Intensive agriculture reduces soil biodiversity across Europe.
Soil biodiversity plays a key role in regulating the processes that underpin the delivery of ecosystem goods and services in terrestrial ecosystems. Agricultural intensification is known to change the diversity of individual groups of soil biota, but less is known about how intensification affects biodiversity of the soil food web as a whole, and whether or not these effects may be generalized across regions. We examined biodiversity in soil food webs from grasslands, extensive, and intensive rotations in four agricultural regions across Europe: in Sweden, the UK, the Czech Republic and Greece. Effects of land-use intensity were quantified based on structure and diversity among functional groups in the soil food web, as well as on community-weighted mean body mass of soil fauna. We also elucidate land-use intensity effects on diversity of taxonomic units within taxonomic groups of soil fauna. We found that between regions soil food web diversity measures were variable, but that increasing land-use intensity caused highly consistent responses. In particular, land-use intensification reduced the complexity in the soil food webs, as well as the community-weighted mean body mass of soil fauna. In all regions across Europe, species richness of earthworms, Collembolans, and oribatid mites was negatively affected by increased land-use intensity. The taxonomic distinctness, which is a measure of taxonomic relatedness of species in a community that is independent of species richness, was also reduced by land-use intensification. We conclude that intensive agriculture reduces soil biodiversity, making soil food webs less diverse and composed of smaller bodied organisms. Land-use intensification results in fewer functional groups of soil biota with fewer and taxonomically more closely related species. We discuss how these changes in soil biodiversity due to land-use intensification may threaten the functioning of soil in agricultural production systems.


Topology, divergence dates, and macroevolutionary inferences vary between different tip-dating approaches applied to fossil theropods (Dinosauria).
Dated phylogenies of fossil taxa allow palaeobiologists to estimate the timing of major divergences and placement of extinct lineages, and to test macroevolutionary hypotheses. Recently developed Bayesian 'tip-dating' methods simultaneously infer and date the branching relationships among fossil taxa, and infer putative ancestral relationships. Using a previously published dataset for extinct theropod dinosaurs, we contrast the dated relationships inferred by several tip-dating approaches and evaluate potential downstream effects on phylogenetic comparative methods. We also compare tip-dating analyses to maximum-parsimony trees time-scaled via alternative a posteriori approaches including via the probabilistic cal3 method. Among tip-dating analyses, we find opposing but strongly supported relationships, despite similarity in inferred ancestors. Overall, tip-dating methods infer divergence dates often millions (or tens of millions) of years older than the earliest stratigraphic appearance of that clade. Model-comparison analyses of the pattern of body-size evolution found that the support for evolutionary mode can vary across and between tree samples from cal3 and tip-dating approaches. These differences suggest that model and software choice in dating analyses can have a substantial impact on the dated phylogenies obtained and broader evolutionary inferences.


New frontiers of HCV therapy in HIV/HCV co-infection.
Hepatitis C virus (HCV) leads to disproportionate morbidity and mortality in the HIV-positive population. A new era of anti-HCV therapeutics is emerging, with many direct antiviral agents and immunomodulating drugs in clinical development. This review discusses HCV treatments in development, with special attention to four agents being studied actively among HIV/HCV-co-infected persons.


Achieving increased resolution and more pixels with Superresolution Optical Fluctuation Imaging (SOFI).
Superresolution Optical Fluctuation Imaging (SOFI) as initially demonstrated allows for a resolution enhancement in imaging by a factor of square-root of two. Here, we demonstrate how to increase the resolution of SOFI images by re-weighting the Optical Transfer Function (OTF). Furthermore, we demonstrate how cross-cumulants can be exploited to obtain a fair approximation of the underlying Point-Spread Function. We show a two-fold increase of resolution (over the diffraction limit) of near-infrared quantum dot labeled tubulin-network of 3T3 fibroblasts.


Toll-like Receptor 3 Is a Therapeutic Target for Pulmonary Hypertension.
Pulmonary arterial hypertension (PAH) is characterized by vascular cell proliferation and endothelial cell apoptosis. TLR3 (Toll-like receptor 3) is a receptor for double-stranded RNA and has been recently implicated in vascular protection. To study the expression and role of TLR3 in PAH and to determine whether a TLR3 agonist reduces pulmonary hypertension in preclinical models. Lung tissue and endothelial cells from patients with PAH were investigated by polymerase chain reaction, immunofluorescence, and apoptosis assays. TLR3-/- and TLR3+/+ mice were exposed to chronic hypoxia and SU5416. Chronic hypoxia or chronic hypoxia/SU5416 rats were treated with the TLR3 agonist polyinosinic/polycytidylic acid (Poly[I:C]). TLR3 expression was reduced in PAH patient lung tissue and endothelial cells, and TLR3-/- mice exhibited more severe pulmonary hypertension following exposure to chronic hypoxia/SU5416. TLR3 knockdown promoted double-stranded RNA signaling via other intracellular RNA receptors in endothelial cells. This was associated with greater susceptibility to apoptosis, a known driver of pulmonary vascular remodeling. Poly(I:C) increased TLR3 expression via IL-10 in rat endothelial cells. In vivo, high-dose Poly(I:C) reduced pulmonary hypertension in both rat models in proof-of-principle experiments. In addition, Poly(I:C) also reduced right ventricular failure in established pulmonary hypertension. Our work identifies a novel role for TLR3 in PAH based on the findings that reduced expression of TLR3 contributes to endothelial apoptosis and pulmonary vascular remodeling.


The impact of screening for Type 2 diabetes in siblings of patients with established diabetes.
Targeted screening for Type 2 diabetes has been proposed as a method of identifying people with, or at risk of, the disease in order to implement preventive care. To assess the changes in anxiety, well-being, and cognitions associated with screening for Type 2 diabetes in people at increased risk of diabetes after 1 year; and to identify potential predictors of increased anxiety and lower well being over this period. One-year follow up of a cohort of non-diabetic siblings of those with Type 2 diabetes registered with general practitioners in Oxfordshire and Northamptonshire who were identified for participation in a programme to undertake sib-pair genetic analysis. Potential families were selected through identification of people with Type 2 diabetes. Family members aged 35-74 years, who did not have diabetes and who were willing to participate in the study, completed measures before receiving the results of a fasting plasma glucose test, and 1 year later. Measures included the Spielberger State Anxiety Scale-short form (SSAI-SF), the Well-Being Questionnaire 12 item scale (WBQ-12), and measures of cognitions about developing diabetes. The Health Anxiety Inventory (HAI) was completed before receiving the results of the tests to assess its relationship with anxiety at 1 year. A cohort of 431 individuals was identified, of whom 328 (76%) returned fully completed WBQ scales both initially and at 1 year. State anxiety measured with the SSAI-SF fell from 34.5 (95% CI 33.4-35.6) to 32.3 (31.2-33.4) at 1 year (P < 0.0001). Mean WBQ-12 scores rose (i.e. improved) from 26.8 (26.0-27.4) to 27.4 (26.7-28.1) (P = 0.008). SSAI-SF and WBQ-12 mean scores over 1 year did not differ between participants receiving a normal or an at-risk test result. However, those receiving an at-risk test result were more likely, at 1 year, to consider themselves at increased likelihood of developing diabetes (P < 0.001) and to report thinking about what it would be like to develop diabetes (P = 0.006). A score in the upper tertile of the initial HAI was associated with an increased level of anxiety at 1 year (adjusted odds ratio 2.0, 95% CI 1.2-3.4, P = 0.006). There is no evidence that an 'at-risk' test result leads to sustained anxiety or reduced well being at 1 year compared with those receiving a normal test result. However, further studies are required to clarify levels of anxiety prior to screening to assess the overall impact of the process.


Serum cortisol and 17-hydroxyprogesterone interrelation in classic 21-hydroxylase deficiency: is current replacement therapy satisfactory?
One of the main aims in the management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency is to achieve adequate suppression of the adrenal cortex with the smallest possible dose of glucocorticoid substitution. To evaluate the administration schedule of current replacement therapy regimens, we investigated the cortisol-17-hydroxyprogesterone interrelation in 36 patients (13 males and 23 females; median age, 12.3 yr; range, 6.1-18.8 yr) with salt-wasting congenital adrenal hyperplasia. As sufficient variation in 17-hydroxyprogesterone concentrations was required to allow analysis of the cortisol-17-hydroxyprogesterone interrelation, patients were divided into 2 groups depending on the adequacy of hypothalamic-pituitary-adrenal axis suppression. The first group consisted of 17 patients with suppressed 17-hydroxyprogesterone concentrations (group 1), and the second group consisted of 19 patients with nonsuppressed 17-hydroxyprogesterone concentrations (group 2). We determined serum cortisol and 17-hydroxyprogesterone concentrations at 20-min intervals for a total of 24 h while patients were receiving their usual replacement treatment with hydrocortisone and 9alpha-fludrocortisone. We also determined the lowest dose of dexamethasone required to suppress the 0800 h serum ACTH concentrations when administered as a single dose (0.3 or 0.5 mg/m(2)) the night before. Mean 24-h cortisol and 17-hydroxyprogesterone concentrations were 3.9 microg/dl (SD = 2.1) and 66.2 ng/dl (SD = 92.7), respectively, in group 1 and 4.1 microg/dl (SD = 2.5) and 4865.7 ng/dl (SD = 6951) in group 2. The 24-h 17-hydroxyprogesterone concentrations demonstrated circadian variation, with peak values observed between 0400-0900 h. In group 2, 17-hydroxyprogesterone concentrations decreased gradually in response to the rise in cortisol concentrations during the day, but remained low during the night despite the almost undetectable cortisol concentrations between 1600-2000 h. Mean 0800 h androstenedione concentrations correlated strongly with integrated 17-hydroxyprogesterone concentrations (r = 0.81; P < 0.0001), but not with integrated cortisol concentrations. There was a significant negative correlation between cortisol and 17-hydroxyprogesterone at lag time 0 min (r = -0.187; P < 0.0001), peaking at lag time 60 min (r = -0.302; P < 0.0001), with cortisol leading 17-hydroxyprogesterone by these time intervals. Finally, 0800 h serum ACTH concentrations were sufficiently suppressed after a dexamethasone dose of 0.3 mg/m(2) in all but three patients. These findings indicate that in classic 21-hydroxylase deficiency, hydrocortisone should be administered during the period of increased hypothalamic-pituitary-adrenal axis activity, between 0400-1600 h, with the biggest dose given in the morning. Blood investigations performed as part of monitoring of congenital adrenal hyperplasia patients should include androstenedione and 17-hydroxyprogesterone concentrations determined in the morning before the administration of hydrocortisone. It should also be emphasized that blood investigations are only complementary to the overall assessment of these patients, which is primarily based on the evaluation of growth and pubertal progress.


