotropic support. Serial transmural left ventricular biopsies revealed in group 1 moderate catabolism of ATP during cold storage. On reperfusion a further decline of the ATP content was seen, and the accumulated nucleosides were washed out.(ABSTRACT TRUNCATED AT 250 WORDS)


Patients' awareness of and attitudes toward gifts from pharmaceutical companies to physicians.
The purpose of this study was to assess patients' awareness of and attitudes toward physicians' receiving gifts from the pharmaceutical industry. The Alger County Community Health Study was a self-report survey targeting rural Alger County, Michigan. The survey (completion rate 10.1%) addressed issues on health, demographics, and patients' awareness of and attitudes toward gifts to physicians. Rates of awareness of gifts were: drug samples, 94 percent; ballpoint pens, 76.2 percent; medical books, 38 percent; conference/travel expenses, 34 percent; dinner out, 36.6 percent; spouse meal at dinner out, 23 percent; golf tournament fees, 19.0 percent. Rates of "approval" of physicians' accepting gifts were: drug samples, 69 percent; ballpoint pens, 54.2 percent; medical books, 49 percent; conference/travel expenses, 14 percent; dinner out, 12.1 percent; spouse meal at dinner out, 7 percent; golf tournament fees, 3.7 percent. Patients' approval of gifts seems to be related to the perceived value of the gift to patients as well as its monetary value. The patient population in the current study seems to be less approving of gifts to physicians than patients surveyed in the 1990s. Patients' opinions should be considered when establishing ethical guidelines and policies regulating physician-industry interaction.


Omega-6 fatty acids and inflammation.
Inflammation is a normal process that is part of host defence and tissue healing. However, excessive or unresolved inflammation can lead to uncontrolled tissue damage, pathology and disease. In humans on a Western diet, the omega-6 polyunsaturated fatty acid arachidonic acid (ARA) makes a significant contribution to the fatty acids present in the membrane phospholipids of cells involved in inflammation. ARA is a precursor to a number of potent pro-inflammatory mediators including well described prostaglandins and leukotrienes, which has led to the development of anti-inflammatory pharmaceuticals that target the ARA pathway to successfully control inflammation. Hence, it is commonly believed that increasing dietary intake of the omega-6 fatty acids ARA or its precursor linoleic acid (LA) will increase inflammation. However, studies in healthy human adults have found that increased intake of ARA or LA does not increase the concentrations of many inflammatory markers. Epidemiological studies have even suggested that ARA and LA may be linked to reduced inflammation. Contrastingly, there is also evidence that a high omega-6 fatty acid diet inhibits the anti-inflammatory and inflammation-resolving effect of the omega-3 fatty acids. Thus, the interaction of omega-3 and omega-6 fatty acids and their lipid mediators in the context of inflammation is complex and still not properly understood.


Controlateral cavernous syndrome, brainstem congestion and posterior fossa venous thrombosis with cerebellar hematoma related to a ruptured intracavernous carotid artery aneurysm.
Intracavernous carotid artery aneurysms (ICCAs) are rarely associated with life-threatening complications. We describe a 55-year-old woman who, after the rupture of an intracavernous carotid artery aneurysm, presented with a contralateral cavernous sinus syndrome and severe posterior fossa and spinal cord symptoms. Following parent artery occlusion, thrombosis of the posterior fossa and spinal cord veins caused a progressive worsening of the neurological status to a "locked-in" state. The patient fully recovered with anticoagulation therapy. Comprehension of the pathophysiological mechanism associated with the rupture of ICCA and early diagnosis of the related symptoms are essential in order to plan a correct treatment that includes the management of the aneurysm rupture and of possible complications related to venous thrombosis.


Characterization of the aminocarboxycyclopropane-forming enzyme CmaC.
The biosynthesis of the coronamic acid fragment of the pseudomonal phytotoxin coronatine involves construction of the cyclopropane ring from a gamma-chloro-L-allo-Ile intermediate while covalently tethered as a phosphopantetheinyl thioester to the carrier protein CmaD. The cyclopropane-forming catalyst is CmaC, catalyzing an intramolecular displacement of the gamma-Cl group by the alpha carbon. CmaC can be isolated as a Zn2+ protein with about 10-fold higher activity over the apo form. CmaC will not cyclize free gamma-chloro amino acids or their S-N-acetylcysteamine (NAC) thioester derivatives but will recognize some other carrier protein scaffolds. Turnover numbers of 5 min-1 are observed for Zn-CmaC, acting on gamma-chloro-L-aminobutyryl-S-CmaD, generating 1-aminocyclopropane-1-carbonyl (ACC)-S-CmaD. Products were detected either while still tethered to the phosphopantetheinyl prosthetic arm by mass spectrometry or after thioesterase-mediated release and derivatization of the free amino acid. In D2O, CmaC catalyzed exchange of one deuterium into the aminobutyryl moiety of the gamma-Cl-aminoacyl-S-CmaD, whereas the product ACC-S-CmaD lacked the deuterium, consistent with a competition for a gamma-Cl-aminobutyryl alpha-carbanion between reprotonation and cyclization. CmaC-mediated cyclization yielded solely ACC, resulting from C-C bond formation and no azetidine carboxylate from an alternate N-C cyclization. CmaC could cyclize gamma,gamma-dichloroaminobutyryl to the Cl-ACC product but did not cyclize delta- or epsilon-chloroaminoacyl-S-CmaD substrates.


