Trends in Diabetes Incidence in the Last Decade Based on Korean National Health Insurance Claims Data.
Epidemiological data is useful to estimate the necessary manpower and resources used for disease control and prevention of prevalent chronic diseases. We aimed to evaluate the incidence of diabetes and identify its trends based on the claims data from the National Health Insurance Service database over the last decade. We extracted claims data on diabetes as the principal and first additional diagnoses of National Health Insurance from January 2003 to December 2012. We investigated the number of newly claimed subjects with diabetes codes, the number of claims and the demographic characteristics of this population. Total numbers of claimed cases and populations with diabetes continuously increased from 1,377,319 in 2003 to 2,571,067 by 2012. However, the annual number of newly claimed diabetic subjects decreased in the last decade. The total number of new claim patients with diabetes codes decreased as 30.9% over 2005 to 2009. Since 2009, the incidence of new diabetes claim patients has not experienced significant change. The 9-year average incidence rate was 0.98% and 1.01% in men and women, respectively. The data showed an increasing proportion of new diabetic subjects of younger age (<60 years) combined with a sharply decreasing proportion of subjects of older age (≥60 years). There were increasing numbers of newly claimed subjects with diabetes codes of younger age over the last 10 years. This increasing number of diabetic patients will require management throughout their life courses because Korea is rapidly becoming an aging society.


Proliferative capacity and cytokine production by cells of HIV-infected and uninfected adults with different helminth infection phenotypes in South Africa.
It has been suggested that the proliferative capacity of cells from individuals with HIV or both HIV and helminth infections is attenuated and cytokine production is dysregulated. This study describes peripheral blood mononuclear cell proliferation capacity and cytokine profile from individuals with HIV or both HIV and helminth infections in South Africa. Forty HIV-infected and 22 HIV-uninfected participants were randomly selected and stratified into different helminth infection phenotypes by egg excretion and Ascaris lumbricoides specific -immunoglobulin-E (IgE) levels. Five day cell cultures of participants, unstimulated or stimulated with Phytohaemaglutinnin, Streptokinase, HIV-1 p24 and Ascaris lumbricoides worm antigens were stained with monoclonal antibody-fluorochrome conjugates (Ki67-FITC and CTLA-APC-4). Percentage expression of Ki67 and CTLA-4 was measured to determine cell proliferation and regulation, respectively. Culture supernatants were analysed for the expression of 13 cytokines using the Bioplex (BioRad) system. Kruskal Wallis was used to test for differences in variables between helminth infected subgroups who were either having eggs in stool and high IgE (egg+IgEhi); or eggs in stool and low IgE (egg+IgElo); or no eggs in stool and high IgE (egg-IgEhi) and those without helminth infection (egg-IgElo). Individuals excreting eggs in stool with high serum IgE (egg+IgEhi phenotype) had potent mitogen responses but consistently produced low, but statistically non-significant antigen-specific (HIV-1 p24 (p = 0.41) and Ascaris (p = 0.19) and recall antigen (Streptokinase; p = 0.31) Ki67 responses. The group also had reduced type 1 cytokines. Individuals excreting eggs in stool with low serum IgE( egg+IgElo phenotype) had a more favourable antiviral profile, characterized by higher IFNγ, IL-2, lower IL-4 and higher IL-10 production. The findings suggest that dual HIV/helminth infection with egg excretion and/or high Ascaris IgE phenotye may be linked with poor proliferative capacity and deleterious cytokine profile with regards to HIV control.


Protein quality and the protein to carbohydrate ratio within a high fat diet influences energy balance and the gut microbiota in C57BL/6J mice.
Macronutrient quality and composition are important determinants of energy balance and the gut microbiota. Here, we investigated how changes to protein quality (casein versus whey protein isolate; WPI) and the protein to carbohydrate (P/C) ratio within a high fat diet (HFD) impacts on these parameters. Mice were fed a low fat diet (10% kJ) or a high fat diet (HFD; 45% kJ) for 21 weeks with either casein (20% kJ, HFD) or WPI at 20%, 30% or 40% kJ. In comparison to casein, WPI at a similar energy content normalised energy intake, increased lean mass and caused a trend towards a reduction in fat mass (P = 0.08), but the protein challenge did not alter oxygen consumption or locomotor activity. WPI reduced HFD-induced plasma leptin and liver triacylglycerol, and partially attenuated the reduction in adipose FASN mRNA in HFD-fed mice. High throughput sequence-based analysis of faecal microbial populations revealed microbiota in the HFD-20% WPI group clustering closely with HFD controls, although WPI specifically increased Lactobacillaceae/Lactobacillus and decreased Clostridiaceae/Clostridium in HFD-fed mice. There was no effect of increasing the P/C ratio on energy intake, but the highest ratio reduced HFD-induced weight gain, fat mass and plasma triacylglycerol, non-esterified fatty acids, glucose and leptin levels, while it increased lean mass and oxygen consumption. Similar effects were observed on adipose mRNA expression, where the highest ratio reduced HFD-associated expression of UCP-2, TNFα and CD68 and increased the diet-associated expression of β3-AR, LPL, IR, IRS-1 and GLUT4. The P/C ratio also impacted on gut microbiota, with populations in the 30/40% WPI groups clustering together and away from the 20% WPI group. Taken together, our data show that increasing the P/C ratio has a dramatic effect on energy balance and the composition of gut microbiota, which is distinct from that caused by changes to protein quality.


Transplanted neural stem cells modulate regulatory T, γδ T cells and corresponding cytokines after intracerebral hemorrhage in rats.
The immune system, particularly T lymphocytes and cytokines, has been implicated in the progression of brain injury after intracerebral hemorrhage (ICH). Although studies have shown that transplanted neural stem cells (NSCs) protect the central nervous system (CNS) from inflammatory damage, their effects on subpopulations of T lymphocytes and their corresponding cytokines are largely unexplored. Here, rats were subjected to ICH and NSCs were intracerebrally injected at 3 h after ICH. The profiles of subpopulations of T cells in the brain and peripheral blood were analyzed by flow cytometry. We found that regulatory T (Treg) cells in the brain and peripheral blood were increased, but γδT cells (gamma delta T cells) were decreased, along with increased anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) and decreased pro-inflammatory cytokines (IL-6, and IFN-γ), compared to the vehicle-treated control. Our data suggest that transplanted NSCs protect brain injury after ICH via modulation of Treg and γδT cell infiltration and anti- and pro-inflammatory cytokine release.


Viscoelastic protection from endothelial damage by air bubbles.
To determine whether viscoelastic materials effectively protect the corneal endothelium from air bubbles. Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea. Human eye-bank and rabbit eyes had a standardized phacoemulsification procedure with or without viscoelastic material (Healon [sodium hyaluronate 1.0%], Healon GV [sodium hyaluronate 1.4%], or Viscoat [chondroitin sulfate 4.0%-sodium hyaluronate 3.0%]). The integrity of the endothelium was examined after the procedure with F-actin staining and scanning electron microscopy. Rabbit eyes with and without viscoelastic material (Healon or Viscoat) had a standardized irrigation/aspiration (I/A) procedure. The mucinous layer of the endothelium was examined after the procedure with transmission electron microscopy. In the phacoemulsification experiment without viscoelastic material, with Healon, and with Healon GV, the endothelium of human and rabbit corneas had many areas of cell loss in a pattern consistent with air-bubble damage. With Viscoat, endothelial cells remained intact. In the I/A experiment, the mucinous layer of Viscoat-exposed rabbit endothelium appeared thinner. In the same experiments without viscoelastic material or with Healon, the mucinous layer of the endothelium appeared normal. Viscoat effectively protected the endothelium from air-bubble damage. Viscoat appears to protect the endothelium by acting as a physical barrier. Its adherence is probably related to the way it interacts with the mucinous layer of the endothelium.


Acute toxicity of ingested fluoride.
This chapter discusses the characteristics and treatment of acute fluoride toxicity as well as the most common sources of overexposure, the doses that cause acute toxicity, and factors that can influence the clinical outcome. Cases of serious systemic toxicity and fatalities due to acute exposures are now rare, but overexposures causing toxic signs and symptoms are not. The clinical course of systemic toxicity from ingested fluoride begins with gastric signs and symptoms, and can develop with alarming rapidity. Treatment involves minimizing absorption by administering a solution containing calcium, monitoring and managing plasma calcium and potassium concentrations, acid-base status, and supporting vital functions. Approximately 30,000 calls to US poison control centers concerning acute exposures in children are made each year, most of which involve temporary gastrointestinal effects, but others require medical treatment. The most common sources of acute overexposures today are dental products - particularly dentifrices because of their relatively high fluoride concentrations, pleasant flavors, and their presence in non-secure locations in most homes. For example, ingestion of only 1.8 ounces of a standard fluoridated dentifrice (900-1,100 mg/kg) by a 10-kg child delivers enough fluoride to reach the 'probably toxic dose' (5 mg/kg body weight). Factors that may influence the clinical course of an overexposure include the chemical compound (e.g. NaF, MFP, etc.), the age and acid-base status of the individual, and the elapsed time between exposure and the initiation of treatment. While fluoride has well-established beneficial dental effects and cases of serious toxicity are now rare, the potential for toxicity requires that fluoride-containing materials be handled and stored with the respect they deserve.