Contribution of CD95 ligand-induced neutrophil infiltration to the bystander effect in p53 gene therapy for human cancer.
Clinical trials of adenoviral p53 gene therapy provide the evidence that the bystander effect induced by the wild-type p53 gene transfer on adjacent tumor cells contributes to tumor progression; its mechanism, however, remains uncharacterized. We report in this work that injection of adenovirus expressing the human wild-type p53 gene (Ad5CMVp53) into established human colorectal tumors in nu/nu mice resulted in CD95 ligand (CD95L) overexpression, followed by a massive neutrophil infiltration. Culture supernatants of human colorectal cancer cells infected with Ad5CMVp53 exhibited a potent chemotactic activity against murine polymorphonuclear neutrophils, which could be abolished by the anti-CD95L mAb (NOK-1). In vivo cell depletion experiments indicated that neutrophils were in part responsible for the antitumor effect of the Ad5CMVp53 infection. Our data directly suggest that overexpression of CD95L by the wild-type p53 gene transfer induces neutrophil infiltration into human colorectal tumors, which may play a critical role in the bystander effect of p53 gene therapy.


Protective effect of theophylline on renal functions in experimental pneumoperitoneum model.
Our objective in this experimental study is to research the effect of the intra-abdominal pressure which rises following pneumoperitoneum and whether Theophylline has a possible protective activity on this situation. In our study, 24 Wistar Albino rats were used. Rats were divided into two groups. The first group was set for only pneumoperitoneum model. The second group was given 15 mg/kg of Theophylline intraperitoneally before setting pneumoperitoneum model. Then urea, creatinine, cystatin-C, tissue and serum total antioxidant capacity, total oxidant capacity and oxidative stress index in two groups were measured and compared with each other. Apoptosis and histopathological conditions in the renal tissues were examined. The differences between the groups were analyzed with the Mann-Whitney U test. Results were considered significant at p < 0.05. No statistically significant difference was determined between tissue and serum averages in two groups in terms of TAS, TOS and OSI values (p > 0.05). The mean value of urea were similar in pneumoperitoneum and pneumoperitoneum + theophylline groups (p = 0.12). The mean cystatin-C value was 2.2 ± 0.3 µg/mL in pneumoperitoneum, 1.74 ± 0.33 µg/mL in pneumoperitoneum + theophylline (p = 0.002). According to our study, lower cystatin-C levels in the group, where Theophylline was given, are suggestive of lower renal injury in this group. However, this opinion is interrogated as there is no difference in terms of tissue and serum TAS, TOS, OSI and urea values between the groups.


Adsorption and recognition characteristics of surface molecularly imprinted polymethacrylic acid/silica toward genistein.
In this paper, on the basis of surface-initiated graft polymerization, a new surface molecular imprinting technique is established by molecular design. And molecularly imprinted polymer MIP-PMAA/SiO2 is successfully prepared with genistein as template. The adsorption and recognition characteristics of MIP-PMAA/SiO2 for genistein are studied in depth by using static method, dynamic method and competitive adsorption experiment. The experimental results show that MIP-PMAA/SiO2 possesses very strong adsorption affinity and specific recognition for genistein. The saturated adsorption capacity could reach to 0.36mmolg(-1). The selectivity coefficients relative to quercetin and rutin are 5.4 and 11.8, respectively. Besides, MIP-PMAA/SiO2 is regenerated easily and exhibits excellent reusability.


TLR8-driven IL-12-dependent reciprocal and synergistic activation of NK cells and monocytes by immunostimulatory RNA.
Immunostimulatory RNA (isRNA) depending on sequence and structure can function as a ligand for Toll-like receptor (TLR) 7 and TLR8. Here we show that isRNA induces high levels of bioactive interleukin-12 in purified human monocytes, whereas purified natural killer (NK) cells did not respond. However, in a coculture of monocytes and NK cells, isRNA dramatically increased NK cell function. Activation of monocytes and NK cells was bidirectional, as monocytes in the presence of NK cells produced higher levels of bioactive interleukin-12. As a result of the monocyte-NK cell interaction in peripheral blood mononuclear cells isRNA induced high levels of interferon (IFN)-gamma in NK cells and strong NK cell-mediated cytotoxic activity. Induction of simultaneous IFN-gamma production and lytic activity by isRNA in NK cells was higher as compared with other established nucleic acid or small molecule TLR ligands. Our studies demonstrate that monocytes play a pivotal role in the orchestration of a strong NK cell response. With early NK cell-dependent IFN-gamma production being critical for the development of antigen-specific cytotoxic T lymphocyte responses, newly developed isRNA-based TLR8 ligands join the list of promising oligonucleotides for immunotherapy of viral infection and cancer.


Key concepts to assess the readiness of data for international research: data quality, lineage and provenance, extraction and processing errors, traceability, and curation. Contribution of the IMIA Primary Health Care Informatics Working Group.
To define the key concepts which inform whether a system for collecting, aggregating and processing routine clinical data for research is fit for purpose. Literature review and shared experiential learning from research using routinely collected data. We excluded socio-cultural issues, and privacy and security issues as our focus was to explore linking clinical data. Six key concepts describe data: (1) DATA QUALITY: the core Overarching concept - Are these data fit for purpose? (2) Data provenance: defined as how data came to be; incorporating the concepts of lineage and pedigree. Mapping this process requires metadata. New variables derived during data analysis have their own provenance. (3) Data extraction errors and (4) Data processing errors, which are the responsibility of the investigator extracting the data but need quantifying. (5) Traceability: the capability to identify the origins of any data cell within the final analysis table essential for good governance, and almost impossible without a formal system of metadata; and (6) Curation: storing data and look-up tables in a way that allows future researchers to carry out further research or review earlier findings. There are common distinct steps in processing data; the quality of any metadata may be predictive of the quality of the process. Outputs based on routine data should include a review of the process from data origin to curation and publish information about their data provenance and processing method.


Comparative photoelastic study of dental and skeletal anchorages in the canine retraction.
To compare dental and skeletal anchorages in mandibular canine retraction by means of a stress distribution analysis. A photoelastic model was produced from second molar to canine, without the first premolar, and mandibular canine retraction was simulated by a rubber band tied to two types of anchorage: dental anchorage, in the first molar attached to adjacent teeth, and skeletal anchorage with a hook simulating the mini-implant. The forces were applied 10 times and observed in a circular polariscope. The stresses located in the mandibular canine were recorded in 7 regions. The Mann-Whitney test was employed to compare the stress in each region and between both anchorage systems. The stresses in the mandibular canine periradicular regions were compared by the Kruskal-Wallis test. Stresses were similar in the cervical region and the middle third. In the apical third, the stresses associated with skeletal anchorage were higher than the stresses associated with dental anchorage. The results of the Kruskal-Wallis test showed that the highest stresses were identified in the cervical-distal, apical-distal, and apex regions with the use of dental anchorage; and in the apical-distal, apical-mesial, cervical-distal, and apex regions with the use of skeletal anchorage. The use of skeletal anchorage in canine retraction caused greater stress in the apical third than the use of dental anchorage, which indicates an intrusive component resulting from the direction of the force due to the position of the mini-implant and the bracket hook of the canine.


Tumor neoantigens: building a framework for personalized cancer immunotherapy.
It is now well established that the immune system can recognize developing cancers and that therapeutic manipulation of immunity can induce tumor regression. The capacity to manifest remarkably durable responses in some patients has been ascribed in part to T cells that can (a) kill tumor cells directly, (b) orchestrate diverse antitumor immune responses, (c) manifest long-lasting memory, and (d) display remarkable specificity for tumor-derived proteins. This specificity stems from fundamental differences between cancer cells and their normal counterparts in that the former develop protein-altering mutations and undergo epigenetic and genetic alterations, resulting in aberrant protein expression. These events can result in formation of tumor antigens. The identification of mutated and aberrantly expressed self-tumor antigens has historically been time consuming and laborious. While mutant antigens are usually expressed in a tumor-specific manner, aberrantly expressed antigens are often shared between cancers and, therefore, in the past, have been the major focus of therapeutic cancer vaccines. However, advances in next-generation sequencing and epitope prediction now permit the rapid identification of mutant tumor neoantigens. This review focuses on a discussion of mutant tumor neoantigens and their use in personalizing cancer immunotherapies.


Reversible T-wave abnormality in severe acute asthma: an electrocardiographic sign of severity.
Reversible electrocardiographic (ECG) abnormalities are well recognized in severe acute asthma. Inferior lead T-wave abnormalities have only rarely been reported, and their frequency and significance have not been well documented. We studied 70 consecutive patients with severe acute asthma on admission to hospital and during recovery, in order to examine the frequency and natural history of such changes and to document their relationship to the severity of the attack. Twenty-two patients (34%) had inferior lead T-wave inversion on ECGs performed within 1 h of admission (group 1), whereas the rest did not (group 2). Apart from sinus tachycardia this was the most common ECG abnormality. Patients with inferior T-wave inversion were found to have more severe asthma in terms of degree of pulsus paradoxus, peak expiratory flow rate, forced expiratory volume in 1 s and arterial blood oxygen tension. Ten group 1 and ten group 2 patients underwent two-dimensional echocardiography during the acute phase of their illness and during recovery. Six (60%) group 1 patients showed echocardiographic evidence of right ventricular pressure overload compared with only one (10%) patient in group 2 (P less than 0.02). Following recovery, voluntary hyperventilation and exercise testing in ten group 1 patients failed to reproduce the ECG changes seen on admission. Reversible inferior lead T-wave abnormalities may occur in the severe acute asthma and appear to be related to the severity of the attack.


A case of capecitabine-induced coronary microspasm in a patient with rectal cancer.
5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmaconkinetics of infusional 5-FU. This new drug is replacing 5-FU as a part of the combined-modality treatment of a number of gastrointestinal cancers. While cardiac events associated with the use of 5-FU are a well known side effect, capecitabine-induced cardiotoxicity has been only rarely reported. Here, we reviewed the case of a patient with rectal cancer who had a capecitabine-induced coronary vasospasm. The most prominent mutation of the dihydropyrimidine dehydrogenase gene was also analyzed.