A counterintuitive approach to treat enzyme deficiencies: use of enzyme inhibitors for restoring mutant enzyme activity.
Pharmacological chaperone therapy is an emerging counterintuitive approach to treat protein deficiencies resulting from mutations causing misfolded protein conformations. Active-site-specific chaperones (ASSCs) are enzyme active-site directed small molecule pharmacological chaperones that act as a folding template to assist protein folding of mutant proteins in the endoplasmic reticulum (ER). As a result, excessive degradation of mutant proteins in the ER-associated degradation (ERAD) machinery can be prevented, thus restoring enzyme activity. Lysosomal storage disorders (LSDs) are suitable candidates for ASSC treatment, as the levels of enzyme activity needed to prevent substrate storage are relatively low. In addition, ASSCs are orally active small molecules and have potential to gain access to most cell types to treat neuronopathic LSDs. Competitive enzyme inhibitors are effective ASSCs when they are used at sub-inhibitory concentrations. This whole new paradigm provides excellent opportunity for identifying specific drugs to treat a broad range of inherited disorders. This review describes protein misfolding as a pathophysiological cause in LSDs and provides an overview of recent advances in the development of pharmacological chaperone therapy for the diseases. In addition, a generalized guidance for the design and screening of ASSCs is also presented.


Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren Gel in Chronic Noncancer Pain.
Pharmacologic treatment of chronic pain is challenging. Oral therapy may require multiple medications; each has side effects, dose limitations, and limited efficacy. Compounded topical formulations have evolved as potential treatment options. The objective of this study was to evaluate the efficacy of 2 compounded topical creams, "Cream I" and "Cream II," in patients with chronic extremity, joint, musculoskeletal, neuropathic, or other chronic topical pain conditions and compare their efficacy with Voltaren gel. The primary efficacy outcome was the change in visual numeric pain intensity score from pretreatment to posttreatment. The Cream I contained Flurbiprofen (20%), Tramadol (5%), Clonidine (0.2%), Cyclobenzaprine (4%), and Bupivacaine (3%). The Cream II contained Flurbiprofen (20%), Baclofen (2%), Clonidine (0.2%), Gabapentin (10%), and Lidocaine (5%). The Voltaren gel contained 1% diclofenac sodium. A total of 2177 patients were evaluated, 826 males and 1351 females. During their medical treatment, 1141 patients received Cream I, 527 patients received Cream II, and 509 patients received Voltaren gel. After treatment, the pain intensity score decreased by 3.11 ± 1.65 (37%) with Cream I (from 8.44 ± 1.19 to 5.33 ± 2.0, P < 0.001), by 2.93 ± 1.58 (35%) with Cream II (from 8.42 ± 1.27 to 5.50 ± 1.96, P < 0.001), and by 1.49 ± 0.73 (19%) with Voltaren gel (from 7.93 ± 0.81 to 6.44 ± 1.14, P < 0.001). Cream I and Cream II did not differ significantly in efficacy, and both were significantly more effective than Voltaren gel (P < 0.001). It is concluded that Voltaren gel had less efficacy than the compounded creams, which were effective and provided pain relief in the majority of the patients studied.


Pandemic planning as risk management: how fared the Australian federation?
The role of law in managing public health challenges such as influenza pandemics poses special challenges. This article reviews Australian plans in the context of the H1N1 09 experience to assess whether risk management was facilitated or inhibited by the "number" of levels or phases of management, the degree of prescriptive detail for particular phases, the number of plans, the clarity of the relationship between them, and the role of the media. Despite differences in the content and form of the plans at the time of the H1N1 09 emerging pandemic, the article argues that in practice, the plans proved to be responsive and robust bases for managing pandemic risks. It is suggested that this was because the plans proved to be frameworks for coordination rather than prescriptive straitjackets, to be only one component of the regulatory response, and to offer the varied tool box of possible responses, as called for by the theory of responsive regulation. Consistent with the principle of subsidiarity, it is argued that the plans did not inhibit localised responses such as selective school closures or rapid responses to selected populations such as cruise ship passengers.


Methacrylate bonding to zirconia by in situ silica nanoparticle surface deposition.
This study introduces an innovative method to enhance adhesion of methacrylate-based cements to yttria-stabilized zirconia (Y-TZP) by means of a silica-nanoparticle deposition process. Two alkoxide organic precursors, tetraethyl-orthosilicate (TEOS) and zirconium tert-butoxide (ZTB) were diluted in hexane at different concentrations in order to obtain several experimental materials to enhance deposition of a SiO(x) reactive layer to Y-TZP. This deposition was attained via sintering alkoxide precursors directly on pre-sintered zirconia (infiltration method—INF) or application on the surface of fully sintered zirconia (coating method—COA). Untreated specimens and a commercial tribochemical silica coating were also tested as controls and all the treated Y-TZP specimens were analyzed using SEM-EDX. Specimens were bonded using silane, adhesive and dual-cure luting cement and submitted to shear bond strength test after different water storage periods (24 h, 3-, 6- and 12-months). SEM-EDX revealed Y-TZP surface covered by silica nanoclusters. The morphology of silica-covered Y-TZP surfaces was influenced by sintering method, employed to deposit nanoclusters. High bond strength (MPa) was observed when using COA method; highest TEOS percentage achieved the greatest bond strengths to Y-TZP surface (36.7±6.3 at 24 h). However, bonds stability was dependent on ZTB presence (32.9±9.7 at 3 months; 32.3±7.1 at 6 months). Regarding INF method, the highest and more stable resin-zirconia bond strength was attained when using experimental solutions containing TEOS and no ZTB. Both sintering methods tested in this study were able to achieve a bonding performance similar to that of classic tribochemical strategies. This study demonstrates that it is possible to achieve a reliable and long-lasting bonding between yttria-stabilized zirconia ceramic and methacrylate-based cements when using this novel, simple, and cost-effective bonding approach.


