[Stimulation of murine natural killer cells by weak electromagnetic waves in the centimeter range].
Irradiation with electromagnetic waves (8.15-18 GHz, 1 Hz within, 1 microW/cm2) in vivo increases the cytotoxic activity of natural killer cells of rat spleen. In mice exposed for 24-72 h, the activity of natural killer cells increased by 130-150%, the increased level of activity persisting within 24 h after the cessation of treatment. Microwave irradiation of animals in vivo for 3.5 and 5 h, and a short exposure of splenic cells in vitro did not affect the activity of natural killer cells.


The Firegoose: two-way integration of diverse data from different bioinformatics web resources with desktop applications.
Information resources on the World Wide Web play an indispensable role in modern biology. But integrating data from multiple sources is often encumbered by the need to reformat data files, convert between naming systems, or perform ongoing maintenance of local copies of public databases. Opportunities for new ways of combining and re-using data are arising as a result of the increasing use of web protocols to transmit structured data. The Firegoose, an extension to the Mozilla Firefox web browser, enables data transfer between web sites and desktop tools. As a component of the Gaggle integration framework, Firegoose can also exchange data with Cytoscape, the R statistical package, Multiexperiment Viewer (MeV), and several other popular desktop software tools. Firegoose adds the capability to easily use local data to query KEGG, EMBL STRING, DAVID, and other widely-used bioinformatics web sites. Query results from these web sites can be transferred to desktop tools for further analysis with a few clicks. Firegoose acquires data from the web by screen scraping, microformats, embedded XML, or web services. We define a microformat, which allows structured information compatible with the Gaggle to be embedded in HTML documents. We demonstrate the capabilities of this software by performing an analysis of the genes activated in the microbe Halobacterium salinarum NRC-1 in response to anaerobic environments. Starting with microarray data, we explore functions of differentially expressed genes by combining data from several public web resources and construct an integrated view of the cellular processes involved. The Firegoose incorporates Mozilla Firefox into the Gaggle environment and enables interactive sharing of data between diverse web resources and desktop software tools without maintaining local copies. Additional web sites can be incorporated easily into the framework using the scripting platform of the Firefox browser. Performing data integration in the browser allows the excellent search and navigation capabilities of the browser to be used in combination with powerful desktop tools.


"You've got to breathe, you know" - asthma patients and carers' perceptions around purchase and use of asthma preventer medicines.
To explore influences on patients' purchase and use of asthma preventer medicines and the perceived acceptability of financial incentives via reduced patient co-payments. Semi-structured telephone or face-to-face interviews were conducted with adults and carers of children with asthma. Interviews were recorded, transcribed verbatim and coded. Data were analysed using thematic analysis via grounded theory. Twenty-four adults and 20 carers for children aged 3-17 years with asthma were interviewed. For medicines choice, most participants did not consider themselves the primary decision-maker; cost of medicines was an issue for some, but effectiveness was described as more important. For adherence, cost, side-effects, perceived benefit and patient behaviours were important. Patient barriers to adherence with asthma preventer medicines including cost are ongoing. Healthcare professionals need to encourage empathic discussion with patients about cost issues. Implications for public health: Asthma patients and carers could benefit from greater involvement and respect within shared decision-making. Healthcare professionals should be aware that cost may be a barrier for patient adherence, and provided with information about the relative costs of guideline-recommended asthma medicines. Patients and healthcare professionals need education around the efficacy of ICS-alone treatment and the rationale behind co-payments, for initiatives around quality use of medicines to succeed.


Salt and hypertension--future directions.
The comments that follow reflect the personal views of this author regarding some useful directions of research in the field of salt and hypertension. From a physiological perspective, salt sensitivity is defined, and the merits and limitations of certain animal models of hypertension used to study this issue are discussed. The need to more clearly define the mechanisms that detect sodium intake and control the renal excretion of sodium is discussed. Additionally, the need to better understand the relation between sodium homeostasis, volume regulation, and the consequences of dysfunction in these regulatory system on the arterial vasculature and interstitial matrix is emphasized. The necessity for the application of new tools and approaches in a number of investigative areas is discussed. Finally, the necessity of equally imaginative whole animal and cell/molecular research and efforts to merge and integrate the data obtained at the cellular level with that of intact systems is emphasized.


Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.
The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures. We analyzed self-reported conditions in 14,290 5-year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, < 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up. Identification of high-risk therapeutic exposures was adopted from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cumulative incidence curves and prevalence estimates quantified and regression models compared risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes mellitus, or gonadal dysfunction between survivors and siblings. The cumulative incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors (P < .01 for all). Risk was significantly higher in survivors exposed to high-risk therapies compared with survivors not so exposed for primary hypothyroidism (hazard ratio [HR], 6.6; 95% CI, 5.6 to 7.8), hyperthyroidism (HR, 1.8; 95% CI, 1.2 to 2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2 to 7.5), thyroid cancer (HR, 9.2; 95% CI, 6.2 to 13.7), growth hormone deficiency (HR, 5.3; 95% CI, 4.3 to 6.4), obesity (relative risk, 1.8; 95% CI, 1.7 to 2.0), and diabetes mellitus (relative risk, 1.9; 95% CI, 1.6 to 2.4). Women exposed to high-risk therapies had six-fold increased risk for premature ovarian insufficiency (P < .001), and men demonstrated higher prevalence of testosterone replacement (P < .001) after cyclophosphamide equivalent dose of 20 g/m(2) or greater or testicular irradiation with 20 Gy or greater. Survivors demonstrated an increased risk for all thyroid disorders and diabetes mellitus regardless of treatment exposures compared with siblings (P < .001 for all). Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk.


Turkish nurses' level of knowledge regarding implantable port catheter care.
The aim of this study was to determine the knowledge levels of Turkish nurses regarding implantable port catheter care. A descriptive method was used inside a university hospital that was located in a Turkish metropolis. The data were collected via a questionnaire that was given to a total of 45 nurses who were employed in the internal medicine clinics where the oncology patients were treated. In this study, 42.2% of the nurses received in-service training about the implantable port catheter. It was determined that the mean knowledge point was 15.13 ± 4.78. The difference between the knowledge points of the nurses regarding implantable port catheter care, based on whether or not the nurses had received in-service training, was statistically significant. Moreover, it was determined that the majority of the nurses did not know where the implantable port catheter is placed, its period of use following implantation, the amount of normal saline to be used for washing the catheter, the special port (Huber) needle, the number of the needle, and the exchange time of these needles. In this study, there existed significant differences between the scores of the nurses who received in-service training about the implantable port catheter and the scores of those who did not receive in-service training. The majority of the nurses who participated in the study were willing to receive in-service training regarding this subject. Thus, the organization of in-service training programs and the implementation of care, according to the developed standards and guidelines, are considered as significant for reducing the occurrence of the complications that are related to the use of the implantable port catheter.


Impact of long-term lifestyle programmes on weight loss and cardiovascular risk factors in overweight/obese participants: a systematic review and network meta-analysis.
The aim of this meta-analysis was to compare the long-term efficacy of diet plus exercise (D+E) vs. diet (D), D+E vs. exercise (E) and D vs. E on anthropometric outcomes and cardiovascular risk factors in overweight and obese participants. Electronic searches were performed in MEDLINE and the Cochrane Central Register of controlled trials. Inclusion criteria were as follows: body mass index≥25 kg/m2 and a minimum intervention period including follow-up of ≥12 months. Outcomes of interest were as follows: anthropometric parameters, blood lipids, blood pressure and cardiorespiratory fitness. Pooled effects were calculated using pairwise random effects and Bayesian random effects network meta-analysis. Results of the corresponding fixed effects models were compared in sensitivity analyses. Overall, 22 trials (24 reports) met the inclusion criteria and 21 (including 3,521 participants) of them were included in the quantitative analysis. As compared with D, D+E resulted in a significantly more pronounced reduction in body weight [mean differences (MD): -1.38 kg, 95% confidence interval (CI) -1.98 to -0.79], and fat mass (MD: -1.65 kg, 95% CI -2.81 to -0.49], respectively. When comparing D+E with E, MD in change of body weight (-4.13 kg, 95% CI -5.62 to -2.64), waist circumference (-3.00 cm, 95% CI -5.81 to -0.20), and fat mass (-3.60 kg, 95% CI -6.15 to -1.05) was in favour of combined diet and exercise, respectively. Comparing E vs. D, diet resulted in a significantly more pronounced decrease in body weight (MD: -2.93 kg, 95% CI -4.18 to -1.68), and fat mass (MD: -2.20 kg, 95% CI -3.75 to -0.66). D+E yielded also the greatest reductions with respect to blood lipids and blood pressure when compared to single applications of D and E, respectively. Results from the network meta-analyses confirmed these findings. Moderate-quality evidence from the present network meta-analysis suggests that D+E can be highly recommended for long-term obesity management. Furthermore, the evidence suggests a moderate superiority of D over E with respect to anthropometric outcomes. PROSPERO CRD42013003906.


Low-picomolar, label-free procalcitonin analytical detection with an electrolyte-gated organic field-effect transistor based electronic immunosensor.
Herein a label-free immunosensor based on electrolyte-gated organic field-effect transistor (EGOFET) was developed for the detection of procalcitonin (PCT), a sepsis marker. Antibodies specific to PCT were immobilized on the poly-3-hexylthiophene (P3HT) organic semiconductor surface through direct physical adsorption followed by a post-treatment with bovine serum albumin (BSA) which served as the blocking agent to prevent non-specific adsorption. Antibodies together with BSA (forming the whole biorecognition layer) served to selectively capture the procalcitonin target analyte. The entire immunosensor fabrication process was fast, requiring overall 45min to be completed before analyte sensing. The EGOFET immunosensor showed excellent electrical properties, comparable to those of bare P3HT based EGOFET confirming reliable biosensing with bio-functional EGOFET immunosensor. The detection limit of the immunosensor was as low as 2.2pM and within a range of clinical relevance. The relative standard deviation of the individual calibration data points, measured on immunosensors fabricated on different chips (reproducibility error) was below 7%. The developed immunosensor showed high selectivity to the PCT analyte which was evident through control experiments. This report of PCT detection is first of its kind among the electronic sensors based on EGOFETs. The developed sensor is versatile and compatible with low-cost fabrication techniques.