The evaluating prescription opioid changes in veterans (EPOCH) study: Design, survey response, and baseline characteristics.
In the United States (US), long-term opioid therapy has been commonly prescribed for chronic pain. Since recognition of the opioid overdose epidemic, clinical practice guidelines have recommended tapering long-term opioids to reduced doses or discontinuation. The Effects of Prescription Opioid Changes for veterans (EPOCH) study is a national population-based prospective observational study of US Veterans Health Administration primary care patients designed to assess effects of evolving opioid prescribing practice on patients treated with long-term opioids for chronic pain. A stratified random sampling design was used to identify a survey sample from the target population of patients treated with opioid analgesics for ≥ 6 months. Demographic, diagnostic, visit, and pharmacy dispensing data were extracted from existing datasets. A 2016 mixed-mode mail and telephone survey collected patient-reported data, including the main patient-reported outcomes of pain-related function (Brief Pain Inventory interference; BPI-I scores 0-10, higher scores = worse) and health-related quality of life. Data on survey participants and non-participants were analyzed to assess potential nonresponse bias. Weights were used to account for design. Linear regression models were used to assess cross-sectional associations of opioid treatment with patient-reported measures. Of 14,160 patients contacted, 9253 (65.4%) completed the survey. Participants were older than non-participants (63.9 ± 10.6 vs. 59.6 ± 13.0 years). The mean number of bothersome pain locations was 6.8 (SE 0.04). Effectiveness of pain treatment and quality of pain care were rated fair or poor by 56.1% and 45.3%, respectively. The opioid daily dosage range was 1.6 to 1038.2 mg, with mean = 50.6 mg (SE 1.1) and median = 30.9 mg (IQR 40.7). Among the 73.2% of patients who did not receive long-acting opioids, the mean daily dosage was 30.4 mg (SE 0.6) and mean BPI-I was 6.4 (SE 00.4). Among patients who received long-acting opioids, the mean daily dosage was 106.2 mg (SE 2.8) and mean BPI-I was 6.8 (SE 0.07). Higher daily dosage was associated with worse pain-related function and quality of life among patients without long-acting opioids, but not among patients with long-acting opioids. Future analyses will use follow-up data to examine effects of opioid dose reduction and discontinuation on patient outcomes.


Relationship between unconjugated hyperbilirubinemia and lipoprotein spectrum.
The aim of this study was to analyze the serum bilirubin level, lipid and lipoprotein parameters with the emphasis on the presence of atherogenic small dense LDL in patients with Gilbert's syndrome and to compare these results with probands in the control group. We used a new electrophoretic method, which enables to analyze up to 12 lipoprotein subpopulations. Atherogenic lipoprotein profile is characterized by the presence of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and the presence of small dense LDL lipoproteins. The presence of LDL1 and LDL2 subpopulations, as well as HDL lipoproteins is considered as protective factor. Molecular - genetic examination of Gilbert\'s syndrome using fragment analysis method was carried out in collaboration with the Centre for Medical Genetics, University Hospital in Bratislava. Total cholesterol and triglycerides in plasma were analyzed from lipid parameters by means of enzymatic CHOD-PAP method, Roche Diagnostics, Germany. Biochemical parameters - bilirubin (total, conjugated and unconjugated), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GMT), (Roche Diagnostics, Germany), TSH, FT3, fT4 (Siemens) were also examined. Serum lipoproteins and their subfractions were examined using Lipoprint LDL System Quantimetrix, CA, USA (12). We found significantly higher levels of total bilirubin and unconjugated bilirubin in patients with Gilbert's syndrome. In the control group, probands had significantly higher triglycerides levels, VLDL cholesterol levels, IDL cholesterol level, and small dense LDL levels compared to the group with Gilbert\'s syndrome. Probands with Gilbert's syndrome had significantly lower presence of atherogenic lipoprotein spectrum than probands in control group (5% vs. 18%). We found significantly negative correlation between serum unconjugated bilirubin levels and LDL 3-7 (r = - 0.594, p <0.01), as well as between bilirubin and triglycerides (r = -0.540, p<0.01). Serum bilirubin concentration and LDL 1-2 concentration correlated significantly positively (r = 0.451, p <0.05). The presence of atherogenic lipoprotein spectrum is determined by the particular representation of small dense LDL. Atherogenic spectrum was presented significantly less in patients with Gilbert\'s syndrome compared with the control group (5% vs. 18%). In our study, we have not followed the risk of coronary heart disease or other manifestations of atherosclerotic arteries disability. However, we found the inverse relationship of serum bilirubin levels and atherogenic small dense LDL. We found out that the protective antiatherogenic effect of hyperbilirubinemia is potentiated by low occurence of strongly atherogenic small dense LDL and persons with byperbilirubionemia (in our case represented Gilbert's syndrome), could be protected against the development of atheroscleosis.


[Profile of notified tuberculosis cases and factors associated with treatment dropout].
To describe the profile of notified tuberculosis cases and analyze the factors associated with treatment dropout. A total of 178 cases of tuberculosis notified in the western region of Belo Horizonte (Southeastern Brazil) in 2001 and 2002 and recorded in the National System for Notifiable Diseases were described. An unmatched case-control study was conducted, with data collected by means of interviews, to compare patients who dropped out of treatment with those who achieved cure. The following variables were analyzed: sociodemographic and behavioral characteristics, associations with AIDS, side effects, information on the disease and interest in treatment. Univariate analysis and unconditional logistic regression for multivariate analysis were used. Adjusted odds ratios with 95% confidence limits were used as the measurement for associations. The coefficient of incidence was 56.6/100,000 inhabitants. There was predominance of men aged 30 to 49 years and of the pulmonary form (76.4%) and bacillary form (72.5%). Among the notified cases, 65.2% achieved cure, 12.4% dropped out of treatment and 9.6% died. Treatment location had no influence on the results. In the case-control study, there was no difference regarding gender, color, schooling, income, occupation, family support, association with AIDS and alcohol consumption. The use of drugs, interest in treatment and information about the disease were shown to be independently associated with dropout. Adherence to treatment is a challenge in controlling tuberculosis. The protection factors (interest in treatment and information about the disease) and recognition that drug use is a risk factor must form part of the strategies for patient care in order to reduce dropout rates and restore health.


Do We Need Full Donor Chimerism? How Alloreactive Cell Therapies without Substantial Engraftment Might Treat Hematologic Cancers.
"Alloreactive cell therapy without substantial engraftment"; (ACT-WiSE) refers to adoptive transfer of natural ("non-engineered") human leukocyte antigen-mismatched lymphocytes to mediate anti-neoplastic alloreactivity in recipients without employing pharmacologic immunosuppression. By definition, ACT-WiSE entails subsequent rejection of most, if not all, donor cells. Macrochimerism is transient and microchimerism may be either short-lived or persistent. This strategy harnesses the anticancer potency of alloreactivity without incurring significant risk of graft-versus-host disease. "Microtransplantation" refers to a form of ACT-WiSE where the donor cell product contains hematopoietic progenitor cells. Microtransplantation therefore accelerates hematopoietic recovery and its immunomodulatory effects may differ from other forms of ACT-WiSE. Recent studies suggest that various forms of ACT-WiSE, including microtransplantation, may improve chemosensitivity in patients with myeloid malignancies, resulting in higher complete remission rates and increased survival. Microtransplantation has also demonstrated promising pilot results in relapsed or refractory Non-Hodgkin and Hodgkin lymphoma. ACT-WiSE and microtransplantation may establish a new class of allogeneic cell therapy of particular relevance to persons not considered candidates for traditional allogeneic hematopoietic cell transplantation (AHCT). Open questions include the optimal timing and cell dose of ACT-WiSE, which donor factors contribute to efficacy, and whether these remissions are durable after eradication of donor cells. We extrapolate from lessons learned in the course of traditional and haploidentical AHCT to propose ways of optimizing ACT-WiSE. We divide these into donor-related strategies (including rational donor selection and boosting NK-cell and T-cell alloreactivity) and patient- related strategies (that may favor development of autologous NK-cell and T-cell mediated anticancer cytotoxicity in the post-ACT-WiSE window).


Factors associated with incident and fatal pancreatic cancer in a cohort of middle-aged women.
Risk factors for pancreatic cancer, other than smoking and diabetes, are not well-established, especially for women. In a cohort of 1.3 million middle-aged women, followed for 9.2 million person-years for cancer incidence and 11.5 million person-years for mortality, there were 1,338 incident pancreatic cancer cases and 1,710 deaths from the disease. Using proportional hazards models, we calculated adjusted relative risks (RRs) and 95% confidence intervals (CIs) by smoking, height, body mass index (BMI), alcohol consumption, physical activity and history of diabetes. Pancreatic cancer incidence was greater in current than never smokers (RR 2.39, CI 2.10-2.73), the risk increasing with the number of cigarettes smoked. The incidence of pancreatic cancer also increased with increasing BMI (RR 1.34, CI 1.13-1.57 for BMI >or= 30 vs. 22.5-25 kg/m(2)), and with a history of diabetes (RR 1.58, CI 1.22-2.03, with vs. without such a history). These factors were also associated with increased mortality from pancreatic cancer. Height, alcohol consumption and physical activity showed little or no association with pancreatic cancer risk.


Pair-by-pair pulse shaping for optical arbitrary waveform generation by dual-comb heterodyne.
We present a novel optical arbitrary waveform generation approach based on pair-by-pair pulse shaping. Based on the heterodyne between a pair of optical frequency combs with different repetition rates, the repetition rate of the generated signals can be flexibly tuned from MHz to GHz without changing the setup. The restriction of the spectral resolution of the optical spectrum processor is overcome by the pair-by-pair approach while the spectral resolution of the system can be improved to MHz by dual-comb heterodyne. Hyperfine control of a higher resolution spectrum at MHz is achieved, which benefits the generation of the ultrawideband signals.


Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study.
Duchenne muscular dystrophy is caused by dystrophin deficiency and muscle deterioration and preferentially affects boys. Antisense-oligonucleotide-induced exon skipping allows synthesis of partially functional dystrophin. We investigated the efficacy and safety of drisapersen, a 2'-O-methyl-phosphorothioate antisense oligonucleotide, given for 48 weeks. In this exploratory, double-blind, placebo-controlled study we recruited male patients (≥5 years of age; time to rise from floor ≤7 s) with Duchenne muscular dystrophy from 13 specialist centres in nine countries between Sept 1, 2010, and Sept 12, 2012. By use of a computer-generated randomisation sequence, we randomly allocated patients (2:2:1:1; block size of six; no stratification) to drisapersen 6 mg/kg or placebo, each given subcutaneously and either continuously (once weekly) or intermittently (nine doses over 10 weeks). The primary endpoint was change in 6-min walk distance (6MWD) at week 25 in patients in the intention-to-treat population for whom data were available. Safety assessments included renal, hepatic, and haematological monitoring and recording of adverse events. This trial is registered with ClinicalTrials.gov, number NCT01153932. We recruited 53 patients: 18 were given continuous drisapersen, 17 were given intermittent drisapersen, and 18 were given placebo (continuous and intermittent groups combined). At week 25, mean 6MWD had increased by 31·5 m (SE 9·8) from baseline for continuous drisapersen, with a mean difference in change from baseline of 35·09 m (95% CI 7·59 to 62·60; p=0·014) versus placebo. We recorded no difference in 6MWD changes from baseline between intermittent drisapersen (mean change -0·1 [SE 10·3]) and placebo (mean difference 3·51 m [-24·34 to 31·35]) at week 25. The most common adverse events in drisapersen-treated patients were injection-site reactions (14 patients given continuous drisapersen, 15 patients given intermittent drisapersen, and six given placebo) and renal events (13 for continuous drisapersen, 12 for intermittent drisapersen, and seven for placebo), most of which were subclinical proteinuria. None of the serious adverse events reported (one for continuous, two for intermittent, and two for placebo) resulted in withdrawal from the study. Continuous drisapersen resulted in some benefit in 6MWD versus placebo at week 25. The safety findings are similar to those from previous studies. Ambulation improvements in this young population with early-stage Duchenne muscular dystrophy are encouraging but need to be confirmed in larger studies. GlaxoSmithKline, Prosensa Therapeutics BV (a subsidiary of Prosensa Holding NV).


Parameter estimation in tree graph metabolic networks.
We study the glycosylation processes that convert initially toxic substrates to nutritionally valuable metabolites in the flavonoid biosynthesis pathway of tomato (Solanum lycopersicum) seedlings. To estimate the reaction rates we use ordinary differential equations (ODEs) to model the enzyme kinetics. A popular choice is to use a system of linear ODEs with constant kinetic rates or to use Michaelis-Menten kinetics. In reality, the catalytic rates, which are affected among other factors by kinetic constants and enzyme concentrations, are changing in time and with the approaches just mentioned, this phenomenon cannot be described. Another problem is that, in general these kinetic coefficients are not always identifiable. A third problem is that, it is not precisely known which enzymes are catalyzing the observed glycosylation processes. With several hundred potential gene candidates, experimental validation using purified target proteins is expensive and time consuming. We aim at reducing this task via mathematical modeling to allow for the pre-selection of most potential gene candidates. In this article we discuss a fast and relatively simple approach to estimate time varying kinetic rates, with three favorable properties: firstly, it allows for identifiable estimation of time dependent parameters in networks with a tree-like structure. Secondly, it is relatively fast compared to usually applied methods that estimate the model derivatives together with the network parameters. Thirdly, by combining the metabolite concentration data with a corresponding microarray data, it can help in detecting the genes related to the enzymatic processes. By comparing the estimated time dynamics of the catalytic rates with time series gene expression data we may assess potential candidate genes behind enzymatic reactions. As an example, we show how to apply this method to select prominent glycosyltransferase genes in tomato seedlings.


Physical activity recommendations for health: what should Europe do?
Accumulating scientific evidence shows physical activity to have profound health benefits amenable to substantial public health gains. Accordingly, recommendations on how much and what kind of physical activity enhances health have been issued. The 1995 recommendation from the U.S. Centres for Disease Control and Prevention and the American College of Sports Medicine has been adapted worldwide, including Europe. Recently an extensive review of new evidence was undertaken and refined recommendations were issued by the U.S. Department of Health and Human Services. We summarise the development of physical activity recommendations and consider the need and possible ways to update the current European situation. The new recommendations include several new elements when compared to the 1995 recommendation, the most notable being the greater emphasis on the contribution of vigorous-intensity activities, and the inclusion of activities for muscle strength and bone health. They also include specific recommendations for young people, middle-aged adults, older adults and some special groups. The existing Pan-European and national physical activity recommendations in Europe are mostly based on the 1995 recommendation and primarily target adults and young people. Thus the degree to which they are compatible with the new recommendations varies. In view of the growing public health importance of physical activity, we discuss the need to review the existing physical activity recommendations at the European level and assess their consistency with the new evidence and the new recommendations. We argue that a review of the current physical activity recommendations in Europe should be undertaken in view of the most recent research evidence. We recommend that such a task should be taken on by WHO Europe in parallel with the ongoing work by WHO global Headquarters. Following this, each country should develop communication strategies and implementation guidelines that take into account their ethnic and cultural diversity.


BioBlocks: Programming Protocols in Biology Made Easier.
The methods to execute biological experiments are evolving. Affordable fluid handling robots and on-demand biology enterprises are making automating entire experiments a reality. Automation offers the benefit of high-throughput experimentation, rapid prototyping, and improved reproducibility of results. However, learning to automate and codify experiments is a difficult task as it requires programming expertise. Here, we present a web-based visual development environment called BioBlocks for describing experimental protocols in biology. It is based on Google's Blockly and Scratch, and requires little or no experience in computer programming to automate the execution of experiments. The experiments can be specified, saved, modified, and shared between multiple users in an easy manner. BioBlocks is open-source and can be customized to execute protocols on local robotic platforms or remotely, that is, in the cloud. It aims to serve as a de facto open standard for programming protocols in Biology.


Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line.
Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2'-Hydroxy-4',6'-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with (1)H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet ((1)H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 μM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 μM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cells treated with 36 μM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time points was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cells were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group) on ring B structure contributed to the selective cytotoxicity against MCF-7 cells compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as a new anticancer drug.


Conservation genetics, foraging distance and nest density of the scarce Great Yellow Bumblebee (Bombus distinguendus).
The conservation genetics of bees is of particular interest because many bee species are in decline, so jeopardizing the essential ecosystem service of plant pollination that they provide. In addition, as social haplodiploids, inbred bees may be vulnerable to the extra genetic load represented by the production of sterile diploid males. Using microsatellite markers, we investigated the genetic structure of populations of the Great Yellow Bumblebee (Bombus distinguendus Morawitz) in the UK, where this species has undergone a precipitous decline. By means of a mixture of analytical methods and simulation, we also extended--and then applied--genetic methods for estimating foraging distance and nest density in wild bees. B. distinguendus populations were characterized by low expected heterozygosity and allelic richness, inbreeding coefficients not significantly different from zero, absence of detected diploid males, absence of substantial demographic bottlenecking, and population substructuring at large (c. 100+ km) but not small (10s of km) spatial scales. The minimum average effective population size at our sampling sites was low (c. 25). In coastal grassland (machair), the estimated modal foraging distance of workers was 391 m, with 95% of foraging activity occurring within 955 m of the nest, and estimated nest density was 19.3 nests km(-2). These findings show that B. distinguendus exhibits some genetic features of scarce, declining or fragmented populations. Moreover, B. distinguendus workers appear to forage over above-average distances and nests remain thinly distributed even in current strongholds. These considerations should inform future conservation actions for this and similar species.


Genomic scale sub-family assignment of protein domains.
Many classification schemes for proteins and domains are either hierarchical or semi-hierarchical yet most databases, especially those offering genome-wide analysis, only provide assignments to sequences at one level of their hierarchy. Given an established hierarchy, the problem of assigning new sequences to lower levels of that existing hierarchy is less hard (but no less important) than the initial top level assignment which requires the detection of the most distant relationships. A solution to this problem is described here in the form of a new procedure which can be thought of as a hybrid between pairwise and profile methods. The hybrid method is a general procedure that can be applied to any pre-defined hierarchy, at any level, including in principle multiple sub-levels. It has been tested on the SCOP classification via the SUPERFAMILY database and performs significantly better than either pairwise or profile methods alone. Perhaps the greatest advantage of the hybrid method over other possible approaches to the problem is that within the framework of an existing profile library, the assignments are fully automatic and come at almost no additional computational cost. Hence it has already been applied at the SCOP family level to all genomes in the SUPERFAMILY database, providing a wealth of new data to the biological and bioinformatics communities.


Cisplatin, fluorouracil, celecoxib, and RT in resectable esophageal cancer: preliminary results.
Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2) enzyme. In preclinical studies, COX-2 inhibition results in decreased cell proliferation and potentiation of chemotherapy and radiation. We report preliminary results of a phase II study conducted by the Hoosier Oncology Group in patients with potentially resectable esophageal cancer. All patients received cisplatin at 75 mg/m2 given on days 1 and 29 and fluorouracil (5-FU) at 1000 mg/m2 on days 1 to 4 and 29 to 32 with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) was administered at 200 mg orally twice daily beginning on day 1 until surgery and then at 400 mg orally twice daily until disease progression or unexpected toxicities, or for a maximum of 5 years. Esophagectomy was performed 4 to 6 weeks after completion of chemoradiation. The primary study endpoint was pathologic complete response (pCR). Secondary endpoints included response rate, toxicity, overall survival, and correlation between COX-2 expression and pCR. Thirty-one patients were enrolled from March 2001 to July 2002. Respective grade 3/4 toxicities were experienced by 58%/19% of patients, and consisted of granulocytopenia (16%), nausea/vomiting (16%), esophagitis (10%), dehydration (10%), stomatitis (6%), and diarrhea (31%). Seven patients (24%) required initiation of enteral feedings. There have been seven deaths so far, resulting from postoperative complications (2), pulmonary embolism (1), pneumonia (1), and progressive disease (3). Of the 22 patients (71%) who underwent surgery, 5 had pCR (22%). We conclude that the addition of celecoxib to chemoradiation is well tolerated. The pCR rate of 22% in this study is similar to that reported with the use of preoperative chemoradiation in other trials. Further follow-up is necessary to assess the impact of maintenance therapy with celecoxib on overall survival.