Brain correlates of subjective reality of physically and psychologically induced pain.
Meaningful behavior requires successful differentiation of events surfacing from one's mind from those arising from the external world. Such judgements may be especially demanding during pain because of the strong contribution from psychological factors to this experience. It is unknown how the subjective reality of pain (SRP) is constructed in the human brain, and neuronal mechanisms of the subjective reality are poorly understood in general. To address these questions, 14 suggestion-prone healthy subjects rated reality of pain that was induced either by laser pulses to the skin or by hypnotic suggestion during functional MRI. Both pain states were associated with activation of the brain's pain circuitry. During laser stimulation, the sensory parts of this circuitry were activated more strongly, and their activation strengths correlated positively with the SRP. During suggestion-induced pain, the reality estimates were lower and correlated positively with activation strengths in the rostral and perigenual anterior cingulate cortex and in the pericingulate regions of the medial prefrontal cortex; a similar trend was evident during laser-induced pain. These findings support the view that information about sensory-discriminative characteristics of pain contributes to the SRP. Differences in such information between physically and psychologically induced pain, however, could be quantitative rather than qualitative and therefore insufficient for judging the reality of pain without knowledge about the source of this information. The medial prefrontal cortex is a likely area to contribute to such source monitoring.


An intervention study in obese mice with astaxanthin, a marine carotenoid--effects on insulin signaling and pro-inflammatory cytokines.
Astaxanthin (ASX), a xanthophyll carotenoid from the marine algae Hematococcus pluvialis, has anti-obesity and insulin-sensitivity effects. The specific molecular mechanisms of its actions are not yet established. The present study was designed to investigate the mechanisms underlying the insulin sensitivity effects of ASX in a non-genetic insulin resistant animal model. A group of male Swiss albino mice was divided into two and fed either a starch-based control diet or a high fat-high fructose diet (HFFD). Fifteen days later, mice in each dietary group were divided into two and were treated with either ASX (6 mg kg(-1) per day) in olive oil or olive oil alone. At the end of 60 days, glucose, insulin and pro-inflammatory cytokines in plasma, lipids and oxidative stress markers in skeletal muscle and adipose tissue were assessed. Further, post-receptor insulin signaling events in skeletal muscle were analyzed. Increased body weight, hyperglycemia, hyperinsulinemia and increased plasma levels of tumor necrosis factor-α and interleukin-6 observed in HFFD-fed mice were significantly improved by ASX addition. ASX treatment also reduced lipid levels and oxidative stress in skeletal muscle and adipose tissue. ASX improved insulin signaling by enhancing the autophosphorylation of insulin receptor-β (IR-β), IRS-1 associated PI3-kinase step, phospho-Akt/Akt ratio and GLUT-4 translocation in skeletal muscle. This study demonstrates for the first time that chronic ASX administration improves insulin sensitivity by activating the post-receptor insulin signaling and by reducing oxidative stress, lipid accumulation and proinflammatory cytokines in obese mice.


MAD 20 alleles of merozoite surface protein-1 (msp-1) are associated with severe Plasmodium falciparum malaria in Pakistan.
Various factors determine the outcome of Plasmodium falciparum infection such as parasite load, sequestration, adhesion molecules, and immune mediators. P. falciparum merozoite surface protein-1 (msp-1) and msp-2 genotypes were also found associated with severe disease. We investigated the association between msp-1 and msp-2 genotypes in patients with uncomplicated malaria (UM) and severe malaria (SM). Twenty-two malaria patients with microscopy-confirmed P. falciparum infection and eight healthy endemic controls were selected for analysis. Nested polymerase chain reaction (PCR) was used to identify P. falciparum genotypes. The plasma concentration of cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ)] and chemokines [chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10] were evaluated using enzyme-linked immunosorbent assay (ELISA). TNF-α levels were significantly higher in both UM (389 pg/mL, p = 0.020) and SM (771 pg/mL, p = 0.004) compared with healthy controls, while they were greater in SM (p = 0.012) as compared to UM. CXCL9 levels were significantly raised in SM as compared to UM and negative controls (NCs). CXCL10 levels were raised in UM (550 pg/mL, p = 0.001) and SM (1480 pg/mL, p = 0.01) as compared with NCs. Increased levels of IL-6 were found in patients carrying the FC27 allelic type of msp-2. A higher prevalence of MAD 20 and K1 msp-1 alleles was observed in the SM group compared to UM. Overall, a greater prevalence of MAD 20 alleles and increased serum TNF-α and CXCL9 levels were associated with severe outcome in malaria. Understanding the diversity of malaria genotypes is important for predicting disease-related outcomes of P. falciparum infection in endemic areas.


Activin/nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions by controlling the H3K4me3 chromatin mark.
Stem cells can self-renew and differentiate into multiple cell types. These characteristics are maintained by the combination of specific signaling pathways and transcription factors that cooperate to establish a unique epigenetic state. Despite the broad interest of these mechanisms, the precise molecular controls by which extracellular signals organize epigenetic marks to confer multipotency remain to be uncovered. Here, we use human embryonic stem cells (hESCs) to show that the Activin-SMAD2/3 signaling pathway cooperates with the core pluripotency factor NANOG to recruit the DPY30-COMPASS histone modifiers onto key developmental genes. Functional studies demonstrate the importance of these interactions for correct histone 3 Lys4 trimethylation and also self-renewal and differentiation. Finally, genetic studies in mice show that Dpy30 is also necessary to maintain pluripotency in the pregastrulation embryo, thereby confirming the existence of similar regulations in vivo during early embryonic development. Our results reveal the mechanisms by which extracellular factors coordinate chromatin status and cell fate decisions in hESCs.


Acute Post-Activation Potentiation Effects in NCAA Division II Female Athletes.
Post-activation potentiation (PAP) is a phenomenon in which the power output of a muscle is immediately enhanced after heavy resistance exercise. Whereas the majority of PAP research has examined males, minimal research exists as to how female athletes respond. Therefore, the purpose of this study was to investigate the acute PAP response of back squats on static squat jump (SSJ) performance among NCAA Division II female athletes. Female athletes (n=29) who were current roster members from basketball, softball, and volleyball, performed 3 SSJ prior to 3 repetitions of the back squat exercise at 90% 1RM. After a 5-min rest, athletes once again performed 3 SSJ for maximal height, with peak power calculated using the Sayers equation. There was a significant interaction effect observed between time and team, p=0.022; post-hoc tests indicated that the volleyball team had a significant decrease in power, p=0.008. The main effect for time was not significant, p=0.279, indicating for the group as a whole, there was no evidence of a PAP response. The main effect for team was also non-significant, p=0.173, indicating no difference in power outputs by team. Strength and conditioning coaches who work with female athletes should be aware that the successful implementation of PAP complexes within this population appears to be highly individualized. Therefore, the use of PAP complexes in female athletes should consider both the absolute and relative strength of each athlete in conjunction with the length of the rest period when attempting to optimize the PAP response.


Motor signals in visual localization.
We demonstrate a strong sensory-motor coupling in visual localization in which experimental modification of the control of saccadic eye movements leads to an associated change in the perceived location of objects. Amplitudes of saccades to peripheral targets were altered by saccadic adaptation, induced by an artificial step of the saccade target during the eye movement, which leads the oculomotor system to recalibrate saccade parameters. Increasing saccade amplitudes induced concurrent shifts in perceived location of visual objects. The magnitude of perceptual shift depended on the size and persistence of errors between intended and actual saccade amplitudes. This tight agreement between the change of eye movement control and the change of localization shows that perceptual space is shaped by motor knowledge rather than simply constructed from visual input.


An electrophysiological study of Duchenne dystrophy.
An electrophysiological study has been made of extensor digitorum brevis muscles in 19 boys with Duchenne dystrophy. The isometric twitches of the dystrophic muscles developed less tension and were usually slower than those in controls. Impulse conduction velocity appeared to be reduced in distal regions of nerve axons but was normal proximally. The most interesting finding was a reduction in the number of functioning units in all but one of the patients. The sizes of the surviving units suggested that the results could be explained more easily in terms of a neurogenic process than a primary myopathic one.


Cardiorespiratory fitness and attentional control in the aging brain.
A growing body of literature provides evidence for the prophylactic influence of cardiorespiratory fitness on cognitive decline in older adults. This study examined the association between cardiorespiratory fitness and recruitment of the neural circuits involved in an attentional control task in a group of healthy older adults. Employing a version of the Stroop task, we examined whether higher levels of cardiorespiratory fitness were associated with an increase in activation in cortical regions responsible for imposing attentional control along with an up-regulation of activity in sensory brain regions that process task-relevant representations. Higher fitness levels were associated with better behavioral performance and an increase in the recruitment of prefrontal and parietal cortices in the most challenging condition, thus providing evidence that cardiorespiratory fitness is associated with an increase in the recruitment of the anterior processing regions. There was a top-down modulation of extrastriate visual areas that process both task-relevant and task-irrelevant attributes relative to the baseline. However, fitness was not associated with differential activation in the posterior processing regions, suggesting that fitness enhances attentional function by primarily influencing the neural circuitry of anterior cortical regions. This study provides novel evidence of a differential association of fitness with anterior and posterior brain regions, shedding further light onto the neural changes accompanying cardiorespiratory fitness.


Mini-FLOTAC and Kato-Katz: helminth eggs watching on the shore of Lake Victoria.
One of the challenges for monitoring helminth control programmes based on preventive chemotherapy is the lack of a copro-parasitological gold-standard method that combines good sensitivity with quantitative performance, low cost, and easy-to-learn technique.The aim of our study was to evaluate and compare, the WHO recommended quantitative diagnostic technique (Kato-Katz) and the Mini-FLOTAC. Mini-FLOTAC is an innovative method based on floatation of helminths eggs with two different solutions (FS2 and FS7) using a close system (Fill-FLOTAC) with 5% fixative. Kato-Katz was performed following WHO recommendation. The study was carried out in a rural part of Tanzania, close to Lake Victoria, where the laboratory facilities are fairly scarce, and the basic technique used in the local laboratory (direct smear) was taken as reference standard. 201 children were screened for intestinal helminths and 91% of them were found to be positive. The agreement among the three techniques was calculated with k Cohen coefficient and was fairly good (k = 0.4), although the Mini-FLOTAC results were more sensitive for hookworm (98%) with FS2, and for S.mansoni (90%) with FS7 followed by Kato-Katz (91% and 60% respectively) and direct smear (30% and 10% respectively). A good agreement was found between Mini-FLOTAC and Kato-Katz (k = 0.81) with FS7 (k = 0.76) for hookworm diagnosis and a fairly good one for S.mansoni diagnosis (k = 0.5). For both infections we had a poor agreement between the two quantitative techniques and the direct smear (k<0.3). Kato-Katz diagnosed a higher number of eggs (calculated by arithmetic mean) both for hookworm (455 vs 424 EPG) and for S.mansoni (71 vs 58 EPG) compared with the Mini-FLOTAC, but the differences were not significant (p = 0.4). Mini-FLOTAC is a promising technique, comparable and as sensitive as the Kato-Katz, which is the recommended method in intestinal helminthology for monitoring helminth control programmes. A comparative advantage of the Mini-FLOTAC is that it comprises of a closed system with preserved samples that both protects the operators and allows subsequent examination of the samples. Further studies are needed to validate the mini-FLOTAC with other quantitative techniques (McMaster) and in different settings where other soil-transmitted helminths are also endemic.