Economic analysis of two structured treatment and teaching programs on asthma.
The aims of the present study were as follows: 1) to evaluate the medical outcomes of two treatment and educational asthma programs 2) to determine by cost-analysis both cost and economic outcome of the programs 3) to perform a cost-benefit analysis (determining the net cost-benefit) and a cost-effectiveness analysis (determining the cost per unit of effect and the incremental cost-effectiveness ratio) from the perspective of health program policy makers (HPP; indirect costs, i.e., loss of productivity, excluded) and of society as a whole (SaW, all costs included). Patients were randomly assigned to a complete (CP; n = 32) or reduced (RP; n = 33) program: the RP group received a reduced education (self-reading of an educational booklet on asthma), while the CP group attended an "asthma school", consisting of six lessons based on the same booklet and including educational videotapes. Both programs included peak-flow monitoring and treatment according to international guidelines, and follow-up. The outcome variables (asthma attacks, urgent medical examinations, admission days, working days lost) did not differ significantly between CP and RP. Morbidity savings were $1894.70 (CP) and $1697.80 (RP) according to SaW, and $1349.50 and $1301.80, respectively, according to HPP. The net cost-benefit was $1181.50 for CP and $1028.00 for RP, and the cost-benefit ratio per dollar spent was 1:2.6 for CP and 1:2.5 for RP, according to SaW. One day of admission prevented had a cost of $110.20 (CP) and $94.10 (RP). CP gave slightly better results and was slightly more cost-effective than RP in improving patients' welfare. It cannot be excluded that the retrospective analysis used to determine baseline costs might have inflated differences for both groups. Sensitivity analysis was slightly in favor of RP when the outcome variables were tested at their upper and lower 95% CI.


An empirical test of the relative validity of expert and lay judgments of risk.
This article investigates how accurately experts (underwriters) and lay persons (university students) judge the risks posed by life-threatening events Only one prior study (Slovic, Fischhoff, & Lichtenstein, 1985) has previously investigated the veracity of expert versus lay judgments of the magnitude of risk. In that study, a heterogeneous grouping of 15 experts was found to judge, using marginal estimations, a variety of risks as closer to the true annual frequencies of death than convenience samples of the lay population. In this study, we use a larger, homogenous sample of experts performing an ecologically valid task. We also ask our respondents to assess frequencies and relative frequencies directly, rather than ask for a "risk" estimate--a response mode subject to possible qualitative attributions-as was done in the Slovic et al. study. Although we find that the experts outperformed lay persons on a number of measures, the differences are small, and both groups showed similar global biases in terms of: (1) overestimating the likelihood of dying from a condition (marginal probability) and of dying from a condition given that it happens to you (conditional probability), and (2) underestimating the ratios of marginal and conditional likelihoods between pairs of potentially lethal events. In spite of these scaling problems, both groups showed quite good performance in ordering the lethal events in terms of marginal and conditional likelihoods. We discuss the nature of expertise using a framework developed by Bolger and Wright (1994), and consider whether the commonsense assumption of the superiority of expert risk assessors in making magnitude judgments of risk is, in fact, sensible.


Vestibular Schwannoma and Ipsilateral Endolymphatic Hydrops: An Unusual Association.
Vestibular schwannoma and endolymphatic hydrops are two conditions that may present with similar audio-vestibular symptoms. The association of the two in the same patient represents an unusual finding that may lead clinicians to errors and delays in diagnosis and clinical management of affected subjects. We discuss the case of a patient with an intrameatal vestibular schwannoma reporting symptoms suggestive for ipsilateral endolymphatic hydrops. The patient presented with fluctuating hearing loss, tinnitus, and acute rotatory vertigo episodes, and underwent a full audiological evaluation and imaging of the brain with contrast-enhanced Magnetic Resonance Imaging. Clinical audio-vestibular and radiological examination confirmed the presence of coexisting vestibular schwannoma and endolymphatic hydrops. Hydrops was treated pharmacologically; vestibular schwannoma was monitored over time with a wait and scan protocol through conventional MRI. The association of vestibular schwannoma and endolymphatic hydrops is rare, but represents a possible finding in clinical practice. It is therefore recommended investigating the presence of inner ear disorders in patients with vestibular schwannoma and, similarly, to exclude the presence of this condition in patients with symptoms typical of inner ear disorders.


A Pilot retrospective analysis of alpha-blockers on recurrence in men with localised prostate cancer treated with radiotherapy.
While alpha-blockers are commonly used to reduce lower urinary tract symptoms in prostate cancer patients receiving radiotherapy, their impact on response to radiotherapy remains unknown. Therefore, this pilot study aimed to retrospectively determine if alpha-blockers use, influenced response to radiotherapy for localised prostate cancer. In total, 303 prostate cancer patients were included, consisting of 84 control (alpha-blocker naïve), 72 tamsulosin and 147 prazosin patients. The main outcomes measured were relapse rates (%), time to biochemical relapse (months) and PSA velocity (ng/mL/year). Recurrence free survival was calculated using Kaplan-Meier analysis. Prazosin significantly reduced biochemical relapse at both two and five-years (2.72%, 8.84%) compared to control (22.61%, 34.52%). Recurrence free survival was also significantly higher in the prazosin group. This remained after multivariable analysis (HR: 0.09, 95% CI: 0.04-0.26, p < 0.001). Patients receiving prazosin had a 3.9 times lower relative risk of biochemical relapse compared to control. Although not statistically significant, tamsulosin and prazosin extended recurrence free survival by 13.15 and 9.21 months respectively. We show for the first time that prazosin may reduce risk of prostate cancer recurrence and delay time to biochemical relapse and provides justification for prospective studies to examine its potential as an adjunct treatment option for localised prostate cancer.


Survival for patients with single and multiple primary melanomas: the genes, environment, and melanoma study.
Little is known about survival after a diagnosis of a second or higher-order (multiple) primary melanoma, and no study has explored survival in a population-based sample that included patients with single primary melanomas (SPMs) and multiple primary melanomas (MPMs) of any stage. Because people with a first primary melanoma are known to have an increased risk of being diagnosed with another, evidence for prognosis is needed. To determine whether survival after diagnosis was better in patients with MPMs than with SPMs, as suggested in a recent study. DESIGN Survival analysis with median follow-up of 7.6 (range, 0.4-10.6) years. The Genes, Environment, and Melanoma Study enrolled incident cases of melanoma from population-based cancer registries in Australia, Canada, Italy, and the United States. Multiple primary melanomas were ascertained during a longer period than SPM. Two thousand three hundred seventy-two patients with SPM and 1206 with MPM. Diagnosis with melanoma. Melanoma-specific fatality hazard ratios (HR) and 95% confidence intervals associated with clinical and pathological characteristics of SPM, MPM, and both in Cox proportional hazards regression models. Melanoma thickness was the main determinant of fatality (HR for >4 mm, 7.68 [95% CI, 4.46-13.23]); other independent predictors were ulceration, mitoses, and scalp location. After adjustment for these other predictors, we found little difference in fatality between MPM and SPM (HR for MPM relative to SPM, 1.24 [95% CI, 0.91-1.69; P = .18]). Thicker SPM, however, had higher fatality (HR for >4 mm, 13.56 [95% CI, 6.47-28.40]) than thicker MPM (2.93 [1.17-7.30]). Although overall fatalities due to SPM and MPM were similar, relative fatality for thicker SPM was greater than that for thicker MPM. This finding may offer support for a difference in outcome between patients with SPM and MPM related to factors other than closer surveillance and earlier diagnosis. The better outcomes are worth further exploration.


Autologous HIV-1 clade-B Nef peptides elicit increased frequency, breadth and function of CD8+ T-cells compared to consensus peptides.
To determine the function and phenotype of CD8(+) T-cells targeting consensus and autologous sequences of entire HIV-1 Nef protein. Multiparameter flow cytometry-based analysis was used to evaluate the responses of two treatment naïve HIV-infected individuals, during primary and the chronic phases of infection. A greater breadth and magnitude of CD8 IFN-γ responses to autologous compared to clade-B consensus peptides was observed in both subjects. Cross recognition between autologous and consensus peptides decreased in both subjects during progression from primary to chronic infection. The frequencies of TEMRA and TEM CD8(+) T-cells targeting autologous peptides were higher than those targeting consensus peptides and were more polyfunctional (IFN-γ(+) Gr-B(+) CD107a(+)). Our data indicate superior sensitivity and specificity of autologous peptides. The functional and maturational aspects of "real" versus "cross-recognized" responses were also found to differ, highlighting the importance of a sequence-specific approach towards understanding HIV immune response.


The role of soil microbes in the global carbon cycle: tracking the below-ground microbial processing of plant-derived carbon for manipulating carbon dynamics in agricultural systems.
It is well known that atmospheric concentrations of carbon dioxide (CO2) (and other greenhouse gases) have increased markedly as a result of human activity since the industrial revolution. It is perhaps less appreciated that natural and managed soils are an important source and sink for atmospheric CO2 and that, primarily as a result of the activities of soil microorganisms, there is a soil-derived respiratory flux of CO2 to the atmosphere that overshadows by tenfold the annual CO2 flux from fossil fuel emissions. Therefore small changes in the soil carbon cycle could have large impacts on atmospheric CO2 concentrations. Here we discuss the role of soil microbes in the global carbon cycle and review the main methods that have been used to identify the microorganisms responsible for the processing of plant photosynthetic carbon inputs to soil. We discuss whether application of these techniques can provide the information required to underpin the management of agro-ecosystems for carbon sequestration and increased agricultural sustainability. We conclude that, although crucial in enabling the identification of plant-derived carbon-utilising microbes, current technologies lack the high-throughput ability to quantitatively apportion carbon use by phylogentic groups and its use efficiency and destination within the microbial metabolome. It is this information that is required to inform rational manipulation of the plant-soil system to favour organisms or physiologies most important for promoting soil carbon storage in agricultural soil.