Knockdown of lncRNA MEG3 inhibits viability, migration, and invasion and promotes apoptosis by sponging miR-127 in osteosarcoma cell.
Osteosarcoma (OS) is one of the most common bone malignancies and occurs almost exclusively in children and adolescents. This study aimed to explore the role of lncRNA maternally expressed gene 3 (MEG3) in OS cells growth and metastasis, and to uncover the possible underlying mechanism. In this study, the expressions of MEG3 in five OS cell lines (MG63, OS-732, SaOS, G292, and 143B) and in a human osteoblast cell line hFOB1.19 were measured by qRT-PCR analysis. The expressions of MEG3, miR-127, and ZEB1 in OS-732 cells were overexpressed or suppressed by transfection. Cell viability, migration, invasion, and apoptosis were then assessed. The results showed that MEG3 was highly expressed in OS cell lines when compared to hFOB1.19 cell. MEG3 silence significantly suppressed OS-732 cells growth and metastasis, as evidenced by the decreases in cell viability, migration, invasion, and increase in apoptotic cell rate. MEG3 acted as an endogenous sponge by binding to miR-127. More interestingly, MEG3 silence could not suppress OS-732 cells growth and metastasis when miR-127 was knocked down. ZEB1 was a target gene of miR-127, and miR-127 overexpression-induced impairments in cell growth and metastasis were attenuated when ZEB1 was overexpressed. Moreover,miR-127 suppression activated JNK and Wnt signaling pathways, while these activations were recovered by ZEB1 silence. To conclude, our findings suggest that lncRNA MEG3 promoted OS cells growth and metastasis in vitro through sponging miR-127. This study provides the evidence that MEG3 may be a potential therapeutic target for OS.


Structure-activity relationship for FR901464: a versatile method for the conversion and preparation of biologically active biotinylated probes.
The structure-activity relationship for FR901464, a potent cell-cycle inhibitor, was examined by synthesizing its analogs. A versatile method for converting FR901464 was devised. This method made it possible to synthesize biologically active FR901464-biotin conjugates which could be used to isolate the binding proteins.


Osteomyelitis.
Osteomyelitis is a challenging diagnosis for every patient because of its protracted treatment process. Very experienced orthopaedic surgeons are needed to diagnose and treat this bacteria-related severe disorder in a right and proper way. Different treatment options are possible for osteomyelitis at any stage: antibiotics in the acute and chronic stage for conservative treatment or radical debridement, bone fenestration, reaming, bone troughing, the Masquelet-technique, segmental resection with callus distraction, bone grafting and even amputation as surgical therapy. Depending on different stages of the disease, there are good results with every technique available-on condition that radical debridement was performed. The complication rate is remarkable so that soft tissue defects should be assessed by using flaps to close the wounds in early stages. The treatment of osteomyelitis should be done in centres with expertise in the treatment of this challenging disease. Different methods should be offered by surgeons and individual treatment concepts acquired together with the patient. The treatment of complications like soft tissue defects should be provided in the same centre and performed in short time lag to the prior surgery. The cooperation of the patient and surgeons of different specialities is mandatory in these cases.


Managed care, medical technology, and the well-being of society.
The growth of managed care could have widespread effects on the structure and functioning of the health care delivery system, potentially influencing all patients, even those not enrolled in managed care plans. One important mechanism by which managed care could have such broad effects is by influencing technology development and adoption. This article examines available literature on the effects of managed care activity on technology adoption and the implications of any effects on patient care, outcomes, and health care costs. Existing literature supports the view that managed care has contributed to slowing the adoption of new technologies, particularly the high-cost, high-profile technologies that have been the focus of the most attention. The literature outlining the effects of managed-care-induced changes in technology adoption on patient care and outcomes is not large, but what literature there is tends not to find negative effects on patient care and outcomes. Specific evidence about costs also is somewhat sparse, but it suggests that managed care has contributed to some reduction in health care spending, although the extent to which savings will persist over time is unclear. Although evidence thus far does not suggest important detrimental effects of managed care on care or outcomes and even indicates some benefit through savings, it should be noted that existing literature has only explored a small number of the many technologies and services that might have been influenced, and there remain issues for the future that deserve vigilance.


Amrubicin for treating elderly and poor-risk patients with small-cell lung cancer.
This study was conducted to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly and poor-risk patients with extensive-disease small-cell lung cancer (ED-SCLC). Untreated SCLC patients who were >75 years of age or had a performance status of 2 or more were eligible. Amrubicin (35 or 40 mg/m(2) on days 1-3 every 3 weeks) was administered. Between January 2003 and May 2009, 27 patients were evaluated. The median number of treatment cycles was 4 (1-6). Grade 3 or 4 hematologic toxicities comprised neutropenia (63%), leukopenia (56%), thrombocytopenia (15%), and anemia (19%). Febrile neutropenia was observed in four (15%) patients. No treatment-related deaths occurred. The nonhematologic toxicities were mild. The overall response rate was 70%. Progression-free survival, median survival time, and the 1-year survival rate were 6.6 months, 9.3 months, and 30%, respectively. The 40 mg/m(2) dose was feasible and had a tendency to be more effective than the 35 mg/m(2) dose. Amrubicin exhibits activity and acceptable toxicities for elderly and poor-risk patients with ED-SCLC in the first-line treatment setting.


