Effect of access to outdoor grazing and stocking density on space and pasture use, behaviour, reactivity, and growth traits of weaned rabbits.
In a context of evolving concern over housing conditions of farmed rabbits, we developed a housing system that allows access to an outdoor area. The aim was to study the health status, growth and behaviour of rabbits raised at two stocking densities with access to a paddock, or not. We distributed 299 weaned rabbits in four groups (YH: 100, NH: 99, YL: 50 and NL: 50) using a 2 × 2 factorial design including access (Y: yes) or not (N: not) to a 23 m2 paddock and the indoor stocking density (H, high: 17 or L, low: 9 rabbits/m2). We measured the growth and health status of each animal weekly for 42 days (from 31 to 73 days of age) and performed reactivity tests to a new environment, a human and new object. We also assessed the rabbits' behaviour at days 26 and 40 by doing a visual scan of each animal at regular time intervals. Our results showed that stocking density had no effect on mortality, but mortality tended to increase with outdoor access from 3.0% to 7.0% (P < 0.10). Although the stocking density had no effect on average daily gain, it was higher in rabbits in the N group than in the Y group (+3.6 g/day; P < 0.05). Rabbits entered the paddocks for the first time in less time at the beginning of the trial (50 s at day 3 vs 10 min at day 31; P < 0.001). The proportion of rabbits outside after 20 min of the new environment test was higher among rabbits in the L group than in the H group (+24% points at day 3 and +11% points at day 20; P < 0.001). Regardless of the stocking density, more rabbits in the N group touched the experimenter's hand (16% vs 27%; P < 0.05) and the new object (34% vs 20%; P < 0.05) than rabbits in the Y group. Inactivity was more frequent in rabbits inside the pens than in the paddocks (70.0% vs 34.2% at days 26 and 40; P < 0.05). Locomotion was more frequent in the paddocks than in the indoor pens (20.0% vs 7.2% at days 26 and 40; P < 0.05). The stocking density did not affect the behavioural traits measured. In conclusion, providing rabbits access to a paddock could allow them to fulfil some natural behaviours but slightly reduced their growth.


Rabies Virus Antibodies from Oral Vaccination as a Correlate of Protection against Lethal Infection in Wildlife.
Both cell-mediated and humoral immune effectors are important in combating rabies infection, although the humoral response receives greater attention regarding rabies prevention. The principle of preventive vaccination has been adopted for strategies of oral rabies vaccination (ORV) of wildlife reservoir populations for decades to control circulation of rabies virus in free-ranging hosts. There remains much debate about the levels of rabies antibodies (and the assays to measure them) that confer resistance to rabies virus. In this paper, data from published literature and our own unpublished animal studies on the induction of rabies binding and neutralizing antibodies following oral immunization of animals with live attenuated or recombinant rabies vaccines, are examined as correlates of protection against lethal rabies infection in captive challenge settings. Analysis of our studies suggests that, though serum neutralization test results are expected to reflect in vivo protection, the blocking enzyme linked immunosorbent assay (ELISA) result at Day 28 was a better predictor of survival. ELISA kits may have an advantage of greater precision and ability to compare results among different studies and laboratories based on the inherent standardization of the kit format. This paper examines current knowledge and study findings to guide meaningful interpretation of serology results in oral baiting monitoring.


Effects of a somatostatin analogue (SMS 201-995) on the growth and development of hepatic tumour derived by intraportal injection of Walker cells in the rat.
Administration of a long active analogue of somatostatin, SMS 201-995 (2 micrograms subcutaneously twice a day) for 3 weeks after intraportal administration of Walker cells significantly inhibited their growth and development in the liver. This was not due to a direct cytotoxic effect of the analogue on Walker cells whose growth was stimulated in vitro. Furthermore, SMS 201-995 had no effect on the growth of Walker cells implanted into the thigh of rats suggesting that the inhibitory action of the analogue could be confined to tumour cells growing in the liver. Further studies suggested that the inhibitory effect of SMS 201-995 on the growth of Walker cells in the liver could be related to a marked stimulation of the hepatic reticuloendothelial system, by a reduction in portal venous flow in the early stages of treatment or by a combination of these effects. Further studies are required to delineate more precisely the mechanism whereby SMS 201-995 inhibits the growth of hepatic tumour derived from intraportal administration of Walker cells.


Embedded multiple description coding of video.
Real-time delivery of video over best-effort error-prone packet networks requires scalable erasure-resilient compression systems in order to 1) meet the users' requirements in terms of quality, resolution, and frame-rate; 2) dynamically adapt the rate to the available channel capacity; and 3) provide robustness to data losses, as retransmission is often impractical. Furthermore, the employed erasure-resilience mechanisms should be scalable in order to adapt the degree of resiliency against transmission errors to the varying channel conditions. Driven by these constraints, we propose in this paper a novel design for scalable erasure-resilient video coding that couples the compression efficiency of the open-loop architecture with the robustness provided by multiple description coding. In our approach, scalability and packet-erasure resilience are jointly provided via embedded multiple description scalar quantization. Furthermore, a novel channel-aware rate-allocation technique is proposed that allows for shaping on-the-fly the output bit rate and the degree of resiliency without resorting to channel coding. As a result, robustness to data losses is traded for better visual quality when transmission occurs over reliable channels, while erasure resilience is introduced when noisy links are involved. Numerical results clearly demonstrate the advantages of the proposed approach over equivalent codec instantiations employing 1) no erasure-resilience mechanisms, 2) erasure-resilience with nonscalable redundancy, or 3) data-partitioning principles.


Strongly coupled plasmonic modes on macroscopic areas via template-assisted colloidal self-assembly.
We present ensembles of surface-ordered nanoparticle arrangements, which are formed by template-assisted self-assembly of monodisperse, protein-coated gold nanoparticles in wrinkle templates. Centimeter-squared areas of highly regular, linear assemblies with tunable line width are fabricated and their extinction cross sections can be characterized by conventional UV/vis/NIR spectroscopy. Modeling based on electrodynamic simulations shows a clear signature of strong plasmonic coupling with an interparticle spacing of 1-2 nm. We find evidence for well-defined plasmonic modes of quasi-infinite chains, such as resonance splitting and multiple radiant modes. Beyond elementary simulations on the individual chain level, we introduce an advanced model, which considers the chain length distribution as well as disorder. The step toward macroscopic sample areas not only opens perspectives for a range of applications in sensing, plasmonic light harvesting, surface enhanced spectroscopy, and information technology but also eases the investigation of hybridization and metamaterial effects fundamentally.


Myotonic dystrophy: molecular windows on a complex etiology.
Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy, with an incidence of approximately 1 in 8500 adults. DM is caused by an expanded number of trinucleotide repeats in the 3'-untranslated region (UTR) of a cAMP-dependent protein kinase (DM protein kinase, DMPK). Although a large number of transgenic animals have been generated with different gene constructions and knock-outs, none of them faithfully recapitulates the multisystemic and often severe phenotype seen in human patients. The transgenic data suggest that myotonic dystrophy is not caused simply by a biochemical deficiency or abnormality in the DM kinase gene product. Emerging studies suggest that two novel pathogenetic mechanisms may play a role in the disease: the expanded repeats appear to cause haploinsufficiency of a neighboring homeobox gene and also abnormal DMPK RNA appears to have a detrimental effect on RNA homeostasis. The complex, multisystemic phenotype may reflect an underlying multifaceted molecular pathophysiology: the facial dysmorphology may be due to pattern defects caused by haploinsufficiency of the homeobox gene, while the muscle disease and endocrine abnormalities may be due to both altered RNA metabolism and deficiency of the cAMP DMPK protein.


Climate change drives warming in the Hudson River Estuary, New York (USA).
Estuaries may be subject to warming due to global climate change but few studies have considered the drivers or seasonality of warming empirically. We analyzed temperature trends and rates of temperature change over time for the Hudson River estuary using long-term data, mainly from daily measures taken at the Poughkeepsie Water Treatment Facility. This temperature record is among the longest in the world for a river or estuary. The Hudson River has warmed 0.945 °C since 1946. Many of the warmest years in the record occurred in the last 16 years. A seasonal analysis of trends indicated significant warming for the months of April through August. The warming of the Hudson is primarily related to increasing air temperature. Increasing freshwater discharge into the estuary has not mitigated the warming trend.


Genetic variation may modify ovarian reserve in female childhood cancer survivors.
Are genetic polymorphisms, previously identified as being associated with age at menopause in the healthy population, associated with ovarian reserve and predicted age at menopause in adult long-term survivors of childhood cancer? The CT genotype of rs1172822 in the BRSK1 gene is associated with lower serum anti-Müllerian hormone (AMH) levels and a younger predicted age at menopause in adult survivors of childhood cancer. Gonadotoxicity is a well-known late side effect of chemotherapy and radiotherapy in adult survivors of childhood cancer. In the healthy population, several genetic polymorphisms are associated with age at natural menopause. Currently, data on the impact of previously identified variants in gene loci associated with ovarian reserve in adult long-term survivors of childhood cancer are lacking. We performed a pilot study in a single-centre cohort of adult female Caucasian childhood cancer survivors (n = 176). We determined serum AMH levels (a marker of ovarian reserve) in adult survivors of childhood cancer (n = 176) and studied single nucleotide polymorphisms (SNPs) previously reported to be associated with age at natural menopause: BRSK1 (rs1172822), ARHGEF7 (rs7333181), MCM8 (rs236114), PCSK1 (rs271924), IGF2R (rs9457827) and TNF (rs909253). Association analysis was performed using the additive genetic model. Linear regression was conducted to assess the effect of significant polymorphisms in two previously published menopause prediction models. The CT genotype of rs1172822 in the BRSK1 (BR serine/threonine kinase 1) gene was negatively associated with serum AMH levels in our cohort (odds ratio: 3.15, 95% confidence interval: 1.35-7.32, P = 0.008) and significantly associated with the predicted age at menopause (P = 0.04). The other five SNPs were not associated with serum AMH levels. This is a pilot study showing preliminary data which must be confirmed. To confirm our findings and enlarge the project, a nationwide genome-wide association (GWA) project on the ovarian reserve in female survivors of childhood cancer should be performed, including a replication cohort. Our findings support the hypothesis that previously identified genetic polymorphisms associated with age at menopause in healthy women may have an effect on the onset of menopause in female survivors of childhood cancer. Our study highlights a new aspect of the influences on the ovarian reserve after childhood cancer, which should be investigated further in a nationwide GWA study. Eventually, this information can help us to improve counselling on fertility preservation prior to cancer treatment based on genetic factors in individual patients. W.D. is supported by the Paediatric Oncology Centre Society for Research (KOCR), Rotterdam, The Netherlands. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Genovum, Merck-Serono, Organon, Schering Plough and Serono. All other authors have nothing to disclose.


Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation.
Membrane rafts are thought to be sphingolipid- and cholesterol-dependent lateral assemblies involved in diverse cellular functions. Their biological roles and even their existence, however, remain controversial. Using an original fluorescence correlation spectroscopy strategy that recently enabled us to identify nanoscale membrane organizations in live cells, we report here that highly dynamic nanodomains exist in both the outer and inner leaflets of the plasma membrane. Through specific inhibition of biosynthesis, we show that sphingolipids and cholesterol are essential and act in concert for formation of nanodomains, thus corroborating their raft nature. Moreover, we find that nanodomains play a crucial role in triggering the phosphatidylinositol-3 kinase/Akt signaling pathway, by facilitating Akt recruitment and activation upon phosphatidylinositol-3,4,5-triphosphate accumulation in the plasma membrane. Thus, through direct monitoring and controlled alterations of rafts in living cells, we demonstrate that rafts are critically involved in the activation of a signaling axis that is essential for cell physiology.


SU-E-T-254: Quantitative Evaluation of Three Mathematical Models for Radiation-Induced Secondary Cancer Risk for Lung in Stereotactic Body Radiotherapy.
Several mathematical models exist to predict secondary cancer risks from radiotherapy treatment. In this study, we aimed to compare three dosimetry-based models in the application of stereotactic body radiotherapy (SBRT) of early-stage non-small cell lung cancer (NSCLC) with three radiotherapy treatment modalities. Ten patients who received definitive SBRT for early-stage NSCLC were retrospectively selected. for each patient, a helical tomotherapy (HT) plan, a three-dimensional conformal radiotherapy (3D-CRT) plan, and a volumetric modulated arc therapy (VMAT) plan were generated to deliver 50 Gy to the planning target volume in five fractions. The excess absolute risk (EAR) for secondary lung cancer occurrence was calculated using three risk models: the linear-exponential model, the plateau model, and the linear model. The sensitivity of the EAR to the prescription dose was evaluated by varying the prescription dose in the range of 40 to 60 Gy. Based on the linear-exponential model, the average EAR's (in occurrences per 10,000 patients per year) were 8.4+/-2.7, 8.3+/-2.1, and 8.4+/-1.9 for the HT plans, 3D-CRT plans, and VMAT plans respectively with 40 Gy prescription dose, and 9.4+/-2.5, 9.0+/-2.1, and 9.3+/-1.8 with 60 Gy. Based on the plateau model, the average EAR's were 10.7+/-3.9, 10.6+/-3.0, and 10.9+/-2.8 with 40 Gy, and 12.9+/-4.2, 12.6+/-3.4, 12.9+/-3.1 with 60 Gy. Based on the linear model, the average EAR's were 29.1+/-13.4, 29.4+/-11.4, and 30.0+/-11.1 with 40 Gy, and 43.8+/-20.1, 44.0+/-11.0, 45.1+/-16.6 with 60 Gy. The difference in EAR's were not statistically significant among the HT, 3D-CRT, and VMAT plans. Three secondary cancer risk models, as well as three SBRT treatment modalities, were compared. There was no significant difference in secondary lung cancer risks among the three treatment modalities in this study.


Lymphatics and blood vessels, lymphangiogenesis and hemangiogenesis: from cell biology to clinical medicine.
The past 15 years have witnessed an explosion of knowledge about blood vascular endothelium due in large part to in vitro growth of endothelial cells from both large blood vessels and capillaries. In contrast, little comparable information has accumulated on endothelium of lymphatics, which lie in intimate contact with parenchymal cells and drain excess fluid, macromolecules, particles, and immunocompetent cells in a continuous recirculation between tissues and bloodstream. While structural and functional differences between the two vascular systems have been described in vivo, in tissue sections, and in isolated preparations, similarities are notable in ultra-structure, biochemistry, physiology, and pharmacologic responsiveness, and these may predominate under pathologic conditions. In 1984, three separate groups described in vitro culture of lymphatic endothelial cells from collecting ducts and cavernous lymphangiomas. Lymphatic, like blood vascular, endothelium grows in confluent monolayers, "sprouts", synthesizes Factor VIII-associated antigen and fibronectin, and ultrastructurally shows Weibel-Palade bodies; overlapping intercellular junctions and anchoring filaments typical of lymphatic endothelium are also found. Genetic, congenital, and acquired disorders such as strangulating fetal nuchal cystic hygromas (Down and Turner syndromes), vascular tumors and dysmorphogenesis (Maffucci and Klippel-Trenaunay syndromes), Kaposi's sarcoma, lymphogenous and hematogenous spread of cancer, and parasitic infestations such as filariasis, share overlapping abnormalities in formation, growth, and/or neoplasia of lymphatics and blood vessels. In these and similar clinical disorders, confusion often exists as to the nature of the cell or tissue of origin, and insight into the role and control of hemangiogenesis and lymphangiogenesis is still in its infancy. Nonetheless, with the ever widening array of investigative techniques, it is not only timely but imperative to explore the endothelial biology underlying these inborn and acquired disorders.


Exercise and intestinal polyp development in APCMin mice.
Epidemiological evidence suggests that physical activity protects against colon cancer. We previously used a mouse predisposed to intestinal polyps (APCMin) to evaluate this association and found the suggestion of fewer polyps in exercised males but not females. The present study was designed to further explore the potential exercise x sex interaction on polyp development and to begin to look at potential mechanisms. Six-week-old APCMin mice (N = 60 males; 60 females) were randomly assigned to one of two groups by sex: treadmill running at 20 m.min-1, 5% grade, 45 min.d-1, 5 d.wk-1 (EX) or nonrunning controls (CON) (N = 30 per group). EX mice ran in running wheels while in quarantine (weeks 0-3), followed by treadmill running weeks 3-8. Body weights were measured weekly. Urine was collected at 5 wk and fasting blood at 7.5 wk. Body composition was measured, serum was frozen, and polyp number and size were measured at sacrifice. EX resulted in lower body weights (P < 0.01) and reduced fat mass (P < 0.01). Fasting glucose was lower in EX (P < 0.01), and leptin was lower in EX (P = 0.05) compared with CON. EX did not affect serum insulin-like growth factor-1 or urinary corticosterone. Total polyp number and size were not statistically different between groups; however, there were fewer jejunal polyps in EX (3.6 +/- 0.7, mean +/- SE) versus CON males (5.2 +/- 0.8; P = 0.04) and an even larger difference when only the consistent runners were kept in the analysis (2.7 +/- 0.5 in EX; P = 0.01). Despite favorable changes in body composition, blood glucose, and leptin, 8 wk of running resulted in only minor changes related to polyp development in male but not female APCMin mice.


A scoping review of registry captured indicators for evaluating quality of critical care in ICU.
Excess morbidity and mortality following critical illness is increasingly attributed to potentially avoidable complications occurring as a result of complex ICU management (Berenholtz et al., J Crit Care 17:1-2, 2002; De Vos et al., J Crit Care 22:267-74, 2007; Zimmerman J Crit Care 1:12-5, 2002). Routine measurement of quality indicators (QIs) through an Electronic Health Record (EHR) or registries are increasingly used to benchmark care and evaluate improvement interventions. However, existing indicators of quality for intensive care are derived almost exclusively from relatively narrow subsets of ICU patients from high-income healthcare systems. The aim of this scoping review is to systematically review the literature on QIs for evaluating critical care, identify QIs, map their definitions, evidence base, and describe the variances in measurement, and both the reported advantages and challenges of implementation. We searched MEDLINE, EMBASE, CINAHL, and the Cochrane libraries from the earliest available date through to January 2019. To increase the sensitivity of the search, grey literature and reference lists were reviewed. Minimum inclusion criteria were a description of one or more QIs designed to evaluate care for patients in ICU captured through a registry platform or EHR adapted for quality of care surveillance. The search identified 4780 citations. Review of abstracts led to retrieval of 276 full-text articles, of which 123 articles were accepted. Fifty-one unique QIs in ICU were classified using the three components of health care quality proposed by the High Quality Health Systems (HQSS) framework. Adverse events including hospital acquired infections (13.7%), hospital processes (54.9%), and outcomes (31.4%) were the most common QIs identified. Patient reported outcome QIs accounted for less than 6%. Barriers to the implementation of QIs were described in 35.7% of articles and divided into operational barriers (51%) and acceptability barriers (49%). Despite the complexity and risk associated with ICU care, there are only a small number of operational indicators used. Future selection of QIs would benefit from a stakeholder-driven approach, whereby the values of patients and communities and the priorities for actionable improvement as perceived by healthcare providers are prioritized and include greater focus on measuring discriminable processes of care.