Are the Traditional Medical Uses of Muricidae Molluscs Substantiated by Their Pharmacological Properties and Bioactive Compounds?
Marine molluscs from the family Muricidae hold great potential for development as a source of therapeutically useful compounds. Traditionally known for the production of the ancient dye Tyrian purple, these molluscs also form the basis of some rare traditional medicines that have been used for thousands of years. Whilst these traditional and alternative medicines have not been chemically analysed or tested for efficacy in controlled clinical trials, a significant amount of independent research has documented the biological activity of extracts and compounds from these snails. In particular, Muricidae produce a suite of brominated indoles with anti-inflammatory, anti-cancer and steroidogenic activity, as well as choline esters with muscle-relaxing and pain relieving properties. These compounds could explain some of the traditional uses in wound healing, stomach pain and menstrual problems. However, the principle source of bioactive compounds is from the hypobranchial gland, whilst the shell and operculum are the main source used in most traditional remedies. Thus further research is required to understand this discrepancy and to optimise a quality controlled natural medicine from Muricidae.


miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that, in general, negatively regulate gene expression. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. Some miRNA genes harboring CpG islands undergo methylation-mediated silencing, a characteristic of many tumor suppressor genes. To identify such miRNAs in hepatocellular carcinoma (HCC), we first examined the methylation status of 43 loci containing CpG islands around 39 mature miRNA genes in a panel of HCC cell lines and non-cancerous liver tissues as controls. Among 11 miRNA genes frequently methylated in HCC cell lines but not in non-cancerous liver tissues, three miRNA genes, i.e. miR-124, miR-203 and miR-375, were selected as silenced miRNAs through CpG-island methylation by comparing methylation and expression status and evaluating restored expression after treatment with 5-aza-2'-deoxycytidine. In primary tumors of HCC with paired non-tumorous liver tissues, only miR-124 and miR-203 showed frequent tumor-specific methylation, and their expression status was inversely correlated with methylation status. Ectopic expression of miR-124 or miR-203 in HCC cells lacking their expression inhibited cell growth, with direct downregulation of possible targets, cyclin-dependent kinase 6 (CDK6), vimentin (VIM), SET and MYND domain containing 3 (SMYD3) and IQ motif containing GTPase activating protein 1 (IQGAP1) or ATP-binding cassette, subfamily E, member 1 (ABCE1), respectively. Our results suggest that miR-124 and miR-203 are novel tumor-suppressive miRNAs for HCC epigenetically silenced and activating multiple targets during hepatocarcinogenesis.


Understanding brain, mind and soul: contributions from neurology and neurosurgery.
Treatment of diseases of the brain by drugs or surgery necessitates an understanding of its structure and functions. The philosophical neurosurgeon soon encounters difficulties when localising the abstract concepts of mind and soul within the tangible 1300-gram organ containing 100 billion neurones. Hippocrates had focused attention on the brain as the seat of the mind. The tabula rasa postulated by Aristotle cannot be localised to a particular part of the brain with the confidence that we can localise spoken speech to Broca's area or the movement of limbs to the contralateral motor cortex. Galen's localisation of imagination, reasoning, judgement and memory in the cerebral ventricles collapsed once it was evident that the functional units-neurones-lay in the parenchyma of the brain. Experiences gained from accidental injuries (Phineas Gage) or temporal lobe resection (William Beecher Scoville); studies on how we see and hear and more recent data from functional magnetic resonance studies have made us aware of the extensive network of neurones in the cerebral hemispheres that subserve the functions of the mind. The soul or atman, credited with the ability to enliven the body, was located by ancient anatomists and philosophers in the lungs or heart, in the pineal gland (Descartes), and generally in the brain. When the deeper parts of the brain came within the reach of neurosurgeons, the brainstem proved exceptionally delicate and vulnerable. The concept of brain death after irreversible damage to it has made all of us aware of 'the cocktail of brain soup and spark' in the brainstem so necessary for life. If there be a soul in each of us, surely, it is enshrined here.


High-resolution Y chromosome haplotypes of Israeli and Palestinian Arabs reveal geographic substructure and substantial overlap with haplotypes of Jews.
High-resolution Y chromosome haplotype analysis was performed in 143 paternally unrelated Israeli and Palestinian Moslem Arabs (I&P Arabs) by screening for 11 binary polymorphisms and six microsatellite loci. Two frequent haplotypes were found among the 83 detected: the modal haplotype of the I&P Arabs (approximately 14%) was spread throughout the region, while its one-step microsatellite neighbor, the modal haplotype of the Galilee sample (approximately 8%), was mainly restricted to the north. Geographic substructuring within the Arabs was observed in the highlands of Samaria and Judea. Y chromosome variation in the I&P Arabs was compared to that of Ashkenazi and Sephardic Jews, and to that of North Welsh individuals. At the haplogroup level, defined by the binary polymorphisms only, the Y chromosome distribution in Arabs and Jews was similar but not identical. At the haplotype level, determined by both binary and microsatellite markers, a more detailed pattern was observed. Single-step microsatellite networks of Arab and Jewish haplotypes revealed a common pool for a large portion of Y chromosomes, suggesting a relatively recent common ancestry. The two modal haplotypes in the I&P Arabs were closely related to the most frequent haplotype of Jews (the Cohen modal haplotype). However, the I&P Arab clade that includes the two Arab modal haplotypes (and makes up 32% of Arab chromosomes) is found at only very low frequency among Jews, reflecting divergence and/or admixture from other populations.


Improving the Robustness of Scagnostics.
In this paper, we examine the robustness of scagnostics through a series of theoretical and empirical studies. First, we investigate the sensitivity of scagnostics by employing perturbing operations on more than 60M synthetic and real-world scatterplots. We found that two scagnostic measures, Outlying and Clumpy, are overly sensitive to data binning. To understand how these measures align with human judgments of visual features, we conducted a study with 24 participants, which reveals that i) humans are not sensitive to small perturbations of the data that cause large changes in both measures, and ii) the perception of clumpiness heavily depends on per-cluster topologies and structures. Motivated by these results, we propose Robust Scagnostics (RScag) by combining adaptive binning with a hierarchy-based form of scagnostics. An analysis shows that RScag improves on the robustness of original scagnostics, aligns better with human judgments, and is equally fast as the traditional scagnostic measures.


Racial differences in abnormal ambulatory blood pressure monitoring measures: Results from the Coronary Artery Risk Development in Young Adults (CARDIA) study.
Several ambulatory blood pressure monitoring (ABPM) measures have been associated with increased cardiovascular disease risk independent of clinic blood pressure (BP). African Americans have higher clinic BP compared with Whites but few data are available on racial differences in ABPM measures. We compared ABPM measures between African American (n = 178) and White (n = 103) participants at the Year 5 Coronary Artery Risk Development in Young Adults study visit. BP was measured during a study visit and the second and third measurements were averaged. ABPM was conducted over the following 24 hours. Mean ± SD age of participants was 29.8 ± 3.8 years and 30.8 ± 3.5 years for African Americans and Whites, respectively. Mean daytime systolic BP (SBP) was 3.90 (SD 1.18) mm Hg higher among African Americans compared with Whites (P < 0.001) after age-gender adjustment and 1.71 (SD 1.03) mm Hg higher after multivariable adjustment including mean clinic SBP (P = 0.10). After multivariable adjustment including mean clinic SBP, nighttime SBP was 4.83 (SD 1.11) mm Hg higher among African Americans compared with Whites (P < 0.001). After multivariable adjustment, the African Americans were more likely than Whites to have nocturnal hypertension (prevalence ratio: 2.44, 95% CI: 0.99-6.05) and nondipping (prevalence ratio: 2.50, 95% CI: 1.39-4.48). The prevalence of masked hypertension among African Americans and Whites was 4.4% and 2.1%, respectively, (P = 0.49) and white coat hypertension was 3.3% and 3.9%, respectively (P = 0.99). Twenty-four hour BP variability on ABPM was higher among African Americans compared with Whites. These data suggest racial differences in several ABPM measures exist.


Comparative assessment of in vitro/in vivo performances of orodispersible electrospun and casting films containing rizatriptan benzoate.
The electrospinning process is a promising approach to produce various drug-loaded orodispersible films (ODFs) with a rapid onset of their actions. However, there is only limited number of studies comparing the pharmacological performances of electrospun ODFs (eODFs) with traditional casting films (CFs). In this study, rizatriptan benzoate (RB), a pain relieving agent was formulated with PVP and PVA into ODFs using electrospinning and casting methods. The ODFs were subsequently characterized with respect to their morphology, solid state properties and mechanical characteristics. The uniformity of the dosage units, disintegration behavior and dissolution patterns of the ODFs were also evaluated prior to the pharmacokinetic study. The obtained CFs and eODFs were semitransparent and white in appearance, respectively. The scanning electron microscopy revealed that the eODFs contained nanoporous structure, while the CFs showed no observable pores. RB was amorphously dispersed in both these films without drug-polymer interactions. The uniformity of dosage units for both eODFs and CFs was complied with European Pharmacopeia. As compared to the CFs, the eODFs were more flexible and lesser rigid in nature and showed faster disintegration and dissolution rates. In addition, the eODFs exhibited a higher bioavailability with a shorter Tmax relative to the CFs and commercial RB tablets. This study demonstrated that eODFs were superior to CFs with respect to in vivo pharmacological effects, which could be attributed to the submicron structure of eODFs obtained through the electrospinning process.