A Single-Molecule Atomic Force Microscopy Study of PARP1 and PARP2 Recognition of Base Excision Repair DNA Intermediates.
Nuclear poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2) catalyze the synthesis of poly(ADP-ribose) (PAR) and use NAD+ as a substrate for the polymer synthesis. Both PARP1 and PARP2 are involved in DNA damage response pathways and function as sensors of DNA breaks, including temporary single-strand breaks formed during DNA repair. Consistently, with a role in DNA repair, PARP activation requires its binding to a damaged DNA site, which initiates PAR synthesis. Here we use atomic force microscopy to characterize at the single-molecule level the interaction of PARP1 and PARP2 with long DNA substrates containing a single damage site and representing intermediates of the short-patch base excision repair (BER) pathway. We demonstrated that PARP1 has higher affinity for early intermediates of BER than PARP2, whereas both PARPs efficiently interact with the nick and may contribute to regulation of the final ligation step. The binding of a DNA repair intermediate by PARPs involved a PARP monomer or dimer depending on the type of DNA damage. PARP dimerization influences the affinity of these proteins to DNA and affects their enzymatic activity: the dimeric form is more effective in PAR synthesis in the case of PARP2 but is less effective in the case of PARP1. PARP2 suppresses PAR synthesis catalyzed by PARP1 after single-strand breaks formation. Our study suggests that the functions of PARP1 and PARP2 overlap in BER after a site cleavage and provides evidence for a role of PARP2 in the regulation of PARP1 activity.


Toll-like receptors and tolerance to ischaemic injury in the brain.
Ischaemic tolerance in the brain is a powerful adaptive defence that involves an endogenous programme of neuroprotection culminating in marked protection against brain injury from ischaemia. A range of preconditioning stimuli exist that differ in ligand and target characteristics but share the common feature of causing mild stress or insult without inducing overt injury. The protective phenotype that emerges confers tolerance to subsequent exposure to injurious insults. Tolerance to injury is the result of genomic reprogramming, an adaptation comprising regulatory processes that countermand injurious effectors and invoke novel neuroprotective pathways. TLRs (Toll-like receptors) play important roles in sensing potential danger/insult in the form of pathogens as well as endogenous stress molecules that occur in response to mild injury (e.g. heat-shock proteins). Recent studies suggest that TLRs are novel and potent preconditioning targets that offer substantial promise to protect the brain from ischaemic injury.


Activation of a remote (1-year old) emotional memory interferes with the retrieval of a newly formed hippocampus-dependent memory in rats.
The persistent intrusion of remote traumatic memories in people with post-traumatic stress disorder (PTSD) may contribute to the impairment of their ongoing hippocampal and prefrontal cortical functioning. In the current work, we have developed a rodent analogue of the intrusive memory phenomenon. We studied the influence of the activation of a remote traumatic memory in rats on their ability to retrieve a newly formed hippocampus-dependent memory. Adult male Sprague-Dawley rats were given inhibitory avoidance (IA) training, and then 24 h or 1, 6 or 12 months later, the same rats were trained to learn, and then remember across a 30-min delay period, the location of a hidden escape platform in the radial-arm water maze (RAWM). When IA-trained rats spent the 30-min delay period in the IA apparatus, they exhibited intact remote (1-year old) memory of the shock experience. More importantly, activation of the rats' memory of the shock experience profoundly impaired their ability to retrieve the newly formed spatial memory of the hidden platform location in the RAWM. Our finding that reactivation of a remote emotional memory exerted an intrusive effect on new spatial memory processing in rats provides a novel approach toward understanding how intrusive memories of traumatic experiences interfere with ongoing cognitive processing in people with PTSD.


Exact analytic reconstruction in x-ray fluorescence CT and approximated versions.
X-ray fluorescence computed tomography (XFCT) is a relatively new synchrotron-based imaging modality aiming at reconstructing the distribution of nonradiative elements within a sample irradiated with high-intensity monochromatic x-rays. In a recent paper La Rivière (2004 Phys. Med. Biol. 49 2391-405) presented an approximated inversion method based on reducing the problem to the inversion of the exponential radon transform. In this paper we compare La Rivière's results with recently derived 'exact' analytic formulae for the generalized attenuated radon transform. We present numerical experiments with real and simulated data.


Transcriptional activation of an intermediate filament protein gene in mice with retinal dystrophy.
We are interested in understanding neuronal interactions that regulate expression of specific genes in glial cells in the nervous system. In the normal mouse retina, the glial intermediate filament protein (GFAP) is not detectable in Müller cells, the predominant glial cells in the retina. Photoreceptor degeneration resulting from retinal degeneration (rd) mutation or environmental light damage, however, leads to the appearance of GFAP in Müller cells. We have investigated the mechanism underlying GFAP accumulation in these retinas. Western blotting analysis, steady-state mRNA level comparisons, and nuclear run-on assays show that transcription of the GFAP gene is activated in these retinas. In situ hybridizations with retinal sections and solitary Müller cells establish that GFAP mRNA levels are elevated in Müller cells. These results show that disruption of neuron-glia interactions resulting from photoreceptor degeneration leads to activation of the GFAP gene in glial cells of mice with retinal dystrophy. The functional significance of this glial response and the need for GFAP expression remain to be understood.