Emergency Laparoscopic Sigmoidectomy for Perforated Diverticulitis with Generalised Peritonitis: A Systematic Review.
Laparoscopic sigmoidectomy for diverticulitis has initially been confined to the elective setting. However, open acute sigmoidectomy for perforated diverticulitis is associated with high morbidity rates that might be reduced after laparoscopic surgery. The aim of this systematic review was to assess the feasibility of emergency laparoscopic sigmoidectomy for perforated diverticulitis. We performed a systematic search of PubMed, EMBASE and CENTRAL. All studies reporting on patients with perforated diverticulitis (Hinchey III-IV) treated by laparoscopic sigmoidectomy in the acute phase were included, regardless of design. We included 4 case series and one cohort study (total of 104 patients) out of 1,706 references. Hartmann's procedure (HP) was performed in 84 patients and primary anastomosis in 20. The mean operating time varied between 115 and 200 min. The conversion rate varied from 0 to 19%. The mean length of hospital stay ranged between 6 and 16 days. Surgical re-intervention was necessary in 2 patients. In 20 patients operated upon without defunctioning ileostomy, no anastomotic leakage was reported. Three patients died during the postoperative period. Stoma reversal after HP was performed in 60 out of 79 evaluable patients (76%). Acute laparoscopic sigmoidectomy for the treatment of perforated diverticulitis is feasible in selected patients provided they are handled by experienced hands.


Annual replication is essential in evaluating the response of the soil microbiome to the genetic modification of maize in different biogeographical regions.
The importance of geographic location and annual variation on the detection of differences in the rhizomicrobiome caused by the genetic modification of maize (Bt-maize, event MON810) was evaluated at experimental field sites across Europe including Sweden, Denmark, Slovakia and Spain. DNA of the rhizomicrobiome was collected at the maize flowering stage in three consecutive years and analyzed for the abundance and diversity of PCR-amplified structural genes of Bacteria, Archaea and Fungi, and functional genes for bacterial nitrite reductases (nirS, nirK). The nirK genes were always more abundant than nirS. Maize MON810 did not significantly alter the abundance of any microbial genetic marker, except for sporadically detected differences at individual sites and years. In contrast, annual variation between sites was often significant and variable depending on the targeted markers. Distinct, site-specific microbial communities were detected but the sites in Denmark and Sweden were similar to each other. A significant effect of the genetic modification of the plant on the community structure in the rhizosphere was detected among the nirK denitrifiers at the Slovakian site in only one year. However, most nirK sequences with opposite response were from the same or related source organisms suggesting that the transient differences in community structure did not translate to the functional level. Our results show a lack of effect of the genetic modification of maize on the rhizosphere microbiome that would be stable and consistent over multiple years. This demonstrates the importance of considering annual variability in assessing environmental effects of genetically modified crops.


Incidence of hydrocephalus in traumatic brain injury: A nationwide population-based cohort study.
The aim of this study was to investigate the risk and peak time of post-traumatic hydrocephalus (PTH) in traumatic brain injury (TBI) patients with traumatic subarachnoid hemorrhage (SAH), compared to TBI patients without traumatic SAH. In this retrospective population-based cohort study, the data was extracted from Longitudinal Health Insurance Database from 2000 to 2010 in Taiwan. A total of 23,775 TBI patients who had a first event TBI during 2000 to 2010 were included and divided into TBI with SAH (TBI-S) group and TBI without SAH (TBI-NS) group. We focused on analyzing the PTH in both groups within 2 years after brain injury. Competing risk regression models were performed to assess the risk of developing PTH in the TBI-S group compared to the TBI-NS group. Comparing to the TBI-NS group, there was a significantly higher cumulative incidence of PTH in the TBI-S group during the 2-year follow-up period. The adjusted hazard ratio (HR) of PTH in TBI-S group within 2 years was between 2.90-3.47, and the highest estimates were obtained within 6 months after injury (HR = 3.47, 95% CI: 2.43-4.94). The occurrence percentage of PTH was highest during 0-3rd month follow-up periods (1.95% in TBI-S group; 0.48% in TBI-NS group). The peak time of PTH occurrence was noted during 0-3rd month post brain injury. Traumatic SAH patients had an approximate 3-fold risk of developing PTH, comparing to TBI patients without traumatic SAH.


Detection of the A302S Rdl mutation in fipronil bait-selected strains of the German cockroach (Dictyoptera: Blattellidae).
Extensive usage and heavy reliance on insecticides have led to the development of insecticide resistance in the German cockroach, Blattella germanica (L.). Six field-collected strains of B. germanica from Singapore were used to investigate resistance to fipronil and dieldrin. The three strains (Boat Quay, Cavenagh Road, and Ghimmoh Road) with greatest resistance to fipronil were subjected to selection with fipronil bait up to the F5 generation. Synergism assay and molecular detection of a target site mutation were used to elucidate the mechanism of fipronil resistance in these strains. With the exception of the Cavenagh Road strain, all parental strains were susceptible to dieldrin. This strain exhibited resistance to dieldrin and fipronil with resistance ratios of 4.1 and 3.0, respectively. Piperonyl butoxide and S,S,S-tributylphosphorotrithioate were antagonistic toward fipronil toxicity in all strains. Bait selection significantly increased fipronil and dieldrin resistance in the three chosen strains, either in topical bioassay or bait evaluations. There was a significant positive relationship [y = (6,852.69 +/- 1,988.37) x - (708.93 +/- 1,226.28), where x = fipronil toxicity and y = dieldrin toxicity] between dieldrin and fipronil resistance levels, indicating significant cross-resistance between the insecticides. High frequencies of individuals possessing the Rdl gene mutation were found in the F5 generation of the three strains selected with fipronil bait. The synergism assays indicated that monooxygenase and esterase were not involved in fipronil resistance in the strains studied herein. The A302S Rdl mutation was the major mechanism contributing to fipronil and dieldrin resistance in these strains.


Mathematical model of intimal thickening in atherosclerosis: vessel stenosis as a free boundary problem.
Atherosclerosis is an inflammatory disease of the artery characterized by an expansion of the intimal region. Intimal thickening is usually attributed to the migration of smooth muscle cells (SMCs) from the surrounding media and proliferation of SMCs already present in the intima. Intimal expansion can give rise to dangerous events such as stenosis (leading to stroke) or plaque rupture (leading to myocardial infarction). In this paper we propose and study a mathematical model of intimal thickening, posed as a free boundary problem. Intimal thickening is driven by damage to the endothelium, resulting in the release of cytokines and migration of SMCs. By coupling a boundary value problem for cytokine concentration to an evolution law for the intimal area, we reduce the problem to a single nonlinear differential equation for the luminal radius. We analyze the steady states, perform a bifurcation analysis and compare model solutions to data from rabbits whose iliac arteries are subject to a balloon pullback injury. In order to obtain a favorable fit, we find that migrating SMCs must enter the intima very slowly compared to cells in dermal wounds. This cell behavior is indicative of a weak inflammatory response which is consistent with atherosclerosis being a chronic inflammatory disease.


A Comparative Evaluation of Time-dependent Changes on the Surface Hardness of Bulk Cure Composites: An in vitro Study.
The objective of this in vitro study was to assess the surface hardness through Vickers hardness (VH) test of one conventional hybrid resin composites (Filtek Z350), compared with that of two bulk cure resin composites (SDR™, Tetric N Ceram®). Twenty specimens of each material were prepared in cylindrical aluminum molds with an internal diameter of 5 mm and depth of 4 mm, 10 (incremental curing) and 10 (bulk curing).The surface of each specimen was covered with a transparent plastic matrix strip before light curing with conventional visible light for 40 seconds. The specimens thus obtained were stored in deionized water and transferred to an incubator at 37°C for 24 hours to simulate clinical conditions. After 24 hours, the microhardness of each specimen was measured using a Vickers indenter, with a load of 100 gm and dwell time of 15 seconds (HV 0.2/40).The specimens were further subjected to VH test in an interval of 7, 30, and 90 days. The data were subjected to statistical analysis-Student's t test, analysis of variance, and post hoc Tukey's test. The present study showed that SDR™ in bulk curing showed consistently greater value of hardness and was comparable to traditional incremental cured Filtek Z350, highlighting the advantages of the new SDR technology.How to cite this article: Sarma A, Nagar P. A Comparative Evaluation of Time-dependent Changes on the Surface Hardness of Bulk Cure Composites: An in vitro Study. Int J Clin Pediatr Dent 2018;11(3):183-187.


Effect of hospital follow-up appointment on clinical event outcomes and mortality.
Decreasing hospital readmission and patient mortality after hospital dismissal is important when providing quality health care. Interventions recently proposed by the Centers for Medicare and Medicaid Services to reduce avoidable hospital readmissions include providing patients with clear discharge instructions and appointments for timely follow-up visits. Although research has demonstrated a correlation between follow-up arrangements and reduced hospital readmission in specific patient populations, the effect of hospital follow-up in general medicine patients has not been assessed. For this study, we reviewed hospital dismissal instructions for general medicine patients dismissed in 2006 from Mayo Clinic hospitals in Rochester, Minnesota (n = 4989), and determined whether specific appointment details for follow-up were documented. Survival analysis and propensity score-adjusted proportional hazards regression models were developed to investigate the association of follow-up appointment arrangements with hospital readmission, emergency department visits, and mortality at 30 and 180 days after discharge. Of the 4989 dismissal summaries, 3037 (60.9%) contained instructions for a follow-up appointment. No difference was found between those with a documented follow-up appointment vs those without regarding hospital readmission, emergency department visits, or mortality 30 days after dismissal. However, those with a documented follow-up appointment were slightly more likely to have an adverse event (hospital readmission, emergency department visit, or death) within 180 days after dismissal. Improved discharge processes, including arrangement of hospital follow-up appointments, do not appear to improve readmission rates or survival in general medicine patients. Therefore, national efforts to ensure follow-up for all patients after hospital dismissal may not be beneficial or cost-effective.


Time-locked association between rapid cerebral blood flow modulation and attentional performance.
The study investigated relationships between rapid cerebral hemodynamic modulation and attentional performance. Based on former results on complex cognitive functioning, a specific association between the first seconds of the hemodynamic response and performance was hypothesized. Using transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 48 healthy subjects. The applied task comprised motor reactions on a visual stimulus which was preceded by an acoustic warning signal (interstimulus interval 5s). Task-induced hemodynamic changes were assessed second-by-second, and related to reaction time using analysis of variance and linear regression. A right dominant blood flow response was observed. Flow velocity increase in the middle fraction of the interstimulus interval, i.e. seconds 2 and 3 after the cuing signal, significantly correlated with reaction time. This was not the case for the very early and late components of the response. The results suggest a time-locked association between cerebral blood flow increase and attentional performance. This is in accordance with neurophysiological studies that revealed the closest relationship between brain perfusion and cortical activity during a similar time window. The study supports the assumption of a specific, relatively early time interval in which relationships between cerebral blood flow and behavior become apparent.


The variation of volatile fatty acid compositions in sewer length, and its effect on the process design of biological nutrient removal.
The potential of enhanced biological phosphorus removal (EBPR) in biological nutrient removal (BNR) systems critically depends on the availability and types of volatile fatty acids (VFAs) in sewage. Although the characteristics of VFAs in sewage are strongly related with the biochemical transformations in the sewer system, they have not been studied thoroughly in terms of BNR process design. We have investigated the characteristics of VFAs in influent of nine sewage treatment plants which represent typical small to very large sewer systems in Korea. We found that influent total VFACOD (VFA as chemical oxygen demand) concentrations ranged from 20.4 to 65.2 mg/L. Acetic acid was a predominant VFA in sewage, and the propionic acid (HPr) portion averaged 38.7% of total VFACOD. However the sewage from longer sewer systems showed more HPr content, indicating that type of VFA varied with the total sewer length. The finding is a particularly important consideration for BNR process design since availability of HPr positively behaved to suppress the unfavorable growth of glycogen-accumulating organisms. The implication of these findings for BNR process design is discussed in this paper.


Assessing the effect of physical differences in the articulation of consonants and vowels on audiovisual temporal perception.
We investigated how the physical differences associated with the articulation of speech affect the temporal aspects of audiovisual speech perception. Video clips of consonants and vowels uttered by three different speakers were presented. The video clips were analyzed using an auditory-visual signal saliency model in order to compare signal saliency and behavioral data. Participants made temporal order judgments (TOJs) regarding which speech-stream (auditory or visual) had been presented first. The sensitivity of participants' TOJs and the point of subjective simultaneity (PSS) were analyzed as a function of the place, manner of articulation, and voicing for consonants, and the height/backness of the tongue and lip-roundedness for vowels. We expected that in the case of the place of articulation and roundedness, where the visual-speech signal is more salient, temporal perception of speech would be modulated by the visual-speech signal. No such effect was expected for the manner of articulation or height. The results demonstrate that for place and manner of articulation, participants' temporal percept was affected (although not always significantly) by highly-salient speech-signals with the visual-signals requiring smaller visual-leads at the PSS. This was not the case when height was evaluated. These findings suggest that in the case of audiovisual speech perception, a highly salient visual-speech signal may lead to higher probabilities regarding the identity of the auditory-signal that modulate the temporal window of multisensory integration of the speech-stimulus.


Immunotherapy of distant metastatic disease.
Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated with significant toxicity and poor efficacy that does not improve overall survival of 96% of patients. Many studies with allogeneic and autologous vaccines have demonstrated no clinical benefit, and some randomised trials even showed a detrimental effect in the vaccine arm. The ongoing effort to develop melanoma vaccines based on dendritic cells and peptides is driven by advances in understanding antigen presentation and processing, and by new techniques of vaccine preparation, stabilisation and delivery. Several agents that have shown promising activity in metastatic melanoma including IL-21 and monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) or CD137 are discussed. Recent advances of intratumour gene transfer technologies and adoptive immunotherapy, which represents a promising although technically challenging direction, are also discussed.


Spider orb webs rely on radial threads to absorb prey kinetic energy.
The kinetic energy of flying insect prey is a formidable challenge for orb-weaving spiders. These spiders construct two-dimensional, round webs from a combination of stiff, strong radial silk and highly elastic, glue-coated capture spirals. Orb webs must first stop the flight of insect prey and then retain those insects long enough to be subdued by the spiders. Consequently, spider silks rank among the toughest known biomaterials. The large number of silk threads composing a web suggests that aerodynamic dissipation may also play an important role in stopping prey. Here, we quantify energy dissipation in orb webs spun by diverse species of spiders using data derived from high-speed videos of web deformation under prey impact. By integrating video data with material testing of silks, we compare the relative contributions of radial silk, the capture spiral and aerodynamic dissipation. Radial silk dominated energy absorption in all webs, with the potential to account for approximately 100 per cent of the work of stopping prey in larger webs. The most generous estimates for the roles of capture spirals and aerodynamic dissipation show that they rarely contribute more than 30 per cent and 10 per cent of the total work of stopping prey, respectively, and then only for smaller orb webs. The reliance of spider orb webs upon internal energy absorption by radial threads for prey capture suggests that the material properties of the capture spirals are largely unconstrained by the selective pressures of stopping prey and can instead evolve freely in response to alternative functional constraints such as adhering to prey.


Quality of End-of-Life Care Provided to Patients With Different Serious Illnesses.
Efforts to improve end-of-life care have focused primarily on patients with cancer. High-quality end-of-life care is also critical for patients with other illnesses. To compare patterns of end-of-life care and family-rated quality of care for patients dying with different serious illnesses. A retrospective cross-sectional study was conducted in all 146 inpatient facilities within the Veteran Affairs health system among patients who died in inpatient facilities between October 1, 2009, and September 30, 2012, with clinical diagnoses categorized as end-stage renal disease (ESRD), cancer, cardiopulmonary failure (congestive heart failure or chronic obstructive pulmonary disease), dementia, frailty, or other conditions. Data analysis was conducted from April 1, 2014, to February 10, 2016. Palliative care consultations, do-not-resuscitate orders, death in inpatient hospices, death in the intensive care unit, and family-reported quality of end-of-life care. Among 57 753 decedents, approximately half of the patients with ESRD, cardiopulmonary failure, or frailty received palliative care consultations (adjusted proportions, 50.4%, 46.7%, and 43.7%, respectively) vs 73.5% of patients with cancer and 61.4% of patients with dementia (P < .001). Approximately one-third of patients with ESRD, cardiopulmonary failure, or frailty (adjusted proportions, 32.3%, 34.1%, and 35.2%, respectively) died in the intensive care unit, more than double the rates among patients with cancer and those with dementia (13.4% and 8.9%, respectively) (P < .001). Rates of excellent quality of end-of-life care reported by 34 005 decedents' families were similar for patients with cancer and those with dementia (adjusted proportions, 59.2% and 59.3%; P = .61), but lower for patients with ESRD, cardiopulmonary failure, or frailty (54.8%, 54.8%, and 53.7%, respectively; all P ≤ .02 vs patients with cancer). This quality advantage was mediated by palliative care consultation, setting of death, and a code status of do-not-resuscitate; adjustment for these variables rendered the association between diagnosis and overall end-of-life care quality nonsignificant. Family-reported quality of end-of-life care was significantly better for patients with cancer and those with dementia than for patients with ESRD, cardiopulmonary failure, or frailty, largely owing to higher rates of palliative care consultation and do-not-resuscitate orders and fewer deaths in the intensive care unit among patients with cancer and those with dementia. Increasing access to palliative care and goals of care discussions that address code status and preferred setting of death, particularly for patients with end-organ failure and frailty, may improve the overall quality of end-of-life care for Americans dying of these illnesses.


Differential arsenic binding in the sediments of two sites in Chile's lower Loa River basin.
Fluvial sediments from two lower Loa River basin sites in northern Chile were compared in order to probe the effects of vegetation and organic matter (OM) on As accumulation in fluvial environments. The two sites were the Sloman dam, which lacks macrophytes and has a low OM content (2.4%) in sediments, and the Quillagua Oasis, which is 23 km downstream from the Sloman site and has a higher OM (6.2%) in sediments and abundant aquatic plant life. The Quillagua site had preferential As enrichment with a co-occurrence pattern that differed from that of the Sloman site, which had a lower As concentration (1528 vs. 262 mg/kg d.w., respectively). At the Quillagua site, As concentration was strongly correlated with Mn and OM (r = 0.91 and 0.85, respectively); while at the Sloman site, As concentration in sediments was significantly correlated with Ca and Sr (r = 0.63 and 0.54, respectively). Sequential extraction analyses showed that the Sloman site had higher percentage of easily exchangeable As within the surface sediment (12%, 45 mg/kg d.w.) compared with the Quillagua site (3%, 40 mg/kg d.w.). These contrasting results suggest that both vegetation and OM control the immobilization and accumulation of As in the arid Loa River basin.


Reorienting risk to resilience: street-involved youth perspectives on preventing the transition to injection drug use.
The Youth Injection Prevention (YIP) project aimed to identify factors associated with the prevention of transitioning to injection drug use (IDU) among street-involved youth (youth who had spent at least 3 consecutive nights without a fixed address or without their parents/caregivers in the previous six months) aged 16-24 years in Metro Vancouver, British Columbia. Ten focus groups were conducted by youth collaborators (peer-researchers) with street-involved youth (n = 47) from November 2009-April 2010. Audio recordings and focus group observational notes were transcribed verbatim and emergent themes identified by open coding and categorizing. Through ongoing data analysis we identified that youth produced risk and deficiency rather than resiliency-based answers. This enabled the questioning guide to be reframed into a strengths-based guide in a timely manner. Factors youth identified that prevented them from IDU initiation were grouped into three domains loosely derived from the risk environment framework: Individual (fear and self-worth), Social Environment (stigma and group norms - including street-entrenched adults who actively discouraged youth from IDU, support/inclusion, family/friend drug use and responsibilities), and Physical/Economic Environment (safe/engaging spaces). Engaging youth collaborators in the research ensured relevance and validity of the study. Participants emphasized having personal goals and ties to social networks, supportive family and role models, and the need for safe and stable housing as key to resiliency. Gaining the perspectives of street-involved youth on factors that prevent IDU provides a complementary perspective to risk-based studies and encourages strength-based approaches for coaching and care of at-risk youth and upon which prevention programs should be built.


Laboratory-scale membrane up-concentration and co-anaerobic digestion for energy recovery from sewage and kitchen waste.
This study assessed an alternative concept for co-treatment of sewage and organic kitchen waste in Vietnam. The goal was to apply direct membrane filtration for sewage treatment to generate a permeate that is suitable for discharge. The obtained chemical oxygen demand (COD) concentrations in the permeate of ultrafiltration tests were indeed under the limit value (50 mg/L) of the local municipal discharge standards. The COD of the concentrate was 5.4 times higher than that of the initial feed. These concentrated organics were then co-digested with organic kitchen wastes at an organic loading rate of 2.0 kg VS/m(3).d. The volumetric biogas production of the digester was 1.94 ± 0.34 m(3)/m(3).d. The recovered carbon, in terms of methane gas, accounted for 50% of the total carbon input of the integrated system. Consequently, an electrical production of 64 Wh/capita/d can be obtained when applying the proposed technology with the current wastes generated in Ho Chi Minh City. Thus, it is an approach with great potential in terms of energy recovery and waste treatment.


The Use of the Immune Epitope Database to Study Autoimmune Epitope Data Related to Alopecia Areata.
The Immune Epitope Database (IEDB) is a repository of published epitope data for infectious diseases, allergy, transplantation and autoimmunity. Herein we provide an introduction to the IEDB search interface, focusing on data related to autoimmune diseases, including alopecia areata (AA). We demonstrate how common questions related can be answered, such as how to search for specific autoantigens, epitope sequences, response types (B- and/or T-cell assays), or host, as well as how to search for epitopes of known major histocompatibility complex restriction and for data related to a specific disease. Our survey of the data found that while as a whole Autoimmunity-specific records represent a significant portion (∼30%); epitopes reported for AA are remarkably few, just 23 epitopes from six antigens. This reveals a significant knowledge gap for AA, and suggests that additional mapping of epitopes and identification of novel AA-associated autoantigens is warranted. Citing recently published examples, we show how bioinformatic, proteomic, and technological advances make it now increasingly feasible to identify epitopes and novel antigens in human disease. The goal herein was to increase awareness of the IEDB as a free resource for the scientific community and to demonstrate its use in finding (existing) and analyzing (prediction) epitope data.


E-cadherin expression in intestinal epithelium.
To investigate E-cadherin expression in normal and inflamed intestine, in the colonic adenocarcinoma cell line HT29, in normal fetal intestine, and in a fetal gut organ culture model where a T cell mediated enteropathy can be generated; to determine whether expression of E-cadherin changes in intestinal inflammation. Immunohistochemistry was used to determine E-cadherin expression in following tissues: frozen and paraffin wax sections of normal and inflamed intestine; HT29 colonic adenocarcinoma cell line cultured on coverslips in the presence or absence of cytokines; frozen sections of fetal small intestinal tissue (gestational age 11-22 weeks); and frozen sections of cultured fetal gut in which a T cell mediated enteropathy had been induced. E-cadherin was strongly and evenly expressed by the epithelium in all specimens of intestine studied. Although there was no change in inflammation generally, in some cases of Crohn's disease groups of glands with the characteristic morphology of "ulcer associated cell lineage" showed lower expression of E-cadherin. In fetal gut organ cultures epithelial expression of E-cadherin was lower when local T cells were activated with mitogens, compared with control explants. By contrast, the HT29 cell line showed low levels of expression which increased after treatment with conditioned medium from activated tonsil cells. E-cadherin is strongly and evenly expressed by epithelium in normal and inflamed intestine, although an increase in E-cadherin expression in cytokine treated HT29 cells was observed. E-cadherin expression is reduced in the epithelium adjacent to ulcers (ulcer associated cell lineage), possibly to assist regeneration.


Physical fitness normative values for 6-18-year-old Greek boys and girls, using the empirical distribution and the lambda, mu, and sigma statistical method.
The aim of the this study was to establish age- and gender-specific physical fitness normative values and to compare percentiles and Z scores values in a large, nationwide sample of Greek children aged 6-18 years. From March 2014 to May 2014, a total of 424,328 boys and girls aged 6-18 years who attended school in Greece were enrolled. The studied sample was representative, in terms of age-sex distribution and geographical region. Physical fitness tests (i.e. 20 m shuttle run test (SRT), standing long jump, sit and reach, sit-ups, and 10 × 5 m SRT) were performed and used to calculate normative values, using the percentiles of the empirical distributions and the lambda, mu, and sigma statistical method. Normative values were presented as tabulated percentiles for five health-related fitness tests based on a large data set comprising 424,328 test performances. Boys typically scored higher than girls on cardiovascular endurance, muscular strength, muscular endurance, and speed/agility, but lower on flexibility (all p values <0.001). Older boys and girls had better performances than younger ones (p < 0.001). Physical fitness tests' performances tended to peak at around the age of 15 years in both sexes. The presented population-based data are the most up-to-date sex- and age-values for the health-related fitness of children and adolescents in Greece and can be used as standard values for fitness screening and surveillance systems and for comparisons among the same health-related fitness scores of children from other countries similar to Greece. Schools need to make efforts to improve the fitness level of the schoolchildren through the physical education curriculum to prevent cardiovascular risk.


The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria: report from the EUCAST Subcommittee.
Whole genome sequencing (WGS) offers the potential to predict antimicrobial susceptibility from a single assay. The European Committee on Antimicrobial Susceptibility Testing established a subcommittee to review the current development status of WGS for bacterial antimicrobial susceptibility testing (AST). The published evidence for using WGS as a tool to infer antimicrobial susceptibility accurately is currently either poor or non-existent and the evidence / knowledge base requires significant expansion. The primary comparators for assessing genotypic-phenotypic concordance from WGS data should be changed to epidemiological cut-off values in order to improve differentiation of wild-type from non-wild-type isolates (harbouring an acquired resistance). Clinical breakpoints should be a secondary comparator. This assessment will reveal whether genetic predictions could also be used to guide clinical decision making. Internationally agreed principles and quality control (QC) metrics will facilitate early harmonization of analytical approaches and interpretive criteria for WGS-based predictive AST. Only data sets that pass agreed QC metrics should be used in AST predictions. Minimum performance standards should exist and comparative accuracies across different WGS laboratories and processes should be measured. To facilitate comparisons, a single public database of all known resistance loci should be established, regularly updated and strictly curated using minimum standards for the inclusion of resistance loci. For most bacterial species the major limitations to widespread adoption for WGS-based AST in clinical laboratories remain the current high-cost and limited speed of inferring antimicrobial susceptibility from WGS data as well as the dependency on previous culture because analysis directly on specimens remains challenging. For most bacterial species there is currently insufficient evidence to support the use of WGS-inferred AST to guide clinical decision making. WGS-AST should be a funding priority if it is to become a rival to phenotypic AST. This report will be updated as the available evidence increases.


Factors Associated with the Development, Progression, and Outcome of Dupuytren Disease Treatment: A Systematic Review.
The factors typically considered to be associated with Dupuytren disease have been described, such as those in the "Dupuytren diathesis." However, the quality of studies describing them has not been appraised. This systematic review aimed to analyze the evidence for all factors investigated for potential association with the development, progression, outcome of treatment, or recurrence of Dupuytren disease. A systematic review of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Cumulative Index to Nursing and Allied Health Literature databases was conducted using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant methodology up to September of 2019. Articles were screened in duplicate. Prognostic studies were quality assessed using the Quality in Prognosis Study tool. This study identified 2301 records; 51 met full inclusion criteria reporting data related to 54,491 patients with Dupuytren disease. In total, 46 candidate factors associated with the development of Dupuytren disease were identified. There was inconsistent evidence between the association of Dupuytren disease and the presence of "classic" diathesis factors. The quality of included studies varied, and the generalizability of studies was low. There was little evidence describing the factors associated with functional outcome. This systematic review challenges conventional notions of diathesis factors. Traditional diathesis factors are associated with disease development and recurrence, although they are not significantly associated with poor outcome following intervention based on the current evidence.


Hypospadias repair with onlay preputial graft: a 25-year experience with long-term follow-up.
To evaluate the long-term outcomes of hypospadias repair using an onlay preputial graft. Patient records from 1989 to 2013 were retrospectively reviewed. One surgeon performed all cases and surgical technique was the same for all patients. There were 62 patients in the cohort, with a mean (range) follow-up of 47.4 (1-185) months. The meatal location was separated into distal (one patient), midshaft (19) and proximal (42). In all, 22 (35.5%) patients had complications. There were three main types of complications, including meatal stenosis in three (4.8%), stricture in three (4.8%), and fistula in 21 (33.9%). The mean (range) timing of presentation with a complication after surgery was 24.9 (1-127) months. In all, 54.5% of the patients with complications presented at ≥1 year after the initial surgery and 31.8% presented at ≥3 years. On univariable analysis age at the time of surgery, length of the graft, presence of chordee or meatal location (proximal or midshaft) did not predict a complication. The width of the graft was associated with a complication, with each 1 mm increase in width decreasing the odds of a complication by 56%. On multivariable analysis width remained statistically significant (odds ratio 0.44, 95% confidence interval 0.230-0.840; P = 0.013) for predicting a complication. Hypospadias repair with onlay preputial graft is an option for single-stage repair, especially in cases of proximal hypospadias or where the urethral plate width and/or the glanular groove is insufficient for other types of repair. Compared with flaps, the use of grafts may decrease the risk of penile torsion and prevent less bulk around the urethra, improving skin and glans closure.


Prevalence and associations of steep cornea/keratoconus in Greater Beijing. The Beijing Eye Study.
To evaluate the prevalence and associated factors of steep cornea/keratoconus in the adult Chinese population. The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50-93 years). A detailed ophthalmic examination was performed including optical low-coherence reflectometry. Steep cornea/keratoconus were defined as an anterior corneal refractive power exceeding 48 diopters. Mean refractive power of the cornea was 43.16±1.45 diopters (range: 36.51 to 48.46 diopters; flattest meridian) and 43.98±1.52 diopters (range: 37.00 to 52.88 diopters; steepest meridian). A steep cornea/keratoconus defined as corneal refractive power of ≥48 diopters and ≥49 diopters was detected in 27 subjects (prevalence rate: 0.9±0.2%) and 6 (0.2± 0.1%) subjects, respectively. Presence of steep cornea/keratoconus was associated with shorter axial length (P<0.001), smaller interpupillary distance (P = 0.038), lower best corrected visual acuity (P = 0.021), higher cylindrical refractive error (P<0.001) and more myopic refractive error (P<0.001). It was not significantly associated with gender, body height, psychic depression, cognitive function, blood concentrations of glucose, lipids, creatinine and C-reactive protein, blood pressure and quality of life score, nor with intraocular pressure, dry eye feeling, and lens thickness. A steep cornea/keratoconus defined as corneal refractive power of 48+ diopters has a prevalence of 0.9±0.2% among Chinese aged 50 years and above. Its prevalence was significantly associated with the ocular parameters of shorter axial length, smaller interpupillary distance, higher cylindrical and myopic refractive error and lower best corrected visual acuity, however, with none of the systemic parameters tested.


Activation of ENaC by AVP contributes to the urinary concentrating mechanism and dilution of plasma.
Arginine vasopressin (AVP) activates the epithelial Na(+) channel (ENaC). The physiological significance of this activation is unknown. The present study tested if activation of ENaC contributes to AVP-sensitive urinary concentration. Consumption of a 3% NaCl solution induced hypernatremia and plasma hypertonicity in mice. Plasma AVP concentration and urine osmolality increased in hypernatremic mice in an attempt to compensate for increases in plasma tonicity. ENaC activity was elevated in mice that consumed 3% NaCl solution compared with mice that consumed a diet enriched in Na(+) with ad libitum tap water; the latter diet does not cause hypernatremia. To determine whether the increase in ENaC activity in mice that consumed 3% NaCl solution served to compensate for hypernatremia, mice were treated with the ENaC inhibitor benzamil. Coadministration of benzamil with 3% NaCl solution decreased urinary osmolality and increased urine flow so that urinary Na(+) excretion increased with no effect on urinary Na(+) concentration. This decrease in urinary concentration further increased plasma Na(+) concentration, osmolality, and AVP concentration in these already hypernatremic mice. Benzamil similarly compromised urinary concentration in water-deprived mice and in mice treated with desmopressin. These results demonstrate that stimulation of ENaC by AVP plays a critical role in water homeostasis by facilitating urinary concentration, which can compensate for hypernatremia or exacerbate hyponatremia. The present findings are consistent with ENaC in addition to serving as a final effector of the renin-angiotensin-aldosterone system and blood pressure homeostasis, also playing a key role in water homeostasis by regulating urine concentration and dilution of plasma.


Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway.
Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER) pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC), a surrogate for tobacco smoke, on the NER pathway in two different human lung cell lines; IMR-90 lung fibroblasts and BEAS-2B bronchial epithelial cells. To measure NER, we employed a slot-blot assay to quantify the introduction and removal of UV light-induced 6-4 photoproducts and cyclobutane pyrimidine dimers. We find a dose-dependent inhibition of 6-4 photoproduct repair in both cell lines treated with CSC. Additionally, the impact of CSC on the abundance of various NER proteins and their respective RNAs was investigated. The abundance of XPC protein, which is required for functional NER, is significantly reduced by treatment with CSC while the abundance of XPA protein, also required for NER, is unaffected. Both XPC and XPA RNA levels are modestly reduced by CSC treatment. Finally, treatment of cells with MG-132 abrogates the reduction in the abundance of XPC protein produced by treatment with CSC, suggesting that CSC enhances proteasome-dependent turnover of the protein that is mediated by ubiquitination. Together, these findings indicate that tobacco smoke can inhibit the same DNA repair pathway that is also essential for the removal of some of the carcinogenic DNA damage introduced by smoke itself, increasing the DNA damage burden of cells exposed to tobacco smoke.


Entrapment of a looped/kinked catheter in the brachial artery and its successful retrieval during transradial coronary catheterization.
Transradial access for cardiac catheterization is widely accepted as a safe and viable approach with markedly decreased incidence of major accessrelated complications compared to the transfemoral approach. Minor catheter looping or kinking during catheter manipulation is common and can be managed with gentle rotation, and thus goes unnoticed without complications. Rarely, this looped/kinked catheter can get entrapped and require an invasive approach for retrieval. To our knowledge, there is only one such case described for the transradial approach, where the authors had to use a 6 Fr Amplatz gooseneck snare kit via right femoral approach to remove the entrapped catheter. We present a case of entrapped looped/kinked 5 Fr catheter during transradial catheterization in the brachial artery and describe a novel approach of removing this entrapped catheter through the same radial access without any complications.


Validation of point-of-care testing for coeliac disease in children in a tertiary hospital in north India.
Some of the conventional serological tests for coeliac disease (CD) are expensive, time-consuming and not readily available in developing countries, leading to a delay in diagnosis. Recently, point-of-care tests (POCT) have been manufactured and tested in Europe but have not been validated in our setting. We therefore aimed to study the diagnostic accuracy of the POCT 'Biocard' test in diagnosing CD in Indian children. Cross-sectional study. Tertiary care centre in north India. Children, aged 2-18 years, with chronic diarrhoea, short stature or refractory anaemia underwent serological testing for CD with antiendomysial antibodies (AEA), antitissue transglutaminase (tTG) antibodies and Biocard test followed by duodenal biopsy irrespective of serological results. CD was diagnosed with positive AEA and duodenal biopsy showing >grade 2 changes using modified Marsh criteria. Those who were both AEA negative and had normal histology were considered CD negative. Of 319 children who underwent the serological testing, 170 agreed for biopsy. Of these, 110 were diagnosed with CD and 30 were found to be CD negative. Remaining 30 had discordant AEA and histology results and were not included in analysis. Biocard test agreed with 92/110 positive and 27/30 negative diagnoses based on reference tests (83.6% sensitivity and 90% specificity). tTG was found to be 93.8% sensitive and 96.4% specific. We successfully validated the POCT for CD in our setting. It could be used to increase case detection rates in developing countries with a large undiagnosed CD burden.


Differences in national influenza vaccination policies across the European Union, Norway and Iceland 2008-2009.
In 2009 the second cross-sectional web-based survey was undertaken by the Vaccine European New Integrated Collaboration Effort (VENICE) project across 27 European Union (EU) member states (MS), Norway and Iceland (n=29) to determine changes in official national seasonal influenza vaccination policies since a survey undertaken in 2008 and to compare the estimates of vaccination coverage between countries using data obtained from both surveys. Of 27 responding countries, all recommended vaccination against seasonal influenza to the older adult population. Six countries recommended vaccination of children aged between six months and <18 years old. Most countries recommended influenza vaccination for those individuals with chronic medical conditions. Recommendations for vaccination of healthcare workers (HCW) in various settings existed in most, but not all countries. Staff in hospitals and long-term care facilities were recommended vaccination in 23 countries, and staff in out-patient clinics in 22 countries. In the 2009 survey, the reported national estimates on vaccine coverage varied by country and risk group, ranging from 1.1% - 82.6% for the older adult population; to between 32.9% -71.7% for clinical risk groups; and from 13.4% -89.4% for HCW. Many countries that recommend the influenza vaccination do not monitor the coverage in risk groups. In 2008 and 2009 most countries recommended influenza vaccination for the main risk groups. However, despite general consensus and recommendations for vaccination of high risk groups, many countries do not achieve high coverage in these groups. The reported vaccination coverage still needs to be improved in order to achieve EU and World Health Organization goals.


Population characteristics and the distribution of general medical practitioners.
By applying the logic of the Resource Allocation Working Party to the analysis of the distribution of general medical practitioners, the relevant Family Practitioner Committee (FPC) populations were weighted according to known patterns of use related to specific characteristics--namely, age, sex, marital state, and socioeconomic group. Comparative weightings were also calculated using standardised mortality ratios. Adjusting the populations to take account of differential use has relatively little impact on national variations in list sizes but an appreciable effect on particular FPCs, notably East and West Sussex, Dorset, and the Isle of Wight. Inequalities in the distribution of general practitioners are increased considerably, however, if figures taking account of the inflation of list sizes and cross-boundary flows are used. To formulate and monitor policy about the distribution of general practitioners more sensitive measures of population and its likely demand for services must be developed.


A reconfigurable continuous-flow fluidic routing fabric using a modular, scalable primitive.
Microfluidic devices, by definition, are required to move liquids from one physical location to another. Given a finite and frequently fixed set of physical channels to route fluids, a primitive design element that allows reconfigurable routing of that fluid from any of n input ports to any n output ports will dramatically change the paradigms by which these chips are designed and applied. Furthermore, if these elements are "regular" regarding their design, the programming and fabrication of these elements becomes scalable. This paper presents such a design element called a transposer. We illustrate the design, fabrication and operation of a single transposer. We then scale this design to create a programmable fabric towards a general-purpose, reconfigurable microfluidic platform analogous to the Field Programmable Gate Array (FPGA) found in digital electronics.


Medication-overuse headache: pathophysiological insights.
Medication overuse headache (MOH) is a clinically important entity and it is now well documented that the regular use of acute symptomatic medication by people with migraine or tensiontype headache increases the risk of aggravation of the primary headache. MOH is one of the most common causes of chronic migraine-like syndrome. Because of easy availability and low expense, the greatest problem appears to be associated with barbiturate-containing combination analgesics and over-the-counter caffeine-containing combination analgesics. Even though triptan overuse headache is not encountered with great frequency, all triptans should be considered potential inducers of MOH. There are several different theories regarding the aetiology of MOH, including: (i) central sensitisation from repetitive activation of nociceptive pathways; (ii) a direct effect of the medication on the capacity of the brain to inhibit pain; (iii) a decrease in blood serotonin due to repetitive medication administration with alteration of serotonin receptors; (iv) cellular adaptation in the brain; and (v) changes in the periaqueductal grey matter. The principal approach to management of MOH is built around cessation of overused medication. Without discontinuation of the offending medication, improvement is almost impossible to attain. Thus, the best management advice is to raise awareness and strive for prevention. In this article, we analyse also the possible mechanisms that underlie sensitisation in MOH by comparing these mechanisms with those reported for other forms of drug addiction.


PAPP-A2 and Inhibin A as Novel Predictors for Pregnancy Complications in Women With Suspected or Confirmed Preeclampsia.
Background We aimed to evaluate the value of inhibin A and PAPP-A2 (pregnancy-associated plasma protein-A2) as novel biomarkers in the prediction of preeclampsia-related complications and how they compare with angiogenic biomarkers. Methods and Results Making use of a secondary analysis of a prospective, multicenter, observational study, intended to evaluate the usefulness of sFlt-1 (soluble Fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio, we measured inhibin A and PAPP-A2 levels in 524 women with suspected/confirmed preeclampsia. Women had a median gestational age of 35 weeks (range, 20-41 weeks) while preeclampsia occurred in 170 (32%) women. Levels of inhibin A and PAPP-A2 were significantly increased in women with preeclampsia and in maternal perfusate of preeclamptic placentas. Inhibin A and PAPP-A2 (C-index = 0.73 and 0.75) significantly improved the prediction of maternal complications when added on top of the traditional criteria; gestational age, parity, proteinuria, and diastolic blood pressure (C-index = 0.60). PAPP-A2 was able to improve the C-index from 0.75 to 0.77 when added on top of the sFlt-1/PlGF ratio for the prediction of maternal complications. To discriminate fetal/neonatal complications on top of traditional criteria, inhibin A and PAPP-A2 showed additive value (C-index = 0.79 to 0.80 and 0.82, respectively) but their discriminative ability remained inferior to that of sFlt-1/PlGF ratio or PlGF. Interestingly, the PAPP-A2/PlGF ratio alone showed remarkable value to predict pregnancy complications, being superior to sFlt-1/PlGF ratio in the case of maternal complications. Conclusions Inhibin A and PAPP-A2 show significant potential to predict preeclampsia-related pregnancy complications and might prove beneficial on top of the angiogenic markers.


Glowing seashells: diversity of fossilized coloration patterns on coral reef-associated cone snail (Gastropoda: Conidae) shells from the Neogene of the Dominican Republic.
The biology of modern Conidae (cone snails)--which includes the hyperdiverse genus Conus--has been intensively studied, but the fossil record of the clade remains poorly understood, particularly within an evolutionary framework. Here, ultraviolet light is used to reveal and characterize the original shell coloration patterns of 28 species of cone snails from three Neogene coral reef-associated deposits from the Cibao Valley, northern Dominican Republic. These fossils come from the upper Miocene Cercado Fm. and lower Pliocene Gurabo Fm., and range in age from about 6.6-4.8 Ma. Comparison of the revealed coloration patterns with those of extant species allow the taxa to be assigned to three genera of cone snails (Profundiconus, Conasprella, and Conus) and at least nine subgenera. Thirteen members of these phylogenetically diverse reef faunas are described as new species. These include: Profundiconus? hennigi, Conasprella (Ximeniconus) ageri, Conus anningae, Conus lyelli, Conus (Atlanticonus?) franklinae, Conus (Stephanoconus) gouldi, Conus (Stephanoconus) bellacoensis, Conus (Ductoconus) cashi, Conus (Dauciconus) garrisoni, Conus (Dauciconus?) zambaensis, Conus (Spuriconus?) kaesleri, Conus (Spuriconus?) lombardii, and Conus (Lautoconus?) carlottae. Each of the three reef deposits contain a minimum of 14-16 cone snail species, levels of diversity that are similar to modern Indo-Pacific reef systems. Finally, most of the 28 species can be assigned to modern clades and thus have important implications for understanding the biogeographic and temporal histories of these clades in tropical America.


Trajectory surface-hopping study of methane photodissociation dynamics.
We use the fewest switches nonadiabatic trajectory surface hopping approach to study the photodissociation of methane on its lowest singlet excited state potential surface (1 (1)T(2)) at 122 nm, with emphasis on product state branching and energy partitioning. The trajectories and couplings are based on CASSCF(8,9) calculations with an aug-cc-pvdz basis set. We demonstrate that nonadiabatic dynamics is important to describe the dissociation processes. We find that CH(3)(X (2)A(2) ("))+H and CH(2)(a (1)A(1))+H(2) are the major dissociation channels, as have been observed experimentally. CH(3)+H is mostly formed by direct dissociation that is accompanied by hopping to the ground state. CH(2)+H(2) can either be formed by hopping to the ground state to give CH(2)(a (1)A(1))+H(2) or by adiabatic dissociation to CH(2)(b (1)B(1))+H(2). In the latter case, the CH(2)(b (1)B(1)) can then undergo internal conversion to the ground singlet state by Renner-Teller induced hopping. Less important dissociation mechanisms lead to CH(2)+H+H and to CH+H(2)+H. Intersystem crossing effects, which are not included, do not seem essential to describe the experimentally observed branching behavior. About 5% of trajectories involve a roaming atom mechanism which can eventually lead to formation of products in any of the dissociation channels. Branching fractions to give H and H(2) are in good agreement with experiment, and the H atom translational energy distribution shows bimodal character which also matches observations.


Evolutionary histories of expanded peptidase families in Schistosoma mansoni.
Schistosoma mansoni is one of the three main causative agents of human schistosomiasis, a major health problem with a vast socio-economic impact. Recent advances in the proteomic analysis of schistosomes have revealed that peptidases are the main virulence factors involved in the pathogenesis of this disease. In this context, evolutionary studies can be applied to identify peptidase families that have been expanded in genomes over time in response to different selection pressures. Using a phylogenomic approach, we searched for expanded endopeptidase families in the S. mansoni predicted proteome with the aim of contributing to the knowledge of such enzymes as potential therapeutic targets. We found three endopeptidase families that comprise leishmanolysins (metallopeptidase M8 family), cercarial elastases (serine peptidase S1 family) and cathepsin D proteins (aspartic peptidase A1 family). Our results suggest that the Schistosoma members of these families originated from successive gene duplication events in the parasite lineage after its diversification from other metazoans. Overall, critical residues are conserved among the duplicated genes/proteins. Furthermore, each protein family displays a distinct evolutionary history. Altogether, this work provides an evolutionary view of three S. mansoni peptidase families, which allows for a deeper understanding of the genomic complexity and lineage-specific adaptations potentially related to the parasitic lifestyle.


Using objective markers to assess participant behavior in HIV prevention trials of vaginal microbicides.
The need to verify participant behavior exists in any study in which behavior may affect outcomes. In vaginal microbicide trials, the act of having sex and the use of study products and condoms all affect the risk of acquiring HIV/sexually transmitted infections (STIs). Until now, these behaviors have been assessed using self-reports. But self-reports are limited by participant cooperation in answering questions, imperfect recall, and social desirability biases. Biomarkers are increasingly being used in medicine to reduce the time and resources needed to bring a drug to market. The use of biomarkers in vaginal microbicide trials has been proposed as a means of assessing factors that affect the risk of sexual acquisition of HIV/STIs, namely, the presence of preexisting infection, cervicovaginal inflammation, and the presence of HIV/STIs. Biomarkers for some of these already exist. What are needed are validated markers of behaviors that might affect risk, namely, markers for sexual behavior and for the use of study products and condoms. Validating and working out the logistics of collecting such markers in large trials will be a challenge. But finding objective markers for behavior may help improve adherence measurement during a trial and is a rate-limiting step in the field of vaginal microbicides. Resources and funding should be mobilized to develop and validate markers of sexual behavior and product use as a high priority in vaginal microbicide research.


Timing in Predictive Coding: The Roles of Task Relevance and Global Probability.
Predictive coding models of attention propose that attention and prediction operate synergistically to optimize perception, as reflected in interactive effects on early sensory neural responses. It is yet unclear whether attention and prediction based on the temporal attributes of expected events operate in a similar fashion. We investigated how attention and prediction based on timing interact by manipulating the task relevance and a priori probability of auditory stimulus onset timing within a go/no-go task while recording EEG. Preparatory activity, as indexed via the contingent negative variation, reflected temporally specific anticipation as a function of both attention and prediction. Higher stimulus probability led to significant predictive N1 suppression; however, we failed to find an effect of task relevance on N1 amplitude and an interaction of task relevance with prediction. We suggest the predictability of sensory timing is the predominant influence on early sensory responses where a priori probabilities allow for strong prior beliefs. When this is the case, we find that the effects of temporal prediction on early sensory responses are independent of the task relevance of sensory stimuli. Our findings contribute to the expansion of predictive coding frameworks to include the role of timing in sensory processing.


Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development.
Gastric cancer (GC) is a deadly malignancy for which new therapeutic strategies are needed. Three transcription factors, KLF5, GATA4 and GATA6, have been previously reported to exhibit genomic amplification in GC. We sought to validate these findings, investigate how these factors function to promote GC, and identify potential treatment strategies for GCs harbouring these amplifications. KLF5, GATA4 and GATA6 copy number and gene expression was examined in multiple GC cohorts. Chromatin immunoprecipitation with DNA sequencing was used to identify KLF5/GATA4/GATA6 genomic binding sites in GC cell lines, and integrated with transcriptomics to highlight direct target genes. Phenotypical assays were conducted to assess the function of these factors in GC cell lines and xenografts in nude mice. KLF5, GATA4 and GATA6 amplifications were confirmed in independent GC cohorts. Although factor amplifications occurred in distinct sets of GCs, they exhibited significant mRNA coexpression in primary GCs, consistent with KLF5/GATA4/GATA6 cross-regulation. Chromatin immunoprecipitation with DNA sequencing revealed a large number of genomic sites co-occupied by KLF5 and GATA4/GATA6, primarily located at gene promoters and exhibiting higher binding strengths. KLF5 physically interacted with GATA factors, supporting KLF5/GATA4/GATA6 cooperative regulation on co-occupied genes. Depletion and overexpression of these factors, singly or in combination, reduced and promoted cancer proliferation, respectively, in vitro and in vivo. Among the KLF5/GATA4/GATA6 direct target genes relevant for cancer development, one target gene, HNF4α, was also required for GC proliferation and could be targeted by the antidiabetic drug metformin, revealing a therapeutic opportunity for KLF5/GATA4/GATA6 amplified GCs. KLF5/GATA4/GATA6 may promote GC development by engaging in mutual crosstalk, collaborating to maintain a pro-oncogenic transcriptional regulatory network in GC cells.


Phase synchronization varies systematically with linguistic structure composition.
Computation in neuronal assemblies is putatively reflected in the excitatory and inhibitory cycles of activation distributed throughout the brain. In speech and language processing, coordination of these cycles resulting in phase synchronization has been argued to reflect the integration of information on different timescales (e.g. segmenting acoustics signals to phonemic and syllabic representations; (Giraud and Poeppel 2012 Nat. Neurosci.15, 511 (doi:10.1038/nn.3063)). A natural extension of this claim is that phase synchronization functions similarly to support the inference of more abstract higher-level linguistic structures (Martin 2016 Front. Psychol.7, 120; Martin and Doumas 2017 PLoS Biol. 15, e2000663 (doi:10.1371/journal.pbio.2000663); Martin and Doumas. 2019 Curr. Opin. Behav. Sci.29, 77-83 (doi:10.1016/j.cobeha.2019.04.008)). Hale et al. (Hale et al. 2018 Finding syntax in human encephalography with beam search. arXiv 1806.04127 (http://arxiv.org/abs/1806.04127)) showed that syntactically driven parsing decisions predict electroencephalography (EEG) responses in the time domain; here we ask whether phase synchronization in the form of either inter-trial phrase coherence or cross-frequency coupling (CFC) between high-frequency (i.e. gamma) bursts and lower-frequency carrier signals (i.e. delta, theta), changes as the linguistic structures of compositional meaning (viz., bracket completions, as denoted by the onset of words that complete phrases) accrue. We use a naturalistic story-listening EEG dataset from Hale et al. to assess the relationship between linguistic structure and phase alignment. We observe increased phase synchronization as a function of phrase counts in the delta, theta, and gamma bands, especially for function words. A more complex pattern emerged for CFC as phrase count changed, possibly related to the lack of a one-to-one mapping between 'size' of linguistic structure and frequency band-an assumption that is tacit in recent frameworks. These results emphasize the important role that phase synchronization, desynchronization, and thus, inhibition, play in the construction of compositional meaning by distributed neural networks in the brain. This article is part of the theme issue 'Towards mechanistic models of meaning composition'.


Cardiac metabolism and performance during L-glutamic acid infusion in postoperative cardiac failure.
Intravenous infusion of L-glutamic acid results in the augmentation of the cardiac output and an improvement of the circulation in patients with postoperative cardiac failure. This effect is not accompanied by increased myocardial oxygen demand. Arterial plasma glutamate level rises 10-fold and arterial-coronary sinus plasma glutamate difference increases fivefold during intravenous L-glutamic acid infusion. This leads to cessation of ammonia release from the myocardium, probably due to augmentation of glutamine synthesis and to an increase in alanine formation coupled with a change from lactate release to lactate uptake by the myocardium. The data obtained suggest that the beneficial effect of L-glutamic acid on depressed cardiac function in postoperative patients is related to changes in myocardial metabolism. Glutamic acid may be useful in treatment of circulatory and metabolic disturbances in cardiac failure.


Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak.
Even under the most expert care, a properly constructed intestinal anastomosis can fail to heal, resulting in leakage of its contents, peritonitis, and sepsis. The cause of anastomotic leak remains unknown, and its incidence has not changed in decades. We demonstrate that the commensal bacterium Enterococcus faecalis contributes to the pathogenesis of anastomotic leak through its capacity to degrade collagen and to activate tissue matrix metalloproteinase 9 (MMP9) in host intestinal tissues. We demonstrate in rats that leaking anastomotic tissues were colonized by E. faecalis strains that showed an increased collagen-degrading activity and also an increased ability to activate host MMP9, both of which contributed to anastomotic leakage. We demonstrate that the E. faecalis genes gelE and sprE were required for E. faecalis-mediated MMP9 activation. Either elimination of E. faecalis strains through direct topical antibiotics applied to rat intestinal tissues or pharmacological suppression of intestinal MMP9 activation prevented anastomotic leak in rats. In contrast, the standard recommended intravenous antibiotics used in patients undergoing colorectal surgery did not eliminate E. faecalis at anastomotic tissues nor did they prevent leak in our rat model. Finally, we show in humans undergoing colon surgery and treated with the standard recommended intravenous antibiotics that their anastomotic tissues still contained E. faecalis and other bacterial strains with collagen-degrading/MMP9-activating activity. We suggest that intestinal microbes with the capacity to produce collagenases and to activate host metalloproteinase MMP9 may break down collagen in the intestinal tissue contributing to anastomotic leak.


110 years of Avipoxvirus in the Galapagos Islands.
The role of disease in regulating populations is controversial, partly owing to the absence of good disease records in historic wildlife populations. We examined birds collected in the Galapagos Islands between 1891 and 1906 that are currently held at the California Academy of Sciences and the Zoologisches Staatssammlung Muenchen, including 3973 specimens representing species from two well-studied families of endemic passerine birds: finches and mockingbirds. Beginning with samples collected in 1899, we observed cutaneous lesions consistent with Avipoxvirus on 226 (6.3%) specimens. Histopathology and viral genotyping of 59 candidate tissue samples from six islands showed that 21 (35.6%) were positive for Avipoxvirus, while alternative diagnoses for some of those testing negative by both methods were feather follicle cysts, non-specific dermatitis, or post mortem fungal colonization. Positive specimens were significantly nonrandomly distributed among islands both for mockingbirds (San Cristobal vs. Espanola, Santa Fe and Santa Cruz) and for finches (San Cristobal and Isabela vs. Santa Cruz and Floreana), and overall highly significantly distributed toward islands that were inhabited by humans (San Cristobal, Isabela, Floreana) vs. uninhabited at the time of collection (Santa Cruz, Santa Fe, Espanola), with only one positive individual on an uninhabited island. Eleven of the positive specimens sequenced successfully were identical at four diagnostic sites to the two canarypox variants previously described in contemporary Galapagos passerines. We conclude that this virus was introduced late in 1890's and was dispersed among islands by a variety of mechanisms, including regular human movements among colonized islands. At present, this disease represents an ongoing threat to the birds on the Galapagos Islands.


WITHDRAWN: Elemene for the treatment of lung cancer.
Elemene, isolated from the Chinese medicinal herb Rhizoma Zedoariae and be used to treat patients with lung cancer in China. Until now, the effects have not been systematically reviewed. The purpose of this review was to determine the effectiveness and safety of elemene in the treatment of patients with lung cancer. We searched according to the strategy suggested by Lung Cancer group: the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 2); MEDLINE (1966 to June 2006); EMBASE (1974 to June 2006); OVID (1950 to June, 2006); CBMdisc on Chinese Biomedical Literature (Issue 1 2004 Chinese Language) and CNKI (Chinese Knowledge Internet 1994 to June 2006). Only randomised controlled trials (RCTs) that compared elemene with chemotherapy agents, radiotherapy, surgery, physical therapy or other effective Chinese herb therapy, either alone or in combination, had been sought in this review, regardless of language or publication status. Two authors telephoned the original trial authors of claimed randomised controlled trials and made a decision about trial inclusion and exclusion. We identified 20 trials which claimed to use random allocation. Sixteen study authors were contacted by telephone and we discovered that they misunderstood the randomisation procedure and the trials were identified as non-RCTs. We were unable to contact the authors of the remaining four studies and these have been allocated to the 'Studies awaiting assessment' section. There is no evidence from randomised controlled trials to confirm or refute the effectiveness of elemene as a treatment for lung cancer. Randomised clinical trials, on elemene for the treatment of lung cancer are needed in order to define the efficacy and acceptability of elemene for lung cancer.


Analgesic activities of crude ethanolic extract and various fractions of Adansonia digitata L. grown at the sindh province of Pakistan.
The current study aimed to evaluate the analgesic effects of crude extract and fractions of leaves of Adansonia digitata L. (Malvaceae). Fresh leaves were collected, dried under shade and then powdered. Moreover, powder was usedto extract with Ethanol and concentrated under reduced pressure, followed by partitioning with organic solvents i.e. Hexane, Ethylacetate, Butanol and Aqueous. These fractions were analyzed for analgesic effect at dose of 50, 100, 200; mg/kg body weight by acetic acid induced writhing, tail flick and hot plate analgesic models. No acute oral toxicity was observed and extracts considered being saved at a dose of 50-3000 mg/kg body weight. Orally administered extract of A. digitata showed analgesic activity described by decrease in writhes counts which was contrast to control. Significant (P<0.05-0.001) increased in latency period in hot plate analgesic test when compared Diclofenac sodium (50 mg/kg) which is used as a standard drug. Furthermore, in tail flick test a dose of (50, 100, 200mg/kg body weight) of extracts exhibited significant (P<0.05-0.001) analgesia which is dose dependent when compared to control group. These findings of analgesic testing have revealed that leaves extract of this nutritional plants possess remarkable antinociceptive effect.