Combined E-cadherin, alpha-catenin, and beta-catenin expression is a favorable prognostic factor in endometrial carcinoma.
Cell adhesion molecules, such as epithelial cadherin (E-cadherin), might be involved in the processes of tumor invasion and differentiation. The aim of this study was to investigate the expression of E-cadherin, alpha-catenin, and beta-catenin in endometrial carcinoma and to determine the prognostic value of these factors. We have investigated the expression of E-cadherin, alpha-catenin, and beta-catenin by immunohistochemistry in 225 endometrial carcinomas. The correlation between the E-cadherin and the catenins and their correlation with several histologic and clinical parameters were analyzed. Negative E-cadherin, alpha-catenin, and beta-catenin expression was observed in 44%, 47%, and 33% of endometrial carcinomas, respectively, and was correlated with histologic FIGO grade 3 (P < 0.001). Negative E-cadherin expression was more often observed in nonendometrioid endometrial carcinomas (NEECs) than in endometrioid carcinomas (75% versus 43%; P= 0.04). Combined positive E-cadherin, alpha-catenin, and beta-catenin expression was an independent positive prognostic factor for survival in patients with grade 1-2 carcinomas (P= 0.02). Negative E-cadherin expression was found to be associated with histologic grade 3 and with NEEC. Combined positive E-cadherin, alpha-catenin, and beta-catenin expression was a significant prognostic factor.


Evidence for superior encoding of detailed visual memories in deaf signers.
Recent evidence shows that deaf signers outperform hearing non-signers in some tests of visual attention and discrimination. Furthermore, they can retain visual information better over short periods, i.e., seconds. However, it is unknown if deaf signers' retention of detailed visual information is superior following more extended periods. We report a study investigating this possibility. Our data revealed that deaf individuals outperformed hearing people in a visual long-term memory test that probed the fine detail of new memories. Deaf individuals also performed better in a scene-discrimination test, which correlated positively with performance on the long-term memory test. Our findings provide evidence that deaf signers can demonstrate superior visual long-term memory, possibly because of enhanced visual attention during encoding. The relative contributions of factors including sign language fluency, protracted practice, and neural plasticity are still to be established. Our findings add to evidence showing that deaf signers are at an advantage in some respects, including the retention of detailed visual memories over the longer term.


Auditory Stimulus Timing Influences Perceived duration of Co-Occurring Visual Stimuli.
There is increasing interest in multisensory influences upon sensory-specific judgments, such as when auditory stimuli affect visual perception. Here we studied whether the duration of an auditory event can objectively affect the perceived duration of a co-occurring visual event. On each trial, participants were presented with a pair of successive flashes and had to judge whether the first or second was longer. Two beeps were presented with the flashes. The order of short and long stimuli could be the same across audition and vision (audio-visual congruent) or reversed, so that the longer flash was accompanied by the shorter beep and vice versa (audio-visual incongruent); or the two beeps could have the same duration as each other. Beeps and flashes could onset synchronously or asynchronously. In a further control experiment, the beep durations were much longer (tripled) than the flashes. Results showed that visual duration discrimination sensitivity (d') was significantly higher for congruent (and significantly lower for incongruent) audio-visual synchronous combinations, relative to the visual-only presentation. This effect was abolished when auditory and visual stimuli were presented asynchronously, or when sound durations tripled those of flashes. We conclude that the temporal properties of co-occurring auditory stimuli influence the perceived duration of visual stimuli and that this can reflect genuine changes in visual sensitivity rather than mere response bias.


Mountain rescue cardiopulmonary resuscitation: a comparison between manual and mechanical chest compressions during manikin cardio resuscitation.
Chest compression devices are useful during mountain rescue but may cause a delay in transport if not immediately available. The aims of this prospective observational study were to compare manual and mechanical cardiopulmonary resuscitation (CPR) during transport on a sledge connected to a snowmobile with a non-moving setting and to compare CPR quality between manual and two mechanical chest compression devices. Sixteen healthcare providers simulated four different combined CPR scenarios on a sledge in a non-moving setting and during transport and two mechanical chest compression devices during transport on the sledge. The study was conducted in May 2015 in a mountain in Norway. The primary outcome measures were compression rate (compressions per minute), compression depth in millimetres, leaning (incomplete chest wall release after compression in millimetres) and chest compression fraction (fraction of total time were compression were performed). The results were analysed by descriptive and graphical methods and paired t-tests were used to compare the differences between techniques. We did not observe a significant difference between moving and non-moving conditions with respect to manual compression rate (p=0.34), compression depth (p=0.50) or leaning (p=0.92). However, both the manual compression depth (p<0.001) and the leaning (p=0.04) showed a significantly larger variance during the moving runs. Manual chest compression is possible on a snowmobile during transport even in challenging terrain. This experimental study shows that high-quality chest compressions and manual ventilation can be performed in an intubated patient during a short-term transportation on a sledge.


Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: randomized controlled trial.
Animal evidence indicates that green tea may modulate insulin sensitivity, with epigallocatechin-3-gallate (EGCG) proposed as a likely health-promoting component. The purpose of this study was to investigate the effect of dietary supplementation with EGCG on insulin resistance and associated metabolic risk factors in man. Overweight or obese male subjects, aged 40-65 years, were randomly assigned to take 400 mg capsules of EGCG (n 46) or the placebo lactose (n 42), twice daily for 8 weeks. Oral glucose tolerance testing and measurement of metabolic risk factors (BMI, waist circumference, percentage body fat, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG) was conducted pre- and post-intervention. Mood was evaluated weekly using the University of Wales Institute of Science and Technology mood adjective checklist. EGCG treatment had no effect on insulin sensitivity, insulin secretion or glucose tolerance but did reduce diastolic blood pressure (mean change: placebo - 0.058 (se 0.75) mmHg; EGCG - 2.68 (se 0.72) mmHg; P = 0.014). No significant change in the other metabolic risk factors was observed. The EGCG group also reported feeling in a more positive mood than the placebo group across the intervention period (mean score for hedonic tone: EGCG, 29.11 (se 0.44); placebo, 27.84 (se 0.46); P = 0.048). In conclusion, regular intake of EGCG had no effect on insulin resistance but did result in a modest reduction in diastolic blood pressure. This antihypertensive effect may contribute to some of the cardiovascular benefits associated with habitual green tea consumption. EGCG treatment also had a positive effect on mood. Further studies are needed to confirm the findings and investigate their mechanistic basis.


Energy and Resources: A plan is outlined according to which solar and wind energy would supply Denmark's needs by the year 2050.
Two possible futures for the industrial world may be distinguished: (i) Large amounts of low-cost energy become available and the more energy-intensive methods for extracting resources from lowergrade deposits continue to sustain industrial expansion until either the environmental impact becomes unacceptable or ultimate limits, such as climate disruptions, put an end to such growth. (ii) The cost of nonrenewable energy resources continue to rise, but a fixed amount of energy from continuous sources may be utilized at constant cost. In this case a lower production level may be set by the amount of energy that is available from renewable sources, and society may thus have to be reshaped with energy economization in focus. If it is possible to choose between these two alternatives, the choice should be based on a discussion of the pros and cons of each one, and in particular on the desirability of having to process an increasing fraction of the earth's crust in search of raw materials in order to maintain growth as long as possible. However, the availability, of the first option is far from certain and it thus seems reasonable to plan for the second alternative. I have tried to propose such a plan for a small, homogeneous geographical region, namely Denmark. The ceiling on the consumption of energy from continuous sources is chosen in accordance with the criterion of not having to convert a major part of the land area to energy-collecting systems. The proposed annual average energy consumption of 19 gigawatts by the year 2050 corresponds to solar energy collecting panels (in use only 50 percent of the time) with an area of roughly 180 square kilometers and a windmill swept area of about 150 square kilometers. These (vertical) areas constitute less than 1 percent of the total land area. The selection of solar or wind energy for different applications has been based on known technology and may be subject to adjustments. The project has been shown to be economically feasible according to estimates of the cost of various alternatives during the 25-year depreciation period adopted. However, the initial cost per energy unit produced is higher than that for most of the alternatives, so that action is not expected to be taken immediately as a result of purely private initiative. In a public economic evaluation, other factors must be considered in addition to the cost of energy per kilowatt-hour. At present, Denmark has over 10 percent of its labor force out of employment and a substantial deficit on its balance of payments, so that an early start on the solar and wind energy project, based on national industry, would have additional payoffs compared with energy systems based on imported technology or imported fuels. Several factories that are now being closed down as a result of the economic crisis could be adapted to the production of parts for solar or wind power systems, and the building industry, badly hit by unemployment, would receive legitimate work.


Utility of a clinical risk factor scoring model in predicting infection with extended-spectrum β-lactamase-producing enterobacteriaceae on hospital admission.
To validate the utility of a previously published scoring model (Italian) to identify patients infected with community-onset extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-EKP) and develop a new model (Duke) based on local epidemiology. This case-control study included patients 18 years of age or more admitted to Duke University Hospital between January 1, 2008, and December 31, 2010, with culture-confirmed infection due to an ESBL-EKP (cases). Uninfected controls were matched to cases (3:1). The Italian model was applied to our patient population for validation. The Duke model was developed through logistic-regression-based prediction scores calculated on variables independently associated with ESBL-EKP isolation. Sensitivities and specificities at various point cutoffs were determined, and determination of the area under the receiver operating characteristic curve (ROC AUC) was performed. A total of 123 cases and 375 controls were identified. Adjusted odds ratios and 95% confidence intervals for variables previously identified in the Italian model were as follows: hospitalization (3.20 [1.62-6.55]), transfer (4.31 [2.15-8.78]), urinary catheterization (5.92 [3.09-11.60]), β-lactam and/or fluoroquinolone therapy (3.76 [2.06-6.95]), age 70 years or more (1.55 [0.79-3.01]), and Charlson Comorbidity Score of 4 or above (1.06 [0.55-2.01]). Sensitivity and specificity were, respectively, more than or equal to 95% and less than or equal to 47% for scores 3 or below and were less than or equal to 50% and more than or equal to 96% for scores 8 or above. The ROC AUC was 0.88. Variables identified in the Duke model were as follows: hospitalization (2.63 [1.32-5.41]), transfer (5.30 [2.67-10.71]), urinary catheterization (6.89 [3.62-13.38]), β-lactam and/or fluoroquinolone therapy (3.47 [1.91-6.41]), and immunosuppression (2.34 [1.14-4.80]). Sensitivity and specificity were, respectively, more than or equal to 94% and less than or equal to 65% for scores 3 or below and were less than or equal to 58% and more than or equal to 95% for scores 8 or above. The ROC AUC was 0.89. While the previously reported model was an excellent predictor of community-onset ESBL-EKP infection, models utilizing factors based on local epidemiology may be associated with improved performance.


The Use of DNA Barcoding in Identification and Conservation of Rosewood (Dalbergia spp.).
The genus Dalbergia contains many valuable timber species threatened by illegal logging and deforestation, but knowledge on distributions and threats is often limited and accurate species identification difficult. The aim of this study was to apply DNA barcoding methods to support conservation efforts of Dalbergia species in Indochina. We used the recommended rbcL, matK and ITS barcoding markers on 95 samples covering 31 species of Dalbergia, and tested their discrimination ability with both traditional distance-based as well as different model-based machine learning methods. We specifically tested whether the markers could be used to solve taxonomic confusion concerning the timber species Dalbergia oliveri, and to identify the CITES-listed Dalbergia cochinchinensis. We also applied the barcoding markers to 14 samples of unknown identity. In general, we found that the barcoding markers discriminated among Dalbergia species with high accuracy. We found that ITS yielded the single highest discrimination rate (100%), but due to difficulties in obtaining high-quality sequences from degraded material, the better overall choice for Dalbergia seems to be the standard rbcL+matK barcode, as this yielded discrimination rates close to 90% and amplified well. The distance-based method TaxonDNA showed the highest identification rates overall, although a more complete specimen sampling is needed to conclude on the best analytic method. We found strong support for a monophyletic Dalbergia oliveri and encourage that this name is used consistently in Indochina. The CITES-listed Dalbergia cochinchinensis was successfully identified, and a species-specific assay can be developed from the data generated in this study for the identification of illegally traded timber. We suggest that the use of DNA barcoding is integrated into the work flow during floristic studies and at national herbaria in the region, as this could significantly increase the number of identified specimens and improve knowledge about species distributions.


Impact of vessel attenuation on quantitative coronary angiography with 64-slice CT.
The aim of the study was to determine the impact of vessel attenuation on quantitative 64-slice computed tomography coronary angiography (CTCA). CTCA and invasive quantitative coronary angiography (QCA) were performed in 100 consecutive patients (42 women, 58 men; mean age 64.4+/-9.4 years; age range 39-87 years). In QCA, stenoses were quantified with dedicated software, whereas in CTCA, stenosis severity was assessed with an electronic caliper tool: stenoses were graded in 10% steps and assigned as either a calcified or non-calcified lesion. Vessel attenuation in the left main (LMA) and the proximal right coronary artery (RCA) were measured and correlated with differences in quantifications of stenosis grade between QCA and CTCA. A total of 113 coronary stenoses were detected by both methods (94 significant and 19 non-significant); 52 stenoses were rated as non-calcified and 61 as calcified lesions. The mean difference between QCA and quantitative CTCA grading was 5.1+/-16.9% (range -27 to 46%) overall; 1.9+/-14.2% (range -27 to 38%) for non-calcified lesions and 7.8+/-18.6% (range -23 to 46%) for calcified lesions. Mean vessel attenuation was 362+/-76 HU (range 191-584 HU) in the LMA and 333+/-81 HU (range 162-564 HU) in the RCA. Attenuation did not significantly correlate with differences in QCA and CTCA gradings, neither overall nor for calcified or non-calcified lesions. When 64-slice CTCA is used, coronary vessel attenuation had no impact on the quantitative grading of stenoses.


Selection for uniformity in livestock by exploiting genetic heterogeneity of residual variance.
In some situations, it is worthwhile to change not only the mean, but also the variability of traits by selection. Genetic variation in residual variance may be utilised to improve uniformity in livestock populations by selection. The objective was to investigate the effects of genetic parameters, breeding goal, number of progeny per sire and breeding scheme on selection responses in mean and variance when applying index selection. Genetic parameters were obtained from the literature. Economic values for the mean and variance were derived for some standard non-linear profit equations, e.g. for traits with an intermediate optimum. The economic value of variance was in most situations negative, indicating that selection for reduced variance increases profit. Predicted responses in residual variance after one generation of selection were large, in some cases when the number of progeny per sire was at least 50, by more than 10% of the current residual variance. Progeny testing schemes were more efficient than sib-testing schemes in decreasing residual variance. With optimum traits, selection pressure shifts gradually from the mean to the variance when approaching the optimum. Genetic improvement of uniformity is particularly interesting for traits where the current population mean is near an intermediate optimum.


Quality improvement and its impact on the use and equality of outpatient health services in India.
This paper examines the impact of quality improvements in conjunction with user fees on the utilization and equality of outpatient services at a range of public sector health facilities in India. Project impact on outpatient visits was estimated via the difference-in-difference method using pooled time series visit data from project and control facilities. The results indicate that the quality improvements significantly increased visits at all facility types. The project effect was largest at primary health center (PHC) and community health center (CHC), followed by district hospital (DH) and female district hospital (FDH). Pro-rich inequalities in outpatient visits increased at DHs and FDHs while at CHCs and PHCs the distribution remained equitable. This suggests that quality improvements at public sector health facilities can increase utilization of outpatient services in the presence of nominal user fees, but can also promote greater inequality favoring the better-off. At the referral hospital level, quality improvements should be made in conjuction with programs which encourage utilization by the poor. In contrast, the benefit of quality improvements at PHCs and CHCs is equitably distributed.


Effect of confinement on water rotation via quantum tunnelling.
Water exhibits different behaviors in confined space compared to free space, which is critical for desalination, biosensing, and many potential applications. Recent studies indicated that quantum tunnelling plays an important role in the orientation of H2O molecules and the H-bond network of water clusters, but whether this effect is important in confined space remains elusive. Here, we studied the quantum tunnelling effect of water dimers in carbon nanotubes with different sizes by first-principles calculations. Our results show that though this effect may be negligible at room temperature, it becomes dominant at low temperatures up to ∼100 Kelvin. In particular, with the injection of a small amount of energy to excite a specific vibrational mode, the tunnelling rotation effect can be significantly enhanced, which provides a new strategy to tune the H-bond network of confined water.


Multicenter evaluation of the Vitek 2 anaerobe and Corynebacterium identification card.
The new anaerobe and Corynebacterium (ANC) identification card for Vitek 2 was compared with a 16S rRNA gene sequencing (16S) reference method for accuracy in the identification of corynebacteria and anaerobic species. Testing was performed on a Vitek 2 XL system with modified software at three clinical trial laboratories. Reproducibility was determined with nine ATCC quality control strains that were tested 20 times over a minimum of 10 days at all three sites. A challenge set of 50 well-characterized strains and 365 recent fresh and frozen clinical isolates were included in the study. The expected positive and negative biochemical well reactions were also evaluated for substrate reproducibility. All strains were tested with the ANC card, and clinical isolates were saved for 16S rRNA gene sequencing. All reproducibility tests yielded expected results within a 95% confidence interval, except for that with Corynebacterium striatum ATCC 6940, for which identification failed at one trial site. For the challenge isolates, there was 98% correct identification, 5% low discrimination, and 2% incorrect identification, and 0% were unidentified. For clinical strains, there was 95.1% correct identification, 4.9% low discrimination, and 4.6% incorrect identification, and 0.3% were unidentified. The 4.6% (17/365) of clinical isolates that were incorrectly identified consisted of 14 isolates that were correct at the genus level and three that were incorrect at the genus level. The new ANC card met all performance criteria within a 95% confidence interval compared to the identification performance by 16S rRNA gene sequencing.


Three-dimensional optical memory with a photorefractive crystal.
We propose a three-dimensional optical-memory device in which refractive dot data are recorded directly into a photorefractive crystal. To record a single bit of datum, one focuses a laser beam with an objective lens onto a specific spot in a crystal, thereby changing its refractive index locally as a result of photorefraction. To record in three dimensions, one keeps the objective lens stationary while the crystal is translated. The beam-spot intensity is modulated with a beam shutter according to the logic state of the data point. The recorded data points are read with a phase-contrast microscope objective lens. We present experimental results of three-dimensional recording and reading with a LiNbO(3) crystal. The distribution of the refractive index formed by a focused beam is also analyzed with the charge-transport model.


Proton NMR relaxation times in ischemic brain edema.
The state of water in cerebral ischemia was studied by using the proton nuclear magnetic resonance (1H-NMR) method. Cerebral ischemia was induced experimentally in Mongolian gerbils by unilateral ligation of the common carotid artery. Longitudinal (T1) and transverse (T2) relaxation times of the ischemic brain were measured with a pulse FT-NMR spectrometer and the water content was determined by the wet/dry method. Quantitative analysis of the relaxation times was performed sequentially during the initial 7 hours following ligation and the data were compared with those of brain edema previously reported by S. Naruse in the rat. Characteristic findings in brain ischemia include prolongation of the slow component of T2 and increase in the water content. A quantitative comparison of relaxation rate and water content demonstrates that ischemic brain edema in Mongolian gerbils is different from cytotoxic and vasogenic types of brain edema. When R2 (1/T2) was plotted against the water content, the slope value of ischemia in the gerbil was between the slope values of the TET intoxication and cold injury induced edemas reported previously. From these results, it might be said that ischemic brain edema includes both the cytotoxic and vasogenic types of brain edema. Glycerol was demonstrated to affect brain ischemia by decreasing the water content and by shortening the slow component of T2. By analysis of the relaxation times and water content, we examined the pathophysiological characteristics of water molecules in ischemic brain tissue.


Organogenic elements and compounds in surface samples from the sea of tranquillity.
Organogenic elements, mainly carbon, nitrogen, phosphorus, and sulfur are present in the particulate material and in a breccia rock from Tranquillity Base in amounts ranging from 5 to 4200 parts per million. The major compounds of carbon released by heating are carbon monoxide and carbon dioxide; the former predominates. Small amounts of other compounds of carbon have also been observed. Sulfur can be released as hydrogen sulfide by treatment with acid. The carbon isotopic delta(13L)C values are definitely nonterrestrial (+ 13 to + 18.5 per mil).


A complex cyst characterized into its individual components: a shared pathogenesis from the superior tibiofibular joint.
In a patient with a peroneal neuropathy, magnetic resonance imaging (MRI) allowed characterization of a complex para-articular cyst into three different types of cysts, all derived from the superior tibiofibular joint: 1) an intraneural cyst extending along the articular branch to the common peroneal nerve; an interconnected intraneural component extending within the extensor digitorum muscle neural branch, penetrating the fascia of the anterior compartment, and reaching the subcutaneous tissues; 2) an intraosseous cyst isolated to the fibular head and neck, and 3) an extraneural cyst heading toward the tibial nerve and vessels. Joint resection and articular branch disconnection led to excellent functional recovery; an MRI confirmed no cyst recurrence. This case illustrates that different types of cysts can derive from a single joint of origin and extend in various locations and that the articular (synovial) theory is versatile for demonstrating a joint connection, even in unusual appearing combinations of cysts.


Changes in gene expression in gills of the euryhaline killifish Fundulus heteroclitus after abrupt salinity transfer.
Maintenance of ion balance requires that ionoregulatory epithelia modulate ion flux in response to internal or environmental osmotic challenges. We have explored the basis of this functional plasticity in the gills of the euryhaline killifish Fundulus heteroclitus. The expression patterns of several genes encoding ion transport proteins were quantified after transfer from near-isosmotic brackish water [10 parts/thousand (ppt)] to either freshwater (FW) or seawater (SW). Many changes in response to SW transfer were transient. Increased mRNA expression occurred 1 day after transfer for Na(+)-K(+)-ATPase-alpha(1a) (3-fold), Na(+)-K(+)-2Cl(-)-cotransporter 1 (NKCC1) (3-fold), and glucocorticoid receptor (1.3-fold) and was paralleled by elevated Na(+)-K(+)-ATPase activity (2-fold). The transient increase in NKCC1 mRNA expression was followed by a later 2-fold rise in NKCC protein abundance. In contrast to the other genes studied in the present work, mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel generally remained elevated (2-fold) in SW. No change in protein abundance was detected, however, suggesting posttranscriptional regulation. The responses to FW transfer were quite different from those to SW transfer. In particular, FW transfer increased Na(+)-K(+)-ATPase-alpha(1a) mRNA expression and Na(+)-K(+)-ATPase activity to a greater extent than did SW transfer but had no effect on V-type H(+)-ATPase expression, supporting the current suggestion that killifish gills transport Na(+) via Na(+)/H(+) exchange. These findings demonstrate unique patterns of ion transporter expression in killifish gills after salinity transfer and illustrate important mechanisms of functional plasticity in ion-transporting epithelia.


[Gemcitabine in the treatment of 4 patients with cholangiocarcinoma].
Cholangiocarcinoma is a biliary tree cancer of unknown etiology, whose symptoms are unspecific and is usually detected in advanced stages. Surgery continues to be the only curative therapy. Median survival in patients with inoperable tumors ranges between 5 and 8 months. There are few studies on the effects of chemotherapy, with a very small response. We report four patients with advanced cholangiocarcinoma, treated with gemcitabine 1000 mg/m2, weekly for 3 weeks every 28 days. There was a stabilization of tumor size and symptoms were alleviated. Toxicity was low and there was a probable prolongation of survival.


Prevalence of hypertension in member countries of South Asian Association for Regional Cooperation (SAARC): systematic review and meta-analysis.
Hypertension is a leading attributable risk factor for mortality in South Asia. However, a systematic review on prevalence and risk factors for hypertension in the region of the South Asian Association for Regional Cooperation (SAARC) has not carried out before.The study was conducted according to the Meta-Analysis of Observational Studies in Epidemiology Guideline. A literature search was performed with a combination of medical subject headings terms, "hypertension" and "Epidemiology/EP". The search was supplemented by cross-references. Thirty-three publications that met the inclusion criteria were included in the synthesis and meta-analyses. Hypertension is defined when an individual had a systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg, was taking antihypertensive drugs, or had previously been diagnosed as hypertensive by health care professionals. Prehypertension is defined as SBP 120-139 mm Hg and DBP 80-89 mm Hg.The overall prevalence of hypertension and prehypertension from the studies was found to be 27% and 29.6%, respectively. Hypertension varied between the studies, which ranged from 13.6% to 47.9% and was found to be higher in the studies conducted in urban areas than in rural areas. The prevalence of hypertension from the latest studies was: Bangladesh: 17.9%; Bhutan: 23.9%; India: 31.4%; Maldives: 31.5%; Nepal: 33.8%; Pakistan: 25%; and Sri Lanka: 20.9%. Eight out of 19 studies with information about prevalence of hypertension in both sexes showed that the prevalence was higher among women than men. Meta-analyses showed that sex (men: odds ratio [OR] 1.19; 95% confidence interval [CI]: 1.02, 1.37), obesity (OR 2.33; 95% CI: 1.87, 2.78), and central obesity (OR 2.16; 95% CI: 1.37, 2.95) were associated with hypertension.Our study found a variable prevalence of hypertension across SAARC countries, with a number of countries with blood pressure above the global average. We also noted that studies are not consistent in their data collection about hypertension and related modifiable risk factors.


Control of the Water Transport Activity of Barley HvTIP3;1 Specifically Expressed in Seeds.
Tonoplast intrinsic proteins (TIPs) are involved in the transport and storage of water, and control intracellular osmotic pressure by transporting material related to the water potential of cells. In the present study, we focused on HvTIP3;1 during the periods of seed development and desiccation in barley. HvTIP3;1 was specifically expressed in seeds. An immunochemical analysis showed that HvTIP3;1 strongly accumulated in the aleurone layers and outer layers of barley seeds. The water transport activities of HvTIP3;1 and HvTIP1;2, which also accumulated in seeds, were measured in the heterologous expression system of Xenopus oocytes. When they were expressed individually, HvTIP1;2 transported water, whereas HvTIP3;1 did not. However, HvTIP3;1 exhibited water transport activity when co-expressed with HvTIP1;2 in oocytes, and this activity was higher than when HvTIP1;2 was expressed alone. This is the first report to demonstrate that the water permeability of a TIP aquaporin was activated when co-expressed with another TIP. The split-yellow fluorescent protein (YFP) system in onion cells revealed that HvTIP3;1 interacted with HvTIP1;2 to form a heterotetramer in plants. These results suggest that HvTIP3;1 functions as an active water channel to regulate water movement through tissues during the periods of seed development and desiccation.


Pulsed out of awareness: EEG alpha oscillations represent a pulsed-inhibition of ongoing cortical processing.
Alpha oscillations are ubiquitous in the brain, but their role in cortical processing remains a matter of debate. Recently, evidence has begun to accumulate in support of a role for alpha oscillations in attention selection and control. Here we first review evidence that 8-12 Hz oscillations in the brain have a general inhibitory role in cognitive processing, with an emphasis on their role in visual processing. Then, we summarize the evidence in support of our recent proposal that alpha represents a pulsed-inhibition of ongoing neural activity. The phase of the ongoing electroencephalography can influence evoked activity and subsequent processing, and we propose that alpha exerts its inhibitory role through alternating microstates of inhibition and excitation. Finally, we discuss evidence that this pulsed-inhibition can be entrained to rhythmic stimuli in the environment, such that preferential processing occurs for stimuli at predictable moments. The entrainment of preferential phase may provide a mechanism for temporal attention in the brain. This pulsed inhibitory account of alpha has important implications for many common cognitive phenomena, such as the attentional blink, and seems to indicate that our visual experience may at least some times be coming through in waves.


An elasto-mechanical unfeelability cloak made of pentamode metamaterials.
Metamaterial-based cloaks make objects different from their surrounding appear just like their surrounding. To date, cloaking has been demonstrated experimentally in many fields of research, including electrodynamics at microwave frequencies, optics, static electric conduction, acoustics, fluid dynamics, thermodynamics and quasi two-dimensional solid mechanics. However, cloaking in the seemingly simple case of three-dimensional solid mechanics is more demanding. Here, inspired by invisible core-shell nanoparticles in optics, we design an approximate elasto-mechanical core-shell 'unfeelability' cloak based on pentamode metamaterials. The resulting three-dimensional polymer microstructures with macroscopic overall volume are fabricated by rapid dip-in direct laser writing optical lithography. We quasi-statically deform cloak and control samples in the linear regime and map the displacement fields by autocorrelation-based analysis of recorded movies. The measured and the calculated displacement fields show very good cloaking performance. This means that one can elastically hide objects along these lines.


Emergency medical dispatch priority in chest pain patients due to life threatening conditions: A cohort study examining circadian variations and impact of the education.
We examined the accuracy in assessments of emergency dispatchers according to their education and time of the day. We examined this in chest pain patients who were diagnosed with a potentially life-threatening condition (LTC) or died within 30days. Among 2205 persons, 482 died, 1631 experienced an acute coronary syndrome (ACS), 1914 had a LTC. Multivariable logistic regression was used to study how time of the call and the dispatcher's education were associated with the risk of missing to give priority 1 (the highest). Among patients who died, a 7-fold increase in odds of missing to give priority 1 was noted at 1.00pm, as compared with midnight. Compared with assistant nurses, odds ratio for dispatchers with no (medical) training was 0.34 (95% CI 0.14 to 0.77). Among patients with an ACS, odds ratio for calls arriving before lunch was 2.02 (95% CI 1.22 to 3.43), compared with midnight. Compared with assistant nurses, odds ratio for operators with no training was 0.23 (95% CI 0.13 to 0.40). Similar associations were noted for those with any LTC. Dispatcher's education was not associated with the patient's survival. In this group of patients, which experience substantial mortality and morbidity, the risk of not obtaining highest dispatch priority was increased up to 7-fold during lunchtime. Dispatch operators without medical education had the lowest risk, compared with nurses and assistant nurses, of missing to give priority 1, at the expense of lower positive predictive value. What is already known about this subject? Use of the emergency medical service (EMS) increases survival among patients with acute coronary syndromes. It is unknown whether the efficiency - as judged by the ability to identify life-threatening cases among patients with chest pain - varies according to the dispatcher's educational level and the time of day. What does this study add? We provide evidence that the dispatcher's education does not influence survival among patients calling the EMS due to chest discomfort. However, medically educated dispatchers are at greatest risk of missing to identify life-threatening cases, which is explained by more parsimonious use of the highest dispatch priority. We also show that the risk of missing life-threatening cases is at highest around lunch time. How might this impact on clinical practice? Dispatch centers are operated differently all over the world and chest discomfort is one of the most frequent symptoms encountered; we provide evidence that it is safe to operate a dispatch center without medically trained personnel, who actually miss fewer cases of acute coronary syndromes. However, non-medically trained dispatchers consume more pre-hospital resources.


Pyrimidine salvage in Trypanosoma brucei bloodstream forms and the trypanocidal action of halogenated pyrimidines.
African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host. However, uptake of pyrimidines in bloodstream form trypanosomes has not been investigated, making it difficult to judge the relative importance of salvage and synthesis or to design a pyrimidine-based chemotherapy. Detailed characterization of pyrimidine transport activities in bloodstream form Trypanosoma brucei brucei found that these cells express a high-affinity uracil transporter (designated TbU3) that is clearly distinct from the procyclic pyrimidine transporters. This transporter had low affinity for uridine and 2'deoxyuridine and was the sole pyrimidine transporter expressed in these cells. In addition, thymidine was taken up inefficiently through a P1-type nucleoside transporter. Of importance, the anticancer drug 5-fluorouracil was an excellent substrate for TbU3, and several 5-fluoropyrimidine analogs were investigated for uptake and trypanocidal activity; 5F-orotic acid, 5F-2'deoxyuridine displayed activity in the low micromolar range. The metabolism and mode of action of these analogs was determined using metabolomic assessments of T. brucei clonal lines adapted to high levels of these pyrimidine analogs, and of the sensitive parental strains. The analysis showed that 5-fluorouracil is incorporated into a large number of metabolites but likely exerts toxicity through incorporation into RNA. 5F-2'dUrd and 5F-2'dCtd are not incorporated into nucleic acids but act as prodrugs by inhibiting thymidylate synthase as 5F-dUMP. We present the most complete model of pyrimidine salvage in T. brucei to date, supported by genome-wide profiling of the predicted pyrimidine biosynthesis and conversion enzymes.


Genistein induces oestrogen receptor-α gene expression in osteoblasts through the activation of mitogen-activated protein kinases/NF-κB/activator protein-1 and promotes cell mineralisation.
Oestrogen and oestrogen receptors (ER) play critical roles in the maintenance of bone remodelling. Genistein, structurally similar to 17β-oestradiol, is a phyto-oestrogen that may be beneficial for treating osteoporosis. In the present study, we evaluated the effects of genistein on the regulation of ERα gene expression and osteoblast mineralisation using MC3T3-E1 cells and primary rat calvarial osteoblasts as our experimental models. Exposure of MC3T3-E1 cells and primary rat osteoblasts to genistein at ≤ 10 μm for 24 h did not affect the cell morphology or viability. However, treatment of MC3T3-E1 cells with 10 μm-genistein enhanced the phosphorylation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2 in a time-dependent manner. Sequentially, genistein increased the translocation of NF-κB and c-Jun from the cytoplasm to the nucleus. Consequently, exposure of MC3T3-E1 cells to genistein induced ERα mRNA expression in concentration- and time-dependent manners. In parallel, the amounts of cytosolic and nuclear ERα in MC3T3-E1 cells were increased following genistein administration. Additionally, genistein also increased the levels of ERα mRNA and nuclear ERα protein in rat calvarial osteoblasts. A bioinformatic search revealed that there are several ERα-specific DNA-binding elements in the 5'-promoter regions of the bone morphogenetic protein-6, collagen type I and osteocalcin genes. As a result, genistein could induce the expressions of these osteoblast differentiation-related genes in primary rat osteoblasts. Co-treatment with genistein and traditional differentiation reagents synergistically increased osteoblast mineralisation. Therefore, the present study showed that genistein can induce ERα gene expression via the activation of MAPK/NF-κB/activator protein-1 and accordingly stimulates differentiation-related gene expressions and osteoblast mineralisation.


Agreement between three ELISAs for Mycobacterium avium subsp. paratuberculosis in dairy cattle.
During a 10-month period in 1999, 994 serum and tissue samples were collected from dairy cows at slaughter in eastern Canada. The sources of these cattle were from all four Atlantic Canadian provinces along with some cows from the state of Maine. The sera were used to assess the agreement of three commercially available ELISAs for Mycobacterium avium subsp. paratuberculosis. Two ELISAs were indirect absorbed ELISAs licensed for use in North America, the third was an indirect non-absorbed ELISA licensed for use in Europe. Overall, there was poor agreement between the three ELISAs. The highest and lowest kappa values were 0.33 and 0.18, which is fair and poor agreement, respectively. However, when only tissue culture-positive cattle were compared, the ELISAs had better agreement (kappa=0.37-0.51). The proportions of positive tests, however, were significantly different among the three ELISAs. The poor agreement among the three ELISAs is as concerning as the fact that these tests have low sensitivity. The implications are greatest when the tests are used at the cow level to make individual animal decisions, which is not the recommended method on the product labels. At the cow level, if the result obtained from one ELISA is positive, using a different ELISA in a pre-clinical animal has a high likelihood of giving a different result due to low predictive values of positive test results.


Differential expression of protein phosphatase 1 isoforms in mammalian brain.
Rat cDNAs encoding neuronal isoforms of protein phosphatase 1 (PP1) were isolated and their primary structures elucidated. The derived amino acid sequences allowed us to design synthetic C-terminal peptides that were used to raise antibodies. Isoform-specific anti-peptide antibodies against PP1 alpha and PP1 gamma 1 were used to investigate the tissue distribution of PP1 isoforms by immunoblotting. Both isoforms were ubiquitously expressed in mammalian tissues, with the highest levels being observed in brain. Of all neuronal tissues examined, PP1 alpha and PP1 gamma 1 were found to be most abundantly expressed in the striatum. Lesion experiments with kainic acid indicated that both the alpha and the gamma 1 isoforms of protein phosphatase 1 were relatively enriched in the medium-size spiny neurons of the striatum. "In situ" hybridization to rat brain slices using highly sensitive riboprobes also showed PP1 alpha, PP1 beta, and PP1 gamma 1 to be widely expressed in mammalian brain. However, some interesting differences were observed. For example, PP1 alpha and PP1 gamma 1 were found to be expressed in the striatum, where DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, M(r) = 32,000 Da) is also known to be highly expressed. PP1 beta appeared to be relatively less abundant in the same cells, as judged both by "in situ" hybridization and by the apparent absence of PP1 beta clones from the striatal cDNA libraries used.


Development of a simple model for studying the effects of antifungal agents on multicellular communities of Aspergillus fumigatus.
Aspergillus fumigatus is an increasingly prevalent opportunistic fungal pathogen of various immunocompromised individuals. It has the ability to form filaments within the lungs, producing dense intertwined mycelial balls, which are difficult to treat. The aim of this study was to develop a suitable model of A. fumigatus to examine the effects of antifungal challenge on these intertwined filamentous communities. A. fumigatus NCPF 7367 growth conditions were optimized on both Thermanox coverslips and on flat-bottomed microtitre plates to establish optimal conidial seeding densities. Isolates were treated with itraconazole, voriconazole, amphotericin B and caspofungin and their overall killing efficiency was measured using an XTT formazan metabolic dye assay. This was compared with the CLSI (formerly NCCLS) methodology of broth microdilution of moulds (standard M38-A). It was shown that 1x10(5) conidia ml(-1) in RPMI 1640 was the optimum concentration of spores for biofilm formation. Filamentous growth characteristics were not observed until 10 h incubation, followed by an exponential increase in the biofilm biomass (hyphae and extracellular material) and cellular activity (metabolism). When susceptibility testing of biofilms was compared with that of planktonic cells by CLSI broth microdilution testing, all antifungal drugs were at least 1000 times less effective at reducing the overall metabolic activity of 90 % of the cells. Overall, this study showed that A. fumigatus has the ability to form coherent multicellular biofilm structures that are resistant to the effects of antifungal drugs.


Can proinflammatory cytokine gene expression explain multifidus muscle fiber changes after an intervertebral disc lesion?
Longitudinal case-controlled animal study. To investigate the effect of an intervertebral disc (IVD) lesion on the proportion of slow, fast, and intermediate muscle fiber types in the multifidus muscle in sheep, and whether muscle fiber changes were paralleled by local gene expression of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1-β. Structure and behavior of the multifidus muscle change in acute and chronic back pain, but the mechanisms are surprisingly poorly understood and the link between structure and behavior is tenuous. Although changes in muscle fiber types have the potential to unify the observations, the effect of injury on muscle fiber distribution has not been adequately tested, and understanding of possible mechanisms is limited. The L1-L2, L3-L4, and L5-L6 IVDs of 11 castrated male sheep received anterolateral lesions. Six control sheep underwent no surgical procedures. Multifidus muscle tissue was harvested at L4 for muscle fiber analysis using immunohistochemistry and L2 for cytokine analysis with polymerase chain reaction for local gene expression of TNF-α and interleukin-1β. The proportion of slow muscle fibers in multifidus was significantly less in the lesioned animals both ipsilateral and contralateral to the IVD lesion. The greatest reduction in slow fibers was in the deep medial muscle region. A greater prevalence of intermediate fibers on the uninjured side implies a delayed fiber-type transformation on that side. TNF-α gene expression in multifidus was greater on both sides in the lesion animals than in the muscle of control animals. Interleukin-1β was increased only on the injured side. These data provide evidence of muscle fiber changes after induction of an IVD lesion and a parallel increase in TNF-α expression. Proinflammatory cytokine changes provide a novel mechanism to explain behavioral and structural changes in multifidus. N/A.


Brachypodium distachyon exhibits compatible interactions with Oculimacula spp. and Ramularia collo-cygni, providing the first pathosystem model to study eyespot and ramularia leaf spot diseases.
Brachypodium distachyon (Bd) has established itself as an essential tool for comparative genomic studies in cereals and increasing attention is being paid to its potential as a model pathosystem. Eyespot and ramularia leaf spot (RLS) are important diseases of wheat, barley and other small-grain cereals for which very little is known about the mechanisms of host resistance despite urgent requirements for plant breeders to develop resistant varieties. This work aimed to test the compatibility of interaction of two Bd accessions with the cereal pathogens Oculimacula spp. and Ramularia collo-cygni, the causal agents of eyespot and RLS diseases, respectively. Results showed that both Bd accessions developed symptoms similar to those on the natural host for all pathogen species tested. Microscopy images demonstrated that R. collo-cygni produced secondary conidia and both Oculimacula spp. formed characteristic infection structures on successive tissue layers. Visual disease assessment revealed that quantitative differences in disease severity exist between the two Bd accessions. The results presented here provide the first evidence that Bd is compatible with the main causal agents of eyespot and RLS diseases, and suggest that future functional genetic studies can be undertaken to investigate the mechanisms of eyespot and RLS disease resistance using Bd.


Cholesteryl ester transfer protein protects against insulin resistance in obese female mice.
Cholesteryl ester transfer protein (CETP) shuttles lipids between lipoproteins, culminating in cholesteryl ester delivery to liver and increased secretion of cholesterol as bile. Since gut bile acids promote insulin sensitivity, we aimed to define if CETP improves insulin sensitivity with high-fat feeding. CETP and nontransgenic mice of both sexes became obese. Female but not male CETP mice had increased ileal bile acid levels versus nontransgenic littermates. CETP expression protected female mice from insulin resistance but had a minimal effect in males. In liver, female CETP mice showed activation of bile acid-sensitive pathways including Erk1/2 phosphorylation and Fxr and Shp gene expression. In muscle, CETP females showed increased glycolysis, increased mRNA for Dio2, and increased Akt phosphorylation, known effects of bile acid signaling. These results suggest that CETP can ameliorate insulin resistance associated with obesity in female mice, an effect that correlates with increased gut bile acids and known bile-signaling pathways.


Asymmetric stability among the transmembrane helices of lactose permease.
Combining structure determinations from nuclear magnetic resonance (NMR) data and molecular dynamics simulations (MD) under the same environmental conditions revealed a startling asymmetry in the intrinsic conformational stability of secondary structure in the transmembrane domain of lactose permease (LacY). Eleven fragments, corresponding to transmembrane segments (TMs) of LacY, were synthesized, and their secondary structure in solution was determined by NMR. Eight of the TMs contained significant regions of helical structure. MD simulations, both in DMSO and in a DMPC bilayer, showed sites of local stability of helical structure in these TMs, punctuated by regions of conformational instability, in substantial agreement with the NMR data. Mapping the stable regions onto the crystal structure of LacY reveals a marked asymmetry, contrasting with the pseudosymmetry in the static structure: the secondary structure in the C-terminal half is more stable than in the N-terminal half. The relative stability of secondary structure is likely exploited in the transport mechanism of LacY. Residues supporting proton conduction are in more stable regions of secondary structure, while residues key to substrate binding are found in considerably unstable regions of secondary structure.


Vitamin D treatment in myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are a group of clonal disturbances with defective cellular differentiation. Vitamin D3 (VD) analogues can act on the differentiation and maturity of different cell lines. We studied the effects of VD on a series of patients with MDS in an open-design trial. Nineteen patients, 12 men and seven women, with MDS were included. Patients were 74.8 +/- 5.6 years (mean +/- SD), seven had refractory anaemia with ringed sideroblasts, five had refractory anaemia, one had refractory anaemia with excess of blasts and six had chronic myelomonocytic leukaemia. All the patients were in a low to intermediate risk group. Mean follow-up period was 26.21 months, range 9-75. Responders were defined as follows: granulocyte or platelet count increase by 50%, or haemoglobin increase of 1.5 g/dl or transfusion needs decrease by 50%. The first five patients received 266 microg of calcifediol three times a week and the other 14 received calcitriol (0.25-0.75 microg/d). Response was observed in 11 patients. In the calcifediol-treated group, one case responded, three were nonresponders, and one showed progression. In the calcitriol group, 10 were responders (two with major response), and four were non-responders. No correlation was observed between baseline levels of vitamin D metabolites and the presence of response. No hypercalcaemia was observed. Treatment with vitamin D3 metabolites could induce a long-standing response of the haematological disturbance in some low-intermediate risk MDS patients without inducing hypercalcaemia.


Oxygen consumption at altitude as a risk factor for altitude decompression sickness.
The existence of a general influence of exercise on the incidence of decompression sickness (DCS) has been known for more than a half-century. However, quantification of the effect has not been done for several reasons, including isolation of exercise as the only variable. The DCS database at Brooks City-Base, TX, contains detailed physiologic information on over 3000 altitude exposures. The purpose of this study was to measure Vo2 during the activities performed during those exposures to retrospectively determine if Vo2, a quantifiable index of exercise intensity, was related to the level of reported DCS. Ground-level activity was designed to duplicate the standardized activity during the altitude exposures. Breath-by-breath Vo2 was determined for each activity using a COSMED metabolic measurement system. Comparison of the Vo2 during four levels of activity performed under otherwise comparable conditions allowed a determination of correlation between Vo2 and DCS risk observed during the altitude exposures. Four previous altitude exposure profiles at 8992 m to 9144 m (29,500 to 30,000 ft; 231 to 226 mmHg) for 4 h following a 1-h prebreathe resulted in 38-86% DCS. This study provided the Vo2 of activities during those studies. The correlation between DCS incidence and the highest 1-min Vo2 of activity was 0.89. The highest 1-min Vo2 showed a high correlation with level of DCS risk. Future exposures involving lower levels of activity could provide data that would allow improvement in modeling of DCS risk.


Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults.
Controversy exists whether anxiety disorders are independently associated (ie, after adjusting for comorbid mental disorders) with suicidal ideation and suicide attempts. To examine whether anxiety disorders are risk factors for suicidal ideation and suicide attempts in a large population-based longitudinal study. Data come from the Netherlands Mental Health Survey and Incidence Study, a prospective population-based survey with a baseline and 2 follow-up assessments over a 3-year period. The Composite International Diagnostic Interview was used to assess DSM-III-R mental disorders. Lifetime diagnoses of anxiety disorders (social phobia, simple phobia, generalized anxiety disorder, panic disorder, agoraphobia, obsessive-compulsive disorder) were assessed at baseline. Multiple logistic regression analyses were used to examine whether anxiety disorders were associated with suicidal ideation and attempts at baseline (n = 7076) and whether anxiety disorders were risk factors for subsequent onset of suicidal ideation and attempts (n = 4796). After adjusting for sociodemographic factors and all other mental disorders assessed in the survey, baseline presence of any anxiety disorder was significantly associated with suicidal ideation and suicide attempts in both the cross-sectional analysis (adjusted odds ratio for suicidal ideation, 2.29; 95% confidence interval, 1.85-2.82; adjusted odds ratio for suicidal attempts, 2.48; 95% confidence interval, 1.70-3.62) and longitudinal analysis (adjusted odds ratio for suicidal ideation, 2.32; 95% confidence interval, 1.31-4.11; adjusted odds ratio for suicide attempts, 3.64; 95% confidence interval, 1.70-7.83). Further analyses demonstrated that the presence of any anxiety disorder in combination with a mood disorder was associated with a higher likelihood of suicide attempts in comparison with a mood disorder alone. This is the first study to demonstrate that a preexisting anxiety disorder is an independent risk factor for subsequent onset of suicidal ideation and attempts. Moreover, the data clearly demonstrate that comorbid anxiety disorders amplify the risk of suicide attempts in persons with mood disorders. Clinicians and policymakers need to be aware of these findings, and further research is required to delineate whether treatment of anxiety disorders reduces the risk of subsequent suicidal behavior.


Development of a [3+3] cycloaddition strategy toward functionalized piperidines.
This paper describes a novel route to functionalized piperidines via a formal [3+3] cycloaddition reaction of activated aziridines and palladium-trimethylenemethane (Pd-TMM) complexes. The cycloaddition reaction generally proceeds enantiospecifically with ring opening at the least hindered site of the aziridine. Therefore, readily available enantiomerically pure 2-substituted aziridines can be utilized to prepare enantiomerically pure 2-substituted piperidines in good to excellent yield. The N-substituent on the aziridine proved to be crucial to the success of this reaction with only 4-toluenesulfonyl (Ts) and 4-methoxybenzenesulfonyl (PMBS) aziridines permitting smooth cycloaddition to take place. Additionally, spirocyclic aziridines have been found to participate in the [3+3] cycloaddition reaction, whereas 2,3-disubstituted aziridines can be applied to provide fused bicyclic piperidines, albeit in low yield.


The Development of the Measure of Adolescent Relationship Harassment and Abuse (MARSHA): Input From Black and Multiracial, Latinx, Native American, and LGBTQ+ Youth.
This formative research study was designed to collect opinion data from adolescents historically underrepresented in adolescent dating abuse (ADA) research measure development. Eight in-person focus groups and 7 telephone-based one-on-one interviews were conducted with U.S. youth aged from 11 to 20 years (N=48). We conducted two focus groups with Black, Multiracial, Latinx, Native American, and LGBTQ+ youth. Seven LGBTQ+ youth participated in one-on-one telephone-based interviews. Focus group participants and interview subjects were asked the same 11 questions from a semi-structured focus group question guide. Five questions were on the topic of dating behaviors in general. In addition, six questions were asked for reactions to a paper-based list of 75 abusive acts. Youth generated ideas for 10 new possible cyber-ADA items and 14 emotionally abusive items for inclusion on the ADA measurement instrument. They did not generate any new physical or sexual ADA items. Youth identified 14 acts that they felt should not be on the measure, either because the acts were not abusive and too common, because they could not understand the item, or because it seemed unrealistic as an act of ADA. The study faced several limitations and was a good first step toward enriching the cultural inclusivity of ADA measurement instrument. Continued attention to inclusionary research that seeks to understand the cultural milieux of diverse participants is essential for violence prevention scholarship and subsequent health programming and policy that derive from it.


Comparison of Clomethiazole and Diazepam in the Treatment of Alcohol Withdrawal Syndrome in Clinical Practice.
The objective of this retrospective study was to compare the effectivity and tolerability of diazepam and clomethiazole in the treatment of alcohol withdrawal syndrome (AWS) in a large clinical sample. The data of 566 patients admitted to an intensive care psychiatric unit in Germany (2010-2014) were evaluated. The course of withdrawal was analyzed on a matched sample (n = 152) consisting of a diazepam group (n = 76) and a clomethiazole group (n = 76). Medical assessment was based on a standardized point-based symptom rating scale called AESB (Alkoholentzugssymptom-Bogen), a German modified version of the Revised Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar). Although the mean daily symptom reduction did not differ significantly, patients treated with clomethiazole were treated significantly shorter and needed less concomitant antipsychotic medication. Numbers of complications and adverse events did not show significant differences. Both clomethiazole and diazepam were effective and equally safe in the treatment of AWS. Clomethiazole provided a faster withdrawal and required less concomitant antipsychotic medication and therefore might be the more favorable option for patients and physicians. Taken into account the methodological limitations of the study (retrospective design, secondary matching, missing randomization, use of clomethiazole as drug of first choice), further studies are needed to confirm this result.


Pain response of healthy workers following a functional capacity evaluation and implications for clinical interpretation.
Functional Capacity Evaluations (FCEs) are used to quantify physical aspects of work capacity. Safety is a critical issue for clinical use of an FCE. Patients with Chronic Low Back Pain (CLBP) are known to report a temporary increase in pain following an FCE, but it is not known whether this increase is a normal pain response to FCE. It is currently unknown how healthy subjects respond to an FCE and whether this should be interpreted as a normal reaction after physical exercise. This study was performed to quantify the intensity, duration, location and nature of the pain response following an FCE in healthy subjects and to compare this pain response with the pain response of patients with CLBP from a previous study. A total of 197 healthy working subjects between 20 and 60 years of age volunteered to participate in this study. All subjects performed a 12-item FCE. Pain response was measured by a self-constructed Pain Response Questionnaire (PRQ). Descriptive statistics were used to describe the pain response following an FCE. Mann-Whitney and t-tests were performed to compare the data from this study with data of patients with CLBP from a previous study. About 82% of all subjects reported a pain response following the FCE. The intensity of the pain response after 24 h post FCE was a median of 3.0 on a numeric rating scale (0-10). About 78% of all pain was reducible to muscle soreness. Pain was most often reported in the upper legs (51%), the lower back (38%) the shoulders (37%) and upper arms (36%). Symptoms decreased to pre-FCE levels in a mean of 3 days. The pain response of 2 subjects (1%) lasted for 3 weeks. The intensity and duration of the pain response of healthy subjects was not significantly different from the response of patients with CLBP. Pain response of 99% of all subjects who reported a pain response was interpreted as normal. It was concluded that a pain response following an FCE can be expected in healthy subjects and that this pain response is a normal musculoskeletal reaction. The pain response of patients with CLBP resembles the pain response of healthy subjects.


Transport of trehalose in Salmonella typhimurium.
We have studied trehalose uptake in Salmonella typhimurium and the possible involvement of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) in this process. Two transport systems could recognize and transport trehalose, the mannose PTS and the galactose permease. Uptake of trehalose via the latter system required that it be expressed constitutively (due to a galR or galC mutation). Introduction of a ptsM mutation, resulting in a defective IIMan/IIIMan system, in S. typhimurium strains that grew on trehalose abolished growth on trehalose. A ptsG mutation, eliminating IIGlc of the glucose PTS, had no effect. In contrast, a crr mutation that resulted in the absence of IIIGlc of the glucose PTS prevented growth on trehalose. The inability of crr and also cya mutants to grow on trehalose was due to lowered intracellular cyclic AMP synthesis, since addition of extracellular cyclic AMP restored growth. Subsequent trehalose metabolism could be via a trehalose phosphate hydrolase, if trehalose phosphate was formed via the PTS, or trehalase. Trehalose-grown cells contained trehalase activity, but we could not detect phosphoenolpyruvate-dependent phosphorylation of trehalose in toluenized cells.


Partitioning, persistence, and accumulation in digested sludge of the topical antiseptic triclocarban during wastewater treatment.
The topical antiseptic agent triclocarban (TCC) is a common additive in many antimicrobial household consumables, including soaps and other personal care products. Long-term usage of the mass-produced compound and a lack of understanding of its fate during sewage treatment motivated the present mass balance analysis conducted at a typical U.S. activated sludge wastewater treatment plant featuring a design capacity of 680 million liters per day. Using automated samplers and grab sampling, the mass of TCC contained in influent, effluent, and digested sludge was monitored by isotope dilution liquid chromatography (tandem) mass spectrometry. The average mass of TCC (mean +/- standard deviation) entering and exiting the plant in influent (6.1 +/- 2.0 microg/L) and effluent (0.17 +/- 0.03 microg/ L) was 3737 +/- 694 and 127 +/- 6 g/d, respectively, indicating an aqueous-phase removal efficiency of 97 +/- 1%. Tertiary treatment by chlorination and sand filtration provided no detectable benefit to the overall removal. Due to strong sorption of TCC to wastewater particulate matter (78 +/- 11% sorbed), the majority of the TCC mass was sequestered into sludge in the primary and secondary clarifiers of the plant. Anaerobic digestion for 19 days did not promote TCC transformation, resulting in an accumulation of the antiseptic compound in dewatered, digested municipal sludge to levels of 51 +/- 15 mg/kg dry weight (2815 +/- 917 g/d). In addition to the biocide mass passing through the plant contained in the effluent (3 +/- 1%), 76 +/- 30% of the TCC input entering the plant underwent no net transformation and instead partitioned into and accumulated in municipal sludge. Based on the rate of beneficial reuse of sludge produced by this facility (95%), which exceeds the national average (63%), study results suggest that approximately three-quarters of the mass of TCC disposed of by consumers in the sewershed of the plant ultimately is released into the environment by application of municipal sludge (biosolids) on land used in part for agriculture.


Functional connectivity between cognitive control regions is sensitive to familial risk for ADHD.
Familial risk for attention-deficit hyperactivity disorder (ADHD) has been associated with changes in brain activity related to cognitive control. However, it is not clear whether changes in activation are the primary deficit or whether they are related to impaired communication between regions involved in this ability. We investigated whether (1) functional connectivity between regions involved in cognitive control was affected by familial risk and (2) changes were specific to these regions. Correlational seed analyses were used to investigate temporal covariance between cognitive control and motor regions in two independent samples of typically developing controls, subjects with ADHD and their unaffected siblings. In both samples, correlation coefficients between cognitive control regions were greater for typically developing controls than for subjects with ADHD, with intermediate values for unaffected siblings. Within the motor network, unaffected siblings showed correlations similar to typically developing children. There were no differences in activity between the brain regions involved. These data show that functional connectivity between cognitive control regions is sensitive to familial risk for ADHD. Results suggest that changes in connectivity associated with cognitive control may be suitable as an intermediate phenotype for future studies.


Complete Genome Sequence of Thermoactinomyces vulgaris Strain CDF, a Thermophilic Bacterium Capable of Degrading Chicken Feathers.
Thermoactinomyces vulgaris strain CDF was isolated from soil and shown to have the ability to degrade chicken feathers at high temperatures. Here, we report the complete genome sequence of this bacterium, which is 2,595,509 bp long with 2,642 predicted genes and an average G+C content of 48.14%.


Inhalation of high-concentration hydrogen gas attenuates cognitive deficits in a rat model of asphyxia induced-cardiac arrest.
Cognitive deficits are a devastating neurological outcome seen in survivors of cardiac arrest. We previously reported water electrolysis derived 67% hydrogen gas inhalation has some beneficial effects on short-term outcomes in a rat model of global brain hypoxia-ischemia induced by asphyxia cardiac arrest. In the present study, we further investigated its protective effects in long-term spatial learning memory function using the same animal model. Water electrolysis derived 67% hydrogen gas was either administered 1 hour prior to cardiac arrest for 1 hour and at 1-hour post-resuscitation for 1 hour (pre- & post-treatment) or at 1-hour post-resuscitation for 2 hours (post-treatment). T-maze and Morris water maze were used for hippocampal memory function evaluation at 7 and 14 days post-resuscitation, respectively. Neuronal degeneration within hippocampal Cornu Ammonis 1 (CA1) regions was examined by Fluoro-Jade staining ex vivo. Hippocampal deficits were detected at 7 and 18 days post-resuscitation, with increased neuronal degeneration within hippocampal CA1 regions. Both hydrogen gas treatment regimens significantly improved spatial learning function and attenuated neuronal degeneration within hippocampal CA1 regions at 18 days post-resuscitation. Our findings suggest that water electrolysis derived 67% hydrogen gas may be an effective therapeutic approach for improving cognitive outcomes associated with global brain hypoxia-ischemia following cardiac arrest. The study was approved by the Animal Health and Safety Committees of Loma Linda University, USA (approval number: IACUC #8170006) on March 2, 2017.


Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: an intricate pathway.
The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an "inflammatory cancer", arising from a context of inflammation, and characterized by inflammation-related mechanisms that favor tumor cell survival, proliferation, and invasion. Molecular mechanisms that link inflammation and neoplasia have been widely investigated, and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species. The latter, in turn, probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation, and ultimately leading to cancer. The relationship amongst chronic liver injury, free radical production, and development of HCC is explored in the present review, particularly in the light of the complex network that involves oxidative DNA damage, cytokine synthesis, telomere dysfunction, and microRNA regulation.


The use of measures of influence in epidemiology.
In epidemiological studies the units of observation often consist of political entities such as countries, each of which has its own specific inner structure. When a multiple regression is performed it is therefore of particular interest to analyse not only the overall behaviour of the dataset, but in addition, to investigate how each individual country contributes to, and deviates from, this overall behaviour. By means of the example 'relation between infant mortality and structural data of countries' several ways are discussed of how each individual country can influence the regression model. Firstly the potential influence which each country might exhibit due to the explanatory variables alone is analysed. Then the actual influence of each country is analysed by taking the explanatory variables and the target variable into account simultaneously. This is done by means of statistical measures not generally familiar to epidemiologists, which have been developed in recent years (leverage values, Cook's distances). These measures also point to deviations of countries from the model, and suggest directions in which to search for explanation. Finally the influence of the 'size' of the countries is investigated.


Men's strategic preferences for femininity in female faces.
Several evolutionarily relevant sources of individual differences in face preference have been documented for women. Here, we examine three such sources of individual variation in men's preference for female facial femininity: term of relationship, partnership status and self-perceived attractiveness. We show that men prefer more feminine female faces when rating for a short-term relationship and when they have a partner (Study 1). These variables were found to interact in a follow-up study (Study 2). Men who thought themselves attractive also preferred more feminized female faces for short-term relationships than men who thought themselves less attractive (Study 1 and Study 2). In women, similar findings for masculine preferences in male faces have been interpreted as adaptive. In men, such preferences potentially reflect that attractive males are able to compete for high-quality female partners in short-term contexts. When a man has secured a mate, the potential cost of being discovered may increase his choosiness regarding short-term partners relative to unpartnered men, who can better increase their short-term mating success by relaxing their standards. Such potentially strategic preferences imply that men also face trade-offs when choosing relatively masculine or feminine faced partners. In line with a trade-off, women with feminine faces were seen as more likely to be unfaithful and more likely to pursue short-term relationships (Study 3), suggesting that risk of cuckoldry is one factor that may limit men's preferences for femininity in women and could additionally lead to preferences for femininity in short-term mates.


Neuron-glia cell adhesion molecule interacts with neurons and astroglia via different binding mechanisms.
The neuron-glia cell adhesion molecule (Ng-CAM) is present in the central nervous system on postmitotic neurons and in the periphery on neurons and Schwann cells. It has been implicated in binding between neurons and between neurons and glia. To understand the molecular mechanisms of Ng-CAM binding, we analyzed the aggregation of chick Ng-CAM either immobilized on 0.5-micron beads (Covaspheres) or reconstituted into liposomes. The results were correlated with the binding of these particles to different types of cells as well as with cell-cell binding itself. Both Ng-CAM-Covaspheres and Ng-CAM liposomes individually self-aggregated, and antibodies against Ng-CAM strongly inhibited their aggregation; the rate of aggregation increased approximately with the square of the concentration of the beads or the liposomes. Much higher rates of aggregation were observed when the ratio of Ng-CAM to lipid in the liposome was increased. Radioiodinated Ng-CAM on Covaspheres and in liposomes bound both to neurons and to glial cells and in each case antibodies against Ng-CAM inhibited 50-90% of the binding. Control preparations of fibroblasts and meningeal cells did not exhibit significant binding. Adhesion between neurons and glia within and across species (chick and mouse) was explored in cellular assays after defining markers for each cell type, and optimal conditions of shear, temperature, and cell density. As previously noted using chick cells (Grumet, M., S. Hoffman, C.-M. Chuong, and G. M. Edelman. 1984 Proc. Natl. Acad. Sci. USA. 81:7989-7993), anti-Ng-CAM antibodies inhibited neuron-neuron and neuron-glia binding. In cross-species adhesion assays, binding of chick neurons to mouse astroglia and binding of mouse neurons to chick astroglia were both inhibited by anti-Ng-CAM antibodies. To identify whether the cellular ligands for Ng-CAM differed for neuron-neuron and neuron-glia binding, cells were preincubated with specific antibodies, the antibodies were removed by washing, and Ng-CAM-Covasphere binding was measured. Preincubation of neurons with anti-Ng-CAM antibodies inhibited Ng-CAM-Covasphere binding but similar preincubation of astroglial cells did not inhibit binding. In contrast, preincubation of astroglia with anti-astroglial cell antibodies inhibited binding to these cells but preincubation of neurons with these antibodies had no effect. Together with the data on Covaspheres and liposome aggregation, these findings suggested that Ng-CAM-Covaspheres bound to Ng-CAM on neurons but bound to different molecules on astroglia.(ABSTRACT TRUNCATED AT 400 WORDS)


DNA polymerase beta mutations in human colorectal cancer.
Increasing numbers of alterations have been found in protooncogenes (e.g., ras, myc), as well as tumor suppressor genes (e.g., p53, Rb) in various types of tumors. The multiple mutations cannot be explained by the spontaneous mutation rate. It has been suggested that mutator phenotypes leading to the accumulation of these mutations may be required in the early stages of tumorigenesis. To test this hypothesis, the entire coding region of DNA polymerase beta, a repair enzyme, mRNA from colorectal tumors, and corresponding normal mucosa were amplified by polymerase chain reaction, cloned, and sequenced. Mutations in the catalytic domain of DNA polymerase beta were detected in colorectal tumor specimens compared to the normal colorectal mucosa, placenta, and blood samples. Since these mutations changed the structure of polymerase beta, it is expected that the efficiency of the DNA repair system would be impaired and thus may account for the high mutation rate observed in colorectal carcinomas.


First Report of Fusarium torulosum Causing Dry Rot of Seed Potato Tubers in the United States.
Fusarium dry rot of potato (Solanum tuberosum L.) is a postharvest disease caused by several Fusarium species and is of worldwide importance. Thirteen species of Fusarium have been implicated in fungal dry rots of potatoes worldwide. Among them, eight species have been reported in the northern United States (2). In Michigan potato production, F. sambucinum was the predominant species reported to be affecting seed potato in storage and causing seed piece decay after planting (3). Some previous identifications of F. sambucinum as dry rot may have been F. torulosum since F. torulosum was previously classified within F. sambucinum (4). To further investigate this, dry rot symptomatic tubers were collected from Michigan seed lots in the summers of 2009 and 2010. Small sections from the margins of necrotic regions were cut with a scalpel, surface sterilized in 0.5% sodium hypochlorite for 10 s, rinsed twice in sterile distilled water, and blotted with sterile filter paper. The tissue pieces were plated on half-strength potato dextrose agar (PDA) amended with 0.5 g/liter of streptomycin sulfate and incubated at 23°C for 5 to 7 days. Cultures resembling Fusarium species were transferred onto water agar, and single hyphal tips from actively growing isolates were removed and plated either on carnation leaf agar (CLA) or on half-strength PDA to generate pure cultures. Among the Fusarium isolates obtained, five isolates were identified as F. torulosum (GenBank Accessions Nos. JF803658-JF803660). Identification was based on colony and conidial morphology on PDA and CLA, respectively. These features included slow growth (2.8 ± 0.2 cm in 5 days), white mycelium that became pigmented with age, narrow concentric rings, red or white pigmentation on agar, macroconidia (32.4 ± 0.4 μm average length) with five septa, a pointed apical cell, and a foot-shaped basal cell (4). The identity was confirmed through DNA extraction followed by amplification and sequencing of the translation elongation factor (EF-1α) gene region (1). The Fusarium-ID.v (1) and the NCBI database were used to obtain the closest match (99%) to previously sequenced materials (GenBank Accession No. AJ543611). Pathogenicity testing was done on disease-free potato tubers cv. Red Norland. Tubers were surface sterilized for 10 min in 0.5% sodium hypochlorite and rinsed twice in distilled water. Three tubers per isolate were injected with 20 μl of a conidial suspension (106 conidia/ml) made from F. torulosum cultures grown on PDA for 7 to 10 days. Control tubers were injected with 20 μl of sterile distilled water. All tubers inoculated with F. torulosum developed typical potato dry rot symptoms consisting of a brown and dry decay. There was no disease incidence on the control tubers. F. torulosum was reisolated from the symptomatic tubers. To our knowledge, this is the first report of F. torulosum causing potato dry rot in the United States. References: (1) D. Geiser et al. Eur. J. Plant Pathol. 110:473, 2004. (2) L. E. Hanson et al. Phytopathology 86:378, 1996. (3) M. L. Lacy and R. Hammerschmidt. Fusarium dry rot. Extension Bulletin. Retrieved from http://web1.msue.msu.edu/msue/iac/onlinepubs/pubs/E/E2448POT , 23 May 2010. (4) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Wiley-Blackwell, Hoboken, NJ, 2006.


Non-uniform effectiveness of structured patient-clinician communication in community mental healthcare: an international comparison.
The effectiveness of psychosocial interventions in community mental healthcare has been shown to depend on the setting in which they are implemented. Recently structured patient-clinician communication was found to be effective in a multi-centre trial in six European countries, the DIALOG trial. In the overall study, differences between centres were controlled for, not studied. Here, we test whether the effectiveness of structured patient-clinician communication varies between services in different countries, and explore setting characteristics associated with outcome. The study is part of the DIALOG trial, which included 507 patients with schizophrenia or related disorder, treated by 134 keyworkers. The keyworkers were allocated to intervention or treatment as usual. Positive effects were found on quality of life (effect size 0.20: 95% CI 0.01-0.39) and treatment satisfaction (0.27: 0.06-0.47) in all centres, but reductions in unmet needs for care were only seen in two centres (-0.83 and -0.60), and in positive, negative and general symptoms in one (-0.87, -0.78, -0.87). The intervention was most effective in settings with patient populations with many unmet needs for care and high symptom levels. Psychosocial interventions in community mental healthcare may not be assumed to have uniform effectiveness across settings. Differences in patient population served and mental healthcare provided, should be studied for their influence on the effectiveness of the intervention. Structured patient-clinician communication has a uniform effect on quality of life and treatment satisfaction, but on unmet needs for care and symptom levels its effect differs between mental healthcare settings.


The Medical Use of Wheatgrass: Review of the Gap Between Basic and Clinical Applications.
A wide range of health benefits have been attributed to wheatgrass, the young grass of the common wheat plant Triticum aestivum. Its components include chlorophyll, flavonoids, and vitamins C and E. Forms of wheatgrass include fresh juice, frozen juice, tablets, and powders, with compositions varying according to their production processes, as well as to the growing conditions of the wheatgrass. Laboratory in vitro studies, mostly using the fermented wheat germ extract, have demonstrated anti-cancer potential and have identified apoptosis as a possible mechanism. In animal experiments, wheatgrass demonstrated benefits in cancer prevention and as an adjunct to cancer treatment, as well as benefits to immunological activity and oxidative stress. Clinical trials show that wheatgrass may induce synergistic benefits to chemotherapy and may attenuate chemotherapy-related side effects, as well as benefit rheumatoid arthritis, ulcerative colitis, hematological diseases, diabetes, obesity, and oxidative stress. However, all the trials were small and a number of methodological problems arose. No adverse events of wheatgrass have been reported, although some forms pose problems of tolerability. The popularity of wheatgrass continues to grow. Nevertheless, the advantages seen in the clinical trials need to be proved in larger studies before clinical recommendations for the public can be given.


Why, After Chemotherapy, is it Necessary to Assess Memory Using Translational Testing?
As the number of cancer survivors rises, so does the importance of understanding what happens post-chemotherapy. The evidence is clear that chemotherapy affects not only cancer cells, but also healthy cells including neurons, leading to long-term cognitive dysfunction in a large portion of survivors. In order to understand the mechanism of action and in the hope of reducing the potential neurocognitive side effects of chemotherapy, pre-clinical testing should be used more effectively. However, the field is lacking translation from clinical studies to animal models. Spatial learning and memory paradigms based on the water maze, the most commonly used rodent model, are available for translational testing in humans and could overcome this weakness. There is an overwhelming need in the field to understand whether the water maze is an adequate model for post-chemotherapy impairments or whether other paradigms should be used. This is of great importance for the understanding of the mechanisms, side effects of new drugs, appropriate pharmacotherapy, and confounding factors related to chemotherapy treatment regiments. This review is very important to both basic scientists and clinicians determining how translational paradigms are critical to future cancer research, as well as what type of paradigms are appropriate in our technically advancing society.


ACR Appropriateness Criteria® Osteoporosis and Bone Mineral Density.
Osteoporosis is a considerable public health risk, with 50% of women and 20% of men >50 years of age experiencing fracture, with mortality rates of 20% within the first year. Dual x-ray absorptiometry (DXA) is the primary diagnostic modality by which to screen women >65 years of age and men >70 years of age for osteoporosis. In postmenopausal women <65 years of age with additional risk factors for fracture, DXA is recommended. Some patients with bone mineral density above the threshold for treatment may qualify for treatment on the basis of vertebral body fractures detected through a vertebral fracture assessment scan, a lateral spine equivalent generated from a commercial DXA machine. Quantitative CT is useful in patients with advanced degenerative bony changes in their spines. New technologies such as trabecular bone score represent an emerging role for qualitative assessment of bone in clinical practice. It is critical that both radiologists and referring providers consider osteoporosis in their patients, thereby reducing substantial morbidity, mortality, and cost to the health care system. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents.
Although East Asians carry the cytochrome P450 (CYP) 2C19*2 allele more frequently than do Caucasians, the impact of the CYP2C19*2 allele on clopidogrel pharmacodynamics and clinical outcomes is unknown. To evaluate the effect of CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in East Asian patients with drug-eluting stents (DES). DES-treated patients taking dual antiplatelet therapy were enrolled from a Korean multicentre genetic registry. The CYP2C19*2 allele was genotyped using the Taqman method (n=2146), and on-treatment platelet reactivity was measured with the VerifyNow P2Y12 assay (n=1415). 1011 patients (47%) carried at least one CYP2C19*2 allele. The mean on-treatment platelet reactivity was significantly higher in carriers than in non-carriers (250±76 vs 231±83 P2Y12 reaction unit, p<0.001). For up to 12 months' follow-up, the composite of cardiovascular death, non-fatal myocardial infarction and stent thrombosis was significantly higher in carriers of the CYP2C19*2 allele than non-carriers (2.0% vs 0.8%, p=0.02). On landmark analysis, there was no difference in clinical outcome after 12 months between the groups. The CYP2C19*2 genetic variant may be associated with worse outcome in Korean patients treated exclusively with DES and dual-antiplatelet therapy due to a significant increase in cardiac death, myocardial infarction or stent thrombosis.


Linguistic and Cultural Challenges in Communication and Translation in US-Sponsored HIV Prevention Research in Emerging Economies.
Linguistic and cultural differences can impede comprehension among potential research participants during the informed consent process, but how researchers and IRBs respond to these challenges in practice is unclear. We conducted in-depth interviews with 15 researchers, research ethics committee (REC) chairs and members from 8 different countries with emerging economies, involved in HIV-related research sponsored by HIV Prevention Trials Network (HPTN), regarding the ethical and regulatory challenges they face in this regard. In the interviews, problems with translating study materials often arose as major concerns. Four sets of challenges were identified concerning linguistic and cultural translations of informed consent documents and other study materials, related to the: (1) context, (2) process, (3) content and (4) translation of these documents. Host country contextual issues included low literacy rates, education (e.g., documents may need to be written below 5th grade reading level), and experiences with research, and different views of written documentation. Certain terms and concepts may not exist in other languages, or have additional connotations that back translations do not always reveal. Challenges arise because of not only the content of word-for-word, literal translation, but the linguistic form of the language, such as tone (e.g., appropriate forms of politeness vs. legalese, seen as harsh), syntax, manner of questions posed, and the concept of the consent); and the contexts of use affect meaning. Problems also emerged in bilateral communications--US IRBs may misunderstand local practices, or communicate insufficiently the reasons for their decisions to foreign RECs. In sum, these data highlight several challenges that have received little, if any, attention in past literature on translation of informed consent and study materials, and have crucial implications for improving practice, education, research and policy, suggesting several strategies, including needs for broader open-source multilingual lexicons, and more awareness of the complexities involved.


Obese older adults suffer foot pain and foot-related functional limitation.
There is evidence to suggest being overweight or obese places adults at greater risk of developing foot complications such as osteoarthritis, tendonitis and plantar fasciitis. However, no research has comprehensively examined the effects of overweight or obesity on the feet of individuals older than 60 years of age. Therefore we investigated whether foot pain, foot structure, and/or foot function is affected by obesity in older adults. Three hundred and twelve Australian men and women, aged over 60 years, completed validated questionnaires to establish the presence of foot pain and health related quality of life. Foot structure (anthropometrics and soft tissue thickness) and foot function (ankle dorsiflexion strength and flexibility, toe flexor strength, plantar pressures and spatiotemporal gait parameters) were also measured. Obese participants (BMI >30) were compared to those who were overweight (BMI=25-30) and not overweight (BMI <25). Obese participants were found to have a significantly higher prevalence of foot pain and scored significantly lower on the SF-36. Obesity was also associated with foot-related functional limitation whereby ankle dorsiflexion strength, hallux and lesser toe strength, stride/step length and walking speed were significantly reduced in obese participants compared to their leaner counterparts. Therefore, disabling foot pain and altered foot structure and foot function are consequences of obesity for older adults, and impact upon their quality of life. Interventions designed to reduce excess fat mass may relieve loading of the foot structures and, in turn, improve foot pain and quality of life for older obese individuals.


GATA: a graphic alignment tool for comparative sequence analysis.
Several problems exist with current methods used to align DNA sequences for comparative sequence analysis. Most dynamic programming algorithms assume that conserved sequence elements are collinear. This assumption appears valid when comparing orthologous protein coding sequences. Functional constraints on proteins provide strong selective pressure against sequence inversions, and minimize sequence duplications and feature shuffling. For non-coding sequences this collinearity assumption is often invalid. For example, enhancers contain clusters of transcription factor binding sites that change in number, orientation, and spacing during evolution yet the enhancer retains its activity. Dot plot analysis is often used to estimate non-coding sequence relatedness. Yet dot plots do not actually align sequences and thus cannot account well for base insertions or deletions. Moreover, they lack an adequate statistical framework for comparing sequence relatedness and are limited to pairwise comparisons. Lastly, dot plots and dynamic programming text outputs fail to provide an intuitive means for visualizing DNA alignments. To address some of these issues, we created a stand alone, platform independent, graphic alignment tool for comparative sequence analysis (GATA http://gata.sourceforge.net/). GATA uses the NCBI-BLASTN program and extensive post-processing to identify all small sub-alignments above a low cut-off score. These are graphed as two shaded boxes, one for each sequence, connected by a line using the coordinate system of their parent sequence. Shading and colour are used to indicate score and orientation. A variety of options exist for querying, modifying and retrieving conserved sequence elements. Extensive gene annotation can be added to both sequences using a standardized General Feature Format (GFF) file. GATA uses the NCBI-BLASTN program in conjunction with post-processing to exhaustively align two DNA sequences. It provides researchers with a fine-grained alignment and visualization tool aptly suited for non-coding, 0-200 kb, pairwise, sequence analysis. It functions independent of sequence feature ordering or orientation, and readily visualizes both large and small sequence inversions, duplications, and segment shuffling. Since the alignment is visual and does not contain gaps, gene annotation can be added to both sequences to create a thoroughly descriptive picture of DNA conservation that is well suited for comparative sequence analysis.