[Nocardia brain abscess: a case report (author's transl)].
A 42 years old woman was noticed to have an abnormal shadow in the left lower field of lung at the time of periodical chest radiographic examination in July 1979. She didn't show any signs or symptoms of inflammation such as fever, increased rate of blood sedimentation, leukocytosis and so on by that time. Four weeks prior to admission she started to complain of mild but continuous headache and then developed anorexia, dysarthria and weakness in the right half of the face. She was admitted to the Kyoto University Hospital on September 14, 1979. On admission, slight bilateral papilledema, right hemiparesis and total dysphasia were present. She was afebrile and no abnormal finding in serological examination was shown. A heterogenously enhanced mass was demonstrated by CT scan in the left posterior frontal lobe, which was surrounded by severe cerebral edema. A provisional diagnosis of metastatic tumor from the lung was made. At the time of craniotomy, an abscess cavity was found and aspirated. Then the radical extracapsular ablation and external decompression was carried out. Histologically many Nocardia species were identified in the abscess cavity. The patient was treated by administration of a mixture of trimethoprine and sulfamethixazole (Bakter), and minocycline. Subsequently the developed Corynebacterial epidural empyema which was successfully evacuated two months after the first operation. She had been placed on Baktar for ten months since the second operation. She presented no sign of recurrence in six months after the cessation of drugs.


Fibrinolysis, fibrinogen and trhombin time in newborns.
Comparative experiments were made on blood samples collected with and without addition of a potent fribinolysis-blocking agent in newborn infants aged up to 12 h. Prevention of the in vitro fibrinolysis resulted in a diminished frequency of an abnormal euglobulin clot lysis time, but there was no significant difference in fibrinogen levels and in the frequency and degree of a prolonged thrombin time. These results indicate that the prolongation of thrombin time in newborn infants cannot be prevented by blocking the in vitro fibrinolysis. The significance of these findings is discussed with regard to the possible existence of an abnormal 'fetal fibrinogen'.


Essaouira and Kala iris: two new orbiviruses of the Kemerovo serogroup, Chenuda complex, isolated from Ornithodoros (Alectorobius) maritimus ticks in Morocco.
Essaouira and Kala Iris viruses were isolated from Ornithodoros (Alectorobius) maritimus ticks parasitizing yellow-legged gulls (Larus cachinnans) on the coast of Morocco in 1979 and 1981, respectively. Serological evidence indicates that these two viruses are new members of the Chenuda complex within the Kemerovo serogroup of the genus Orbivirus. Ecological, pathological, morphological, and physicochemical properties are compatible with these findings. The infectivity of these viruses for man and animals, including seabirds, remains unknown.


Detection of anti-neutrophil cytoplasmic antibodies under actual clinical testing conditions.
Anti-neutrophil cytoplasmic antibodies (ANCA) are a useful diagnostic tool for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). To maximize diagnostic utility, current guidelines recommend dual testing by standard indirect immunofluorescence (IIF) and target antigen-specific assays. Most published data come from specialized research laboratories, not reflecting the performance of assays under routine clinical conditions. Therefore, we compared the performance of standard IIF, PR3-, and MPO-ANCA-specific direct ELISA, and a PR3-ANCA-specific capture ELISA used alone and in combination under routine clinical conditions. Consecutive serum samples (615) submitted for routine ANCA testing over a 10-month period were assayed. Diagnoses were WG/MPA (n = 86), other autoimmune disease (n = 118), and various others (n = 411). The combination of PR3-ANCA and MPO-ANCA ELISA had the highest sensitivity (72.1%), and C-ANCA determination using IIF, the highest specificity (99.6%). While maintaining maximal diagnostic accuracy, significant labor savings are achieved by screening for WG/MPA by ELISA followed by confirmatory IIF.


The Cost and Threshold Analysis of Retention in Care (RiC): A Multi-Site National HIV Care Program.
Persons diagnosed with HIV but not retained in HIV medical care accounted for the majority of HIV transmissions in 2009 in the United States (US). There is an urgent need to implement and disseminate HIV retention in care programs; however little is known about the costs associated with implementing retention in care programs. We assessed the costs and cost-saving thresholds for seven Retention in Care (RiC) programs implemented in the US using standard methods recommended by the US Panel on Cost-effectiveness in Health and Medicine. Data were gathered from accounting and program implementation records, entered into a standardized RiC economic analysis spreadsheet, and standardized to a 12 month time frame. Total program costs for from the societal perspective ranged from $47,919 to $423,913 per year or $146 to $2,752 per participant. Cost-saving thresholds ranged from 0.13 HIV transmissions averted to 1.18 HIV transmission averted per year. We estimated that these cost-saving thresholds could be achieved through 1 to 16 additional person-years of viral suppression. Across a range of program models, retention in care interventions had highly achievable cost-saving thresholds, suggesting that retention in care programs are a judicious use of resources.


Misuse and abuse of pregabalin and gabapentin: cause for concern?
Gabapentinoids (e.g. pregabalin and gabapentin) are widely used in neurology, psychiatry and primary healthcare but are increasingly being reported as possessing a potential for misuse. In fact, increasing levels of both prescriptions and related fatalities, together with an anecdotally growing black market, have been reported from a range of countries. This article reviews the current evidence base of this potential, in an attempt to answer the question of whether there is cause for concern about these drugs. Potent binding of pregabalin/gabapentin at the calcium channel results in a reduction in the release of excitatory molecules. Furthermore, gabapentinoids are thought to possess GABA-mimetic properties whilst possibly presenting with direct/indirect effects on the dopaminergic 'reward' system. Overall, pregabalin is characterized by higher potency, quicker absorption rates and greater bioavailability levels than gabapentin. Although at therapeutic dosages gabapentinoids may present with low addictive liability levels, misusers' perceptions for these molecules to constitute a valid substitute for most common illicit drugs may be a reason of concern. Gabapentinoid experimenters are profiled here as individuals with a history of recreational polydrug misuse, who self-administer with dosages clearly in excess (e.g. up to 3-20 times) of those that are clinically advisable. Physicians considering prescribing gabapentinoids for neurological/psychiatric disorders should carefully evaluate a possible previous history of drug abuse, whilst being able to promptly identify signs of pregabalin/gabapentin misuse and provide possible assistance in tapering off the medication.