Fast Mek1 Hit Identification with TRIC Technology Correlates Well with Other Biophysical Methods.
The variety and complexity of drug targets are expanding rapidly. At the same time, there is significant interest in exploring a larger chemical space to identify new candidates. Fragment-based screening (FBS) has emerged as a popular alternative to traditional high-throughput screening campaigns to identify such drug candidates. FBS identifies hit fragments that exhibit weak interactions with the target of interest, thereby enabling the rational design of small-molecule compounds from the identified hit fragments, which serve as building blocks. This strategy reduces the number of molecules to screen while also allowing the exploration of a greater chemical space.Here we use temperature-related intensity change (TRIC) technology to perform FBS against the target MAPK/ERK kinase-1 (Mek1). TRIC describes the change in fluorescence intensity of a fluorescently labeled molecule upon a change in temperature. This intensity variation is dependent on the physicochemical environment in the vicinity of the dye and strongly affected by binding events. Thus, the detection of binding events is independent of mass, making TRIC an ideal tool for FBS.Using only 150 pmol of labeled Mek1, the authors screened 193 fragments from a prescreened library in less than 1 h of measurement time, leading to 66 hits. Among those hits, they identified more than 80% of the published top hits found using orthogonal techniques. Furthermore, TRIC allowed the identification of fragments that were of poor solubility but could be mistaken as false-positive hits in other methods.


Alzheimer's disease: research advances and medical reality.
Alzheimer's disease was the eighth-leading cause of death in 2001. There is no cure and no effective treatment. Alzheimer's disease presents policy-makers with several challenges, including the level of funding and direction of federally funded research, as well as the cost pressures on Medicare and Medicaid of long-term care. These challenges will increase in intensity as demographic changes, particularly the aging of baby boomers, take hold. Better prevention of Alzheimer's, advances in therapy, and appropriate care modalities will likely require significant investment.


The effect of cooperative Jahn-Teller interactions on C60(-) anions.
Singly charged buckminsterfullerene anions, C60(-), are subject to a strong intramolecular [Formula: see text] Jahn-Teller (JT) effect. When such ions interact with other C60(-) ions in a solid through a cooperative JT effect, they will be subject to an additional interaction. There are a number of different mechanisms that can cause this interaction. However, in the molecular field approximation, all can be modelled phenomenologically in terms of a symmetry-lowering interaction written in terms of a linear combination of electronic operators for the h modes involved in the intramolecular JT effect. We will consider the combined effect of this distortion and the intramolecular JT effect. We will analyse the lowest adiabatic potential energy surface, and calculate the energies of the resultant vibronic states. The results are shown to have a complicated dependence on the particular combination of h modes chosen, and the energies of the resultant vibronic states cannot easily be deduced from the form of the potential alone.


Conversational responsiveness in specific language impairment: evidence of disproportionate pragmatic difficulties in a subset of children.
Eighteen children with specific language impairment (SLI), from 6 to 8 years of age, were compared with 9 control children matched on age and nonverbal ability (CA controls) and with 9 younger control children of comparable language level (LA controls). Half of the SLI group were rated on a teacher checklist as having pragmatic difficulties: these were referred to as the pragmatic language impairment (PLI) group; the remainder were the typical (SLI-T) group. Children's responses to adult soliciting utterances were compared. All children usually responded to conversational solicitations, but children in the PLI group were more likely than control children to give no response, and they also made very little use of nonverbal responses, such as nodding. Nonverbal responding was closely related to the quality of children's responses. Children who failed to use nonverbal responses also had a relatively high level of pragmatically inappropriate responses that were not readily accounted for in terms of limited grammar or vocabulary. This study lends support to the notion that there is a subset of the language-impaired population who have broader communicative impairments, extending beyond basic difficulties in mastering language form, reflecting difficulty in responding to and expressing communicative intents. The analytic methods developed for this project have promise for the study of pragmatic difficulties in other clinical groups.


Super learner.
When trying to learn a model for the prediction of an outcome given a set of covariates, a statistician has many estimation procedures in their toolbox. A few examples of these candidate learners are: least squares, least angle regression, random forests, and spline regression. Previous articles (van der Laan and Dudoit (2003); van der Laan et al. (2006); Sinisi et al. (2007)) theoretically validated the use of cross validation to select an optimal learner among many candidate learners. Motivated by this use of cross validation, we propose a new prediction method for creating a weighted combination of many candidate learners to build the super learner. This article proposes a fast algorithm for constructing a super learner in prediction which uses V-fold cross-validation to select weights to combine an initial set of candidate learners. In addition, this paper contains a practical demonstration of the adaptivity of this so called super learner to various true data generating distributions. This approach for construction of a super learner generalizes to any parameter which can be defined as a minimizer of a loss function.


Isolation and characterization of mutations in the HXK2 gene of Saccharomyces cerevisiae.
Several hundred new mutations in the gene (HXK2) encoding hexokinase II of Saccharomyces cerevisiae were isolated, and a subset of them was mapped, resulting in a fine-structure genetic map. Among the mutations that were sequenced, 35 were independent missense mutations. The mutations were obtained by mutagenesis of cloned HXK2 DNA carried on a low-copy-number plasmid vector and screened for a number of different phenotypes in yeast strains bearing chromosomal hxk1 and hxk2 null mutations. Some of these mutants were characterized both in vivo and in vitro; they displayed a wide spectrum of residual hexokinase activities, as indicated by three assays: in vitro enzyme activity, ability to grow on glucose and fructose, and ability to repress invertase production when growing on glucose. Of those that failed to support growth on fructose, only a small minority made normal-size, stable, and inactive protein. Analysis of the amino acid changes in these mutants in light of the crystallographically determined three-dimensional structure of hexokinase II suggests important roles in structure or catalysis for six amino acid residues, only two of which are near the active site.


Telomerase activity and telomere length in primary and metastatic tumors from pediatric bone cancer patients.
The presence of telomerase activity has been analyzed in almost all tumor types and tumor-derived cell lines. However, there are very few studies that focus on the presence of telomerase activity in bone tumors, and most of them report analysis on very few samples or bone-derived cell lines. The objective of this study was to analyze the telomere length and telomerase activity in primary tumors and metastatic lesions from pediatric osteosarcoma and Ewing's sarcoma patients. The presence of telomerase activity was analyzed by the telomeric repeat amplification protocol assay, and the telomere length was measured by Southern blot. Results were related to survival and clinical outcome. Telomerase activity was detected in 85% of the bone tumor metastases (100% Ewing's sarcomas and 75% osteosarcomas) but only in 12% of the primary tumors (11.1% osteosarcomas and 12.5% Ewing's sarcomas). Bone tumor tissues with telomerase activity had mean telomere lengths 3 kb shorter than those with no detectable telomerase activity (p = 0.041). The presence of telomerase activity was associated with survival (p = 0.009), and longer event-free survival periods were found in patients who lacked telomerase activity compared with those who had detectable telomerase activity levels in their tumor tissues (p = 0.037). The presence of longer telomeres in primary pediatric bone tumors than in metastases could be indicative of alternative mechanisms of lengthening of telomeres for their telomere maintenance rather than telomerase activity. Nevertheless, the activation of telomerase seems to be a crucial step in the malignant progression and acquisition of invasive capability of bone tumors.


A multicenter cross-sectional study on the prevalence of overactive bladder and its impacts on the quality of life in gynecologic outpatients.
The present study assessed the prevalence of overactive bladder (OAB) symptoms in gynecologic outpatients and the effects of OAB on a patient's quality of life. The survey was completed by adult female patients who visited the gynecology clinic for examination or treatment of gynecologic conditions. The subjects who met the exclusion criteria were excluded. The survey included a questionnaire assessing general characteristics, the purpose of the visit, diagnosis, and the presence or absence of OAB. The subjects were asked whether they were under medical treatment for OAB symptoms, and the degree of discomfort in daily activities was evaluated. In total, 1,990 female subjects visiting the gynecology clinics of 4 different institutions were recruited. On OAB Symptom Score, 188 subjects responded with scores of ≥2 for question #3 (≥1 time(s) weekly). The severity of OAB symptoms was as follows: 345 subjects had mild OAB, 127 subjects had moderate OAB, and 12 subjects had severe OAB. The prevalence of OAB symptoms was 10.30%. The present study confirmed that OAB symptoms are common, with a prevalence of 10.30%. Patients with OAB symptoms frequently neglect to seek medical intervention. Our findings will help inform patients to recognize their condition and seek medical assistance, especially in gynecologic outpatient clinics.


Endocrine cells in atresic chick embryo intestine: histochemical and immunohistochemical study.
Intestinal motility disorders are an important problem in the postoperative management of patients with intestinal atresia. Intestinal motility could be initiated by luminal factors that activate intrinsic and extrinsic primary afferent nerves involved in the peristaltic reflex. Endocrine cells act as a key point, because they transfer information regarding the intestinal contents and intraluminal pressure to nerve fibers lying in close proximity to the basolateral surface of the epithelium. In chick embryo, experimental intestinal atresia is associated with disorders in the development of the enteric nervous system, related to the severity of intestinal dilation. Our aim was to investigate the distribution pattern of endocrine cells in the developing endocrine system of chick embryo small intestine with experimentally-induced atresia on day 12 and on day 16. Changes in enteroendocrine population were examined in gut specimens (excised proximal and distal to the atresia) from experimental embryos 19 days old and in control sham-operated chick embryos at the same age. Sections from proximal and distal bowel and control bowel were stained with Grimelius silver stain, a valuable histochemical method for detecting the argyrophil and argentophilic cells, and with an immunohistochemical procedure for detecting serotonin and neurotensin immunoreactive cells. In chick embryo proximal bowel, intestinal dilation differed in the various embryos. We found significantly higher enteroendocrine cell counts in proximal bowel than in distal and control bowel. The differences depended on the precociousness of surgery and the severity of dilation. Considering the major contribution of enteroendocrine cells to the peristaltic reflex, our data may help to explain the pathogenesis of motility disorders related to intestinal atresia.