Cloning and functional expression of voltage-gated ion channel subunits from cnidocytes of the Portuguese Man O'War Physalia physalis.
Cnidocytes were dissociated from the tentacles of the Portuguese Man O'War Physalia physalis using heat treatment, and purified using density centrifugation. Visual observation confirmed that these cnidocytes contained a nucleus, a cnidocyst and an apical stereocilium, confirming that the cells were intact. A cnidocyte-specific amplified cDNA library was then prepared using RNA isolated from the cnidocytes, and screened for voltage-gated ion channel subunits using conventional molecular cloning techniques. A variety of channel proteins were identified and full-length sequence obtained for two of them, a Ca(2+) channel beta subunit (PpCa(V)beta) and a Shaker-like K(+) channel (PpK(V)1). The location of the transcripts was confirmed by RT-PCR of total RNA isolated from individually selected and rinsed cnidocytes. The functional properties of these two channel proteins were characterized electrophysiologically using heterologous expression. PpCa(V)beta modulates currents carried by both cnidarian and mammalian alpha(1) subunits although the specifics of the modulation differ. PpK(V)1 produces fast transient outward currents that have properties typical of other Shaker channels. The possible role of these channel proteins in the behavior of cnidocytes is discussed.


Antibiotic Treatment Shapes the Antigenic Environment During Chronic TB Infection, Offering Novel Targets for Therapeutic Vaccination.
The lengthy and complicated current regimen required to treat drug-susceptible tuberculosis (TB) reflects the ability of Mycobacterium tuberculosis (Mtb) to persist in host tissues. The stringent response pathway, governed by the dual (p)ppGpp synthetase/hydrolase, Rel Mtb , is a major mechanism underlying Mtb persistence and antibiotic tolerance. In the current study, we addressed the hypothesis that Rel Mtb is a "persistence antigen" presented during TB chemotherapy and that enhanced immunity to Rel Mtb can enhance the tuberculocidal activity of the first-line anti-TB drug, isoniazid, which has reduced efficacy against Mtb persisters. C57BL/6 mice and Hartley guinea pigs were aerosol-infected with M. tuberculosis (Mtb) and, 4 weeks later, received either human-equivalent daily doses of isoniazid alone, or isoniazid in combination with a DNA vaccine targeting relMtb . After isoniazid treatment, there was a significant reduction in dominant antigen ESAT6-reactive CD4+ or TB10.4-reactive CD8+ T cells in the lungs and spleens of mice. However, the total number of Rel Mtb -reactive CD4+ T cells remained stable in mouse lungs and spleens, as did the number of Rel Mtb -reactive CD8+T cells. Therapeutic vaccination with relMtb DNA vaccine enhanced the activity of isoniazid in Mtb-infected C57BL/6 mice and guinea pigs. When treatment with isoniazid was discontinued, mice immunized with the relMtb DNA vaccine showed a lower mean lung bacterial burden at relapse compared to the control group. Our work shows that antitubercular treatment shapes the antigenic environment, and that therapeutic vaccination targeting the Mtb stringent response may represent a novel approach to enhance immunity against Mtb persisters, with the ultimate goal of shortening curative TB treatment.


Copper pillar and memory characteristics using Al2O3 switching material for 3D architecture.
A novel idea by using copper (Cu) pillar is proposed in this study, which can replace the through-silicon-vias (TSV) technique in future three-dimensional (3D) architecture. The Cu pillar formation under external bias in an Al/Cu/Al2O3/TiN structure is simple and low cost. The Cu pillar is formed in the Al2O3 film under a small operation voltage of <5 V and a high-current-carrying conductor of >70 mA is obtained. More than 100 devices have shown tight distribution of the Cu pillars in Al2O3 film for high current compliance (CC) of 70 mA. Robust read pulse endurances of >10(6) cycles are observed with read voltages of -1, 1, and 4 V. However, read endurance is failed with read voltages of -1.5, -2, and -4 V. By decreasing negative read voltage, the read endurance is getting worst, which is owing to ruptured Cu pillar. Surface roughness and TiO x N y on TiN bottom electrode are observed by atomic force microscope and transmission electron microscope, respectively. The Al/Cu/Al2O3/TiN memory device shows good bipolar resistive switching behavior at a CC of 500 μA under small operating voltage of ±1 V and good data retention characteristics of >10(3) s with acceptable resistance ratio of >10 is also obtained. This suggests that high-current operation will help to form Cu pillar and lower-current operation will have bipolar resistive switching memory. Therefore, this new Cu/Al2O3/TiN structure will be benefited for 3D architecture in the future.


DNA flow cytometric analysis of clinical stage I endometrial carcinomas with lymph node metastases.
Twenty-one (8%) of 264 consecutive evaluable patients with clinical stage 1 endometrial carcinoma had histologic evidence of pelvic and/or para-aortic lymph node metastases. DNA flow cytometry was performed on both the primary tumor and nodal metastasis. Seventeen of 21 sets could be analyzed. Overall, 11 (65%) of the primary carcinomas were aneuploid. Nine of 17 (53%) had consistent ploidy patterns when the primary tumor and lymphatic metastasis were compared. The remaining 8 (47%) had aneuploid primaries with diploid nodal metastases. Five (83%) of the 6 patients with diploid primary tumors were alive without evidence of disease compared to 3 of 11 (27%) patients with aneuploid tumors (P < 0.05). Other predictors of disease outcome included tumor histology, lymph vascular space invasion, and depth of myometrial invasion. Ploidy status of the lymphatic metastasis was not important in terms of overall survival. All 8 patients with para-aortic nodal metastases had aneuploid primary carcinomas compared to 4 (44%) of 9 patients with pelvic node involvement only (P < 0.01). Mean survival was 31 months for patients with para-aortic node metastases compared to 51 months for patients with only pelvic node metastases. Comparison of survival curves among these two groups demonstrated a significant survival advantage in patients with regional nodal metastases (P = 0.032). S-phase fraction of both the primary tumor and lymphatic metastasis did not correlate with survival or predict disease outcome. DNA index of the primary tumor, as a continuous variable, was inversely proportional to survival, demonstrating poorer survivorship with incremental increases of DI. Ploidy status of the lymph node metastasis was an inconsistent reflection of the primary tumor's expression and behavior and, therefore, little additional information was gained by knowledge of the lymphatic ploidy status.


Effects of right ventricular septal versus apical pacing on plasma natriuretic peptide levels.
To investigate the contribution of right ventricular (RV) pacing sites to the cardiac function, this study compares plasma B-type natriuretic peptide (BNP) levels during RV septal and apical pacing in patients implanted with a pacemaker. Seventy-four consecutive patients with indication for permanent pacing were included. To provide for the possibility of appropriate subgroup analyses, patients were stratified according to their pacing mode into two groups: Those with dual chamber DDD(R)/VDD pacemakers (41 patients, mean age 54.1±18.4 years), and those with single chamber VVI pacemakers (33 patients, mean age 60.6±18.4 years). A prospective single-blinded randomized design was used. Randomization (1:1 way) was between lead placement on the RV septum or RV apex and occurred during the implant in both groups. Compared to baseline, a significant decrease in BNP (429.8±103 pg/ml and 291.7±138 pg/ml, respectively) levels was observed during DDD(R) /VDD pacing after two months. In contrast, during VVI (R) pacing, a significant increase in BNP levels was observed (657.5±104 pg/ml and 889.5±139 pg/ml, respectively). To determine the impact of pacing sites on cardiac function, we assessed the changes in BNP levels in each group separately. Despite the significant difference in the pattern of changes between the two groups (P < 0.02), no significant changes were observed within groups regarding the acute effect of the pacing site (RV apex vs. RV septal) on BNP levels (P=NS). Our main result showed no significant differences between pacing sites and concluded that hemodynamic improvement could be substantially influenced by pacing mode, more than by pacing site.


Typology of eaters based on conventional and organic food consumption: results from the NutriNet-Santé cohort study.
Limited information is available on large-scale populations regarding the socio-demographic and nutrient profiles and eating behaviour of consumers, taking into account both organic and conventional foods. The aims of this study were to draw up a typology of consumers according to their eating habits, based both on their dietary patterns and the mode of food production, and to outline their socio-demographic, behavioural and nutritional characteristics. Data were collected from 28 245 participants of the NutriNet-Santé study. Dietary information was obtained using a 264-item, semi-quantitative, organic FFQ. To identify clusters of consumers, principal component analysis was applied on sixteen conventional and sixteen organic food groups followed by a clustering procedure. The following five clusters of consumers were identified: (1) a cluster characterised by low energy intake, low consumption of organic food and high prevalence of inadequate nutrient intakes; (2) a cluster of big eaters of conventional foods with high intakes of SFA and cholesterol; (3) a cluster with high consumption of organic food and relatively adequate nutritional diet quality; (4) a group with a high percentage of organic food consumers, 14 % of which were either vegetarians or vegans, who exhibited a high nutritional diet quality and a low prevalence of inadequate intakes of most vitamins except B12; and (5) a group of moderate organic food consumers with a particularly high intake of proteins and alcohol and a poor nutritional diet quality. These findings may have implications for future aetiological studies investigating the potential impact of organic food consumption.


Functional properties of parietal visual neurons: radial organization of directionalities within the visual field.
Parietal visual neurons (PVNs) were studied in waking monkeys as they executed a simple fixation-detection task. Test visual stimuli of varied direction, speed, and extent were presented during the fixation period; these stimuli did not control behavior. Most PVNs subtend large, bilateral receptive fields and are exquisitely sensitive to stimulus motion and direction but insensitive to stimulus speed. The directional preferences of PVNs along meridians are opponently organized, with the preferred directions pointing either inward toward or outward away from the fixation point. Evidence presented in the preceding paper (Motter et al., 1987) indicates that opponent directionality along a single meridian is produced by a feed-forward inhibition of 20 degrees-30 degrees spatial extent. The observations fit a double-Gaussian model of superimposed but unequal excitatory and inhibitory receptive fields: When the former is larger, inward directionality results; when smaller, outward directionality results. We examine here the distribution of the meridional directional preferences in the visual field. Tests showed that opponent organization is not produced by differences in local directional properties in different parts of the receptive field. The distribution of response intensities from one meridian to another is adequately described by a sine wave function. These data indicate a best radial direction for each neuron with a broad distribution of response intensities over successive meridians. Thus, any single PVN, with rare exceptions, cannot signal radial stimulus direction precisely. We then determined how accurately the population response predicted radial stimulus direction by the application of a linear vector summation model. The resulting population vector varied from stimulus direction by an average of 9 degrees. Whether or not the perception of the direction of motion depends upon a population vector remains uncertain. PVNs are especially sensitive to object movement in the visual surround, particularly in the periphery of the visual field. This, combined with their large receptive fields and their wide but flat sensitivity to stimulus speed, makes them especially sensitive to optic flow. This is discussed in relation to the role of the parietal visual system in the visual guidance of projected movements of the arm and hand, in the guidance of locomotion, and in evoking the illusion of vection.