Transmission of methicillin-resistant Staphylococcus aureus in the neonatal intensive care unit from a patient with community-acquired disease.
Methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been a nosocomial pathogen. However, several recent studies have noted community-acquired MRSA among young, healthy patients with no risk factors or healthcare system exposure. We report the transmission of a strain of community-acquired MRSA in our neonatal intensive care unit.


The role of the immune system in preeclampsia.
Recent data demonstrate that an altered immune response may play a key role in the development of preeclampsia. Some epidemiological findings and animal models support this idea. In this article, we review the innate immune system and adaptive immune system in preeclampsia and discuss the pathophysiology of preeclampsia from an immunological viewpoint. The most characteristic immunological finding in preeclampsia is the activation of both the innate and adaptive immune system. Activated neutrophils, monocytes, and NK cells initiate inflammation which induce endothelial dysfunction, and activated T cells may support inadequate tolerance during pregnancy. The cytokine profile in preeclampsia shows that the production of type 1 cytokines, which induce inflammation, is dominant while the production of type 2 cytokines, which regulates inflammation, is suppressed. Furthermore, the immunoregulatory system is down-regulated in preeclampsia and persistent inflammation reduces regulatory T cell function. Therefore, systematical immunoactivation may be one cause of preeclampsia.


Plasminogen and plasminogen proactivator in liver diseases.
The behaviour of plasminogen (PLg) and plasminogen proactivator (PPLg) and some currently employed enzyme parameters were prospectively studied in 1047 subjects, of whom: 748 patients with liver diseases and jaundice; 52 tumor patients and 247 healthy persons. The patients with parenchymal liver diseases showed significantly reduced PLg and PPLg activity in direct relation with the severity and the stage of diseases. In patients with obstructive jaundice the activity of the fibrinolytic enzymes was usually normal, rarely increased. Other parameters such as: ALAT, LAP, G--GT and bilirubin were elevated most often in patients with viral hepatitis as well as in patients with obstructive jaundice. Quick time was found less affected during acute viral hepatitis and acute liver failure. It seems possible to recommend PLg and PPLg as liver function tests in association with the other function tests.


The effect of predictable and unpredictable motor tasks on postural control after traumatic brain injury.
This study examined the effects of environmental predictability on postural control during functional reaching while seated in healthy individuals and patients with traumatic brain injury (TBI). The postural perturbation used required reaching to the left versus reaching to the right, while seated, under predictable versus unpredictable conditions. Indexes of postural control--trajectory stability and response reach times--were measured using an electromechanical system in ten patients with TBI and ten healthy subjects. In the TBI group, greater trajectory stability and shorter response reach time were recorded under unpredictable conditions when reaching to both the right and left (d-index 0.57-2.3). In the control group, greater trajectory stability and shorter response time were recorded under predictable and unpredictable environments compared with the TBI group (d-index 0.46-0.95). This study refutes the hierarchical, predictable-to-unpredictable-environment model of postural control evaluation and treatment. The relationship between information processing demands and postural skill appears more complex than a simple linear association. Predictable and unpredictable conditions may be used concurrently, not sequentially, in TBI rehabilitation.


Predictors of responses to stress among families coping with poverty-related stress.
This study tested how poverty-related stress (PRS), psychological distress, and responses to stress predicted future effortful coping and involuntary stress responses one year later. In addition, we explored age, sex, ethnicity, and parental influences on responses to stress over time. Hierarchical linear modeling analyses conducted with 98 low-income families (300 family members: 136 adults, 82 school-aged children, 82 adolescents) revealed that primary control coping, secondary control coping, disengagement, involuntary engagement, and involuntary disengagement each significantly predicted future use of that response. Primary and secondary control coping also predicted less maladaptive future responses to stress, while involuntary responses to stress undermined the development of adaptive responding. Age, sex, and interactions among PRS and prior coping were also found to predict certain responses to stress. In addition, child subgroup analyses demonstrate the importance of parental modeling of coping and involuntary stress responses, and warmth/nurturance and monitoring practices. Results are discussed with regard to the implications for preventive interventions with families in poverty.


A complication of interference screw fixation in anterior cruciate ligament reconstruction.
Bone-tendon autografts using patellar tendon are rapidly becoming the autogenous grafts of choice for anterior cruciate ligament reconstruction. Patellar tendon is the strongest type of available autogenous tissue, and it is easily adaptable to arthroscopically assisted techniques. Secure immediate fixation is critical for the success of this procedure. The Kurosaka screw has emerged as one of the most reliable graft fixation methods. Although we have enjoyed much success with the Kurosaka screw, the following case represents the first report of failure with this fixation technique.


Aerobic treatment of swine manure to enhance anaerobic digestion and microalgal cultivation.
Aerobic treatment of swine manure was coupled with anaerobic digestion and microalgal cultivation. A 14-day aerobic treatment reduced the total solid content of swine manure by >15%. Ammonia and carbon dioxide were stripped by the air supplied, and this off-gas was further used to aerate the culture of Chlorella vulgaris. The microalgal growth rates in Bristol medium and the wastewater with the off-gas increased from 0.08 to 0.22 g/L/d and from 0.15 to 0.24 g/L/d, respectively. Meanwhile, the aerobically treated swine manure showed a higher methane yield during anaerobic digestion. The experimental results were used to establish a demonstration unit consisting of a 100 L composter, a 200 L anaerobic digester, a 60 L tubular photobioreactor, and a 300 L micro-open raceway pond.