High-Throughput Metabolic Profiling of Soybean Leaves by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.
As a relatively recent research field, plant metabolomics has gained increasing interest in the past few years and has been applied to answer biological questions through large-scale qualitative and quantitative analyses of the plant metabolome. The combination of sensitivity and selectivity offered by mass spectrometry (MS) for measurement of many metabolites in a single shot makes it an indispensable platform in metabolomics. In this regard, Fourier-transform ion cyclotron resonance (FTICR) has the unique advantage of delivering high mass resolving power and mass accuracy simultaneously, making it ideal for the study of complex mixtures such as plant extracts. Here we optimize soybean leaf extraction methods compatible with high-throughput reproducible MS-based metabolomics. In addition, matrix-assisted laser desorption ionization (MALDI) and direct LDI of soybean leaves are compared for metabolite profiling. The extraction method combined with electrospray (ESI)-FTICR is supported by the significant reduction of chlorophyll and its related metabolites as the growing season moves from midsummer to the autumn harvest day. To our knowledge for the first time, the use of ESI-FTICR MS and MALDI-FTICR MS is described in a complementary manner with the aim of metabolic profiling of plant leaves that have been collected at different time points during the growing season.


Neutrophil alterations in pregnancy-associated malaria and induction of neutrophil chemotaxis by Plasmodium falciparum.
Pregnancy-associated malaria (PAM) is a severe form of the disease caused by sequestration of Plasmodium falciparum-infected red blood cells (iRBCs) in the developing placenta. Pathogenesis of PAM is partially based on immunopathology, with frequent monocyte infiltration into the placenta. Neutrophils are abundant blood cells that are essential for immune defence but may also cause inflammatory pathology. Their role in PAM remains unclear. We analysed neutrophil alterations in the context of PAM to better understand their contribution to disease development. Pregnant women exposed to Plasmodium falciparum had decreased numbers of circulating neutrophils. Placental-like BeWo cells stimulated with malaria parasites produced the neutrophil chemoattractant IL-8 and recruited neutrophils in a trans-well assay. Finally, immunostaining of a PAM placenta confirmed neutrophil accumulation in the intervillous space. Our data indicate neutrophils may play a role in placental malaria and should be more closely examined as an etiological agent in the pathophysiology of disease.


Associations of religiosity, attitudes towards suicide and religious coping with suicidal ideation and suicide attempts in 11 muslim countries.
The study investigated the associations of religiosity, religious coping and suicide acceptance to suicide ideation and attempts in 7427 young adults affiliating with Islam from 11 Muslim countries. A self-administered questionnaire was used to collect the data. We used F and χ2 tests and correlation analyses to report descriptive statistics. Multi-group path models with (i) a zero-inflated Poisson distribution and, (ii) a Binomial distribution were used to model the number of occurrences of suicidal ideation, and occurrence of a suicide attempt, respectively. Religiosity was negatively associated with acceptability of suicide, but it was positively related to punishment after death across the 11 countries. Religiosity was negatively associated with ever experiencing suicidal ideation, both directly and indirectly through its association with attitudes towards suicide, especially the belief in acceptability of suicide. Neither positive nor negative religious coping were related to suicidal ideation. However, religiosity was negatively related to suicide attempts among those who experienced suicidal ideation at least once. This association was mediated through the belief in acceptability of suicide and religious coping. Negative religious coping was positively associated with suicide attempts probably because it weakened the protective effects of religiosity. Findings from this study suggest that the effects of religiosity in the suicidal process operate through attitudes towards suicide. We therefore conclude that clinical assessment as well as research in suicidology may benefit from paying due attention to attitudes towards suicide.


Pulmonary hypertension in Switzerland: treatment and clinical course.
The prognosis of pulmonary hypertension (PH), especially idiopathic pulmonary arterial hypertension (IPAH), has improved during the recent years. The Swiss Registry for PH represents the collaboration of the various centres in Switzerland dealing with PH and serves as an important tool in quality control. The objective of the study was to describe the treatment and clinical course of this orphan disease in Switzerland. We analyzed data from 222 of 252 adult patients, who were included in the registry between January 1999 and December 2004 and suffered from either PAH, PH associated with lung diseases or chronic thromboembolic PH (CTEPH) with respect to the following data: NYHA class, six-minute walking distance (6-MWD), haemodynamics, treatments and survival. If compared with the calculated expected figures the one, two and three year mean survivals in IPAH increased from 67% to 89%, from 55% to 78% and from 46% to 73%, respectively. Most patients (90%) were on oral or inhaled therapy and only 10 patients necessitated lung transplantation. Even though pulmonary endarterectomy (PEA) was performed in only 7 patients during this time, the survival in our CTEPH cohort improved compared with literature data and seems to approach outcomes usually seen after PEA. The 6-MWD increased maximally by 52 m and 59 m in IPAH and CTEPH, respectively, but in the long term returned to or below baseline values, despite the increasing use of multiple specific drugs (overall in 51% of IPAH and 29% of CTEPH). Our national registry data indicate that the overall survival of IPAH and presumably CTEPH seems to have improved in Switzerland. Although the 6-MWD improved transiently, it decreased in the long term despite specific and increasingly combined drug treatment. Our findings herewith underscore the progressive nature of the diseases and the need for further intense research in the field.


Clinician Perspectives on the Benefits of Practice Facilitation for Small Primary Care Practices.
Small independent primary care practices (SIPs) often lack the resources to implement system changes. HealthyHearts NYC, funded through the EvidenceNOW initiative of the Agency for Healthcare Research and Quality, studied the effectiveness of practice facilitation to improve cardiovascular disease- related care in 257 SIPs. We sought to understand SIP clinicians' perspectives on the benefits of practice facilitation. We conducted in-depth interviews with 19 SIP clinicians enrolled in HealthyHearts NYC. Interviews were transcribed and coded using deductive and inductive approaches. To understand whether the perceived benefits of practice facilitation differ based on the availability of internal staff for quality improvement (QI), we compared themes pertaining to benefits between practices with 3 or fewer office staff vs more than 3 office staff. Clinicians perceived 2 main benefits of practice facilitation. First, facilitators served as a connection to the external health care environment for SIPs, often through teaching and information sharing. Second, facilitators provided electronic health record (EHR)/data expertise, often by teaching functionality and completing technical assistance and tasks. SIPs with more than 3 office staff felt that facilitators provided benefits primarily through teaching, whereas SIPs with 3 or fewer staff felt that facilitators also provided hands-on support. At the intersections of these benefits, there emerged 3 central practice facilitation benefits: (1) creating awareness of quality gaps, (2) connecting practices to information, resources, and strategies, and (3) optimizing the EHR for QI goals. SIP clinicians perceived practice facilitation to be an important resource for connecting their practice to the external health care environment and resources, and helping their practice build QI capacity through teaching, hands-on support, and EHR-driven solutions.


Generation of a mouse tumor necrosis factor mutant with antiperitonitis and desensitization activities comparable to those of the wild type but with reduced systemic toxicity.
In this study, we investigated whether the recently identified lectin-like domain of tumor necrosis factor (TNF) is implicated in its biological activities on mammalian cells. To this end, a mouse TNF (mTNF) triple mutant, T104A-E106A-E109A mTNF (referred to hereafter as triple mTNF), lacking the lectin-like affinity of mTNF for specific oligosaccharides, was compared with the wild-type molecule for various TNF effects in vitro and in vivo. The triple mTNF displayed a 50-fold-reduced TNF receptor 2 (TNFR2)-mediated bioactivity but only a 5-fold-reduced TNFR1-mediated bioactivity in vitro. The specific activity of the triple mutant on L929 fibrosarcoma cells was slightly reduced compared with that of the wild type. We subsequently assessed the systemic toxicity of triple versus wild-type mTNF, since TNFR2 is partially implicated in this activity. The triple mTNF had a significantly reduced toxicity compared with that of wild-type mTNF in vivo. Moreover, we compared the effects of the triple and the wild-type mTNFs in TNFR1-mediated phenomena, such as (i) induction of tolerance towards a lethal mTNF dose and (ii) protective activity in cecal ligation and puncture-induced septic peritonitis. No significant differences between the mutant and wild-type forms were observed. In conclusion, these results indicate that triple mTNF, lacking TNF's lectin-like binding capacity, has reduced systemic toxicity but retains the tolerance-inducing and peritonitis-protective activities of wild-type mTNF.


An analysis of the structural and functional similarities of insect hemocytes and mammalian phagocytes.
The insect immune response demonstrates a number of structural and functional similarities to the innate immune system of mammals. As a result of these conserved features insects have become popular choices for evaluating the virulence of microbial pathogens or for assessing the efficacy of antimicrobial agents and give results which are comparable to those that can be obtained using mammals. Analysis of the cellular component of the insect and mammalian immune systems demonstrates many similarities. Insect hemocytes recognize pathogens and phagocytose material in a similar manner to neutrophils. The killing of ingested microbes is achieved in both cell types by the production of superoxide and by the release of enzymes in the process of degranulation. Insect hemocytes and mammalian neutrophils are sensitive to the same inhibitors. This review highlights the strong similarities between the phagocytic cells of both groups of animals and demonstrates the potential benefits of using selected insects as in vivo screening systems.