Optic nerve oedema at high altitude occurs independent of acute mountain sickness.
The study aims to investigate changes in the optic nerve sheath diameter (ONSD) at high altitude and to assess correlation to optic disc oedema (ODE) and acute mountain sickness (AMS). This investigation is part of the Tübingen High Altitude Ophthalmology study. Fourteen volunteers ascended to 4559 m for 4 days before returning to low altitude. Ultrasonography of ONSD, quantification of optic disc parameters using a scanning laser ophthalmoscope and fluorescein angiography were performed at 341 m and at high altitude. Pearson's coefficient was used to correlate changes in ONSD with the optic disc and AMS. Assessment of AMS was performed using the Lake Louise (LL) and AMS-cerebral (AMS-C) scores of the Environmental Symptom Questionnaire-III. All volunteers were clinically monitored for heart rate (HR) and oxygen saturation (SpO2). The mean ONSD at high altitude (4.6±0.3 mm, p<0.05) was significantly increased compared with baseline (3.8±0.4 mm) and remained enlarged throughout high-altitude exposure. This change in ONSD did not correlate with AMS (AMS-C, r=0.26, p=0.37; LL, r=0.21, p=0.48) and high-altitude headache (r=0.54, p=0.046), or clinical parameters of SpO2 (r=0.11, p=0.72) and HR (r=0.22, p=0.44). Increased ONSD did not correlate with altered key stereometric parameters of the optic disc describing ODE at high altitude (r<0.1, p>0.5). High-altitude exposure leads to marked oedema formation of the optic nerve independent of AMS. Increased ONSD and ODE reflect hypoxia-driven oedema formation of the optic nerve at high altitude, providing important pathophysiological insight into high-altitude illness development and for future research.


Use of GFP to analyze morphology, connectivity, and function of cells in the central nervous system.
We here describe various approaches using GFP that are being used in the morphological and functional analysis of specific cell types in the normal and injured central nervous system. Incorporation of GFP into viral vectors allows phenotypic characterization of transduced cells and can be used to label their axons and terminal projections. Characterization of transduced cell morphology can be enhanced by intracellular injection of living GFP-labeled cells with appropriate fluorescent dyes. Ex vivo labeling of precursor or glial cells using viral vectors that encode GFP permits long-term identification of these cells after transplantation into the brain or spinal cord. In utero electroporation methods result in expression of gene products in developing animals, allowing both functional and morphological studies to be carried out. GFPCre has been developed as a marker gene for viral vector-mediated expression of the bacterial recombinase Cre in the brain of adult mice with "floxed" transgenes. GFPCre-mediated induction of transgene expression can be monitored by GFP expression in defined populations of neurons in the adult brain. Finally, GFP can be used to tag proteins, permitting dynamic visualization of the protein of interest in living cells.


Comparison of blood smear microscopy to a rapid diagnostic test for in-vitro testing for P. falciparum malaria in Kenyan school children.
To compare the diagnostic performance of microscopy using Giemsa-stained thick and thin blood smears to a rapid malaria dipstick test (RDT) in detecting P. falciparum malaria in Kenyan school children. Randomised, controlled feeding intervention trial from 1998-2001. Rural Embu district, Kenya. The area is considered endemic for malaria, with four rainy seasons per year. Chloroquine resistance was estimated in 80% of patients. Children had a spleen rate of 45%. A sample of 515 rural Kenyan primary school children, aged 7-11 years, who were enrolled in a feeding intervention trial from 1998-2001. Percent positive and negative P. falciparum malaria status, sensitivity, specificity and positive and negative predictive values of RDT. For both years, the RDT yielded positive results of 30% in children compared to microscopy (17%). With microscopy as the "gold standard", RDT yielded a sensitivity of 81.3% in 1998 and 79.3% in 2000. Specificity was 81.6% in 1998 and 78.3% in 2000. Positive predictive value was 47.3% in 1998 and 42.6% in 2000, and negative predictive value was 95.6% in 1998 and 94.9% in 2000. Rapid diagnostic testing is a valuable tool for diagnosis and can shorten the interval for starting treatment, particularly where microscopy may not be feasible due to resource and distance limitations.


Dietetic and lifestyle recommendations for stone formers.
Nutrition is tightly associated with the risk of stone events. A part from genetic predisposition, a correct and balanced diet might prevent incident kidney stones. Several studies analyzed each dietary component and different diets to better understand their impact on stone recurrence. Fluids: High fluids intake is the most important factor for preventing kidney stones disease and for every 200 mL of water, the risk of stones is reduced by 13%. Soft drinks seems to be associated to a greater risk of stone events, whereas caffeine and citrus fruits juice are not. Calcium: Normally calcium intake with diet does not exceed 1.2 g/day. A balanced consumption of dairy products is capable of reducing oxalate intestinal absorption and urinary excretion compared to low calcium diet, being protective for stone disease. Oxalate: The exact amount of oxalate contained in different foods is difficult to estimate for its variability, even in the same aliment. In addition, the amount of oxalate consumed was shown to be only a minor risk factor for stone disease, whereas its intestinal absorption is strongly influenced by external factors, such as calcium intake. Dietary oxalate restriction is advisable only in patients with known elevated consumption. Sodium: High sodium intake is both associated with hypertension, heart disease and stone risk. Increased sodium consumption is directly associated to hypercalciuria in both calcium stone formers and healthy subjects. Although dietary sodium restriction to recommended values is always desirable in stone formers, it is difficult to achieve for its broad use in food preparation. Proteins: Animal proteins are associated to increased risk for stone formation, whereas vegetable and dairy proteins are not. Increased meat intake was associated to acidic urine pH, negative calcium balance and reduced anti-lithogenic urinary solutes excretion.Fruits and vegetables: Alkalizing foods are one of the most important factors for stone protection. Their consumption increases anti-lithogenic solutes as citrate, potassium and magnesium. A diet rich in fruits and vegetables is strongly recommended for stone formers. Uric acid: Elevated meat consumption is either associated to increased purine metabolism and acid load, favoring uric acid nephrolithiasis by reducing urine pH and increasing urinary excretion of uric acid, especially in patients affected by metabolic syndrome and diabetes.In conclusion, the most effective diet for stone protection is rich in fruits and vegetables, low in animal proteins and salt, with balanced dairy product consumption and obviously, with elevated fluid intake. These characteristics make vegetarian and Mediterranean diets protective and useful for stone formers, whereas western diet is at risk for stone formation.


Characterization, localization and actions of endothelins in umbilical vessels and placenta of man.
Endothelin-like immunoreactivity was observed in the endothelial lining of umbilical vein and artery as well as in the epithelium of the amniotic membrane. High levels of endothelin-like immunoreactivity (0.4-1.4 pmol g-1) were detected in human amniotic membrane, umbilical vessels and placenta. The concentration of endothelin-like immunoreactivity in the amniotic fluid was much higher (77 pmol l-1) than in umbilical cord plasma (10 pmol l-1). Characterization by reverse phase HPLC revealed that most of the endothelin-like immunoreactivity eluted in the position of synthetic endothelin-1 or oxidized endothelin-1. Specific, high affinity binding sites for endothelin-1 were present in placenta and umbilical artery. Endothelin binding sites were also found in cultured smooth muscle cells from the umbilical artery and vein. In the placenta, endothelin-1 and -3 were almost equipotent as competing ligands for endothelin-1 binding sites, whereas in the umbilical artery endothelin-3 was much less potent than endothelin-1. Scatchard analysis of the binding for placental membranes displayed a straight line (r = -0.994) indicating a single class of endothelin receptors with a Kd-value of 80 pmol l-1 and Bmax of 113 fmol mg-1. Endothelin-1 caused potent contractions of umbilical arteries and veins with threshold effects at 10 pmol l-1 while endothelin-3 had no contractile effect up to 10(-7) mol l-1. It is concluded that endothelin-1 predominates over other endothelins in umbilical vessels, amnion and placenta, and high levels of endothelin-1 was observed in foetal circulation and amniotic fluid. Endothelin-receptors seem to be of different types in placenta (ETB type) and umbilical vessels (ETA type).


Posttranscriptional regulation of neurotensin in the gut.
Previous studies have suggested an important role for neurotensin as an enterotrophic factor in the adaptive response of the gut. The purpose of this study was to determine the specific tissue distribution of neurotensin messenger RNA (mRNA) and to examine the molecular mechanisms that regulate intestinal neurotensin gene expression and content. In the first experiment, various segments of gut tissue from three Sprague-Dawley rats were harvested, and polyadenylated RNA was extracted for Northern hybridization with a rat neurotensin probe. In the second experiment, 32 Sprague-Dawley rats were fasted for 72 hours and then killed at 0, 3, 12, and 24 hours after refeeding (n = 8 rats/group). Rats fed ad libitum were killed before fasting (control, n = 8). Distal ileal segments (30 cm) were resected for measurement of neurotensin tissue concentration by radioimmunoassay and extraction of poly (A)+ RNA for Northern hybridization with a rat neurotensin complementary DNA probe. Blots were stripped and reprobed for beta-actin as a control for RNA loading. A nuclear run-on transcription assay was performed to determine the relative rate of neurotensin transcription. In the first experiment, neurotensin messenger RNA transcripts of 1.0 and 1.5 Kb sizes were found throughout the small intestine and proximal colon; the greatest abundance was found in the distal small intestine. In the second experiment, neurotensin tissue concentration was significantly reduced with fasting. Refeeding a diet for 24 hours returned neurotensin concentration to control levels. However, neither the amount of neurotensin messenger RNA nor its rate of transcription were altered by fasting and refeeding. These findings suggest that a posttranscriptional mechanism is responsible for regulation of neurotensin synthesis in gut mucosa.