Retinal circulatory changes related to retinopathy progression in insulin-dependent diabetes mellitus.
To quantify the vascular deterioration of the diabetic retina, retinal circulatory changes in 45 insulin-dependent diabetic patients, and in 17 normal controls, were measured and divided into four groups according to severity of retinopathy. The noninvasive laser Doppler technique was used to measure the systolic/diastolic variation of red blood cell velocity (V) at sites along temporal retinal arteries. Flow pulsatility [V (systole)/V (diastole)] was 18% lower (P less than 0.00001) in the mild-retinopathy group than in normal controls, but 35% higher (P less than 0.001) in the severe-retinopathy group than in the mild-retinopathy group. Repeated measurements in three eyes during the progression from mild or moderate to severe retinopathy showed progressive increases in both flow pulsatility and mean retinal blood flow. Altered flow pulsatility appears to be a sensitive indicator of vascular alterations during the progression of diabetic retinopathy.


Breast cancer stem cells phenotype and plasma cell-predominant breast cancer independently indicate poor survival.
Cancer stem cell-tumor microenvironment ecosystem is proposed to drive tumor heterogeneity. Tumor-infiltrating lymphocytes (TILs) in breast cancer ecosystem were demonstrated to indicate better prognosis and benefit from chemotherapy. This study sought to detect the association between breast cancer stem cells and TILs. 92 patients with breast cancer were enrolled. Matched cancerous and paracancerous tissues were assembled in a tissue microarray and immunohistochemistry was employed to test expression of breast cancer stem cells (BCSCs) markers. TILs counts were estimated with global hematoxylin-eosin staining. The association between TILs and BCSCs phenotypes was analysed by multivariate analysis. Although it was unable to find direct significant association between BCSCs phenotypes and TILs, the BCSCs phenotype with CD44(+)CD24(-)ALDH1A1(+)EpCAM(+)CD49f(+) was proved to be associated with worse DFS and OS (P=0.037 and 0.001). This result was confirmed by cox proportional-hazards regression model (for DFS and OS respectively, HR=2.438 and 3.383, P=0.019 [95%CI 1.418-3.457] and 0.025 [95%CI 1.162-9.843]). Additionally, in results of TILs, plasma cell-predominant breast cancer (PPBC) was unexpectedly found to indicate worse OS and HR was 2.686 (P=0.038 [95%CI 1.582-3.789]). The BCSCs phenotype and PPBC may be helpful stratified factors in future clinical trials. The underlying mechanism needs further research.


Resistance training changes LDL metabolism in normolipidemic subjects: a study with a nanoemulsion mimetic of LDL.
To evaluate the effects of resistance training (RT) on the metabolism of an LDL-like nanoemulsion and on lipid transfer to HDL, an important step of HDL metabolism. LDL-like nanoemulsion plasma kinetics was studied in 15 healthy men under regular RT for 1-4 years (age = 25 ± 5 years, VO(2)peak = 50 ± 6 mL/kg/min) and in 15 healthy sedentary men (28 ± 7 years, VO(2)peak = 35 ± 9 mL/kg/min). LDL-like nanoemulsion labeled with (14)C-cholesteryl-ester and (3)H-free-cholesterol was injected intravenously, plasma samples were collected over 24-h to determine decay curves and fractional clearance rates (FCR). Lipid transfer to HDL was determined in vitro by incubating of plasma samples with nanoemulsions (lipid donors) labeled with radioactive free-cholesterol, cholesteryl-ester, triacylglycerols and phospholipids. HDL size, paraoxonase-1 activity and oxidized LDL levels were also determined. The two groups showed similar LDL and HDL-cholesterol and triacylglycerols, but oxidized LDL was lower in RT (30 ± 9 vs. 61 ± 19 U/L, p = 0.0005). In RT, the nanoemulsion (14)C-cholesteryl-ester was removed twice as fast than in sedentary individuals (FCR: 0.068 ± 0.023 vs. 0.037 ± 0.028, p = 0.002), as well as (3)H-free-cholesterol (0.041 ± 0.025 vs. 0.022 ± 0.023, p = 0.04). While both nanoemulsion labels were removed at the same rate in sedentary individuals, RT (3)H-free-cholesterol was removed slower than (14)C-cholesteryl-ester (p = 0.005). HDL size, paraoxonase 1 and the transfer rates to HDL of the four lipids were the same in both groups. RT accelerated the clearance of LDL-like nanoemulsion, which probably accounts for the oxidized LDL levels reduction in RT. RT also changed the balance of free and esterified cholesterol FCR's. However, RT had no effect on HDL metabolism related parameters.


Behavior problems and group-based parent education programs.
Behavior problems in children are an important social, educational, and health issue. The prevalence of these problems, their stability over time, their poor prognosis, and their costs to both individuals and the society, all point to the need for primary prevention and early effective interventions. A systematic review examined the effectiveness of group parent education programs that aimed to improve behavior problems in 3- to 10-year-old children. The phrase "parent education program" is used here to refer to group-based programs with a standardized format aimed at enhancing parenting skills. The term "behavior problems" is used to refer to children exhibiting externalizing problems such as temper tantrums, aggression, and noncompliance. It does not include children diagnosed as having attention-deficit hyperactivity disorder. This review focused explicitly on measures of child behavioral outcomes, which are only small, albeit important, outcomes of parent education programs. Reviews focusing on other clinically relevant outcomes are also needed, including parental well-being and attitudes towards parenting. Other reviews are also needed to collate evidence concerning the effectiveness of parent education programs with other age-groups, i.e., preschoolers and adolescents, and in improving other aspects of child well-being. The review included published studies only and as such may have been influenced by a "publication bias." Inclusion criteria comprised the use of a waiting list, a no-treatment or placebo control group, and at least one standardized measure assessing the child's behavior. Only studies published after 1970 that included at least one "group-based" parent education program were included. A total of 255 primary studies were identified, but only 16 of these and 2 follow-up studies met all of the specified inclusion criteria. Critical appraisal of these 16 studies revealed considerable heterogeneity in the interventions, the populations studied, and the outcome measures used. Nevertheless, these studies suggest that structured parent education programs can be effective in producing positive change in both parental perceptions and objective measures of children's behavior and that these changes are maintained over time. Because of the small number of controlled studies and their methodological variations, caution should be exercised before these findings are generalized broadly.