Uncovering the nutritional landscape of food.
Recent progresses in data-driven analysis methods, including network-based approaches, are revolutionizing many classical disciplines. These techniques can also be applied to food and nutrition, which must be studied to design healthy diets. Using nutritional information from over 1,000 raw foods, we systematically evaluated the nutrient composition of each food in regards to satisfying daily nutritional requirements. The nutrient balance of a food was quantified and termed nutritional fitness; this measure was based on the food's frequency of occurrence in nutritionally adequate food combinations. Nutritional fitness offers a way to prioritize recommendable foods within a global network of foods, in which foods are connected based on the similarities of their nutrient compositions. We identified a number of key nutrients, such as choline and α-linolenic acid, whose levels in foods can critically affect the nutritional fitness of the foods. Analogously, pairs of nutrients can have the same effect. In fact, two nutrients can synergistically affect the nutritional fitness, although the individual nutrients alone may not have an impact. This result, involving the tendency among nutrients to exhibit correlations in their abundances across foods, implies a hidden layer of complexity when exploring for foods whose balance of nutrients within pairs holistically helps meet nutritional requirements. Interestingly, foods with high nutritional fitness successfully maintain this nutrient balance. This effect expands our scope to a diverse repertoire of nutrient-nutrient correlations, which are integrated under a common network framework that yields unexpected yet coherent associations between nutrients. Our nutrient-profiling approach combined with a network-based analysis provides a more unbiased, global view of the relationships between foods and nutrients, and can be extended towards nutritional policies, food marketing, and personalized nutrition.


The impact of indoor thermal stratification on the dispersion of human speech droplets.
Exhaled jets from an infected person are found to be locked at a certain height when thermal stratification exists in rooms, causing a potential high risk of disease transmission. This work is focused on the theoretical analysis of the dynamic characteristics of human speech droplets and the residual droplet nuclei in both thermally uniform and stratified environments. Results show that most droplets generated from human speaking can totally evaporate or deposit to the ground within 1.5-2 m. For small droplets of < 80μm, thermal stratification shows a more significant impact on their residues. The lock-up height of the droplet nuclei is a function of droplet size and the temperature gradient, and within this lock-up layer, these droplet nuclei can travel a long distance, much more than 2m. For medium droplets of 80-180 μm, thermal stratification can weaken the evaporation and accelerate the deposition processes, equivalent to a higher relative humidity (RH). Accordingly, more droplets can deposit to the ground, reducing the exposure to large droplets in close proximity to the source. Large droplets of > 180μm show no dependence on stratification and RH. These findings can have implications for developing effective engineering methods to limit the spread of infectious disease.


Toward a consensus nomenclature for insect neuropeptides and peptide hormones.
The nomenclature currently in use for insect neuropeptide and peptide hormone families is reviewed and suggestions are made as to how it can be rationalized. Based upon this review, a number of conventions are advanced as a guide to a more rationale nomenclature. The scheme that is put forward builds upon the binomial nomenclature scheme proposed by Raina and Gäde in 1988, when just over 20 insect neuropeptides had been identified. Known neuropeptides and peptide hormones are assigned to 32 structurally distinct families, frequently with overlapping functions. The names given to these families are those that are currently in use, and describe a biological function, homology to known invertebrate/vertebrate peptides, or a conserved structural motif. Interspecific isoforms are identified using a five-letter code to indicate genus and species names, and intraspecific isoforms are identified by Roman or Arabic numerals, with the latter used to signify the order in which sequences are encoded on a prepropeptide. The proposed scheme is sufficiently flexible to allow the incorporation of novel peptides, and could be extended to other arthropods and non-arthropod invertebrates.


Tetrahedral (T) Closed-Shell Cluster of 29 Silver Atoms & 12 Lipoate Ligands, [Ag29(R-α-LA)12](3-): Antibacterial and Antifungal Activity.
Here we report on the identification and applications of an aqueous 29-atom silver cluster stabilized with 12 lipoate ligands, i.e. Ag29(R-α-LA)12 or (29,12), wherein R-α-LA = R-α-lipoic acid, a natural dithiolate. Its uniformity is checked by HPLC-ESI-MS and analytical ultracentrifugation, which confirms its small dimension (~3 nm hydrodynamic diameter). For the first time, this cluster has been detected intact via electrospray ionization mass spectrometry, allowing one to confirm its composition, its [3-] charge-state, and the 8-electron shell configuration of its metallic silver core. Its electronic structure and bonding, including T-symmetry and profound chirality in the outer shell, have been analyzed by DFT quantum-chemical calculations, starting from the known structure of a nonaqueous homologue. The cluster is effective against Methicillin-Resistant Staphylococcus aureus bacteria (MRSA) at a minimum inhibitory concentration (MIC) of 0.6 mg-Ag/mL. A preformed Candida albicans fungal biofilm, impermeable to other antifungal agents, was also inhibited by aqueous solutions of this cluster, in a dose-response manner, with a half-maximal inhibitory concentration (IC50) of 0.94 mg-Ag/mL. Scanning electron micrographs showed the post-treatment ultrastructural changes on both MRSA and C. albicans that are characteristic of those displayed after treatment by larger silver nanoparticles.


Flash masking and facilitation by nearby luminance perturbations.
Light-adapted foveal luminance increment thresholds were measured for white photopic targets of 1.5-arc min diameter and 220-ms duration. We aimed to learn about the properties of mechanisms that subserve the detection of these targets. To study this subject we developed a noise probe technique that inserts noise close to the site of the stimulus. Threshold is more than doubled when zero-mean luminance noise is placed at a pair of flanking spots in the horizontal meridian centered on the test spot and 1.5 arc min distant. The detection mechanisms thus has a broad field, since noise effects persist at 5-arc min separation. The masking effect increases when the noise is in antiphase at the two flanking spots. Neither even- nor odd-symmetric mechanisms are able to explain these findings, regardless of whether linear or nonlinear processing is employed. The target detection may be mediated in part by a motion-sensitive mechanism.


Novel insights into Chk1 regulation by phosphorylation.
Checkpoint kinase 1 (Chk1) is a conserved protein kinase central to the cell-cycle checkpoint during DNA damage response (DDR). Until recently, ATR, a protein kinase activated in response to DNA damage or stalled replication, has been considered as the sole regulator of Chk1. Recent progress, however, has led to the identification of additional protein kinases involved in Chk1 phosphorylation, affecting the subcellular localization and binding partners of Chk1. In fact, spatio-temporal regulation of Chk1 is of critical importance not only in the DDR but also in normal cell-cycle progression. In due course, many potent inhibitors targeted to Chk1 have been developed as anticancer agents and some of these inhibitors are currently in clinical trials. In this review, we summarize the current knowledge of Chk1 regulation by phosphorylation.


Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort.
The aim of the study was to assess associations between intake of combined soft drinks (sugar sweetened and artificially sweetened) and fruit and vegetable juices and the risk of hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBC) and biliary tract cancers (GBTC) using data from the European Prospective Investigation into Cancer and Nutrition cohort of 477,206 participants from 10 European countries. After 11.4 years of follow-up, 191 HCC, 66 IHBC and 236 GBTC cases were identified. Hazard ratios and 95% confidence intervals (HR; 95% CI) were estimated with Cox regression models with multivariable adjustment (baseline total energy intake, alcohol consumption and intake pattern, body mass index, physical activity, level of educational attainment and self-reported diabetes status). No risk associations were observed for IHBC or GBTC. Combined soft drinks consumption of >6 servings/week was positively associated with HCC risk: HR 1.83; 95% CI 1.11-3.02, p trend = 0.01 versus non-consumers. In sub-group analyses available for 91% of the cohort artificially sweetened soft drinks increased HCC risk by 6% per 1 serving increment (HR 1.06, 95% CI 1.03-1.09, n cases = 101); for sugar-sweetened soft drinks, this association was null (HR 1.00, 95% CI 0.95-1.06; n cases = 127, p heterogeneity = 0.07). Juice consumption was not associated with HCC risk, except at very low intakes (<1 serving/week: HR 0.60; 95% CI 0.38-0.95; p trend = 0.02 vs. non-consumers). Daily intake of combined soft drinks is positively associated with HCC, but a differential association between sugar and artificially sweetened cannot be discounted. This study provides some insight into possible associations of HCC with sugary drinks intake. Further exploration in other settings is required.


Erectile dysfunction therapy in countries where implant is economically not feasible.
Erectile dysfunction (ED), a frequent complaint in the primary care setting, is strongly associated with obesity, cigarette smoking and other common cardiovascular risk factors like hypertension, diabetes mellitus (DM), lipid disorders and the metabolic syndrome. The prevalence of these cardiovascular disorders is rising at staggering rates in most Latin American countries. ED is a symptom that mainly affects economically productive men (40-70 years of age) potentially causing major psychosocial repercussions and reduced quality of life. The management of ED in these developing countries is increasingly challenging due to poor patient education and non-adherence to the medical treatment of theses concomitant comorbidities. The financial implications of commonly prescribed medications and surgical procedures limit their use to a minority of patients. For this reason, the clinician must adopt a holistic approach in the management of this disease focusing on preventive measures based on patient education and non-surgical interventions. This review summarizes common associated risk factors of ED and outlines non-pharmacological interventions for the management of this disease.