Recurrent liver failure caused by IgG4 associated cholangitis.
Immunoglobulin G4 associated cholangitis (IAC) is an autoimmune disease associated with autoimmune pancreatitis (AIP). It presents with clinical and radiographic findings similar to primary sclerosing cholangitis (PSC). IAC commonly has a faster, more progressive onset of symptoms and it is more common to see obstructive jaundice in IAC patients compared to those with PSC. One of the hallmarks of IAC is its responsiveness to steroid therapy. Current recommendations for treatment of AIP demonstrate excellent remission of the disease and associated symptoms with initiation of steroid therapy followed by steroid tapering. If untreated, it can progress to irreversible liver failure. This report describes a 59 year-old female with undiagnosed IAC who previously had undergone a pancreaticoduodenectomy for a suspected pancreatic cancer and later developed liver failure from presumed PSC. The patient underwent an uncomplicated liver transplantation at our institution, but experienced allograft failure within five years due to progressive and irreversible bile duct injury. Radiology and histology suggested recurrence of PSC, but the diagnosis of IAC was suspected based on her past history and confirmed when IgG4 positive cells were found within the intrahepatic bile duct walls on a liver biopsy. A successful liver retransplantation was performed and the patient is currently on triple immunosuppressive therapy. Our experience in this case and review of the current literature regarding IAC management suggest that patients with suspected or recurrent PSC with atypical features including history of pancreatitis should undergo testing for IAC as this entity is highly responsive to steroid therapy.


Enamel Matrix Derivative has No Effect on the Chondrogenic Differentiation of Mesenchymal Stem Cells.
Treatment of large bone defects due to trauma, tumor resection, or congenital abnormalities is challenging. Bone tissue engineering using mesenchymal stem cells (MSCs) represents a promising treatment option. However, the quantity and quality of engineered bone tissue are not sufficient to fill large bone defects. The aim of this study was to determine if the addition of enamel matrix derivative (EMD) improves in vitro chondrogenic priming of MSCs to ultimately improve in vivo MSC mediated endochondral bone formation. MSCs were chondrogenically differentiated in 2.0 × 10(5) cell pellets in medium supplemented with TGFβ3 in the absence or presence of 1, 10, or 100 μg/mL EMD. Samples were analyzed for gene expression of RUNX2, Col II, Col X, and Sox9. Protein and glycoaminoglycan (GAG) production were also investigated via DMB assays, histology, and immunohistochemistry. Osteogenic and adipogenic differentiation capacity were also assessed. The addition of EMD did not negatively affect chondrogenic differentiation of adult human MSCs. EMD did not appear to alter GAG production or expression of chondrogenic genes. Osteogenic and adipogenic differentiation were also unaffected though a trend toward decreased adipogenic gene expression was observed. EMD does not affect chondrogenic differentiation of adult human MSCs. As such the use of EMD in combination with chondrogenically primed MSCs for periodontal bone tissue repair is unlikely to have negative effects on MSC differentiation.


Highlights From an Expert Meeting on Opportunities for Cancer Prevention Among Older Adults.
This paper provides highlights from an expert meeting to explore opportunities to reduce cancer risk and promote health at older ages. Factors that increase cancer risk among older adults include exposure to carcinogens from multiple sources, chronic conditions such as obesity and diabetes, and unhealthy behaviors. Emerging research points to chronic social stressors - social isolation, loneliness, and financial hardship - as being linked to accelerated biological aging and increased cancer risk later in life. Older adults may disproportionately encounter these stressors as well as barriers to preventive health care services, accurate health information, and environments that promote health. Researchers can use existing cohort studies of older adults to deepen our understanding of the relative benefit of modifying specific behaviors and circumstances. The evidence points to the value of comprehensive, transdisciplinary approaches to promote health and reduce cancer risk across the entire lifespan, extending through older adulthood. Clinical encounters with older adults provide opportunities for psychosocial and behavioral screening and counseling. In the presence of multiple morbidities, preventive health services may offer greater health benefits than cancer-screening tests. Strategies that involve families and caregivers, promote positive attitudes about aging, and engage many different community sectors have the potential to prevent or delay the development of cancer at older ages.


Effects of hyperventilation on conjunctival oxygen tension in humans.
A polarographic conjunctival oxygen sensor was used to measure oxygen tension in a tissue bed supplied by the internal carotid artery. The shared vascular source of the conjunctiva and brain suggests that conjunctival PO2 monitoring may provide an index of cerebral perfusion. We studied the effects of hyperventilation, a known stimulus of cerebral vasoconstriction, on conjunctival oxygen tension (PcjO2) in six normal, healthy adults; arterial blood gases were simultaneously measured in four of these subjects. A 5-min period of hyperventilation to a PaCO2 near 20 torr resulted in a rapid and significant (p less than .01) increase in systemic oxygen tension as measured by arterial blood gases and a transcutaneous oxygen monitor. These values gradually returned to baseline upon cessation of hyperventilation. PcjO2, however, decreased significantly (p less than .01) during hyperventilation, suggesting vasoconstriction of the conjunctival vascular supply. Because these changes temporally correlate with the cerebral vasoconstriction during hyperventilation, the conjunctival index of tissue oxygen tension may correlate with cerebral perfusion.


Prospective multi-center study on expansion sphincter pharyngoplasty.
The aim of this study was to demonstrate the long-term effectiveness of Expansion Sphincter Pharyngoplasty (ESP) as a standalone surgical treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) patients through a prospective multi-center study. A prospective non-comparative multicenter study of patients suffering from OSHAS selected after drug-induced sleep endoscopy, with ESP as standing alone procedure was performed. Inclusion criteria were lateral collapse on oropharynx and preoperative AHI between 5 and 70. Minimum follow-up was >12 months. Outcome measures were Epworth sleepiness scale (ESS), AHI, success rate and CPAP need after surgery. A total of 75 ESP were performed. Mean patient age was 46.7 ± 10.5 years. Mean pre-operative and post-operative AHI was 22.1 ± 12.2 and 8.6 ± 6.7, respectively (p < .001). Mean pre-operative and post-operative ESS score was 11.5 ± 4.7 and 4.6 ± 6.6, respectively (p < .001). AHI <5 was obtained in 25 patients (33.3%), and CPAP was not further needed after surgery in a total of 62 patients (82.6%). In this prospective multi-center study, patients undergoing ESP standing alone for the treatment of OSAHS have a reasonable expectation for success with minimal morbidity.


Is asthma prevalence still increasing?
Increased awareness of asthma in society and altered diagnostic practices makes evaluation of data on prevalence change difficult. In most parts of the world the asthma prevalence seems to still be increasing. The increase is associated with urbanization and has been documented particularly among children and teenagers in urban areas of middle- and low-level income countries. Use of validated questionnaires has enabled comparisons of studies. Among adults there are few studies based on representative samples of the general population which allow evaluation of time trends of prevalence. This review focuses mainly on studies of asthma prevalence and symptoms among adults. Parallel with increased urbanization, we can assume that the increase in asthma prevalence in most areas of the world will continue. However, in Australia and North-West Europe studies performed, particularly among children and adolescents, indicate that the increase in asthma prevalence may now be leveling off.


[Handling G-protein-coupled receptors: expression, purification and in vitro stabilization].
Among the different classes of integral membrane proteins, G protein-coupled receptors (GPCR) constitute the largest family. They are involved in most essential physiological functions and particularly play a key role in cell-to-cell communication and sensory signal transduction. They represent targets for approximately 30% of currently marketed drugs. In order to better understand their functioning, define their tridimensional structure and develop novel selective and efficient therapeutic compounds, it is crucial to purify these proteins for a full characterization. However, this biochemical step is not trivial since GPCR are present in membranes at very low levels and they require detergents to be extracted from their natural lipid environment and be handled as functional proteins. No universal strategy for GPCR production, purification and stabilization is currently available; each single GPCR possesses a unique set of physicochemical characteristics, preference for some detergents upon solubilization and specific conditions for purification. During the last decade, major breakthroughs regarding overexpression, purification and above all GPCR stabilization, thanks to amphipols and nanodiscs, opened very exciting perspectives for structural and dynamic investigations of these membrane proteins. The aim of this chapter is to provide an overview of the different aspects of GPCR handling.


Polyubiquitin insertions and the phylogeny of Cercozoa and Rhizaria.
A single or double amino acid insertion at the monomer-monomer junction of the universal eukaryotic protein polyubiquitin is unique to Cercozoa and Foraminifera, closely related 'core' phyla in the protozoan infrakingdom Rhizaria. We screened 11 other candidate rhizarians for this insertion: Radiozoa (polycystine and acantharean radiolaria), a 'microheliozoan', and Apusozoa; all lack it, supporting suggestions that Foraminifera are more closely related to Cercozoa than either is to other eukaryotes. The insertion's size was ascertained for 12 additional Cercozoa to help resolve their basal branching order. The earliest branching Cercozoa generally have a single amino acid insertion, like all Foraminifera, but a large derived clade consisting of all Monadofilosa except Metopion, Helk-esimastix, and Cercobodo agilis has two amino acids, suggesting one doubling event and no reversions to a single amino acid. Metromonas and Sainouron, cercozoans of uncertain position, have a double insertion, suggesting that they belong in Monadofilosa. An alternative interpretation, suggested by the higher positions for Metopion and Cercobodo on Bayesian trees compared with most distance trees, cannot be ruled out, i.e. that the second insertion took place earlier, in the ancestral filosan, and was followed by three independent reversions to a single amino acid in Chlorarachnea, Metopion and Cercobodo.


Ecological studies of enzootic Venezuelan equine encephalitis in north-central Venezuela, 1997-1998.
From 1997-1998, we investigated the possible continuous circulation of epizootic Venezuelan equine encephalitis (VEE) virus suggested by a 1983 subtype IC interepizootic mosquito isolate made in Panaquire, Miranda State, Venezuela. The study area was originally covered by lowland tropical rainforest but has been converted into cacao plantations. Sentinel hamsters, small mammal trapping, mosquito collections, and human serosurveys were used to detect active or recent virus circulation. Six strains of subtype ID VEE virus were isolated from hamsters that displayed no apparent disease. Four other arboviruses belonging to group A (Togaviridae: Alphavirus), two Bunyamwera group (Bunyaviridae), and three Gamboa group (Bunyaviridae) arboviruses were also isolated from hamsters, as well as 8 unidentified viruses. Venezuelan equine encephalitis-specific antibodies were detected in 5 small mammal species: Proechimys guairae, Marmosa spp., and Didelphis marsupialis. Mosquito collections comprised of 38 different species, including 8 members of the subgenus Culex (Melanoconion), did not yield any virus isolates. Sera from 195 humans, either workers in the cacao plantation or nearby residents, were all negative for VEE virus antibodies. Sequences of 1,677 nucleotides from the P62 gene of 2 virus isolates indicated that they represent a subtype ID lineage that is distinct from all others characterized previously, and are unrelated to epizootic VEE emergence.


Validation of QuEChERS method for the determination of some pesticide residues in two apple varieties.
This study was undertaken to validate the "quick, easy, cheap, effective, rugged and safe" (QuEChERS) method using Golden Delicious and Starking Delicious apple matrices spiked at 0.1 maximum residue limit (MRL), 1.0 MRL and 10 MRL levels of the four pesticides (chlorpyrifos, dimethoate, indoxacarb and imidacloprid). For the extraction and cleanup, original QuEChERS method was followed, then the samples were subjected to liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) for chromatographic analyses. According to t test, matrix effect was not significant for chlorpyrifos in both sample matrices, but it was significant for dimethoate, indoxacarb and imidacloprid in both sample matrices. Thus, matrix-matched calibration (MC) was used to compensate matrix effect and quantifications were carried out by using MC. The overall recovery of the method was 90.15% with a relative standard deviation of 13.27% (n = 330). Estimated method detection limit of analytes blew the MRLs. Some other parameters of the method validation, such as recovery, precision, accuracy and linearity were found to be within the required ranges.


Probiotics for patients with hepatic encephalopathy.
Hepatic encephalopathy is a disorder of brain function as a result of liver failure and/or portosystemic shunt. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning and represent a significant burden on health care resources. Probiotics are live microorganisms, which when administered in adequate amounts may confer a health benefit on the host. To quantify the beneficial and harmful effects of any probiotic in any dosage, compared with placebo or no intervention, or with any other treatment for patients with any grade of acute or chronic hepatic encephalopathy as assessed from randomised trials. We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, conference proceedings, reference lists of included trials and the WHO international clinical trials registry until April 2011 registry platform to identify new and ongoing trials. We included randomised trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in patients with hepatic encephalopathy. Three authors independently assessed the risk of bias of the included trials and extracted data on relevant outcomes, with differences resolved by consensus. We conducted random-effects model meta-analysis due to obvious heterogeneity of patients and interventions. A P value of 0.05 or less was defined as significant. Dichotomous outcomes are expressed as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). We included seven trials of which 550 participants were randomised. Four of the seven trials compared a probiotic with placebo or no treatment in 245 participants, another trial compared a probiotic with lactulose in 40 participants , and the remaining two trials compared a probiotic with both placebo and lactulose in 265 participants. Each trial used different types of probiotics. Duration of administration of the experimental intervention varied from 10 days to 180 days. Two trials were industry funded, and five were unclear about origin of funding. All trials had high risk of bias. When probiotics were compared with no treatment, there was no significant difference in all-cause mortality (2 trials, 105 participants; 1/57 (2%) versus 1/48 (2%): RR 0.72; 95% CI 0.08 to 6.60), lack of recovery (4 trials, 206 participants; 54/107 (50%) versus 68/99 (69%): RR 0.72; 95% CI 0.49 to 1.05), adverse events (3 trials, 145 participants; 2/77 (3%) versus 6/68 (9%): RR 0.34; 95% CI 0.08 to 1.42), quality of life (1 trial, 20 participants contributed to the physical quality of life measurement, 20 participants contributed to the mental quality of life: MD Physical 0.00; 95% CI -5.47 to 5.47; MD Mental 4.00; 95% CI -1.82 to 9.82), or change of/or withdrawal from treatment (3 trials, 175 participants; 11/92 (12%) versus 7/83 (8%): RR 1.28; 95% CI 0.52 to 3.19). No trial reported sepsis or duration of hospital stay as an outcome. Plasma ammonia concentration was significantly lower for participants treated with probiotic at one month (3 trials, 226 participants: MD -2.99 μmol/L; 95% CI -5.70 to -0.29) but not at two months (3 trials, 181 participants: MD -1.82 μmol/L; 95% CI -14.04 to 10.41). Plasma ammonia decreased the most in the participants treated with probiotic at three months (1 trial, 73 participants: MD -6.79 μmol/L; 95% CI -10.39 to -3.19). When probiotics were compared with lactulose no trial reported all-cause mortality, quality of life, duration of hospital stay, or septicaemia. There were no significant differences in lack of recovery (3 trials, 173 participants; 47/87 (54%) versus 44/86 (51%): RR 1.05; 95% CI 0.75 to 1.47), adverse events (2 trials, 111 participants; 3/56 (5%) versus 6/55 (11%): RR 0.57; 95% CI 0.06 to 5.74), change of/or withdrawal from treatment at one month (3 trials, 190 participants; 8/95 (8%) versus 7/95 (7%): RR 1.10; 95% CI 0.40 to 3.03), plasma ammonia concentration (2 trials, 93 participants: MD -6.61 μmol/L; 95% CI -30.05 to 16.84), or change in plasma ammonia concentration (1 trial, 77 participants: MD 1.16 μmol/L; 95% CI -1.96 to 4.28). The trials we located suffered from a high risk of systematic errors ('bias') and high risk of random errors ('play of chance'). While probiotics appear to reduce plasma ammonia concentration when compared with placebo or no intervention, we are unable to conclude that probiotics are efficacious in altering clinically relevant outcomes. Demonstration of unequivocal efficacy is needed before probiotics can be endorsed as effective therapy for hepatic encephalopathy. Further randomised clinical trials are needed.


[How can serology contribute to the diagnosis of parasitic diseases?].
From a technical standpoint the most widely used tests for serology include the ELISA (enzyme linked immunosorbent assay), the IFA (indirect fluorescence assay), and the immunoblot. ELISA tests are widely used as screening assays since they harbor a high sensitivity. The main pitfall of serologies is the frequency of cross-reactions, especially between the different helminths. This is why positive results should be confirmed by a second test method with a higher specificity. Results need also to be put in the perspective of the patient history, clinical signs and laboratory findings. Serological tests are most appropriate when the parasite cannot be documented by direct examination (by eye or under the microscope) and during the pre-patent period. Serologies for parasites are also useful when an unexplained eosinophilia is present.


Current situation and the development of the dairy industry in Jordan, Saudi Arabia, and Syria.
The development of the dairy industry plays an important role in the economy of Middle Eastern countries. Judged by its growth rate, the dairy industry is viewed as one of the most progressive food industries in the Middle East. During the early 1970s, countries established executive programs to promote dairy farming; the major objective was to attain self-sufficiency in milk production. A massive investment was set up for importing top class cattle, complying with top industry operating standards, and a simultaneous introduction of the latest technology in processing, packaging, and distributing. Milk production has grown tremendously at rates of 6.6% and 4.9% in Syria and Saudi Arabia, respectively, between 2002 and 2007, which resulted in these nations being almost self-sufficient. Regarding Jordan, milk production has not yet met this target. An excessive growth in the dairy industry is quite noticeable in this region with an expanding capacity for exports. The aim of this study is to show the most recent trends and future prospects of the dairy industries in Syria, Saudi Arabia, and Jordan. It also attempts to investigate the drivers for the development of milk production, consumption, and trade in the region.


Validation of the Eating Disorder Examination Questionnaire: an online version.
Internet-based interventions can facilitate an anonymous environment for the management of eating disorders and there is a need for online assessment tools to be readily available. The present study aimed to validate an online version of the Eating Disorder Examination Questionnaire (EDE-Q) and to compare the goodness-of-fit of five models of EDE-Q data, using a sample of university students in Hong Kong. The EDE-Q data were collected online from 310 Hong Kong university students. Confirmatory factor analysis was used to compare the validity of the original four-factor EDE-Q with that of the three-factor, two-factor, one-factor and brief one-factor models. The superior model was further examined for scale reliability, convergent validity and construct validity using contrast-group comparisons. The brief one-factor model consisting of eight Weight and Shape Concern items was the only model to provide an acceptable fit to the data. Estimations of internal consistency and scale validity were conducted using contrast-group comparisons and convergent validity, with satisfactory results. The brief one-factor model was the only one among the alternate models that provided good fit to the data. The brief model is promising for use in research and has good practical application because the model was satisfactorily tested in terms of internal consistency, ability to discriminate between genders, and good association with other measures of similar constructs. By validating an online version of the EDE-Q using a university sample with a cultural background different from Western culture, the present study complements findings from previous research on the EDE-Q.


Predictors of ovarian malignancy in children: overcoming clinical barriers of ovarian preservation.
Ovarian preservation is desirable in girls with benign ovarian masses. We aimed to 1) identify clinical predictors of malignant ovarian masses, 2) investigate how often ovarian tissue is present to preserve in benign masses, and 3) identify factors associated with successful ovarian preservation. Retrospective analysis (1997-2012) of girls age 1-18years with an ovarian mass managed operatively. Data on presenting symptoms, imaging, biochemical markers, treatment, outcome, and pathology were extracted. We identified 150 patients. Large mass size, solid components, and elevated tumor markers (AFP, βHCG, and/or LDH) were significantly predictive of malignancy. All masses <10cm, predominantly cystic, and with negative tumor markers were benign. Masses with all three of these characteristics would decrease a 20% malignancy pretest probability to a posttest probability of 0.25%. Benign masses managed by oophorectomy contained normal ovarian tissue in 76% of the specimens. For benign masses, successful ovarian preservation was significantly associated with size <10cm, predominantly cystic, laparoscopy, and absence of torsion or calcifications. Ovarian masses that are <10cm, primarily cystic, and have negative tumor markers are most likely benign. Viable ovarian tissue is frequently present in benign masses, so significant efforts should be made for ovarian preservation.


Long-Term Effects of (-)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PIA) in Female Dark Agouti Rats.
Rheumatoid arthritis (RA)--a widespread chronic inflammatory disease in industrialized countries--is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the pharmacological mode of action of this polyphenol.


Neural correlates of endogenous attention, exogenous attention and inhibition of return in touch.
Selective attention helps process the myriad of information constantly touching our body. Both endogenous and exogenous mechanisms are relied upon to effectively process this information; however, it is unclear how they relate in the sense of touch. In three tasks we contrasted endogenous and exogenous event-related potential (ERP) and behavioural effects. Unilateral tactile cues were followed by a tactile target at the same or opposite hand. Clear behavioural effects showed facilitation of expected targets both when the cue predicted targets at the same (endogenous predictive task) and opposite hand (endogenous counter-predictive task), and these effects also correlated with ERP effects of endogenous attention. In an exogenous task, where the cue was non-informative, inhibition of return (IOR) was observed. The electrophysiological results demonstrated early effects of exogenous attention followed by later endogenous attention modulations. These effects were independent in both the endogenous predictive and exogenous tasks. However, voluntarily directing attention away from a cued body part influenced the early exogenous marker (N80). This suggests that the two mechanisms are interdependent, at least when the task requires more demanding shifts of attention. The early marker of exogenous tactile attention, the N80, was not directly related to IOR, which may suggest that exogenous attention and IOR are not necessarily two sides of the same coin. This study adds valuable new insight into how we process and select information presented to our body, showing both independent and interdependent effects of endogenous and exogenous attention in touch.


Achilles tendinosis does not always precede Achilles tendon rupture.
Degenerative change is a typical histologic finding of Achilles tendinosis and is thought to be a factor associated with Achilles tendon rupture; however, this relationship remains controversial. Therefore, the aim of this study was to review the histological findings of ruptured Achilles tendons and analyze demographics and injury patterns. Retrospective analysis was performed for all patients who underwent Achilles tendon repair for acute Achilles tendon rupture at our institution between 2008 and 2015. The presence of Achilles tendinosis was determined by light microscopic histology of ruptured Achilles tendons. Patients were grouped according to the presence of Achilles tendinosis and patient demographics, sports activities, and clinical outcomes were compared. Ankle activity score was used to evaluate the level of sports activity and Achilles tendon total rupture score (ATRS) was used to evaluate clinical outcomes. A total of 152 Achilles tendon ruptures were included: 112 (77%) showed Achilles tendinosis at a ruptured Achilles tendon on histology and 40 (23%) did not. Patients who had no Achilles tendinosis prior to rupture had a lower ankle activity score (P < 0.05) and higher incidence of non-sports related injury (P < 0.05). ATRS was not significantly different between the groups at final follow-up (P = n.s.). In contrast to previous reports, Achilles tendon rupture can occur without prior Achilles tendinosis, especially in non-sports-related injuries and in patients with low sports activity. Although the direct clinical applications of these results are limited, the findings of this study can improve our understanding of the etiology of Achilles tendon rupture. Prognostic, Level III.


Optogenetic Rescue of a Patterning Mutant.
Animal embryos are patterned by a handful of highly conserved inductive signals. Yet, in most cases, it is unknown which pattern features (i.e., spatial gradients or temporal dynamics) are required to support normal development. An ideal experiment to address this question would be to "paint" arbitrary synthetic signaling patterns on "blank canvas" embryos to dissect their requirements. Here, we demonstrate exactly this capability by combining optogenetic control of Ras/extracellular signal-related kinase (ERK) signaling with the genetic loss of the receptor tyrosine-kinase-driven terminal signaling patterning in early Drosophila embryos. Blue-light illumination at the embryonic termini for 90 min was sufficient to rescue normal development, generating viable larvae and fertile adults from an otherwise lethal terminal signaling mutant. Optogenetic rescue was possible even using a simple, all-or-none light input that reduced the gradient of Erk activity and eliminated spatiotemporal differences in terminal gap gene expression. Systematically varying illumination parameters further revealed that at least three distinct developmental programs are triggered at different signaling thresholds and that the morphogenetic movements of gastrulation are robust to a 3-fold variation in the posterior pattern width. These results open the door to controlling tissue organization with simple optical stimuli, providing new tools to probe natural developmental processes, create synthetic tissues with defined organization, or directly correct the patterning errors that underlie developmental defects.


Protective or deleterious role of scavenger receptors SR-A and CD36 on host resistance to Staphylococcus aureus depends on the site of infection.
Staphylococcus aureus is a major human opportunistic pathogen responsible for a broad spectrum of infections ranging from benign skin infection to more severe life threatening disorders (e.g. pneumonia, sepsis), particularly in intensive care patients. Scavenger receptors (SR-A and CD36) are known to be involved in S. aureus recognition by immune cells in addition to MARCO, TLR2, NOD2 and α5β1 integrin. In the present study, we further deciphered the contribution of SR-A and CD36 scavenger receptors in the control of infection of mice by S. aureus. Using double SR-A/CD36 knockout mice (S/C-KO) and S. aureus strain HG001, a clinically relevant non-mutagenized strain, we showed that the absence of these two scavenger receptors was protective in peritoneal infection. In contrast, the deletion of these two receptors was detrimental in pulmonary infection following intranasal instillation. For pulmonary infection, susceptible mice (S/C-KO) had more colony-forming units (CFU) in their broncho-alveolar lavages fluids, associated with increased recruitment of macrophages and neutrophils. For peritoneal infection, susceptible mice (wild-type) had more CFU in their blood, but recruited less macrophages and neutrophils in the peritoneal cavity than resistant mice. Exacerbated cytokine levels were often observed in the susceptible mice in the infected compartment as well as in the plasma. The exception was the enhanced compartmentalized expression of IL-1β for the resistant mice (S/C-KO) after peritoneal infection. A similar mirrored susceptibility to S. aureus infection was also observed for MARCO and TLR2. Marco and tlr2 -/- mice were more resistant to peritoneal infection but more susceptible to pulmonary infection than wild type mice. In conclusion, our results show that innate immune receptors can play distinct and opposite roles depending on the site of infection. Their presence is protective for local pulmonary infection, whereas it becomes detrimental in the peritoneal infection.


Accumulation of a recombinant immunotoxin in a tumor in vivo: fewer than 1000 molecules per cell are sufficient for complete responses.
Recombinant immunotoxins have been shown to cure human tumor xenografts in mice, but their biodistribution to both tumors and normal organs has not been reported. Anti-Tac(Fv)-PE38 is a single-chain recombinant immunotoxin composed of the variable heavy and light domains of the anti-Tac monoclonal antibody that reacts with the primate interleukin 2 (IL2) receptor alpha subunit (IL2R alpha or CD25) fused to a truncated form of Pseudomonas exotoxin (PE). 125I-labeled anti-Tac(Fv)-PE38 was given i.v. to immunodeficient mice each bearing two A431 tumors, one that expresses IL2R alpha (ATAC-4) and one that does not (A431, parental). A single i.v. dose of 4 microg/mouse caused complete regression of the IL2R alpha + tumor. At 6 h, over 6% of the injected dose/g was found in the ATAC-4 tumor, and 2% was in the A431 tumor. Uptake in the ATAC-4 tumor was higher than in any other tissue. Sections of tumor examined by autoradiography indicated that anti-Tac(Fv)-PE38 was distributed throughout the entire tumor, with some portions having higher uptake than others. By subtracting uptake in tumors without receptor (A431) from uptake in receptor-containing tumors (ATAC-4), we calculated that at least 400 molecules/cell specifically bound to IL2R alpha-positive tumor cells at 90 min and 750 molecules/cell bound at 360 min. This is similar to the 400-870 molecules/cell required for >99.9% killing of ATAC-4 cells growing as a monolayer. The results show that solid tumors in mice can be eradicated like cells in tissue culture, and that delivery of less than 1000 molecules/cell is sufficient to cause complete tumor regressions.


Developing a national performance indicator framework for the Dutch health system.
To report on the first phase of the development of a national performance indicator framework for the Dutch health system. In January 2002, we initiated an informed interactive process with the intended users-policymakers at the Ministry of Health, Welfare and Sport-and academics to develop both the conceptual framework and its content. Decisions were based on consensus after discussing strategic goals of the health system, information needs of policy makers at the Ministry of Health, Welfare and Sport, and studying existing theory and international experiences with national performance indicator frameworks. We identified objectives and criteria for a framework at the national level, constructed a conceptual model, and selected indicator areas. As a starting point we chose a balanced scorecard reflecting four perspectives towards health system management information at the national level. These perspectives are consumer orientation, finances, delivery of high quality care, and the ability to learn and grow. We then linked the Lalonde model for population health to a balanced scorecard model. The constructed model makes the relationship between population health and health system management apparent, and facilitates the presentation of performance information from various perspectives. The model reflects the strategic goals of the Dutch health system, i.e. contributing to the production of health by providing necessary health care of good quality that is accessible for all Dutch citizens while simultaneously informing policy makers about the performance of the entire health system in all sectors (care, cure, prevention, and social services). The selected indicator areas for health system management information (20 in total) reflect the policy and management functions of the government and the defined public goals of the health system. The model was formally adopted by the Ministry of Health, Welfare and Sport in February 2003, and since then individual indicator areas have been operationalized by 30 representatives of various departments at the Ministry with continuous external research support. The merit of linking the balanced scorecard inspired model to public health data is that it facilitates the visualization of the contribution of the health system to the improvement of population health. The method of an intensive interactive indicator development process between policy makers and researchers has so far proven successful.


Use of systemic agents in the treatment of acne vulgaris.
Effective treatment of acne vulgaris can prevent emotional and physical scarring. Therapy varies according to the severity of the disease. Topical medication is generally adequate in clearing comedonal acne, while inflammatory acne usually requires the addition of oral medication. Systemic antibiotics are used most frequently and can be highly effective. Newer formulations of combined oral contraceptives are also helpful in modulating sebum production in the female patient. Severe nodulocystic acne that does not respond to topical retinoids and systemic antibiotics may be treated with isotretinoin. However, the side effect profile of this medication is extensive, and physicians should be well-versed in its potential adverse effects.


Zen meditation: an integration of current evidence.
Despite the growing interest in the neurobiological and clinical correlates of many meditative practices, in particular mindfulness meditations, no review has specifically focused on current evidence on electroencephalographic, neuroimaging, biological, and clinical evidence about an important traditional practice, Zen meditation. A literature search was conducted using MEDLINE, the ISI Web of Knowledge, the Cochrane collaboration database, and references of selected articles. Randomized controlled and cross-sectional studies with controls published in English prior to May 2008 were included. Electroencephalographic studies on Zen meditation found increased alpha and theta activity, generally related to relaxation, in many brain regions, including the frontal cortex. Theta activity in particular seemed to be related to the degree of experience, being greater in expert practitioners and advanced masters. Moreover, Zen meditation practice could protect from cognitive decline usually associated with age and enhance antioxidant activity. From a clinical point of view, Zen meditation was found to reduce stress and blood pressure, and be efficacious for a variety of conditions, as suggested by positive findings in therapists and musicians. To date, actual evidence about Zen meditation is scarce and highlights the necessity of further investigations. Comparison with further active treatments, explanation of possible mechanisms of action, and the limitations of current evidence are discussed.


Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.
To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy. GRADE-based systematic review followed by expert consensus achieved using Web-based Delphi methodology, conference calls and face-to-face meetings. Predictors based on clinical examination, electrophysiology, biomarkers and imaging were included. Evidence from a total of 73 studies was reviewed. The quality of evidence was low or very low for almost all studies. In patients who are comatose with absent or extensor motor response at ≥ 72 h from arrest, either treated or not treated with controlled temperature, bilateral absence of either pupillary and corneal reflexes or N20 wave of short-latency somatosensory evoked potentials were identified as the most robust predictors. Early status myoclonus, elevated values of neuron-specific enolase at 48-72 h from arrest, unreactive malignant EEG patterns after rewarming, and presence of diffuse signs of postanoxic injury on either computed tomography or magnetic resonance imaging were identified as useful but less robust predictors. Prolonged observation and repeated assessments should be considered when results of initial assessment are inconclusive. Although no specific combination of predictors is sufficiently supported by available evidence, a multimodal prognostication approach is recommended in all patients.


Feeding in billfishes: inferring the role of the rostrum from a biomechanical standpoint.
Perhaps the most striking feature of billfishes is the extreme elongation of the premaxillary bones forming their rostra. Surprisingly, the exact role of this structure in feeding is still controversial. The goal of this study is to investigate the use of the rostrum from a functional, biomechanical and morphological standpoint to ultimately infer its possible role during feeding. Using beam theory, experimental and theoretical loading tests were performed on the rostra from two morphologically different billfish, the blue marlin (Makaira nigricans) and the swordfish (Xiphias gladius). Two loading regimes were applied (dorsoventral and lateral) to simulate possible striking behaviors. Histological samples and material properties of the rostra were obtained along their lengths to further characterize structure and mechanical performance. Intraspecific results show similar stress distributions for most regions of the rostra, suggesting that this structure may be designed to withstand continuous loadings with no particular region of stress concentration. Although material stiffness increased distally, flexural stiffness increased proximally owing to higher second moment of area. The blue marlin rostrum was stiffer and resisted considerably higher loads for both loading planes compared with that of the swordfish. However, when a continuous load along the rostrum was considered, simulating the rostrum swinging through the water, swordfish exhibited lower stress and drag during lateral loading. Our combined results suggest that the swordfish rostrum is suited for lateral swiping to incapacitate their prey, whereas the blue marlin rostrum is better suited to strike prey from a wider variety of directions.


Value of information and pricing new healthcare interventions.
Previous application of value-of-information methods to optimal clinical trial design have predominantly taken a societal decision-making perspective, implicitly assuming that healthcare costs are covered through public expenditure and trial research is funded by government or donation-based philanthropic agencies. In this paper, we consider the interaction between interrelated perspectives of a societal decision maker (e.g. the National Institute for Health and Clinical Excellence [NICE] in the UK) charged with the responsibility for approving new health interventions for reimbursement and the company that holds the patent for a new intervention. We establish optimal decision making from societal and company perspectives, allowing for trade-offs between the value and cost of research and the price of the new intervention. Given the current level of evidence, there exists a maximum (threshold) price acceptable to the decision maker. Submission for approval with prices above this threshold will be refused. Given the current level of evidence and the decision maker's threshold price, there exists a minimum (threshold) price acceptable to the company. If the decision maker's threshold price exceeds the company's, then current evidence is sufficient since any price between the thresholds is acceptable to both. On the other hand, if the decision maker's threshold price is lower than the company's, then no price is acceptable to both and the company's optimal strategy is to commission additional research. The methods are illustrated using a recent example from the literature.


Research Techniques Made Simple: Web-Based Survey Research in Dermatology: Conduct and Applications.
Web-based surveys, or e-surveys, are surveys designed and delivered using the internet. The use of these survey tools is becoming increasingly common in medical research. Their advantages are appealing to surveyors because they allow for rapid development and administration of surveys, fast data collection and analysis, low cost, and fewer errors due to manual data entry than telephone or mailed questionnaires. Internet surveys may be used in clinical and academic research settings with improved speed and efficacy of data collection compared with paper or verbal survey modalities. However, limitations such as potentially low response rates, demographic biases, and variations in computer literacy and internet access remain areas of concern. We aim to briefly describe some of the currently available Web-based survey tools, focusing on advantages and limitations to help guide their use and application in dermatologic research.


Comparision of health needs of older people between affected rural and urban areas after the 2005 Kashmir, Pakistan earthquake.
On 08 October 2005, an earthquake measuring 7.6 on the Richter scale, struck Pakistan's autonomous state of Kashmir and part of Indian-administrated Kashmir.The official death toll in Pakistan was 79,000, and nearly 1,400 in Kashmir. This study reports the findings of a three-week health needs assessment to understand the needs of rural, older people postearthquake. This study was conducted in February 2006 in the Neelum Valley of Kashmir, Pakistan, four months after the earthquake. During emergency relief, the vulnerability and health needs of older people in rural settings are different than are those in of urban areas. A comparative, descriptive study was performed using health information to compare the differences between rural and urban health needs and the utilization of services of older people after the earthquake. Semi-structured interviews were conducted to collect information regarding demographic background, medical and drug history, self-reported health status, healthcare access and utilization, and social/financial concerns. Clinical records were reviewed and physical indicators for older patients also were collected on-site. The health profile, access to health care, service availability, and prevalence of non-communicable diseases differ between urban and rural settings. The greatest gap in health services at all sites was that non-communicable disease management was inadequate during non-acute, post-earthquake medical care. Health service utilization varied by gender, as in conservative rural areas, older, traditional women were less likely to receive medical services while older men were less likely to access psychological services in all sites. This is the first study to compare the post-earthquake healthcare needs of older people in urban and rural settings. Findings highlight specific health needs and issues related to long-term, chronic disease management. Given the global pattern of aging of the population, it is important to strengthen the capacity to respond appropriately to medical disasters, which includes preparedness for treating the health needs of older people.


Triathlete Risk of Pelvic Floor Disorders, Pelvic Girdle Pain, and Female Athlete Triad.
Our primary objective was to describe the prevalence of pelvic floor disorders (PFDs), pelvic girdle pain (PGP), and the female athlete triad (disordered eating, menstrual irregularities, and osteoporosis) in a female triathlete population. We also evaluated for an association between these conditions. We administered an online survey to women who self-identified as female triathletes. Using validated questionnaires, Epidemiology of Prolapse and Incontinence Questionnaire and Pelvic Girdle Questionnaire, along with the female athlete triad questionnaire, we identified the prevalence of PFDs, PGP, and female athlete triad in this specific population. Demographic and exercise intensity were also queried to characterize these female triathletes. Three hundred eleven female triathletes responded to the Internet survey. There was a significant prevalence of PFDs with stress urinary incontinence and anal incontinence symptoms being most common (37.4% and 28%, respectively). Urgency urinary incontinence and pelvic organ prolapse were less common (16% and 5%, respectively). Stress urinary incontinence and pelvic organ prolapse were more common in parous triathletes (P = 0.001, P = 0.05). Pelvic girdle pain was noted in 18% of these triathletes but was not disabling. Twenty-four percent of participants screened positive for at least 1 arm of the female athlete triad. No association was found between the female athlete triad and PFDs. Pelvic floor disorders are common and bothersome in female triathletes. Pelvic girdle pain, while present, does not limit these athletes from their training. These female triathletes may be at risk for the female athlete triad. Female triathletes may be at risk for both metabolic and PFDs and should be screened when identified.


Innovation in creating a strategic plan for research within an academic community.
Strategic planning for research priorities in schools of nursing requires consensus building and engagement of key stakeholders. However, traditional approaches to strategic planning using work groups and committees sometimes result in low rates of faculty participation and fail to engage other important stakeholders. The purpose of this article is to describe the unique low-cost, high-yield processes that contributed to the rapid development of our school's strategic research plan over the course of 1 month. Using the name recognition of the National Collegiate Athletic Association's annual basketball tournament, we were able to encourage high levels of participation by faculty, doctoral students, and postdoctoral fellows in not only developing a consensus around eight broad lines of inquiry but also offering tangible recommendations for accomplishing those goals within the next 5 years. Other schools of nursing seeking to evaluate their research enterprise and align their science with national priorities could easily replicate this approach.


Honokiol inhibits U87MG human glioblastoma cell invasion through endothelial cells by regulating membrane permeability and the epithelial-mesenchymal transition.
Glioblastoma is one of the most lethal and prevalent malignant human brain tumors, with aggressive proliferation and highly invasive properties. There is still no effective cure for patients with glioblastoma. Honokiol, derived from Magnolia officinalis, can cross the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), making it a strong candidate for an effective drug for the treatment of brain tumors, including glioblastoma. In our previous study, we demonstrated that honokiol effectively induced apoptotic cell death in glioblastoma. Metastasis poses the largest problem to cancer treatment and is the primary cause of death in cancer patients. Thus, in this study, we investigated the effect of honokiol on the cell invasion process of U87MG human glioblastoma cells through brain microvascular endothelial cells (BMECs) and its possible mechanisms. Honokiol dose-dependently inhibited TNF-α-induced VCAM-1 expression in BMECs and adhesion of U87MG to BMECs. Moreover, honokiol effectively blocked U87MG invasion through BMEC-Matrigel-coated transwell membranes. Increased phosphorylation of VE-cadherin and membrane permeability by TNF-α were suppressed by honokiol in BMECs. Furthermore, we investigated the effect of honokiol on the epithelial-mesenchymal transition (EMT) in U87MG cells. Honokiol reduced the expression levels of Snail, N-cadherin and β-catenin, which are mesenchymal markers, but increased E-cadherin, an epithelial marker. In conclusion, these results suggest that honokiol inhibits metastasis by targeting the interaction between U87MG and BMECs, regulating the adhesion of U87MG to BMECs by inhibiting VCAM-1, and regulating the invasion of U87MG through BMECs by reducing membrane permeability and EMT processes of U87MG cells.


Characterization of fetal cells from the maternal circulation by microarray gene expression analysis--could the extravillous trophoblasts be a target for future cell-based non-invasive prenatal diagnosis?
Circulating fetal cells in maternal blood provide a tool for risk-free, non-invasive prenatal diagnosis. However, fetal cells in the maternal circulation are scarce, and to effectively isolate enough of them for reliable diagnostics, it is crucial to know which fetal cell type(s) should be targeted. Fetal cells were enriched from maternal blood by magnetic-activated cell sorting using the endothelial cell marker CD105 and identified by XY fluorescence in situ hybridization. Expression pattern was compared between fetal cells and maternal blood cells using stem cell microarray analysis. 39 genes were identified as candidates for unique fetal cell markers. More than half of these are genes known to be expressed in the placenta, especially in extravillous trophoblasts (EVTs). Immunohistochemical staining of placental tissue confirmed CD105 staining in EVTs and 76% of fetal cells enriched by CD105 were found to be cytokeratin-positive. The unique combination of mesodermal (CD105) and ectodermal (cytokeratin) markers in EVTs could be a potential marker set for cell enrichment of this cell type in maternal blood and could be the basis for future cell-based non-invasive prenatal diagnosis.


Pain and Disability in the Jaw and Neck Region following Whiplash Trauma.
The relationship between whiplash trauma and chronic orofacial pain is unclear, especially with regard to the time elapsed from trauma to development of orofacial pain. The aim was to analyze prevalence of jaw pain and disability, as well as the relationship between pain and disability in the jaw and neck regions in the early nonchronic stage after whiplash trauma. In this case-control study, 70 individuals (40 women, 30 men, mean age 35.5 y) who visited an emergency department with neck pain following a car accident were examined within 3 wk of trauma (group 1) and compared with 70 individuals (42 women, 28 men, mean age 33.8 y), who declined to attend a clinical examination but agreed to fill in questionnaires (group 2). The 2 case groups were compared with a matched control group of 70 individuals (42 women, 28 men, mean age 37.6 y) without a history of neck trauma. All participants completed questionnaires regarding jaw pain and dysfunction, rating pain intensity in jaw and neck regions on the Numerical Rating Scale, the Neck Disability Index, and Jaw Disability Checklist. Compared with controls, individuals with a recent whiplash trauma reported more jaw pain and dysfunction. Furthermore, there was a moderate positive correlation between jaw and neck pain ratings for group 1 (r = 0.61, P < 0.0001) and group 2 (r = 0.59, P < 0.0001). In the logistic regression analysis, cases showed higher odds ratios (range, 6.1 to 40.8) for jaw and neck pain and disability compared with controls. Taken together, the results show that individuals with a recent whiplash trauma report more jaw pain and disability compared with controls without a history of neck trauma. Furthermore, the correlation between jaw and neck pain intensity implies that intensity of neck pain in the acute stage after whiplash trauma might be a possible risk factor also for development of chronic orofacial pain.


Proposals for the classification of human rhinovirus species C into genotypically assigned types.
Human rhinoviruses (HRVs) are common respiratory pathogens associated with mild upper respiratory tract infections, but also increasingly recognized in the aetiology of severe lower respiratory tract disease. Wider use of molecular diagnostics has led to a recent reappraisal of HRV genetic diversity, including the discovery of HRV species C (HRV-C), which is refractory to traditional virus isolation procedures. Although it is heterogeneous genetically, there has to date been no attempt to classify HRV-C into types analogous to the multiple serotypes identified for HRV-A and -B and among human enteroviruses. Direct investigation of cross-neutralization properties of HRV-C is precluded by the lack of methods for in vitro culture, but sequences from the capsid genes (VP1 and partial VP4/VP2) show evidence for marked phylogenetic clustering, suggesting the possibility of a genetically based system comparable to that used for the assignment of new enterovirus types. We propose a threshold of 13% divergence for VP1 nucleotide sequences for type assignment, a level that classifies the current dataset of 86 HRV-C VP1 sequences into a total of 33 types. We recognize, however, that most HRV-C sequence data have been collected in the VP4/VP2 region (currently 701 sequences between positions 615 and 1043). We propose a subsidiary classification of variants showing > 10% divergence in VP4/VP2, but lacking VP1 sequences, to 28 provisionally assigned types (subject to confirmation once VP1 sequences are determined). These proposals will assist in future epidemiological and clinical studies of HRV-C conducted by different groups worldwide, and provide the foundation for future exploration of type-associated differences in clinical presentations and biological properties.


Evolutionary history of hunter-gatherer marriage practices.
The universality of marriage in human societies around the world suggests a deep evolutionary history of institutionalized pair-bonding that stems back at least to early modern humans. However, marriage practices vary considerably from culture to culture, ranging from strict prescriptions and arranged marriages in some societies to mostly unregulated courtship in others, presence to absence of brideservice and brideprice, and polyandrous to polygynous unions. The ancestral state of early human marriage is not well known given the lack of conclusive archaeological evidence. Comparative phylogenetic analyses using data from contemporary hunter-gatherers around the world may allow for the reconstruction of ancestral human cultural traits. We attempt to reconstruct ancestral marriage practices using hunter-gatherer phylogenies based on mitochondrial DNA sequences. Arranged marriages are inferred to go back at least to first modern human migrations out of Africa. Reconstructions are equivocal on whether or not earlier human marriages were arranged because several African hunter-gatherers have courtship marriages. Phylogenetic reconstructions suggest that marriages in early ancestral human societies probably had low levels of polygyny (low reproductive skew) and reciprocal exchanges between the families of marital partners (i.e., brideservice or brideprice). Phylogenetic results suggest a deep history of regulated exchange of mates and resources among lineages that enhanced the complexity of human meta-group social structure with coalitions and alliances spanning across multiple residential communities.