Community treatment orders: the ethical balancing act in community mental health.
Community treatment orders (CTOs) are legal mechanisms by which an individual with a mental illness and a history of non-compliance and potential for violence can be mandated (against their will) to undergo psychiatric treatment in an outpatient setting. Although CTOs are increasingly being adopted by governments as a means of protecting both mentally ill persons and society itself, their use continues to stimulate considerable debate. While there is some evidence of their potential benefits in promoting treatment compliance and reducing hospital stays, there is concern that they infringe on the mental health client's human rights and freedoms. Consideration of the ethical and practical implications of the use of CTOs must continue. In this paper, some of the most pressing issues are identified and discussed.


[Combined effect of gemcitabine and lomustine in mice with intracranial transplanted lymphosarcoma LIO-1].
SHR mice with intracranial transplanted lymphosarcoma LIO-1 received a single intraperitoneal gemcitabine injection in maximal tolerated dose of 25 mg/kg or single maximal tolerated oral dose of lomustine, 50 mg/kg. Compared to control group gemcitabine injection increased the mice lifespan 1.4-fold (p < 0,01) and oral lomustine 1.6-fold (p < 0,01). The median lifespan of the mice receiving both gemcitabine and lomustine in maximal dose underwent a significant 3.3-fold increase (p < 0,01) compared to controls (2.4-fold compared to gemcitabine and 2.1-fold compared to lomustine group). Combined therapy didn't cause an increase of toxicity.


Estimate of gastric acid output by evaluation of fasting gastric juice collected endoscopically.
Using an endoscope we collected fasting gastric juice for estimation of gastric acid in subjects examined by upper gastrointestinal endoscopy. Subjects were 53 in- and out-patients (46 males and 7 females) at our hospital. Seventy-five gastric secretory studies were performed in this population before and after stimulation by tetragastrin, following the guidelines of The Japanese Society of Gastroenterology and using a specially devised endoscope of narrow caliber under direct vision. Acid in fasting gastric juice was correlated with basal acid output (BAO) and with maximal acid output (MAO). There was a statistically significant correlation between them. Thus, an estimation of gastric acid secretion can be obtained from the fasting gastric juice which we usually aspirate and discard during the routine endoscopic examination.


Responses of a looming-sensitive neuron to compound and paired object approaches.
The lobula giant movement detector (LGMD) and its target neuron, the descending contralateral movement detector (DCMD), constitute a motion-sensitive pathway in the locust visual system that responds preferentially to objects approaching on a collision course. LGMD receptive field properties, anisotropic distribution of local retinotopic inputs across the visual field, and localized habituation to repeated stimuli suggest that this pathway should be sensitive to approaches of individual objects within a complex visual scene. We presented locusts with compound looming objects while recording from the DCMD to test the effects of nonuniform edge expansion on looming responses. We also presented paired objects approaching from different regions of the visual field at nonoverlapping, closely timed and simultaneous approach intervals to study DCMD responses to multiple looming stimuli. We found that looming compound objects evoked characteristic responses in the DCMD and that the time of peak firing was consistent with predicted values based on a weighted ratio of the half size of each distinct object edge and the absolute approach velocity. We also found that the azimuthal position and interval of paired approaches affected DCMD firing properties and that DCMDs responded to individual objects approaching within 106 ms of each other. Moreover, comparisons between individual and paired approaches revealed that overlapping approaches are processed in a strongly sublinear manner. These findings are consistent with biophysical mechanisms that produce nonlinear integration of excitatory and feed-forward inhibitory inputs onto the LGMD that have been shown to underlie responses to looming stimuli.


Envelope Proteins Pertain with Evolution and Adaptive Mechanism of the Novel Influenza A/H1N1 in Humans.
The novel swine-origin influenza A/H1N1 virus (S-OIV) first detected in April 2009 has been identified to transmit from human to human directly and is the cause of currently emerged pandemic. In this study, nucleotide and deduced amino acid sequences of hemagglutinin (HA) and neuraminidase (NA) of the S-OIV and other influenza A viruses were analyzed through bioinformatic tools for phylogenetic analysis, genetic recombination and point mutation to investigate the emergence and adaptation of the S-OIV in human. The phylogenetic analysis showed that the HA comes from triple reassortant influenza A/H1N2 and the NA from Eurasian swine influenza A/H1N1 indicating HA and NA to descend from different lineages during the genesis of the S-OIV. Recombination analysis nullified the possibility of occurrence of recombination in HA and NA denoting the role of reassortment in the outbreak. Several conservative mutations are observed in the amino acid sequences of the HA and NA and this mutated residues are identical in the S-OIV. The results reported herein suggested the notion that the recent pandemic is the result of reassortment of different genes from different lineages of two envelope proteins, HA and NA which are responsible for antigenic activity of virus. This study further suggests that the adaptive capability of the S-OIV in human is acquired by the unique mutations generated during emergence.