Bovine Viral Diarrhea Virus Type 2 Impairs Macrophage Responsiveness to Toll-Like Receptor Ligation with the Exception of Toll-Like Receptor 7.
Bovine viral diarrhea virus (BVDV) is a member of the Flaviviridae family. BVDV isolates are classified into two biotypes based on the development of cytopathic (cp) or non-cytopathic (ncp) effects in epithelial cell culture. BVDV isolates are further separated into species, BVDV1 and 2, based on genetic differences. Symptoms of BVDV infection range from subclinical to severe, depending on strain virulence, and may involve multiple organ systems and induction of a generalized immunosuppression. During BVDV-induced immune suppression, macrophages, critical to innate immunity, may have altered pathogen recognition receptor (PRR) signaling, including signaling through toll-like receptors (TLRs). Comparison of BVDV 2 strains with different biotypes and virulence levels is valuable to determining if there are differences in host macrophage cellular responses between viral phenotypes. The current study demonstrates that cytopathic (cp), noncytopathic (ncp), high (hv) or low virulence (lv) BVDV2 infection of bovine monocyte-derived macrophages (MDMΦ) result in differential expression of pro-inflammatory cytokines compared to uninfected MDMΦ. A hallmark of cp BVDV2 infection is IL-6 production. In response to TLR2 or 4 ligation, as might be observed during secondary bacterial infection, cytokine secretion was markedly decreased in BVDV2-infected MDMΦ, compared to non-infected MDMΦ. Macrophages were hyporesponsive to viral TLR3 or TLR8 ligation. However, TLR7 stimulation of BVDV2-infected MDMΦ induced cytokine secretion, unlike results observed for other TLRs. Together, these data suggest that BVDV2 infection modulated mRNA responses and induced a suppression of proinflammatory cytokine protein responses to TLR ligation in MDMΦ with the exception of TLR7 ligation. It is likely that there are distinct differences in TLR pathways modulated following BVDV2 infection, which have implications for macrophage responses to secondary infections.


Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia.
Anorexia and weight loss are negative prognostic factors in patients with cancer. Although total ghrelin levels are increased in energy-negative states, levels of the biologically active octanoylated ghrelin and the anorexigenic peptide YY (PYY) have not been reported in patients with cancer-induced cachexia. We hypothesized that abnormal ghrelin and/or PYY levels contribute to cancer-induced cachexia. We evaluated 21 patients with cancer-induced cachexia; 24 cancer patients without cachexia; and 23 age-, sex-, race-, and BMI-matched subjects without cancer. Active ghrelin levels and the active to total ghrelin ratio were significantly increased in subjects with cancer-induced cachexia, compared with cancer and noncancer controls. PYY levels were similar among groups. Appetite measured by a visual analog scale was not increased in subjects with cachexia. The increase in active ghrelin levels is likely to be a compensatory response to weight loss. Cachexia may be a state of ghrelin resistance because appetite does not correlate with ghrelin levels. Changes in the active to total ghrelin ratio suggest that a mechanism other than increased secretion must be responsible for the increase in active ghrelin levels. PYY is unlikely to play an important role in cancer-induced cachexia.


Topical antifungals for seborrhoeic dermatitis.
Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults.A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS. We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials. Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life. Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high. We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies.Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another. KetoconazoleTopical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low-quality evidence) at four weeks of follow-up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I² = 74%). The median proportion of those who did not have clearance in the placebo groups was 69%.Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low-quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate-quality evidence).Ketoconozale yielded a similar remission failure rate as ciclopirox (RR 1.09, 95% CI 0.95 to 1.26, three studies, low-quality evidence). Most comparisons between ketoconazole and other antifungals were based on single studies that showed comparability of treatment effects. CiclopiroxCiclopirox 1% led to a lower failed remission rate than placebo at four weeks of follow-up (RR 0.79, 95% CI 0.67 to 0.94, eight studies, moderate-quality evidence) with similar rates of side effects (RR 0.9, 95% CI 0.72 to 1.11, four studies, moderate-quality evidence). Other antifungalsClotrimazole and miconazole efficacies were comparable with those of steroids on short-term assessment in single studies.Treatment effects on individual symptoms were less clear and were inconsistent, possibly because of difficulties encountered in measuring these symptoms.Evidence was insufficient to conclude that dose or mode of delivery influenced treatment outcome. Only one study reported on treatment compliance. No study assessed quality of life. One study assessed the maximum rash-free period but provided insufficient data for analysis. One small study in patients with HIV compared the effect of lithium versus placebo on seborrhoeic dermatitis of the face, but treatment outcomes were similar. Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class. Very few studies have assessed symptom clearance for longer periods than four weeks. Ketoconazole produced findings similar to those of steroids, but side effects were fewer. Treatment effect on overall quality of life remains unknown. Better outcome measures, studies of better quality and better reporting are all needed to improve the evidence base for antifungals for seborrhoeic dermatitis.


Metabolic Responses to the Yukon Arctic Ultra: Longest and Coldest in the World.
The Yukon Arctic Ultra is considered the longest and coldest ultraendurance event in the world. Cold exposure and exercise has been reported to influence circulating levels of myokines, adipokines, and hepatokines that may influence considerable alterations in the regulation of metabolism. The purpose of the study was to evaluate the influence of the Yukon Arctic Ultra (430-mile event) on potential activators of brown fat, metabolites, and body composition in healthy individuals. Eight male and female participants (mean ± SEM: age, 44 ± 3 yr; body mass index, 23.4 ± 0.9) were recruited for participation. Blood samples were collected at pre-event, mid-event, and post-event checkpoints. The temperature during the event ranged from -45°C to -8°C. Because of these extremely challenging conditions, 50% of the participants withdrew from competition by the 300-mile mark, and those that surpassed 300 miles lost a significant (P = 0.002; P = 0.01) amount of body weight (76 ± 5 kg to 73 ± 4 kg) and fat mass (13 ± 1 kg to 12 ± 3 kg), respectively. With respect to serum irisin, there was a trend (P = 0.06) toward significance from pre-event (1033 ± 88 ng·mL), mid-event (1265 ± 23 ng·mL) to post-event (1289 ± 24 ng·mL). Serum meteorin-like and fibroblast growth factor-21 remained stable throughout the event. There were no changes in creatinine, acetoacetate, acetate, and valine. Serum lactate decreased (P = 0.04) during the event. The influence of cold exposure and extreme physical exertion may promote substantial increases in serum irisin, and specific alterations in substrate metabolism that largely preserve skeletal muscle and physiological resilience.


Reduction of UV-B radiation causes an enhancement of photoinhibition in high light stressed aquatic plants from New Zealand lakes.
Anthropogenic stratospheric ozone depletion causes an increase of UV-B radiation impinging on the earth surface, which is a threat to plants not adapted to higher UV-B irradiances. Investigations were undertaken with aquatic plants from New Zealand, where UV-irradiances are naturally higher due to the southern latitude, to compare with former results of polar species. The experiments reported in this study were undertaken with plants collected from different lakes of the South Island, with different UV transparencies. Photoinhibition was induced under controlled conditions using a sun simulator, which mimicked the natural underwater radiation spectrum. Photosynthetic activity during high light stress, and during recovery in dim light, was determined in vivo by measuring fluorescence changes, using a PAM fluorometer device. A comparison of different species showed that the extent to which UV causes an additional decrease of photosynthetic performance during high light stress varies according to the depth of growth and UV transparency of the water body. This observation fits with previous studies. However, a new finding was that some species were even more strongly inhibited when UV-B was filtered out of the simulated sun spectrum, indicating a supporting effect of the short UVR wavelength range against photoinhibition. These results were also confirmed by field experiments under natural radiation conditions. Thus, UV-B does not solely cause negative effects on photosynthesis, but it may even support recovery processes in aquatic plants adapted to a high UV-radiation environment. The latter is in contrast to earlier studies, in which UV-B radiation was considered causing only harmful effects on photosynthesis of aquatic plants.


Effects of Community Water Fluoridation on Dental Caries Disparities in Adolescents.
Despite improvements in the prevalence of dental caries, disparities are still observed globally and in the U.S. This study examined whether community water fluoridation (CWF) reduced dental caries disparities in permanent teeth of 10- to 19-year-old schoolchildren in North Carolina. We used cross-sectional data representing K-12 schoolchildren in North Carolina (NC) public schools. A poisson regression model was used to determine whether the association between children's parental educational attainment and the prevalence of dental caries of children differed by children's lifetime CWF exposure. We analyzed data on 2075 students. Among the children without any CWF exposure in their life, statistically significant caries disparities by parental educational attainment were observed. Compared to the children of parents with more than high school education, the relative risk for those with a parent with a high school education was 1.16 (95% CI = 1.01, 1.33) and those with less than a high school education was 1.27 (95% CI = 1.02, 1.60). In contrast, these disparities were not observed among children exposed to CWF throughout their lives. Socioeconomic disparities in dental caries were not observed among 10-19-year-old schoolchildren with lifetime CWF exposure. CWF seemed to reduce dental caries disparities.


[Arterial stenosis after coil migration in embolization of an aneurysm].
A case of arterial stenosis after coil migration in intracranial aneurysm embolization is presented. A 51-year-old woman suffered sudden onset of headache and unconsciousness. Computed tomography demonstrated diffuse subarachnoid hemorrhage and cerebral angiography disclosed a right internal carotid artery (ICA) bifurcation aneurysm and a right ICA-anterior choroidal artery aneurysm. The aneurysms were treated by endovascular embolization with Guglielmi detachable coils. During the embolization procedure of the ICA bifurcation aneurysm, a coil strand detached in the sac had migrated into the ICA. We did not retrieve the migrated coil, because the free coil strand was stable in the ICA and did not cause distal flow reduction. The patient suffered vasospasm of the right ICA and underwent intra-arterial infusion of fasudil hydrochloride and percutaneous transluminal angioplasty of the ICA on day 9. The patient experienced infarction in the territory of the right anterior cerebral artery area and needed a ventriculo-peritoneal shunt for hydrocephalus. The patient was discharged with mild right hemiparesis. Follow-up angiography after six months revealed right ICA and middle cerebral artery stenosis, but the free strand of the migrated coil had not moved in the right ICA. We suspect that the coil strand might have induced thrombosis or intimal hyperplasia of the proximal M1 segment and right ICA. Although late stenosis of the parent artery might be rare, it should be recognized as a long term complication of a migrated free coil strand in the endovascular treatment of intracranial aneurysms.