Xanthomonas citri jumbo phage XacN1 exhibits a wide host range and high complement of tRNA genes.
Xanthomonas virus (phage) XacN1 is a novel jumbo myovirus infecting Xanthomonas citri, the causative agent of Asian citrus canker. Its linear 384,670 bp double-stranded DNA genome encodes 592 proteins and presents the longest (66 kbp) direct terminal repeats (DTRs) among sequenced viral genomes. The DTRs harbor 56 tRNA genes, which correspond to all 20 amino acids and represent the largest number of tRNA genes reported in a viral genome. Codon usage analysis revealed a propensity for the phage encoded tRNAs to target codons that are highly used by the phage but less frequently by its host. The existence of these tRNA genes and seven additional translation-related genes as well as a chaperonin gene found in the XacN1 genome suggests a relative independence of phage replication on host molecular machinery, leading to a prediction of a wide host range for this jumbo phage. We confirmed the prediction by showing a wider host range of XacN1 than other X. citri phages in an infection test against a panel of host strains. Phylogenetic analyses revealed a clade of phages composed of XacN1 and ten other jumbo phages, indicating an evolutionary stable large genome size for this group of phages.


Differentiation of Coxiella burnetii isolates by analysis of restriction-endonuclease-digested DNA separated by SDS-PAGE.
Thirty-two isolates of Coxiella burnetii collected from various hosts ranging from arthropods to man were compared by restriction endonuclease (RE) digestion patterns of chromosomal DNA using SDS-PAGE. SDS-PAGE provided better DNA fragment separation than agarose gel electrophoresis and enabled the differentiation of these isolates into six distinct groups on the basis of DNA restriction fingerprints. Two groups of chronic disease isolates could be distinguished, each having unique RE digestion patterns of chromosomal DNA. Three similar but distinct RE digestion patterns were seen among the group of acute disease isolates. Three additional isolates included in this study exhibited a unique RE digestion pattern and also had a unique plasmid type, designated QpDG. DNA-DNA hybridization on selected isolates quantified the relatedness between several groups and supported the classification of these groups as distinct strains.


Early hemopoietic progenitors in the peripheral blood of patients with severe aplastic anemia (SAA) after treatment with antilymphocyte globulin (ALG), cyclosporin-A and G-CSF.
We previously reported that patients with acquired severe aplastic anemia (SAA) treated with antilymphocyte globulin (ALG), 6-methylprednisolone, cyclosporin A (CyA) and granulocyte colony-stimulating factor (G-CSF) can mobilize peripheral blood hemopoietic progenitors (PBHP). The aim of the present study was to assess phenotypic and functional properties of these PBHP. We studied seven patients who underwent 43 leukophereses (median 5) between day +30 and +80 following ALG, while in treatment with CyA and G-CSF. Mobilized peripheral blood hemopoietic progenitors were analyzed using surface markers, conventional assays for clonogenic cells (CFU-GM, BFU-E, CFU-GEMM) as well as the recently developed assay for long-term culture initiating cells (LTC-ICs). The proportion of CD34+ cells ranged between 0% and 5.4% (median 0.3%), CD34+DR between 0% and 3.5% (median 0.1%) and CD8+ cells between 3.3% and 56% (median 31%). When light density mononuclear cells (MNC) were plated in vitro, we could grow colony-forming units-granulo-macrophage (CFU-GM) (range 0-45/10(5) MNC; normal controls 21-200/10(5) MNC), burst-forming units-erythroid (BFU-E) (range 0-5/10(5) MNC; normal controls 0-6/10(5) MNC), multipotent colonies (CFU-GEMM) (range 0-3/10(5) MNC; normal controls 0-6/10(5) MNC) and high proliferative potential colony-forming cells (HPP-CFC) (range 0-3.4/10(5) MNC). We studied long-term culture-initiating cells (LTC-ICs) in 18 leukophereses from 4 patients; in 7/18 samples LTC-ICs were grown at low frequency (range 0.4-2/10(6) MNC) (normal controls 5-130/10(6) MNC), and in one patient in the absence of CFU-GM growth. The total yield of LTC-ICs in two patients was 7.64 and 10.5 x 10(2)/kg of body weight. This study suggests that cells with the phenotype and in vitro function of early hemopoietic progenitors are found, though in small numbers, in the peripheral blood of patients with SAA after treatment with immunosuppressants and prolonged G-CSF administration. Whether G-CSF-mobilized progenitors contribute to hemopoietic recovery in these patients remains to be determined.


[Influence of Mg ions and spermine on ATP-dependent Ca2+ transport in myometrial intracellular structures. II. Comparative study of spermine, Mg ions and cyclosporin A effects on Ca2+ transport in mitochondria].
In experiments carried out with the use of the radioactive label (45Ca2+) on suspension of the rat uterus myocytes processed by digitonin solution (0.1 mg/ml), influence of spermine and cyclosporin A on Mg2+, ATP-dependent Ca2+ transport in mitochondria at different Mg2+ concentration were investigated. Ca2+ accumulation in mitochondria was tested as such which was not sensitive to thapsigargin (100 nM) and was blocked by ruthenium red (10 microM). It has been shown, that spermine (1 mM) stimulates Mg2+, ATP-dependent Ca2+ accumulation in mitochondria irrespective of Mg2+ concentration (3 or 7 mM) in the incubation medium. At the same time cyclosporin A (5 microM) effects on Ca2+ accumulation in mitochondria depend on Mg2+ concentration in the incubation medium: at 3 mM Mg2+ the stimulating effect was observed, and at 7 mM Mg2+ - the inhibitory one. In conditions which led to the increase of nonspecific mitochondrial permeability and, accordingly, to dissipation of electrochemical potential (it was reached by 5 min. preincubation of myocytes suspension in the medium that contained 10 microM Ca2+, 2 mM phosphate and 3 or 7 mM Mg2+, but not ATP) significant inhibition of Mg2+, ATP-dependent Ca2+ accumulation in mitochondria was observed. The inhibition to the greater degree was observed when medium ATP and Mg2+ were absent simultaneously in the preincubation. Thus the quality of spermine effects on Ca2+ accumulation was kept: stimulation in the presence both of 3 mM and 7 mM Mg2+. Ca2+ accumulation did not reach the control level when 3 mM Mg2+ and 1 mM spermine was present and ATP absent in the preincubation medium. However, in the presence of 7 mM Mg2+ and 1 mM spermine practically full restoration (up to a control level) of Ca2+ accumulation was observed. At the same time with other things being equal such restoration was not observed at simultaneous absence of ATP and Mg2+ in the preincubation medium. The quality of cyclosporin A effects on Ca2+ accumulation in mitochondria was also kept: stimulation - in the presence of 3 mM Mg2+, inhibition - in the presence of 7 mM Mg2+ in the preincubation medium. And, at last, in the presence of cyclosporin A irrespective of the fact which preincubation medium was used, Ca2+ accumulation level practically did not depend on Mg2+ concentration.


The malaria genome sequencing project: complete sequence of Plasmodium falciparum chromosome 2.
An international consortium has been formed to sequence the entire genome of the human malaria parasite Plasmodium falciparum. We sequenced chromosome 2 of clone 3D7 using a shotgun sequencing strategy. Chromosome 2 is 947 kb in length, has a base composition of 80.2% A + T, and contains 210 predicted genes. In comparison to the Saccharomyces cerevisiae genome, chromosome 2 has a lower gene density, a greater proportion of genes containing introns, and nearly twice as many proteins containing predicted non-globular domains. A group of putative surface proteins was identified, rifins, which are encoded by a gene family comprising up to 7% of the protein-encoding gene in the genome. The rifins exhibit considerable sequence diversity and may play an important role in antigenic variation. Sixteen genes encoded on chromosome 2 showed signs of a plastid or mitochondrial origin, including several genes involved in fatty acid biosynthesis. Completion of the chromosome 2 sequence demonstrated that the A + T-rich genome of P. falciparum can be sequenced by the shotgun approach. Within 2-3 years, the sequence of almost all P. falciparum genes will have been determined, paving the way for genetic, biochemical, and immunological research aimed at developing new drugs and vaccines against malaria.


Functional Architecture and Encoding of Tactile Sensorimotor Behavior in Rat Posterior Parietal Cortex.
The posterior parietal cortex (PPC) in rodents is reciprocally connected to primary somatosensory and vibrissal motor cortices. The PPC neuronal circuitry could thus encode and potentially integrate incoming somatosensory information and whisker motor output. However, the information encoded across PPC layers during refined sensorimotor behavior remains largely unknown. To uncover the sensorimotor features represented in PPC during voluntary whisking and object touch, we performed loose-patch single-unit recordings and extracellular recordings of ensemble activity, covering all layers of PPC in anesthetized and awake, behaving male rats. First, using single-cell receptive field mapping, we revealed the presence of coarse somatotopy along the mediolateral axis in PPC. Second, we found that spiking activity was modulated during exploratory whisking in layers 2-4 and layer 6, but not in layer 5 of awake, behaving rats. Population spiking activity preceded actual movement, and whisker trajectory endpoints could be decoded by population spiking, suggesting that PPC is involved in movement planning. Finally, population spiking activity further increased in response to active whisker touch but only in PPC layers 2-4. Thus, we find layer-specific processing, which emphasizes the computational role of PPC during whisker sensorimotor behavior.SIGNIFICANCE STATEMENT The posterior parietal cortex (PPC) is thought to merge information on motor output and sensory input to orchestrate interaction with the environment, but the function of different PPC microcircuit components is poorly understood. We recorded neuronal activity in rat PPC during sensorimotor behavior involving motor and sensory pathways. We uncovered that PPC layers have dedicated function: motor and sensory information is merged in layers 2-4; layer 6 predominantly represents motor information. Collectively, PPC activity predicts future motor output, thus entailing a motor plan. Our results are important for understanding how PPC computationally processes motor output and sensory input. This understanding may facilitate decoding of brain activity when using brain-machine interfaces to overcome loss of function after, for instance, spinal cord injury.


Targeted disruption of the murine Bin1/Amphiphysin II gene does not disable endocytosis but results in embryonic cardiomyopathy with aberrant myofibril formation.
The mammalian Bin1/Amphiphysin II gene encodes an assortment of alternatively spliced adapter proteins that exhibit markedly divergent expression and subcellular localization profiles. Bin1 proteins have been implicated in a variety of different cellular processes, including endocytosis, actin cytoskeletal organization, transcription, and stress responses. To gain insight into the physiological functions of the Bin1 gene, we have disrupted it by homologous recombination in the mouse. Bin1 loss had no discernible impact on either endocytosis or phagocytosis in mouse embryo-derived fibroblasts and macrophages, respectively. Similarly, actin cytoskeletal organization, proliferation, and apoptosis in embryo fibroblasts were all unaffected by Bin1 loss. In vivo, however, Bin1 loss resulted in perinatal lethality. Bin1 has been reported to affect muscle cell differentiation and T-tubule formation. No striking histological abnormalities were evident in skeletal muscle of Bin1 null embryos, but severe ventricular cardiomyopathy was observed in these embryos. Ultrastructurally, myofibrils in ventricular cardiomyocytes of Bin1 null embryos were severely disorganized. These results define a developmentally critical role for the Bin1 gene in cardiac muscle development.


Role of radiofrequency ablation in unresectable hepatocellular carcinoma: An Indian experience.
To evaluate the role of radiofrequency ablation (RFA) as an ablative technique in patients with unresectable hepatocellular carcinoma (HCC). A tertiary care center, prospective study. The subjects comprised 31 patients (30 males, one female; age range 32-75 years) with HCC (41 lesions) who were treated with image-guided RFA. The follow-up period ranged from 3 months to 6 years, and included a multiphasic computed tomography (CT) at 1, 3 and 6 months post-RFA, and every 6 months thereafter. Patient outcome was evaluated and the tumor recurrence, survival and complications were assessed. Discrete categorical data were presented as n (%) and continuous data as mean ± SD. Pearson correlation coefficient was used to determine the relationship between the different variables. Kaplan-Meier survival curve and Log-rank test were used to test the significance of difference between the survival time of the different groups. The ablation success rate was 80.5% (33/41 HCC lesions). 12.2% (5/41) of the lesions were managed with repeat RFA due to tumor residue. 4.9% (2/41) of the lesions were managed with repeated RFA and transarterial chemoembolization. Eight patients had tumor recurrence (five patients (16.1%) had local recurrence and three patients (9.6%) had distant recurrence). Eleven patients died within 3.5-20 months post-RFA. The survival rate at 1 year in patients who completed at least 1 year of follow-up was 63.3%. There was one major complication (1/31, 3.2%) in a patient with a subcapsular lesion and ascites. This patient developed hemoperitoneum in the immediate postprocedure period and was managed with endovascular treatment. She, however, had hepatic decompensation and died 48 h post-RFA. RFA is an effective and safe treatment for small unresectable HCC.


Synthetic microbial ecosystems: an exciting tool to understand and apply microbial communities.
Many microbial ecologists have described the composition of microbial communities in a plenitude of environments, which has greatly improved our basic understanding of microorganisms and ecosystems. However, the factors and processes that influence the behaviour and functionality of an ecosystem largely remain black boxes when using conventional approaches. Therefore, synthetic microbial ecology has gained a lot of interest in the last few years. Because of their reduced complexity and increased controllability, synthetic communities are often preferred over complex communities to examine ecological theories. They limit the factors that influence the microbial community to a minimum, allowing their management and identifying specific community responses. However, besides their use for basic research, synthetic ecosystems also found their way towards different applications, like industrial fermentation and bioremediation. Here, we review why and how synthetic microbial communities are applied for research purposes and for which applications they have been and could be successfully used.


Systematic review of the surgical management of rotator cuff repair with an augmentative patch: a feasibility study protocol.
Shoulder pain is a common problem in the general population and is responsible for prolonged periods of disability, loss of productivity, absence from work and inability to carry out household activities. Rotator cuff problems account for up to 70% of shoulder pain problems and are the third most prevalent musculoskeletal disorder after those occurring in the lower back and neck. Rotator cuff surgery has high failure rates (25-50% within 12 months), and as a result, there is a pressing need to improve the outcome of rotator cuff surgery. Patch augmented surgery for rotator cuff repairs has recently been developed and is increasingly being used within the UK National Health Service. Patch augmented surgery could lead to a dramatic improvement in patient and surgical outcomes, but its clinical and cost effectiveness needs rigorous evaluation. The existing evidence on the use of patches may be at risk of bias as currently only a small number of single-centre comparative studies appear to have been carried out. Additionally, it is unclear for which patches a clinical study (comparative and non-comparative) has been conducted. This paper outlines the protocol for a systematic review intended to summarise the best available clinical evidence and will indicate what further research is required. Electronic databases (Medline, Embase and Cochrane) will be systematically searched between April 2006 and the present day for relevant publications using a specified search strategy, which can be adapted for the use in multiple electronic databases, and inclusion criteria. Screening of both titles and abstracts will be done by two independent reviewers with any discrepancies resolved by a third independent reviewer. Data extraction will include information regarding the type of participants, type of intervention and outcomes including but not limited to shoulder-specific function and pain scores, patch-related adverse events and type of study. The results will be summarised in a narrative review where qualitative analysis is not possible. This review aims to collate the current evidence base regarding the use of patches to augment rotator cuff repair. The results of this review will help to develop, using consensus methods, the design of a definitive randomised trial assessing the clinical and cost-effectiveness of a patch to augment surgical repair of the rotator cuff that is both acceptable to stakeholders and is feasible. CRD42017057908.


Parameterization of cloud lidar backscattering profiles by means of asymmetrical Gaussians.
A fitting procedure for cloud lidar data processing is shown that is based on the computation of the first three moments of the vertical-backscattering (or -extinction) profile. Single-peak clouds or single cloud layers are approximated to asymmetrical Gaussians. The algorithm is particularly stable with respect to noise and processing errors, and it is much faster than the equivalent least-squares approach. Multilayer clouds can easily be treated as a sum of single asymmetrical Gaussian peaks. The method is suitable for cloud-shape parametrization in noisy lidar signatures (like those expected from satellite lidars). It also permits an improvement of cloud radiative-property computations that are based on huge lidar data sets for which storage and careful examination of single lidar profiles can't be carried out.


Interferon-gamma induces HLA-DR expression by thyroid epithelium.
We recently showed that human thyroid epithelial cells, which are normally negative for HLA-DR molecules, express HLA-DR in thyroid autoimmunity. Furthermore, induction of HLA-DR on normal thyroid cells can be achieved by culture with plant lectins. We have now found that recombinant human interferon-gamma (IFN-gamma) induces expression of HLA-DR molecules on cultured human thyroid cells, whereas Namalva IFN-alpha, recombinant IFN-beta or recombinant interleukin-2 (IL-2) do not. All three IFN, but not IL-2, enhanced thyroid cell HLA-A,B,C expression. The results strongly implicate T cells (which are the source of IFN-gamma) in the aberrant induction of DR on thyroid epithelial cells which is proposed to be a central feature of the immunopathological processes leading to autoimmunity.


Nordic walking improves daily physical activities in COPD: a randomised controlled trial.
In patients with COPD progressive dyspnoea leads to a sedentary lifestyle. To date, no studies exist investigating the effects of Nordic Walking in patients with COPD. Therefore, the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages. Furthermore we aimed to determine the short- and long-term effects of Nordic Walking on COPD patients' daily physical activity pattern as well as on patients exercise capacity. Sixty COPD patients were randomised to either Nordic Walking or to a control group. Patients of the Nordic Walking group (n = 30; age: 62 +/- 9 years; FEV1: 48 +/- 19% predicted) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75% of their initial maximum heart rate three times per week, whereas controls had no exercise intervention. Primary endpoint: daily physical activities (measured by a validated tri-axial accelerometer); secondary endpoint: functional exercise capacity (measured by the six-minute walking distance; 6MWD). Assessment time points in both groups: baseline, after three, six and nine months. After three month training period, in the Nordic Walking group time spent walking and standing as well as intensity of walking increased (Delta walking time: +14.9 +/- 1.9 min/day; Delta standing time: +129 +/- 26 min/day; Delta movement intensity: +0.40 +/- 0.14 m/s2) while time spent sitting decreased (Delta sitting time: -128 +/- 15 min/day) compared to baseline (all: p < 0.01) as well as compared to controls (all: p < 0.01). Furthermore, 6MWD significantly increased compared to baseline (Delta 6MWD: +79 +/- 28 meters) as well as compared to controls (both: p < 0.01). These significant improvements were sustained six and nine months after baseline. In contrast, controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points. Nordic Walking is a feasible, simple and effective physical training modality in COPD. In addition, Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation.


The phylogenetic diversity of metagenomes.
Phylogenetic diversity--patterns of phylogenetic relatedness among organisms in ecological communities--provides important insights into the mechanisms underlying community assembly. Studies that measure phylogenetic diversity in microbial communities have primarily been limited to a single marker gene approach, using the small subunit of the rRNA gene (SSU-rRNA) to quantify phylogenetic relationships among microbial taxa. In this study, we present an approach for inferring phylogenetic relationships among microorganisms based on the random metagenomic sequencing of DNA fragments. To overcome challenges caused by the fragmentary nature of metagenomic data, we leveraged fully sequenced bacterial genomes as a scaffold to enable inference of phylogenetic relationships among metagenomic sequences from multiple phylogenetic marker gene families. The resulting metagenomic phylogeny can be used to quantify the phylogenetic diversity of microbial communities based on metagenomic data sets. We applied this method to understand patterns of microbial phylogenetic diversity and community assembly along an oceanic depth gradient, and compared our findings to previous studies of this gradient using SSU-rRNA gene and metagenomic analyses. Bacterial phylogenetic diversity was highest at intermediate depths beneath the ocean surface, whereas taxonomic diversity (diversity measured by binning sequences into taxonomically similar groups) showed no relationship with depth. Phylogenetic diversity estimates based on the SSU-rRNA gene and the multi-gene metagenomic phylogeny were broadly concordant, suggesting that our approach will be applicable to other metagenomic data sets for which corresponding SSU-rRNA gene sequences are unavailable. Our approach opens up the possibility of using metagenomic data to study microbial diversity in a phylogenetic context.


Co3O4 nanocrystals as an efficient catalase mimic for the colorimetric detection of glutathione.
Nanomaterial-based artificial enzymes (nanozymes), as an emerging generation of artificial enzymes, have received extensive attention in recent years owing to their striking merits. In this study, the obtained Co3O4 nanocrystals exhibited catalase-like activity and could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, and a clear absorption peak at 652 nm can be observed. It was verified that the catalytic activity for the oxidation of TMB originated from the oxygen, which is generated by Co3O4 catalyzed H2O2 decomposition. Upon addition of glutathione (GSH), the catalytic ability of the Co3O4 nanocrystals was inhibited. And, the changes of absorbance at 652 nm could be utilized to quantify the concentration of GSH. Under the optimized conditions, the proposed assay showed good linear relationships and a low detection limit towards GSH. Moreover, the Co3O4 nanocrystals had excellent stability and can maintain the catalytic activity for a long time. Thus, a simple, sensitive and selective nanozyme-based biosensor was developed for the colorimetric detection of GSH.