The effects of five weeks of kickboxing training on physical fitness.
the purpose of this study was to examine the effect of kickboxing training on physical fitness. 30 subjects were randomized into a kickboxing-group (n=15) and control group (n=15). Each group trained approximately 1-hour per day, three-times per a week during five weeks. Muscle-power (upper-body: bench-press-test, medicine-ball-test; lower-body: squat-jump and counter-movement-jump-test), flexibility, speed and agility, aerobic (progressive maximal exercise test), anaerobic fitness (Wingate test) and body composition were assessed before and after the training period. the kickboxing group showed significant improvement (p < 0.05) in upper-body muscle power, aerobic power, anaerobic fitness, flexibility, speed and agility after training whereas body composition, squat jump and counter movement jump (height, power and velocity components) did not change for both groups. kickboxing-practice was effective to change many physical variables. Thus, this activity can be useful for enhancing physical fitness, but complementary activities and/or nutritional interventions should be necessary.


Expanded adult day program as a transition option from hospital to home.
This article describes a pilot program for provision of postacute care (PAC) in an established adult day program. Demographic, clinical, utilization, and satisfaction data were abstracted retrospectively from program records; postdischarge readmission and emergency department visit data were obtained from the electronic health record. Comparative data were obtained from the health records of patients who were offered but declined the adult day program. Between 2005 and 2008, 78 patients requiring PAC were approached by the RN coordinator; 33 selected the adult day program, and 45 selected alternative destinations. The majority of patients had a neurological diagnosis, most commonly stroke. Participants and their family caregivers were highly satisfied with the program. The 30-day readmission rate for adult day program participants was significantly lower than that for nonparticipants. An expanded adult day program may represent a viable Transitional Care Model for selected patients and a feasible alternative to skilled nursing facility and home health care for PAC.


Maternal ageing impairs mitochondrial DNA kinetics during early embryogenesis in mice.
Does ageing affect the kinetics of the mitochondrial pool during oogenesis and early embryogenesis? While we found no age-related change during oogenesis, the kinetics of mitochondrial DNA content and the expression of the factors involved in mitochondrial biogenesis appeared to be significantly altered during embryogenesis. Oocyte mitochondria are necessary for embryonic development. The morphological and functional alterations of mitochondria, as well as the qualitative and quantitative mtDNA anomalies, observed during ovarian ageing may be responsible for the alteration of oocyte competence and embryonic development. The study, conducted from November 2016 to November 2017, used 40 mice aged 5-8 weeks and 45 mice aged 9-11 months (C57Bl6/CBA F(1)). A total of 488 immature oocytes, with a diameter ranging from 20 μm to more than 80 μm, were collected from ovaries, and 1088 mature oocytes or embryos at different developmental stages (two PN, one-cell, i.e. syngamy, two-cell, four-cell, eight-cell, morula and blastocyst) were obtained after ovarian stimulation and, for embryos, mating. Mitochondrial DNA was quantified by quantitative PCR. We used quantitative reverse transcriptase PCR (RT-PCR) (microfluidic method) to study the relative expression of three genes involved in the key steps of embryogenesis, i.e. embryonic genome activation (HSPA1) and differentiation (CDX2 and NANOG), two mtDNA genes (CYB and ND2) and five genes essential for mitochondrial biogenesis (PPARGC1A, NRF1, POLG, TFAM and PRKAA). The statistical analysis was based on mixed linear regression models applying a logistic link function (STATA v13.1 software), with values of P < 0.05 being considered significant. During oogenesis, there was a significant increase in oocyte mtDNA content (P < 0.0001) without any difference between the two groups of mice (P = 0.73). During the first phase of embryogenesis, i.e. up to the two-cell stage, embryonic mtDNA decreased significantly in the aged mice (P < 0.0001), whereas it was stable for young mice (young/old difference P = 0.015). The second phase of embryogenesis, i.e. between the two-cell and eight-cell stages, was characterized by a decrease in embryonic mtDNA for young mice (P = 0.013) only (young/old difference P = 0.038). During the third phase, i.e. between the eight-cell and blastocyst stage, there was a significant increase in embryonic mtDNA content in young mice (P < 0.0001) but not found in aged mice (young/old difference P = 0.002). We also noted a faster expression of CDX2 and NANOG in the aged mice than in the young mice during the second (P = 0.007 and P = 0.02, respectively) and the third phase (P = 0.01 and P = 0.008, respectively) of embryogenesis. The expression of mitochondrial genes CYB and ND2 followed similar kinetics and was equivalent for both groups of mice, with a significant increase during the third phase (P < 0.01). Of the five genes involved in mitochondrial biogenesis, i.e. PPARGC1A, NRF1, POLG, TFAM and PRKAA, the expression of three genes decreased significantly during the first phase only in young mice (NRF1, P = 0.018; POLGA, P = 0.002; PRKAA, P = 0.010), with no subsequent difference compared to old mice. In conclusion, during early embryogenesis in the old mice, we suspect that the lack of a replicatory burst before the two-cell stage, associated with the early arrival at the minimum threshold value of mtDNA, together with the absence of an increase of mtDNA during the last phase, might potentially deregulate the key stages of early embryogenesis. N/A. Because of the ethical impossibility of working on a human, this study was conducted only on a murine model. As superovulation was used, we cannot totally exclude that the differences observed were, at least partially, influenced by differences in ovarian response between young and old mice. Our findings suggest a pathophysiological explanation for the link observed between mitochondria and the deterioration of oocyte quality and early embryonic development with age. This work was supported by the University of Angers, France, by the French national research centres INSERM and the CNRS and, in part, by PHASE Division, INRA. There are no competing interests.


An East-Asian-type cagA Helicobacter pylori Infected Patient with Clinical Manifestation of Gastric Ulcer.
We reported a male, 72 yo, Chinese ethnic with chief complaint black mushy defecation. Physical examination revealed pale on conjunctival palpebra which confirmed as anemia on complete blood count. Gastroduodenoscopy revealed a 3 mm ulcer at the antrum (Forrest stage III). H. pylori infection was positive based on five different test methods (urinary antibody tests, rapid urease test, culture, histology ad immunohistochemistry). Used polymerase chain reaction-based sequencing, we found the patient infected by CagA producing, East-Asian-type cagA and vacA s1m1-strain. Further analysis using 7 housekeeping genes confirmed that the strain categorized in to hspEAsia group. The patient was given continuous intravenous infusions of proton pump inhibitor and standard triple therapy regimens eradication of H. pylori.


Extracting optical modes of organic light-emitting diodes using quasi-periodic WO3 nanoislands.
Quasi-periodic WO(3) nanoislands are introduced to extract two optical modes in organic light-emitting diodes. The nano-scaled and size-tunable WO(3) islands were fabricated by use of wet-etching with self-aggregated Ag mask. The improvement of light extraction efficiency originates to the recovery of light losses which are surface plasmon mode and waveguide mode. As a result, external quantum efficiency and power efficiency were increased. No changes in emission spectrum and CIE color coordinates with WO(3) nanoislands at various observation angles are desirable if this device is to be utilized in optical system. Furthermore, cost-effective fabrication makes it possible to adopt this system in large area fabrication.


Brain-computer interface based on generation of visual images.
This paper examines the task of recognizing EEG patterns that correspond to performing three mental tasks: relaxation and imagining of two types of pictures: faces and houses. The experiments were performed using two EEG headsets: BrainProducts ActiCap and Emotiv EPOC. The Emotiv headset becomes widely used in consumer BCI application allowing for conducting large-scale EEG experiments in the future. Since classification accuracy significantly exceeded the level of random classification during the first three days of the experiment with EPOC headset, a control experiment was performed on the fourth day using ActiCap. The control experiment has shown that utilization of high-quality research equipment can enhance classification accuracy (up to 68% in some subjects) and that the accuracy is independent of the presence of EEG artifacts related to blinking and eye movement. This study also shows that computationally-inexpensive bayesian classifier based on covariance matrix analysis yields similar classification accuracy in this problem as a more sophisticated Multi-class Common Spatial Patterns (MCSP) classifier.


miR-135b suppresses tumorigenesis in glioblastoma stem-like cells impairing proliferation, migration and self-renewal.
Glioblastoma multiforme (GBM) is the most common and fatal malignant adult primary brain tumor. Currently, the overall prognosis for GBM patients remains poor despite advances in neurosurgery and adjuvant treatments. MicroRNAs (miRNAs) contribute to the pathogenesis of various types of tumor, including GBM. In this study we analyzed the expression of a panel of miRNAs, which are known to be differentially expressed by the brain and GBM tumor, in a collection of patient-derived GBM stem-like cells (GSCs). Notably, the average expression level of miR-135b, was the most downregulated compared to its normal counterpart, suggesting a potential role as anti-oncogene.Restoration of miR-135b in GSCs significantly decreased proliferation, migration and clonogenic abilities. More importantly, miR-135b restoration was able to significantly reduce brain infiltration in mouse models of GBM obtained by intracerebral injection of GSC lines. We identified ADAM12 and confirmed SMAD5 and GSK3β as miR-135b targets and potential mediators of its effects. The whole transcriptome analysis ascertained that the expression of miR-135b downmodulated additional genes driving key pathways in GBM survival and infiltration capabilities.Our results identify a critical role of miR-135b in the regulation of GBM development, suggesting that miR-135b might act as a tumor-suppressor factor and thus providing a potential candidate for the treatment of GBM patients.


Drying the leaves of Perilla frutescens increases their content of anticancer nutraceuticals.
A regular intake of plant-derived bioactive agents has gained popularity because of the health benefits. Fresh leafy greens, however, normally have a low concentration of such bioactive agents. In this study, we found that drying markedly affected the accumulation of secondary metabolites and that dried leaves of Perilla frutescens L. (perilla) contained more anticancer flavonoids than fresh leaves. Drying is a major method of food preparation, particularly for plant-based foods, but the quality of the bioactive agents contained in the fresh and dried leaves of perilla has received only scant attention. Quantitative analysis of the concentrations of perillaldehyde, rosmarinic acid, apigenin, luteolin, 4-hydroxyphenyllactic acid, and 4-coumaric acid, some of which are known as nutraceuticals, revealed that the effect of drying significantly increased apigenin (28-fold) and luteolin (86-fold), but decreased rosmarinic acid in all leaf stages. We examined the positive effect on flavonoid levels on perilla leaves and confirmed that, by comparison with fresh perilla leaves, the dried leaves contained greater concentrations of anticancer flavonoids regardless of variety, form, or manner of cultivation. This indicates that drying can significantly increase the level of flavonoids in perilla leaves without a loss of flavor. Therefore, drying is a simple and effective method to improve the concentrations of bioactive agents, which increases the intake of beneficial substances derived from herbs and edible plants. This finding serves as a method for the supply of raw plant materials rich in bioactive agents that are suitable for labeling as edible nutraceuticals.


Ion channel density and threshold dynamics of repetitive firing in a cortical neuron model.
Modifying the density and distribution of ion channels in a neuron (by natural up- and down-regulation, by pharmacological intervention or by spontaneous mutations) changes its activity pattern. In the present investigation, we analyze how the impulse patterns are regulated by the density of voltage-gated channels in a model neuron, based on voltage clamp measurements of hippocampal interneurons. At least three distinct oscillatory patterns, associated with three distinct regions in the Na-K channel density plane, were found. A stability analysis showed that the different regions are characterized by saddle-node, double-orbit, and Hopf bifurcation threshold dynamics, respectively. Single strongly graded action potentials occur in an area outside the oscillatory regions, but less graded action potentials occur together with repetitive firing over a considerable range of channel densities. The presently found relationship between channel densities and oscillatory behavior may be relevance for understanding principal spiking patterns of cortical neurons (regular firing and fast spiking). It may also be of relevance for understanding the action of pharmacological compounds on brain oscillatory activity.


[Posttraumatic primary cutaneous aspergillosis with Candida guilliermondii infection in a healthy host].
Opportunistic fungal infections are usually seen in immunocompromised patients. While Candida is the most prevalent agent in such infections, Aspergillus is at the second order. Primary cutaneous aspergillosis is most common in immunocompromised patients but can rarely be seen in healthy hosts as well. We report a case of posttraumatic primary cutaneous aspergillosis and Candida guilliermondii coinfection in a 70-years-old healthy man. The patient had an ulcerous lesion which developed in the site of a trauma on the middle finger of the right hand. Histopathological examination of the biopsy specimens revealed septate hyphae with dichotomous branching small circular blastospores. The cultures of the biopsy specimen yielded yellow-green colored, granular mold colonies and creamy white yeast colonies. Microscopic examination of the lactophenol cotton blue stained mold colonies indicated long conidiophores with vesicles surrounded by uniseriate phialides, compatible with Aspergillus flavus. Yeast colonies were identified as Candida guilliermondii by ID32C (BioMerieux, France) and by their microscopical morphology detected in corn meal-Tween 80 agar incubated at 25°C for 72 hours. The patient was treated properly with surgical debridement and itraconazole therapy. Since the immune system is compressed as a consequence of aging, cutaneous opportunistic fungal infections should be considered in the differential diagnosis of posttraumatic necrotic ulcers and black eschar in aged patients.


Does prolonged exposure increase suicide risk? Results from an active duty military sample.
The efficacy of prolonged exposure (PE) on suicide ideation (SI) as a secondary outcome among individuals with posttraumatic stress disorder (PTSD) is unclear. The purpose of this study was to compare the efficacy of PE in two formats (spaced, S-PE, 10 sessions over 8 weeks, and massed, M-PE, 10 sessions over 2 weeks) to Present Centered Therapy (PCT) and minimal contact control (MCC) on SI exacerbation among patients without suicide intent or plans. Active duty military personnel (n = 335) were randomized to: (1) S-PE vs. PCT and (2) M-PE vs. MCC. All participants completed the Beck Scale for Suicide Ideation and the Beck Depression Inventory (Suicide item) at baseline, posttreatment, and follow-ups. S-PE and PCT had significant and comparable reductions in SI during treatment. M-PE had significantly steeper reductions in SI during treatment compared to MCC. Specifically, more participants in M-PE compared to MCC had reliable improvement versus reliable exacerbation. Reduction in PTSD symptoms was significantly associated with reduction of SI. PE was associated with significant reductions in SI over time that were comparable to PCT and superior to MCC. These findings suggest that both trauma- and non-trauma-focused treatments are associated with reductions in SI, and that trauma-focused treatments improve SI relative to waitlist.


Cadherin cell adhesion receptors as a morphogenetic regulator.
Cadherins are a family of cell adhesion receptors that are crucial for the mutual association of vertebrate cells. Through their homophilic binding interactions, cadherins play a role in cell-sorting mechanisms, conferring adhesion specificities on cells. The regulated expression of cadherins also controls cell polarity and tissue morphology. Cadherins are thus considered to be important regulators of morphogenesis. Moreover, pathological examinations suggest that the down-regulation of cadherin expression is associated with the invasiveness of tumor cells.


The role of motivation, glucose and self-control in the antisaccade task.
Research shows that self-control is resource limited and there is a gradual weakening in consecutive self-control task performance akin to muscle fatigue. A body of evidence suggests that the resource is glucose and consuming glucose reduces this effect. This study examined the effect of glucose on performance in the antisaccade task - which requires self-control through generating a voluntary eye movement away from a target - following self-control exertion in the Stroop task. The effects of motivation and individual differences in self-control were also explored. In a double-blind design, 67 young healthy adults received a 25g glucose or inert placebo drink. Glucose did not enhance antisaccade performance following self-control exertion in the Stroop task. Motivation however, predicted performance on the antisaccade task; more specifically high motivation ameliorated performance decrements observed after initial self-control exertion. In addition, individuals with high levels of self-control performed better on certain aspects of the antisaccade task after administration of a glucose drink. The results of this study suggest that the antisaccade task might be a powerful paradigm, which could be used as a more objective measure of self-control. Moreover, the results indicate that level of motivation and individual differences in self-control should be taken into account when investigating deficiencies in self-control following prior exertion.


Shared-control brain-computer interface for a two dimensional reaching task using EEG error-related potentials.
One of the main problems of EEG-based brain computer interfaces (BCIs) is their low information rate, thus for complex tasks the user needs large amounts of time to solve the task. In an attempt to reduce this time and improve the application robustness, recent works have explored shared-control strategies where the device does not only execute the decoded commands, but it is also involved in executing the task. This work proposes a shared-control BCI using error potentials for a 2D reaching task with discrete actions and states. The proposed system has several interesting properties: the system is scalable without increasing the complexity of the user's mental task; the interaction is natural for the user, as the mental task is to monitor the device performance to promote its task learning (in this context the reaching task); and the system has the potential to be combined with additional brain signals to recover or learn from interaction errors. Online control experiments were performed with four subjects, showing that it was possible to reach a goal location from any starting point within a 5×5 grid in around 23 actions (about 19 seconds of EEG signal), both with fixed goals and goals freely chosen by the users.


Covalent modification of the beta-1,4-N-acetylmuramoylhydrolase of Streptococcus faecium with 5-mercaptouridine monophosphate.
Purified beta-1,4-N-acetylmuramoylhydrolase (muramidase-1; EC 18.104.22.168) of Streptococcus faecium ATCC 9790 has been shown to be covalently substituted with approximately 12 mol equivalents of monomeric 5-mercaptouridine monophosphate. All 12 residues are present on the proteolytically processed 87-kDa active form of the enzyme. A peptide fragment containing 5-mercaptouridine, tyrosine, alanine, glycine, and leucine was isolated consistent with an O-phosphate linkage of the nucleotide to tyrosine.


Comparison of Anterior Segment Optical Coherence Tomography Bleb Grading, Moorfields Bleb Grading System, and Intraocular Pressure After Trabeculectomy.
To compare a novel anterior segment optical coherence tomography (AS-OCT) bleb grading system with a clinical bleb grading system and both with intraocular pressure (IOP) following trabeculectomy surgery. A novel AS-OCT grading system based on bleb size and internal reflectivity was developed. An imaging center was tasked with masked grading of AS-OCT images acquired by multiple surgical sites at postoperative week (POW) 2, postoperative month (POM) 4, 6, and 12, respectively. The Moorfields Bleb Grading System was used by another independent imaging center to grade clinical photos. The results of the 2 grading systems were compared and correlated with IOP. Blebs of 124 eyes were assessed in this study. Higher (worse) AS-OCT bleb grades was significantly associated with: decreased bleb height at POM4, 6, and 12 (P<0.001, 0.001, and 0.0001), increased central bleb vascularity at POM4 and 12 (P=0.0026;0.036) and decreased maximal bleb area at POM6 and 12 (P=0.026; 0.01). A higher AS-OCT bleb grade correlated with a higher IOP at POM4 and 6 (P=0.004; 0.02), though no longer significant at POM12 (P=0.1). Increased maximum bleb vascularity was associated with increased IOP at POM4 (P=0.003) though none of the remaining MGBS parameters correlated significantly with IOP. Eyes with a final IOP of ≤12 mm Hg had significantly lower AS-OCT bleb grades at POM6 (P=0.045). A novel AS-OCT bleb grading system correlated well with a number of Moorfields Bleb Grading System variables throughout the 1-year postoperative period. Although the AS-OCT grades also correlated well with IOP throughout most of the postoperative period, it was limited in their abilities to predict final IOP.


Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi-site analysis pipeline.
Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be well-powered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS.