The responsiveness of Bactrocera jarvisi (Diptera: Tephritidae) to two naturally occurring phenylbutaonids, zingerone and raspberry ketone.
The males of different species of Bactrocera and Zeugodacus fruit flies are commonly attracted to plant-derived phenylpropanoids (e.g. methyl eugenol (ME)) or phenylbutanoids (e.g. raspberry ketone (RK)) but almost never to both. However, one particular plant-derived phenylbutanoid, zingerone (ZN), which possesses an intermediate chemical structure between ME and RK, weakly attracts both ME- and RK-responding fruit fly species. Bactrocera jarvisi, an Australian fruit fly species, is weakly attracted to cue lure (an analogue of RK) but strongly attracted to ZN. Here, we investigated the minimum olfactory threshold and optimum sensitivity of B. jarvisi males to ZN and RK as a function of dose, time and sexual maturation. Our results show that B. jarvisi males had a marked preferential response to ZN, with a much lower olfactory threshold and faster response time to ZN than RK. Probit analysis demonstrated that ZN was at least >1600× more potent than RK as a male attractant to B. jarvisi. Although fruit fly male attraction to the phytochemicals is generally associated with sexual maturity, in B. jarvisi immature males were also attracted to ZN. Our results suggest that B. jarvisi males have a fine-tuned olfactory response to ZN, which appears to play a central role in the chemical ecology of this species.


The citation advantage of linking publications to research data.
Efforts to make research results open and reproducible are increasingly reflected by journal policies encouraging or mandating authors to provide data availability statements. As a consequence of this, there has been a strong uptake of data availability statements in recent literature. Nevertheless, it is still unclear what proportion of these statements actually contain well-formed links to data, for example via a URL or permanent identifier, and if there is an added value in providing such links. We consider 531, 889 journal articles published by PLOS and BMC, develop an automatic system for labelling their data availability statements according to four categories based on their content and the type of data availability they display, and finally analyze the citation advantage of different statement categories via regression. We find that, following mandated publisher policies, data availability statements become very common. In 2018 93.7% of 21,793 PLOS articles and 88.2% of 31,956 BMC articles had data availability statements. Data availability statements containing a link to data in a repository-rather than being available on request or included as supporting information files-are a fraction of the total. In 2017 and 2018, 20.8% of PLOS publications and 12.2% of BMC publications provided DAS containing a link to data in a repository. We also find an association between articles that include statements that link to data in a repository and up to 25.36% (± 1.07%) higher citation impact on average, using a citation prediction model. We discuss the potential implications of these results for authors (researchers) and journal publishers who make the effort of sharing their data in repositories. All our data and code are made available in order to reproduce and extend our results.


A population balance equation model of aggregation dynamics in Taxus suspension cell cultures.
The nature of plant cells to grow as multicellular aggregates in suspension culture has profound effects on bioprocess performance. Recent advances in the measurement of plant cell aggregate size allow for routine process monitoring of this property. We have exploited this capability to develop a conceptual model to describe changes in the aggregate size distribution that are observed over the course of a Taxus cell suspension batch culture. We utilized the population balance equation framework to describe plant cell aggregates as a particulate system, accounting for the relevant phenomenological processes underlying aggregation, such as growth and breakage. We compared model predictions to experimental data to select appropriate kernel functions, and found that larger aggregates had a higher breakage rate, biomass was partitioned asymmetrically following a breakage event, and aggregates grew exponentially. Our model was then validated against several datasets with different initial aggregate size distributions and was able to quantitatively predict changes in total biomass and mean aggregate size, as well as actual size distributions. We proposed a breakage mechanism where a fraction of biomass was lost upon each breakage event, and demonstrated that even though smaller aggregates have been shown to produce more paclitaxel, an optimum breakage rate was predicted for maximum paclitaxel accumulation. We believe this is the first model to use a segregated, corpuscular approach to describe changes in the size distribution of plant cell aggregates, and represents an important first step in the design of rational strategies to control aggregation and optimize process performance.


Ban the sunset? Nonpropositional content and regulation of pharmaceutical advertising.
The risk that direct-to-consumer advertising of prescription pharmaceuticals (DTCA) may increase inappropriate medicine use is well recognized. The U.S. Food and Drug Administration addresses this concern by subjecting DTCA content to strict scrutiny. Its strictures are, however, heavily focused on the explicit claims made in commercials, what we term their "propositional content." Yet research in social psychology suggests advertising employs techniques to influence viewers via nonpropositional content, for example, images and music. We argue that one such technique, evaluative conditioning, is operative in DTCA. We further argue that evaluative conditioning fosters unjustified beliefs about drug safety and efficacy, antagonising the autonomy of viewers' choices about advertised medicines. We conclude that current guidelines are deficient in failing to account for evaluative conditioning, and that more research and debate are needed to determine the permissibility of this and other forms of nonpropositional persuasion.


Picking winners. Interview by Diane Coutu.
In the business world, "creativity" has become the latest buzzword. How to attract, nurture, and direct the extraordinarily talented people who will come up with the next Lipitor, SonyWalkman, or iPod is an enduring topic among business-people. As the director of the MacArthur Fellows Program, Daniel J. Socolow has considerable experience with the process of rooting out creativity. In this conversation with HBR senior editor Diane Coutu, he describes how recipients of the "genius grant"--half a million dollars with no strings attached--are chosen. As significant as the money is, the recognition that comes with a fellowship may be more so. MacArthur grants provide powerful validation of the fellows' work, Socolow says, and that validation opens doors for people, whatever the field. Although the program keeps a lookout for entrepreneurs who are on the brink of major new advances, he believes that the market does a good job of rewarding the best ideas in business. Replicating the MacArthur model in a company would entail giving some employees unlimited time and lots of money to follow their own inclinations--not very feasible in most contexts. Nevertheless, the program has learned a lesson that may be valuable for business: The kind of creativity that leads to important breakthroughs is extremely hard to find. And, says Socolow, exceptionally creative people aren't always the obvious suspects, who may simply be good at promoting themselves: "Listen to others and look in the least likely places ... Extend your networks and try to get information from as many people as possible, just as we do".


Genetic classification of severe early childhood caries by use of subtracted DNA fragments from Streptococcus mutans.
Streptococcus mutans is one of several members of the oral indigenous biota linked with severe early childhood caries (S-ECC). Because most humans harbor S. mutans, but not all manifest disease, it has been proposed that the strains of S. mutans associated with S-ECC are genetically distinct from those found in caries-free (CF) children. The objective of this study was to identify common DNA fragments from S. mutans present in S-ECC but not in CF children. Using suppressive subtractive hybridization, we found a number of DNA fragments (biomarkers) present in 88 to 95% of the S-ECC S. mutans strains but not in CF S. mutans strains. We then applied machine learning techniques including support vector machines and neural networks to identify the biomarkers with the most predictive power for disease status, achieving a 92% accurate classification of the strains as either S-ECC or CF associated. The presence of these gene fragments in 90 to 100% of the 26 S-ECC isolates tested suggested their possible functional role in the pathogenesis of S. mutans associated with dental caries.


Fish oil supplementation inhibits endoplasmic reticulum stress and improves insulin resistance: involvement of AMP-activated protein kinase.
The beneficial effects of fish oil consumption on glucose metabolism have been generally reported. However, the mechanism underlying the fish oil-induced protective effects against insulin resistance remains unclear. Endoplasmic reticulum (ER) stress is recognized as an important contributor to insulin resistance. The aim of this study is to evaluate whether fish oil supplementation reduces ER stress and ameliorates insulin resistance in diet-induced obese mice, and to investigate the molecular mechanism of fish oil-induced benefits on ER stress. C57BL/6J mice were fed one of the following diets for 12 weeks: the low-fat diet (LFD), the high-fat diet (HFD) or the fish oil-supplemented high-fat diet (FOD). Fish oil supplementation led to lower blood glucose, better glucose tolerance and improved insulin sensitivity in high-fat diet-induced obese mice. Importantly, fish oil administration inhibited high-fat feeding-induced ER stress and reduced adipose tissue dysfunction. The fish oil-induced improvements were accompanied by the elevation of phosphorylated AMP-activated protein kinase (AMPK) expression in white adipose tissue. Correspondingly, the results of in vitro experiments showed that docosahexaenoic acid (DHA), the main n-3 polyunsaturated fatty acid (PUFA) in the fish oil used in the study, led to a dose-dependent increase in AMPK phosphorylation and suppressed palmitic acid (PA)-triggered ER stress in differentiated 3T3-L1 adipocytes. Furthermore, AMPK inhibitor (compound C) treatment largely blocked the effects of DHA to inhibit PA-induced ER stress. Our data indicate that n-3 PUFAs suppress ER stress in adipocytes through AMPK activation, and may thereby exert protective effects against high-fat feeding-induced adipose tissue dysfunction and insulin resistance.


Experimental studies addressing the longevity of Bacillus subtilis spores - The first data from a 500-year experiment.
The ability to form endospores allows certain Gram-positive bacteria (e.g. Bacillus subtilis) to challenge the limits of microbial resistance and survival. Thus, B. subtilis is able to tolerate many environmental extremes by transitioning into a dormant state as spores, allowing survival under otherwise unfavorable conditions. Despite thorough study of spore resistance to external stresses, precisely how long B. subtilis spores can lie dormant while remaining viable, a period that potentially far exceeds the human lifespan; is not known although convincing examples of long term spore survival have been recorded. In this study, we report the first data from a 500-year microbial experiment, which started in 2014 and will finish in 2514. A set of vials containing a defined concentration of desiccated B. subtilis spores is opened and tested for viability every two years for the first 24 years and then every 25 years until experiment completion. Desiccated baseline spore samples were also exposed to environmental stresses, including X-rays, 254 nm UV-C, 10% H2O2, dry heat (120°C) and wet heat (100°C) to investigate how desiccated spores respond to harsh environmental conditions after long periods of storage. Data from the first 2 years of storage show no significant decrease in spore viability. Additionally, spores of B. subtilis were subjected to various short-term storage experiments, revealing that space-like vacuum and high NaCl concentration negatively affected spore viability.


Tyrosine and phenylalanine catabolism by Lactobacillus cheese flavor adjuncts.
Bacterial metabolism of Tyr and Phe has been associated with the formation of aromatic compounds that impart barny-utensil and floral off-flavors in cheese. In an effort to identify possible mechanisms for the origin of these compounds in Cheddar cheese, we investigated Tyr and Phe catabolism by Lactobacillus casei and Lactobacillus helveticus cheese flavor adjuncts under simulated Cheddar cheese-ripening (pH 5.2, 4% NaCl, 15 degrees C, no sugar) conditions. Enzyme assays of cell-free extracts indicated that L. casei strains catabolize Tyr and Phe by successive, constitutively expressed transamination and dehydrogenation reactions. Similar results were obtained with L. helveticus strains, except that the dehydrogenase enzymes were induced during incubation under cheese-ripening conditions. Micellar electrokinetic capillary chromatography of supernatants from L. casei and L. helveticus strains incubated under simulated cheese-ripening conditions confirmed that Tyr and Phe transamination and dehydrogenation pathways were active in both species and also showed these reactions were reversible. Major products of Tyr catabolism were phydroxy phenyl lactic acid and p-hydroxy phenyl acetic acid, while Phe degradation gave rise to phenyl lactic acid, phenyl acetic acid, and benzoic acid. However, some of these products were likely formed by nonenzymatic processes, since spontaneous chemical degradation of the Tyr intermediate p-hydroxy phenyl pyruvic acid produced p-hydroxy phenyl acetic acid, p-hydroxy phenyl propionic acid, and p-hydroxy benzaldehyde, while chemical degradation of the Phe intermediate phenyl pyruvic acid gave rise to phenyl acetic acid, benzoic acid, phenethanol, phenyl propionic acid, and benzaldehyde.


The left inferior frontal gyrus is involved in adjusting response bias during a perceptual decision-making task.
Changing the way we make decisions from one environment to another allows us to maintain optimal decision-making. One way decision-making may change is how biased one is toward one option or another. Identifying the regions of the brain that underlie the change in bias will allow for a better understanding of flexible decision-making. An event-related, perceptual decision-making task where participants had to detect a picture of an animal amongst distractors was used during functional magnetic resonance imaging. Positive and negative financial motivation were used to affect a change in response bias, and changes in decision-making behavior were quantified using signal detection theory. Response bias became relatively more liberal during both positive and negative motivated trials compared to neutral trials. For both motivational conditions, the larger the liberal shift in bias, the greater the left inferior frontal gyrus (IFG) activity. There was no relationship between individuals' belief that they used a different strategy and their actual change in response bias. The present findings suggest that the left IFG plays a role in adjusting response bias across different decision environments. This suggests a potential role for the left IFG in flexible decision-making.


Talking about learning disability: promoting positive perceptions of people with intellectual disabilities in Scottish schools.
Pupils with intellectual disabilities are one of the most bullied groups in the school system and in local communities. Moreover, young people also play a significant role in hate crimes against people with intellectual disabilities of all ages beyond the school gates. This paper describes the development of a research informed program of lessons for children in mainstream secondary schools, aimed at counteracting bullying towards people with intellectual disabilities by promoting empathy and more positive attitudes towards them. A literature review, a review of current practice, and the experiences and views of young people with intellectual disabilities and their families all contributed to the development of the program. Data from subsequent piloting and feasibility work were used to finalize the program which consists of the following five lessons concerning: (i) difference and disability, (ii) an understanding of intellectual disability, (iii) the nature and impact of disablist bullying towards people with intellectual disabilities, and (iv) opportunities for inclusion. One conclusion from this work is that that there needs to be further research to explore the impact of school-based interventions, promoting an understanding of people with intellectual disabilities, in the wider community. Teachers delivering the lessons may have greater influence than transitory campaigns to counteract bullying and promote positive attitudes towards people with intellectual disabilities. However, a first step is to ensure that teachers delivering the lessons have an understanding of people with intellectual disabilities.


Analysis of single-cell gene transcription by RNA fluorescent in situ hybridization (FISH).
Adhesion of Plasmodium falciparum infected erythrocytes (IE) to human endothelial receptors during malaria infections is mediated by expression of PfEMP1 protein variants encoded by the var genes. The haploid P. falciparum genome harbors approximately 60 different var genes of which only one has been believed to be transcribed per cell at a time during the blood stage of the infection. How such mutually exclusive regulation of var gene transcription is achieved is unclear, as is the identification of individual var genes or sub-groups of var genes associated with different receptors and the consequence of differential binding on the clinical outcome of P. falciparum infections. Recently, the mutually exclusive transcription paradigm has been called into doubt by transcription assays based on individual P. falciparum transcript identification in single infected erythrocytic cells using RNA fluorescent in situ hybridization (FISH) analysis of var gene transcription by the parasite in individual nuclei of P. falciparum IE(1). Here, we present a detailed protocol for carrying out the RNA-FISH methodology for analysis of var gene transcription in single-nuclei of P. falciparum infected human erythrocytes. The method is based on the use of digoxigenin- and biotin- labeled antisense RNA probes using the TSA Plus Fluorescence Palette System(2) (Perkin Elmer), microscopic analyses and freshly selected P. falciparum IE. The in situ hybridization method can be used to monitor transcription and regulation of a variety of genes expressed during the different stages of the P. falciparum life cycle and is adaptable to other malaria parasite species and other organisms and cell types.


The Bordetella avium BAV1965-1962 fimbrial locus is regulated by temperature and produces fimbriae involved in adherence to turkey tracheal tissue.
Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica cause respiratory tract disease in mammals, whereas Bordetella avium causes respiratory tract disease in avian hosts. While there are striking similarities between the diseases caused by the mammalian- and avian-adapted bordetellae, differences at the genetic level may account for their different host tropisms. Bacterial pathogens utilize the chaperone-usher pathway to assemble extracellular multisubunit structures (fimbriae) that play a role in virulence. Fimbriae of the mammalian bordetellae mediate attachment to the host respiratory epithelium. They are assembled by a single chaperone/usher system encoded by the fimbrial biogenesis operon fimA-D. B. avium contains a homologous fimbrial operon (BAV1965-1962), and we report here the functionality of this locus. Reverse transcription (RT)-PCR and quantitative PCR analyses demonstrated that transcription of the locus is regulated by temperature. By immuno-transmission electron microscopy (TEM), BAV1965-containing fimbriae were observed on bacteria grown at 37°C but not those grown at 22°C. A mutant in which BAV1965-1962 was deleted displayed significantly lower levels of adherence to turkey tracheal rings than the wild type. Thus, the BAV1965-1962 fimbrial locus is functional, its expression is regulated in response to temperature, and it produces fimbriae involved in adherence to host respiratory tract tissue.


Effects of guanidinoacetic acid supplementation on lactation performance, nutrient digestion and rumen fermentation in Holstein dairy cows.
Considering the high energy demand of lactation and the potential of guanidinoacetic acid (GAA) addition on the increase in creatine supply for cows, the present study investigated the effects of 0, 0.3, 0.6 and 0.9 g kg-1 dry matter (DM) of GAA supplementation on lactation performance, nutrient digestion and ruminal fermentation in dairy cows. The study used 40 mid-lactation multiparous Holstein cows and the study duration was 100 days. DM intake was not affected, but milk and milk component yields and feed efficiency increased linearly with increasing GAA addition. The total-tract digestibility of DM, organic matter, neutral detergent fibre, acid detergent fibre and non-fibre carbohydrates increased linearly and that of crude protein increased quadratically with increasing GAA addition. When the addition level of GAA increased, ruminal pH, molar percentages of butyrate, isobutyrate and isovalerate and the acetate-to-propionate ratio decreased linearly, and the total volatile fatty acids concentration and propionate molar percentage also increased linearly, whereas the acetate molar percentage and ammonia-N concentration were unaltered. The activities of fibrolytic enzymes, α-amylase and protease increased linearly. The populations of total bacteria, fungi, Ruminococcus albus, Fibrobacter succinogenes, Ruminococcus flavefaciens, Ruminobacter amylophilus and Prevotella ruminicola increased linearly, whereas protozoa and methanogens decreased linearly with increasing GAA addition. As for the blood metabolites, concentrations of glucose, urea nitrogen and methionine were unchanged, total protein, albumin, creatine and homocysteine increased linearly, and folate decreased linearly with increasing GAA supply. The results of the present study indicate that supplementation of GAA improved milk performance and rumen fermentation in lactating dairy cows. © 2022 Society of Chemical Industry.


Optical method for measuring optical rotation angle and refractive index of chiral solution.
Based on the phenomena of Brewster's angle and the principles of common-path heterodyne interferometry, we present an optical method for measuring the optical rotation angle and the refractive index of a chiral solution simultaneously in one optical configuration. A heterodyne light beam and a circularly polarized heterodyne light beam are separately guided to project onto the interface of a semicircle glass and a chiral solution. One of the beams is transmitted through the solution, and the other is reflected near Brewster's angle at the interface. Then the two beams pass through polarization components respectively for interference. The phase differences of the two interference signals used to determine the rotation angle and the refractive index become very high with the proper azimuth angles of some polarization components, hence achieving an accurate rotational angle and a refractive index. The feasibility of the measuring method was demonstrated by our experimental results. This method should bear the merits of high accuracy, short sample medium length, and simpler operational endeavor.


Novel therapeutic avenues in myeloma: changing the treatment paradigm.
Our better understanding of the complex interaction of multiple myeloma (MM) cells with their bone marrow microenvironment and the signaling pathways that are dysregulated in this process has resulted in a dramatic increase in the therapeutic agents available for this disease. A number of these new agents have demonstrated significant activity in patients with MM. Over the past 5 years, three drugs have received approval from the US Food and Drug Administration for therapy in MM--bortezomib, thalidomide, and lenalidomide. To date, the choice of therapy for MM is not individualized according to the biologic characteristics of the disease, but future studies should enable us to identify patients who may benefit most from certain therapeutic interventions, and thus develop individualized therapy for MM. In this review, we will present some of the treatment algorithms currently developed for patients with MM and focus on established advances in therapy, specifically with thalidomide, bortezomib, and lenalidomide. We will also discuss some of the emerging novel therapeutic agents showing promise in phase I/II clinical trials in MM.


Clinical effects and antivenom use for snake bite victims treated at three US hospitals in Afghanistan.
Annually, more than 100,000 US and international military and civilian personnel work in Afghanistan within terrain harboring venomous snakes. Current literature insufficiently supports Afghan antivenom treatment and stocking guidelines. We report the clinical course and treatments for snakebite victims presenting to US military hospitals in Afghanistan. All snakebite victims presenting to 3 US military emergency departments between July 2010 and August 2011 in northern and southern Afghanistan were examined via chart review. Case information included patient demographics, snake description, bite details and complications, laboratory results, antivenom use and adverse effects, procedures performed, and hospital course. Of 17 cases, median patient age was 20 years (interquartile range [IQR], 12-30), 16 were male, and 82% were Afghans. All bites were to an extremity, and median time to care was 2.8 hours (IQR, 2-5.8). On arrival, 8 had tachycardia and none had hypotension or hypoxia. A viper was implicated in 5 cases. Ten cases received at least 1 dose of polyvalent antivenom, most commonly for coagulopathy, without adverse effects. Six received additional antivenom, 6 had an international normalized ratio (INR) > 10, and none developed delayed coagulopathy. Three received blood transfusions. Hospital stay ranged from 1 to 4 days. None required vasopressors, fasciotomy, or other surgery, and none died. All had resolution of marked coagulopathies and improved swelling and pain on discharge. We report the largest series of snake envenomations treated by US physicians in Afghanistan. Antivenom was tolerated well with improvement of coagulopathy and symptoms. All patients survived with minimal advanced interventions other than blood transfusion.


Role of hypothermia in the mechanism of protection against serotonergic toxicity. I. Experiments using 3,4-methylenedioxymethamphetamine, dizocilpine, CGS 19755 and NBQX.
High doses of 3,4-methylenedioxymethamphetamine (MDMA) have been shown to cause long-lasting depletions of central serotonin (5-HT) which are indicative of neuronal toxicity. The noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (DZ) attenuates depletions of 5-HT induced by MDMA. Because DZ has been shown to induce hypothermia in rat models of ischemia, the purpose of this study was to assess whether DZ and two other glutamate antagonists, CGS 19755 (CGS) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), protect against MDMA-induced 5-HT depletions by induction of hypothermia. Male Sprague-Dawley rats were injected with either saline (SAL), DZ (2.5 mg/kg), CGS (25.0 or 50.0 mg/kg x 2 injections) or NBQX (30.0 mg/kg x 2 injections or 55.0 mg/kg x 3 injections) followed by either MDMA (40.0 mg/kg) or SAL. Core body temperature (TEMP) was monitored for 4 h or longer using radiotelemetry. Base-line TEMP was between 37.0 and 37.6 degrees C. Administration of DZ with MDMA decreased TEMP to 34.0 +/- 0.39 degrees C within 2 h of the MDMA injection, and also protected against serotonergic toxicity. Neither SAL/MDMA nor DZ/SAL had an effect on TEMP over the same period. When rats were treated with DZ/MDMA and TEMP was maintained between 38.4 degrees C and 40.4 degrees C for 4 h, protection against 5-HT depletion was abolished. Coadministration of the competitive NMDA antagonist CGS with MDMA-resulted in a decrease in TEMP to 34.5 +/- 0.27 degrees C, and provided partial protection against 5-HT depletions.(ABSTRACT TRUNCATED AT 250 WORDS)


Preservatives in cosmetics: reactivity of allergenic formaldehyde-releasers towards amino acids through breakdown products other than formaldehyde.
Compounds slowly releasing formaldehyde, the so-called formaldehyde-releasers, are commonly employed as preservatives in cosmetics instead of free formaldehyde, which is a strong skin sensitizer. It has been long accepted that formaldehyde-releaser sensitization is attributable to released formaldehyde. However, clinical studies show the existence of patients allergic to formaldehyde-releasers but not to formaldehyde itself. To prove that, for certain formaldehyde-releasers, reactive intermediates other than formaldehyde could be involved in the formation of the hapten-protein antigenic complex, a key step of the sensitization process, thus explaining their sensitizing potential. DMDM hydantoin, 2-bromo-2-nitropropane-1,3-diol and methenamine were synthesized, (13) C-labelled at the position(s) precursor of formaldehyde. Their reactivity towards amino acids was followed by one-dimensional and two-dimensional (13) C-nuclear magnetic resonance. Many adducts formed by reacting formaldehyde-releasers with amino acids resulted from a direct interaction of the releaser or from reaction of a breakdown product, and not from a reaction involving simply released formaldehyde. DMDM hydantoin was reactive per se, and 2-bromo-2-nitropropane-1,3-diol and methenamine decomposed in water, producing bromoethanol and diaminomethane, respectively, which were reactive towards some of the amino acids tested. The reactivity of distinctive formaldehyde-releasers towards amino acids is not limited to formaldehyde release.


Molecular phylogeny of Aerides (Orchidaceae) based on one nuclear and two plastid markers: a step forward in understanding the evolution of the Aeridinae.
Phylogenetic relationships of the orchid genus Aerides (Epidendroideae, Vandeae, Aeridinae) from Southeast Asia were inferred from DNA sequences of one nuclear (nrITS) and two plastid (matK, trnL-trnL-F) regions of 48 taxa (21 Aerides, 25 other Aeridinae, 2 outgroup). Analyses of the combined datasets with parsimony, maximum likelihood and Bayesian methods revealed that Aerides is monophyletic and consists of three well-supported subclades which are only partly in accordance with previous sectional delimitations based on floral characters. The two different flower types in Aerides (hidden versus open spur entrance) seem to have evolved at least twice in geographically distinct areas. The phylogeny presented here is yet another example in Orchidaceae where floral morphology cannot be relied on to reconstruct phylogenetic history but rather is the result of pollinator-driven selection. The Aerides subclades are characterized by three different length classes of the mutation-rich P8 region in the trnL intron. To our knowledge, this is the first time that the P8 region was studied in orchids. The matK gene has been assumed to be a pseudogene in orchids due to occasional occurrence of frameshift indels, low transition/transversion (ts:tv) ratios and low substitution rates at the 3rd codon position. However, matK does not appear to be a pseudogene in Aerides and a comparison with data from other angiosperms suggests that ts:tv ratios and low substitution rates have been overestimated as arguments for a pseudogene status of matK in orchids.


Safety-net hospitals more likely than other hospitals to fare poorly under Medicare's value-based purchasing.
Medicare's value-based purchasing (VBP) program potentially puts safety-net hospitals at a financial disadvantage compared to other hospitals. In 2014, the second year of the program, patient mortality measures were added to the VBP program's algorithm for assigning penalties and rewards. We examined whether the inclusion of mortality measures in the second year of the program had a disproportionate impact on safety-net hospitals nationally. We found that safety-net hospitals were more likely than other hospitals to be penalized under the VBP program as a result of their poorer performance on process and patient experience scores. In 2014, 63 percent of safety-net hospitals versus 51 percent of all other sample hospitals received payment rate reductions under the program. However, safety-net hospitals' performance on mortality measures was comparable to that of other hospitals, with an average VBP survival score of thirty-two versus thirty-one among other hospitals. Although safety-net hospitals are still more likely than other hospitals to fare poorly under the VBP program, increasing the weight given to mortality in the VBP payment algorithm would reduce this disadvantage.


Characterization of Linum usitatissimum L. oil obtained from different extraction technique and in vitro antioxidant potential of supercritical fluid extract.
Present investigation was aimed to characterize the fixed oil of Linum usitatissimum L. using five different extraction methods: Supercritical fluid extraction (SFE), ultrasound-assistance, soxhlet extraction, solvent extraction, and three phase partitioning method. The SFE conditions (temperature, pressure, and volume of CO2) were optimized prior for better yield. The extracted oils were analyzed and compared for their physiochemical parameters, high performance thin layer chromatography (HPTLC), gas chromatography-mass spectrometry (GC-MS), and Fourier-transformed infrared spectroscopy (FT-IR) fingerprinting. Antioxidant activity was also determined using 1,1-diphenyl-2-picrylhydrazyl and superoxide scavenging method. The main fatty acids were α-linolenic acid, linoleic acid, palmitic acid, and stearic acid as obtained by GC-MS. HPTLC analysis revealed the presence of similar major components in chromatograms. Similarly, the pattern of peaks, as obtained in FT-IR and GC-MS spectra of same oils by different extraction methods, were superimposable. Analysis reported that the fixed oil of L. usitatissimum L. is a good source of n-3 fatty acid with the significant antioxidant activity of oil obtained from SFE extraction method.


Improving the radical cure of vivax malaria (IMPROV): a study protocol for a multicentre randomised, placebo-controlled comparison of short and long course primaquine regimens.
Plasmodium vivax malaria is a major cause of morbidity and recognised as an important contributor to mortality in some endemic areas. The current recommended treatment regimen for the radical cure of P. vivax includes a schizontocidal antimalarial, usually chloroquine, combined with a 14 day regimen of primaquine. The long treatment course frequently results in poor adherence and effectiveness. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and thus effectiveness without compromising safety. The proposed multicentre randomised clinical trial aims to provide evidence across a variety of endemic settings on the safety and efficacy of high dose short course primaquine in glucose-6-phosphate-dehydrogenase (G6PD) normal patients. This study is designed as a placebo controlled, double blinded, randomized trial in four countries: Indonesia, Vietnam, Afghanistan and Ethiopia. G6PD normal patients diagnosed with vivax malaria are randomized to receive either 7 or 14 days high dose primaquine or placebo. G6PD deficient (G6PDd) patients are allocated to weekly primaquine doses for 8weeks. All treatment is directly observed and recurrent episodes are treated with the same treatment than allocated at the enrolment episode. Patients are followed daily until completion of treatment, weekly until 8 weeks and then monthly until 1 year after initiation of the treatment. The primary endpoint is the incidence rate (per person year) of symptomatic recurrent P. vivax parasitaemia over 12 months of follow-up, for all individuals, controlling for site, comparing the 7 versus 14-day primaquine treatment arms. Secondary endpoints are other efficacy measures such as incidence risk at different time points. Further endpoints are risks of haemolysis and severe adverse events. This study has been approved by relevant institutional ethics committees in the UK and Australia, and all participating countries. Results will be disseminated to inform P. vivax malaria treatment policy through peer-reviewed publications and academic presentations. Findings will contribute to a better understanding of the risks and benefits of primaquine which is crucial in persuading policy makers as well as clinicians of the importance of radical cure of vivax malaria, contributing to decreased transmission and a reduce parasite reservoir. ClinicalTrials.gov Identifier: NCT01814683 . Registered March 18, 2013.


Response to Noise Emitted by Wind Farms in People Living in Nearby Areas.
The aim of this study was to evaluate the perception and annoyance of noise from wind turbines in populated areas of Poland. A questionnaire inquiry was carried out among 517 subjects, aged 18⁻88, living within 204⁻1726 m from the nearest wind turbine. For areas where respondents lived, A-weighted sound pressure levels (SPLs) were calculated as the sum of the contributions from the wind power plants in the specific area. It has been shown that the wind turbine noise at the calculated A-weighted SPL of 33⁻50 dB was perceived as annoying or highly annoying by 46% and 28% of respondents, respectively. Moreover, 34% and 18% of them said that they were annoyed or highly annoyed indoors, respectively. The perception of high annoyance was associated with the A-weighted sound pressure level or the distance from the nearest wind turbine, general attitude to wind farms, noise sensitivity and terrain shape (annoyance outdoors) or road-traffic intensity (annoyance indoors). About 48⁻66% of variance in noise annoyance rating might be explained by the aforesaid factors. It was estimated that at the distance of 1000 m the wind turbine noise might be perceived as highly annoying outdoors by 43% and 2% of people with negative and positive attitude towards wind turbines, respectively. There was no significant association between noise level (or distance) and various health and well-being aspects. However, all variables measuring health and well-being aspects, including stress symptoms, were positively associated with annoyance related to wind turbine noise.


The insecticidal potential of scorpion beta-toxins.
Voltage-gated sodium channels are a major target for toxins and insecticides due to their central role in excitability, but due to the conservation of these channels in Animalia most insecticides do not distinguish between those of insects and mammals, thereby imposing risks to humans and livestock. Evidently, as long as modern agriculture depends heavily on the use of insecticides there is a great need for new substances capable of differentiating between sodium channel subtypes. Such substances exist in venomous animals, but ways for their exploitation have not yet been developed due to problems associated with manufacturing, degradation, and delivery to the target channels. Engineering of plants for expression of anti-insect toxins or use of natural vectors that express toxins near their target site (e.g. baculoviruses) are still problematic and raise public concern. In this problematic reality a rational approach might be to learn from nature how to design highly selective anti-insect compounds preferably in the form of peptidomimetics. This is a complex task that requires the elucidation of the face of interaction between insect-selective toxins and their sodium channel receptor sites. This review delineates current progress in: (i) elucidation of the bioactive surfaces of scorpion beta-toxins, especially the excitatory and depressant groups, which show high preference for insects and bind insect sodium channels with high affinity; (ii) studies of the mode of interaction of scorpion beta-toxins with receptor site-4 on voltage-gated sodium channels; and (iii) clarification of channel elements that constitute receptor site-4. This information may be useful in future attempts to mimic the bioactive surface of the toxins for the design of anti-insect selective peptidomimetics.


DNA-Coated Gold Nanoparticles for the Detection of mRNA in Live Hydra Vulgaris Animals.
Advances in nanoparticle design have led to the development of nanoparticulate systems that can sense intracellular molecules, alter cellular processes, and release drugs to specific targets in vitro. In this work, we demonstrate that oligonucleotide-coated gold nanoparticles are suitable for the detection of mRNA in live Hydra vulgaris, a model organism, without affecting the animal's integrity. We specifically focus on the detection of Hymyc1 mRNA, which is responsible for the regulation of the balance between stem cell self-renewal and differentiation. Myc deregulation is found in more than half of human cancers, thus the ability to detect in vivo related mRNAs through innovative fluorescent systems is of outmost interest.


Cactus juice as bioflocculant in the coagulation-flocculation process for industrial wastewater treatment: a comparative study with polyacrylamide.
Most industries in the world treat their wastewaters with a conventional coagulation-flocculation process using alum as coagulant, polyacrylamide (PAM) as flocculant and lime as coagulant aid. To reduce the use of chemical products in the process, experiments were conducted to substitute the PAM with cactus juice (CJ) as flocculant. From the obtained data, it was concluded that the substitution of PAM with CJ in the coagulation-flocculation process was very effective, compared with PAM. Depending on the wastewater's origin, the bioflocculant showed removal efficiencies of 83.3-88.7% for suspended solids (SS) and 59.1-69.1% for chemical oxygen demand (COD). Lime addition enhanced the coagulation-flocculation process in the presence of CJ similarly to the PAM with efficiencies greater than 90% for both SS and COD. The CJ powder's infrared (IR) spectrum showed the main functional groups present in PAM. It was concluded that CJ as a flocculant fits well with the definition of sustainability and it is appropriate for countries that have regions where cactuses grow naturally.


Learning in Alzheimer's disease is facilitated by social interaction.
Seminal work in Gary Van Hoesen's laboratory at Iowa in the early 1980s established that the hallmark neuropathology of Alzheimer's disease (AD; neurofibrillary tangles) had its first foothold in specific parts of the hippocampal formation and entorhinal cortex, effectively isolating the hippocampus from much of its input and output and causing the distinctive impairment of new learning that is the leading early characteristic of the disease (Hyman et al., 1984). The boundaries and conditions of the anterograde memory defect in patients with AD have been a topic of intense research interest ever since (e.g., Graham and Hodges, 1977; Nestor et al., 2006). For example, it has been shown that patients with AD may acquire some new semantic information through methods such as errorless learning, but learning under these conditions is typically slow and inefficient. Drawing on a learning paradigm (a collaborative referencing task) that was previously shown to induce robust and enduring learning in patients with hippocampal amnesia, we investigated whether this task would be effective in promoting new learning in patients with AD. We studied five women with early-stage AD and 10 demographically matched healthy comparison participants, each interacting with a familiar communication partner. AD pairs displayed significant and enduring learning across trials, with increased accuracy and decreased time to complete trials, in a manner indistinguishable from healthy comparison pairs, resulting in efficient and economical communication. The observed learning here most likely draws on neural resources outside the medial temporal lobes. These interactive communication sessions provide a potent learning environment with significant implications for memory intervention.


Group dream work: a holistic resource for oncology nurses.
To explore dream work as a possible means for nurses to increase self-understanding and problem solving in personal and professional life. Hermeneutic phenomenologic, descriptive, and interpretive. A comprehensive cancer center in the southern United States. Six nurses with a mean age of 40 and 1-10 years of oncology nursing experience. Interviews, guided by descriptive and interpretive phenomenology, were conducted with nurses before and one and six months after they participated in eight weekly sessions of a group focused on dream work. Phenomenologic analysis was done on verbatim transcriptions of all interviews. Nurses found value in participating in dream groups, including having more open discussions about feelings and death, managing difficult situations, and attending to patients in the present. The value of learning to attend to dreams may be subtle but has value to nurses. Incorporating dream work is one holistic intervention that may be useful to improve job satisfaction, communication, and relationships in this time of nursing shortage.


Closed-loop adaptive optics in the human eye.
We have developed a prototype apparatus for real-time closed-loop measurement and correction of aberrations in the human eye. The apparatus uses infrared light to measure the wave-front aberration at 25 Hz with a Hartmann-Shack sensor. Defocus is removed by a motorized optometer, and higher-order aberrations are corrected by a membrane deformable mirror. The device was first tested with an artificial eye. Correction of static aberrations takes approximately five iterations, making the system capable of following aberration changes at 5 Hz. This capability allows one to track most of the aberration dynamics in the eye. Results in living eyes showed effective closed-loop correction of aberrations, with a residual uncorrected wave front of 0.1microm for a 4.3-mm pupil diameter. Retinal images of a point source in different subjects with and without adaptive correction of aberrations were estimated in real time. The results demonstrate real-time closed-loop correction of aberration in the living eye. An application of this device is as electro-optic "spectacles" to improve vision.


Despite modern off-pump coronary artery bypass grafting women fare worse than men.
Female gender is an established risk factor for worse outcomes after cardiac surgery. Avoiding cardiopulmonary bypass (CPB) for coronary bypass grafting has an unknown effect on gender differences. Herein, we evaluate if gender has an impact on outcomes after modern off-pump coronary artery bypass grafting (OPCAB). From 2002 to 2007, we analyzed 983 patients (male: n=807/female: n=176) who underwent OPCAB with symptomatic multi-vessel disease at our institution. The link between gender and outcome was assessed by multivariate analysis and logistic regression. A composite endpoint was constructed from: 30-day-mortality, renal failure, prolonged intensive care unit (ICU) stay, neurological complications, use of intra-aortic balloon pump (IABP) and conversion to CPB. Mortality was 3.2% in women vs.1.8% in men (P=0.15) and the EuroSCORE was significantly correlated to gender (6.8 vs. 5.2; P<0.001), even after correction (P=0.036). Significant more occurrence of the composite endpoint was noted in women (39.8% vs. 29.0%; P=0.007) whereas for men the risk was much lower [odds ratio (OR) 0.65; 95% confidence interval (CI) 0.46-0.92; P=0.015]. For both genders the logistic regression revealed a risk increase of 15% per one-point-increase of EuroSCORE (corrected) (OR 1.15; 95% CI: 1.10-1.19; P<0.0001). Women had more frequently a prolonged stay at ICU (P=0.006) and had a higher stroke rate (2.3% vs. 1.2%; P=0.29). Complete revascularization was achieved similarly (95% vs. 94%; P=0.93). OPCAB offers low mortality and excellent clinical outcome. Women are more likely to experience postoperative complications. Even if partially neutralized by avoiding CPB, gender differences remain present with modern OPCAB strategies.


Estimated health benefits of exhaust free transport in the city of Malmö, Southern Sweden.
Air pollution is responsible for one in eight premature deaths worldwide, and thereby a major threat to human health. Health impact assessments of hypothetic changes in air pollution concentrations can be used as a mean of assessing the health impacts of policy, plans and projects, and support decision-makers in choices to prevent disease. The aim of this study was to estimate health impacts attributable to a hypothetical decrease in air pollution concentrations in the city of Malmö in Southern Sweden corresponding to a policy on-road transportations without tail-pipe emissions in the municipality. We used air pollution data modelled for each of the 326,092 inhabitants in Malmö by a Gaussian dispersion model combined with an emission database with >40,000 sources. The dispersion model calculates Nitrogen Oxides (NOx) (later transformed into Nitrogen Dioxide (NO2)) and particulate matter with an aerodynamic diameter < 2.5 μg/m3 (PM2.5) with high spatial and temporal resolution (85 m and 1 h, respectively). The average individual reduction was 5.1 (ranging from 0.6 to 11.8) μg/m3 in NO2, which would prevent 55 (2% of all deaths) to 93 (4%) deaths annually, depending on dose-response function used. Furthermore, we estimate that the NO2 reduction would result in 21 (6%) fewer cases of incident asthma in children, 95 (10%) fewer children with bronchitis every year, 30 (1%) fewer hospital admissions for respiratory disease, 87(4%) fewer dementia cases, and 11(11%) fewer cases of preeclampsia every year. The average reduction in PM2.5 of 0.6 (ranging from 0.1 till 1.7) μg/m3 would mean that 2729 (0.3%) work days would not be lost due to sick-days and that there would be 16,472 fewer restricted activity days (0.3%) that year had all on-road transportations been without tail-pipe emissions. Even though the estimates are sensitive to the dose-response functions used and to exposure misclassification errors, even the most conservative estimate of the number of prevented deaths is 7 times larger than the annual traffic fatalities in Malmö, indicating a substantial possibility to reduce the health burden attributed to tail-pipe emissions in the study area.


Recontact in clinical practice: a survey of clinical genetics services in the United Kingdom.
To ascertain whether and how recontacting occurs in the United Kingdom. A Web-based survey was administered online between October 2014 and July 2015. A link to the survey was circulated via an e-mail invitation to the clinical leads of the United Kingdom's 23 clinical genetics services, with follow-up with senior clinical genetics staff. The majority of UK services reported that they recontact patients and their family members. However, recontacting generally occurs in an ad hoc fashion when an unplanned event causes clinicians to review a file (a "trigger"). There are no standardized recontacting practices in the United Kingdom. More than half of the services were unsure whether formalized recontacting systems should be implemented. Some suggested greater patient involvement in the process of recontacting. This research suggests that a thorough evaluation of the efficacy and sustainability of potential recontacting systems within the National Health Service would be necessary before deciding whether and how to implement such a service or to create guidelines on best-practice models.Genet Med 18 9, 876-881.


Human NKT cells promote monocyte differentiation into suppressive myeloid antigen-presenting cells.
NKT cells have been shown to promote peripheral tolerance in a number of model systems, yet the processes by which they exert their regulatory effects remain poorly understood. Here, we show that soluble factors secreted by human NKT cells instruct human peripheral blood monocytes to differentiate into myeloid APCs that have suppressive properties. NKT instructed monocytes acquired a cell surface phenotype resembling myeloid DCs. However, whereas control DCs that were generated by culturing monocytes with recombinant GM-CSF and IL-4 had a proinflammatory phenotype characterized by the production of IL-12 with little IL-10, NKT-instructed APCs showed the opposite cytokine production profile of high IL-10 with little or no IL-12. The control DCs efficiently stimulated peripheral blood T cell IFN-gamma secretion and proliferation, whereas NKT-instructed APCs silenced these T cell responses. Exposure to NKT cell factors had a dominant effect on the functional properties of the DCs, since DCs differentiated by recombinant GM-CSF and IL-4 in the presence of NKT cell factors inhibited T cell responses. To confirm their noninflammatory effects, NKT-instructed APCs were tested in an in vivo assay that depends on the activation of antigen-specific human T cells. Control DCs promoted substantial tissue inflammation; however, despite a marked neutrophilic infiltrate, there was little edema in the presence of NKT-instructed APCs, suggesting the inflammatory cascade was held in check. These results point to a novel pathway initiated by NKT cells that can contribute to the regulation of human antigen-specific Th1 responses.


Three Ia species with different structures and alloantigenic determinants in an HLA-homozygous cell line.
Three distinct molecular subsets with different structures and alloantigenic determinants were identified in human Ia antigens from cells of an HLA-Dw7 homozygous cell line. The subsets carried DR7 specificity, BR4X7 supertypic specificity and MB2 supertypic specificity, respectively, and were immunospecifically separated by the use of operationally monospecific alloantisera. These specificities showed HLA-linked segregation in families and they were distributed in the population according to different but partially overlapping patterns. On peptide mapping analysis, the three subsets showed marked differences in the beta-chains. The alpha-chains of DR7 and BR4X7 subsets were very similar to each other, whereas the alpha-chains of MB2 subset were distinctive from those of DR7 and BR4X7. These data indicate the presence of a minimum of three HLA-linked loci; DR locus, a locus that encodes BR4X7, and a locus that encodes MB2, and substantiate the three-loci concept for the genetic control of human I antigens.


The role of T-cell receptor dimerization in T-cell activation.
T-cell specificity is encoded in single T-cell receptors (TCRs) but monovalent interactions with peptide bound to the major histocompatibility complex (MHC) may not sufficiently account for the complexities associated with T-cell activation. This review proposes that TCRs undergo dimerization before activation and that this property might be essential for both T-cell antagonism and T-cell specificity, and may be pivotal for T-cell survival versus T-cell activation.


Gene targeting by the TAL effector PthXo2 reveals cryptic resistance gene for bacterial blight of rice.
Bacterial blight of rice is caused by the γ-proteobacterium Xanthomonas oryzae pv. oryzae, which utilizes a group of type III TAL (transcription activator-like) effectors to induce host gene expression and condition host susceptibility. Five SWEET genes are functionally redundant to support bacterial disease, but only two were experimentally proven targets of natural TAL effectors. Here, we report the identification of the sucrose transporter gene OsSWEET13 as the disease-susceptibility gene for PthXo2 and the existence of cryptic recessive resistance to PthXo2-dependent X. oryzae pv. oryzae due to promoter variations of OsSWEET13 in japonica rice. PthXo2-containing strains induce OsSWEET13 in indica rice IR24 due to the presence of an unpredicted and undescribed effector binding site not present in the alleles in japonica rice Nipponbare and Kitaake. The specificity of effector-associated gene induction and disease susceptibility is attributable to a single nucleotide polymorphism (SNP), which is also found in a polymorphic allele of OsSWEET13 known as the recessive resistance gene xa25 from the rice cultivar Minghui 63. The mutation of OsSWEET13 with CRISPR/Cas9 technology further corroborates the requirement of OsSWEET13 expression for the state of PthXo2-dependent disease susceptibility to X. oryzae pv. oryzae. Gene profiling of a collection of 104 strains revealed OsSWEET13 induction by 42 isolates of X. oryzae pv. oryzae. Heterologous expression of OsSWEET13 in Nicotiana benthamiana leaf cells elevates sucrose concentrations in the apoplasm. The results corroborate a model whereby X. oryzae pv. oryzae enhances the release of sucrose from host cells in order to exploit the host resources.


Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.
Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.


TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch.
Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. In many cases, pathological itch is insensitive to antihistamine treatment. Recent studies have identified members of the Mas-related G protein-coupled receptor (Mrgpr) family that are activated by mast cell mediators and promote histamine-independent itch. MrgprA3 and MrgprC11 act as receptors for the pruritogens chloroquine and BAM8-22, respectively. However, the signaling pathways and transduction channels activated downstream of these pruritogens are largely unknown. We found that TRPA1 is the downstream target of both MrgprA3 and MrgprC11 in cultured sensory neurons and heterologous cells. TRPA1 is required for Mrgpr-mediated signaling, as sensory neurons from TRPA1-deficient mice exhibited markedly diminished responses to chloroquine and BAM8-22. Similarly, TRPA1-deficient mice displayed little to no scratching in response to these pruritogens. Our findings indicate that TRPA1 is an essential component of the signaling pathways that promote histamine-independent itch.


Clinical auscultation skills in pediatric residents.
The aim of this study is to determine the level of clinical auscultation skills in pediatric residents at Duke University Medical Center. Forty-seven residents from pediatrics and joint medicine/pediatrics training programs at Duke University Medical Center were enrolled in this study. They were asked to examine the cardiovascular patient simulator, Harvey, and report their findings. Five common conditions seen in the pediatric population were presented: ventricular septal defect, atrial septal defect, pulmonary valve stenosis, combined aortic valve stenosis and insufficiency, and innocent systolic ejection murmur. The responses were scored by the number of features and diagnoses accurately reported. Five pediatric cardiologists and cardiologists in training were also asked to participate in a manner similar to the trainees. The mean score of features identified for the resident group was 11.4 +/- 2.6 of a possible 19. The diagnostic accuracy was 33%. There was no significant difference between residents by year of training or by type of residency program, although there was a trend toward improved performance with more training. The difference in performance between the pediatric cardiology group and the residents group was striking. The condition that was most frequently misdiagnosed was the innocent systolic ejection murmur. The clinical auscultation skills of pediatric residents in this study were suboptimal. There was a trend toward improvement as training progressed, although not statistically significant. These skills are likely to improve further with increased exposure to patients with cardiovascular disease especially in the ambulatory care setting.


Intravenous lidocaine to prevent postoperative airway complications in adults: a systematic review and meta-analysis.
In surgical patients undergoing general anaesthesia, coughing at the time of extubation is common and can result in potentially dangerous complications. We performed a systematic review and meta-analysis to assess the efficacy and safety of i.v. lidocaine administration during the perioperative period to prevent cough and other airway complications. We searched Medical Literature Analysis and Retrieval System, Excerpta Medica database, and Cochrane Central Register of Controlled Trials for RCTs comparing the perioperative use of i.v. lidocaine with a control group in adult patients undergoing surgery under general anaesthesia. The RCTs were assessed using risk-of-bias assessment, and the quality of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). In 16 trials (n=1516), the administration of i.v. lidocaine compared with placebo or no treatment led to large reductions in post-extubation cough (risk ratio [RR]: 0.64; 95% confidence interval [CI]: 0.48-0.86) and in postoperative sore throat at 1 h (RR: 0.46; 95% CI: 0.32-0.67). There was no difference in incidence of laryngospasm (risk difference [RD]: 0.02; 95% CI: -0.07 to 0.03) or incidence of adverse events related to the use of lidocaine. The use of i.v. lidocaine perioperatively decreased airway complications, including coughing and sore throat. There was no associated increased risk of harm.


Frontal sinus and recess osteomas: an endonasal endoscopic approach.
Over the last decade, there has been an increase in the use of the endonasal endoscopic approach for removing frontal sinus and frontal recess osteomas. This study aimed to describe an endoscopic endonasal treatment of osteomas without the need for an external approach. We performed a retrospective analysis of patients that had received operations over a 5-year period in a single center. Twenty-nine patients underwent endoscopic osteoma resections. The osteomas were graded according to the Chiu and Kennedy grading system: 12 had type I, 2 had type II, 13 had type III, and 2 had type IV osteomas. The most common indication for surgery was frontal pain. Removal of the osteoma was incomplete in three patients. Of these, one underwent successful transnasal reoperation, and the other two had tumors that extended near the mid-orbital line and were attached to the orbital roof. Based on an 11-point scale (0--no pain, 10--maximum pain), the mean pain intensity decreased from 7.5 before surgery to 3.3 (p < 0.005) after surgery for patients that underwent surgery due to frontal pain. We found that exclusively transnasal endoscopic resections of frontal sinus osteomas were safe. However, this approach can be inadequate under some conditions. An auxiliary external approach may be required when the frontal ostium is narrow and/or when tumors are extensively attached to the orbital roof, and grow close to the midorbital point.


Characteristics of gap plasmon waveguide with stub structures.
We found that metal-dielectric-metal plasmon waveguides with a stub structure, i.e. a branch of the waveguide with a finite length, can function as wavelength selective filters of a submicron size. It was found that the transmission characteristics of such structures depend on the phase relationship between the plasmon wave passing through the stub and the one returning to the waveguide from the stub. We also propose structures with a lossless 90 degrees bend in a plasmon waveguide, utilizing a stub structure. Furthermore, we present a functional stub structure, e.g., a 1:1 demultiplexer and a wavelength selective demultiplexer.


Growing up in the family or growing up alone influences behavior and hormones, but not arginine vasopressin receptor 1a expression in male African striped mice.
In many species males display alternative reproductive tactics (ARTs). While males of different tactics differ behaviorally in the field, it is often not known whether these behavioral differences would also occur under standardized laboratory conditions, nor how ARTs are regulated by the brain. In the present study we kept male African striped mice (Rhabdomys pumilio) in captivity either in family groups or solitary, to mimic ARTs observed in the field. This allowed us to study these males behaviorally under standardized conditions, to replicate physiological findings from the field, and to study the expression of the arginine vasopressin 1a receptor (AVPR1a) in their brains. Changes in either peptide release or receptor expression (or both) might regulate ARTs with differential timelines, with peptide secretion being faster than receptor expression. As observed in the field, family living males had higher corticosterone but lower testosterone levels than singly housed males. Surprisingly, singly housed males were less aggressive while at the same time having higher testosterone levels. We found no differences in AVPR1a expression. In a previous study it was shown that singly housed males have higher levels of AVP stored in their brain, which potentially could be secreted when the social situation changes, for example to establish social bonds. Our study on AVPR1a suggests the hypothesis that, given that the receptor distribution and expression of singly housed males do not differ from that of family-living males, the brains of singly-housed males have a similar capacity to be responsive to AVP when given the chance to interact socially.


Risk of complications in patients with conservatively managed ovarian tumours (IOTA5): a 2-year interim analysis of a multicentre, prospective, cohort study.
Ovarian tumours are usually surgically removed because of the presumed risk of complications. Few large prospective studies on long-term follow-up of adnexal masses exist. We aimed to estimate the cumulative incidence of cyst complications and malignancy during the first 2 years of follow-up after adnexal masses have been classified as benign by use of ultrasonography. In the international, prospective, cohort International Ovarian Tumor Analysis Phase 5 (IOTA5) study, patients aged 18 years or older with at least one adnexal mass who had been selected for surgery or conservative management after ultrasound assessment were recruited consecutively from 36 cancer and non-cancer centres in 14 countries. Follow-up of patients managed conservatively is ongoing at present. In this 2-year interim analysis, we analysed patients who were selected for conservative management of an adnexal mass judged to be benign on ultrasound on the basis of subjective assessment of ultrasound images. Conservative management included ultrasound and clinical follow-up at intervals of 3 months and 6 months, and then every 12 months thereafter. The main outcomes of this 2-year interim analysis were cumulative incidence of spontaneous resolution of the mass, torsion or cyst rupture, or borderline or invasive malignancy confirmed surgically in patients with a newly diagnosed adnexal mass. IOTA5 is registered with ClinicalTrials.gov, number NCT01698632, and the central Ethics Committee and the Belgian Federal Agency for Medicines and Health Products, number S51375/B32220095331, and is ongoing. Between Jan 1, 2012, and March 1, 2015, 8519 patients were recruited to IOTA5. 3144 (37%) patients selected for conservative management were eligible for inclusion in our analysis, of whom 221 (7%) had no follow-up data and 336 (11%) were operated on before a planned follow-up scan was done. Of 2587 (82%) patients with follow-up data, 668 (26%) had a mass that was already in follow-up at recruitment, and 1919 (74%) presented with a new mass at recruitment (ie, not already in follow-up in the centre before recruitment). Median follow-up of patients with new masses was 27 months (IQR 14-38). The cumulative incidence of spontaneous resolution within 2 years of follow-up among those with a new mass at recruitment (n=1919) was 20·2% (95% CI 18·4-22·1), and of finding invasive malignancy at surgery was 0·4% (95% CI 0·1-0·6), 0·3% (<0·1-0·5) for a borderline tumour, 0·4% (0·1-0·7) for torsion, and 0·2% (<0·1-0·4) for cyst rupture. Our results suggest that the risk of malignancy and acute complications is low if adnexal masses with benign ultrasound morphology are managed conservatively, which could be of value when counselling patients, and supports conservative management of adnexal masses classified as benign by use of ultrasound. Research Foundation Flanders, KU Leuven, Swedish Research Council.


The future of emergency medicine.
The specialty of emergency medicine (EM) continues to experience a significant workforce shortage in the face of increasing demand for emergency care. In July 2009, representatives of the leading EM organizations met in Dallas for the Future of Emergency Medicine Summit. Attendees at the Future of Emergency Medicine Summit agreed on the following: 1) Emergency medical care is an essential community service that should be available to all; 2) An insufficient emergency physician workforce also represents a potential threat to patient safety; 3) Accreditation Council for Graduate Medical Education/American Osteopathic Association (AOA)-accredited EM residency training and American Board of Medical Specialties/AOA EM board certification is the recognized standard for physician providers currently entering a career in emergency care; 4) Physician supply shortages in all fields contribute to-and will continue to contribute to-a situation in which providers with other levels of training may be a necessary part of the workforce for the foreseeable future; 5) A maldistribution of EM residency-trained physicians persists, with few pursuing practice in small hospital or rural settings; 6) Assuring that the public receives high quality emergency care while continuing to produce highly skilled EM specialists through EM training programs is the challenge for EM's future; 7) It is important that all providers of emergency care receive continuing postgraduate education.


Predicting the impact of vaccination on the transmission dynamics of typhoid in South Asia: a mathematical modeling study.
Modeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however, relevant typhoid models rooted in data have rarely been deployed. We developed a parsimonious age-structured model describing the natural history and immunity to typhoid infection. The model was fit to data on culture-confirmed cases of typhoid fever presenting to Christian Medical College hospital in Vellore, India from 2000-2012. The model was then used to evaluate the potential impact of school-based vaccination strategies using live oral, Vi-polysaccharide, and Vi-conjugate vaccines. The model was able to reproduce the incidence and age distribution of typhoid cases in Vellore. The basic reproductive number (R 0) of typhoid was estimated to be 2.8 in this setting. Vaccination was predicted to confer substantial indirect protection leading to a decrease in the incidence of typhoid in the short term, but (intuitively) typhoid incidence was predicted to rebound 5-15 years following a one-time campaign. We found that model predictions for the overall and indirect effects of vaccination depend strongly on the role of chronic carriers in transmission. Carrier transmissibility was tentatively estimated to be low, consistent with recent studies, but was identified as a pivotal area for future research. It is unlikely that typhoid can be eliminated from endemic settings through vaccination alone.


Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients.
Clinical, radiological, and histopathological features of 51 surgically treated gangliogliomas were evaluated retrospectively. The most common presenting symptoms were epileptic seizures (47 patients (92%)). Focal neurological deficits occurred in 8% of the patients. The duration of symptoms at the time of operation ranged from three months to 45 years, mean 11 years. The temporal lobe was affected in 43 patients (84%), the frontal lobe in five patients (10%), and the occipital lobe in one patient (2%). Two of the tumours (4%) were localised infratentorially. On MRI, solid tumour parts usually showed a pronounced signal increase on proton density images and a less pronounced signal increase on T2 weighted images, whereas solid components were mainly isointense on T1 weighted images. Contrast enhancement was noted in 16 of 36 patients (44%). Cystic tumour parts were found in 23 of 40 patients (57%), all characterised by signal increase on T2 weighted images and decreased T1 signals. Signal deviation of cystic tumour parts on proton density images was variable. Computed tomography was performed in 17 patients and showed hypodense lesions in 10 (59%), and calcifications in seven (41%) cases. Surgery included complete tumour removal in 44 patients (86%) and partial resection in seven (14%). In six patients (12%) there were transient postoperative complications. One patient (2%) died postoperatively due to pulmonary embolism. Histopathological examination of the surgical specimens showed low grade gangliogliomas in 49 cases (96%) and anaplastic gangliogliomas in two (4%). Control MRI of 31 patients with a mean follow up period of 16 months was uneventful in all but one case of an anaplastic ganglioglioma. In all patients in whom the ganglioglioma was associated with medically intractable seizures the operation resulted in complete relief of seizures or a noticeable improvement of the epilepsy.


A new spontaneous mutation in the mouse protocadherin 15 gene.
We have characterized a new allele of the protocadherin 15 gene (designatedPcdh15(av-6J)) that arose as a spontaneous, recessive mutation in the C57BL/6J inbred strain at Jackson Laboratory. Analysis revealed an inframe deletion in Pcdh15, which is predicted to result in partial deletion of cadherin domain (domain 9) in Pcdh15. Morphologic study revealed normal to moderately defective cochlear hair cell stereocilia in Pcdh15(av-6J) mutants at postnatal day 2 (P2). Stereocilia abnormalities were consistently present at P5 and P10. Degenerative changes including loss of inner and outer hair cells were seen at P20, with severe sensory cell loss in all cochlear turns occurring by P40. The hair cell phenotype observed in the 6J allele between P0 and P20 is the least severe phenotype yet observed in Pcdh15 alleles. However, young Pcdh15(av-6J) mice are unresponsive to auditory stimulation and show circling behavior indicative of vestibular dysfunction. Since these animals show severe functional deficits but have relatively mild stereocilia defects at a young age they may provide an appropriate model to test for a direct role of Pcdh15 in mechanotransduction.


Action of natural products on p2 receptors: a reinvented era for drug discovery.
Natural products contribute significantly to available drug therapies and have been a rich source for scientific investigation. In general, due to their low cost and traditional use in some cultures, they are an object of growing interest as alternatives to synthetic drugs. With several diseases such as cancer, and inflammatory and neuropathic diseases having been linked to the participation of purinergic (P2) receptors, there has been a flurry of investigations on ligands within natural products. Thirty-four different sources of these compounds have been found so far, that have shown either agonistic or antagonistic effects on P2 receptors. Of those, nine different plant sources demonstrated effects on P2X2, P2X3, P2X7, and possibly P2Y12 receptor subtypes. Microorganisms, which represent the largest group, with 26 different sources, showed effects on both receptor subtypes, ranging from P2X1 to P2X4 and P2X7, and P2Y1, P2Y2, P2Y4, and P2Y6. In addition, there were seventeen animal sources that affected P2X7 and P2Y1 and P2Y12 receptors. Natural products have provided some fascinating new mechanisms and sources to better understand the P2 receptor antagonism. Moreover, current investigations should clarify further pharmacological mechanisms in order to consider these products as potential new medicines.


A meta-synthesis on parenting a child with autism.
The lifelong nature of autism in a child has deep implications on parents as they are faced with a range of challenges and emotional consequences in raising the child. The aim of this meta-synthesis was to explore the perspectives of parents in raising a child with autism in the childhood period to gain an insight of the adaptations and beliefs of parents toward autism, their family and social experiences, as well as their perceptions toward health and educational services. A systematic search of six databases (PubMed, EMBASE, PsychInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects [DARE]) was conducted from inception up to September 30, 2014. Full-text English articles of qualitative studies describing parents' perceptions relating to the care of children younger than 12 years of age and diagnosed with a sole disorder of autism were included. A total of 50 eligible articles were appraised and analyzed, identifying four core themes encompassing all thoughts, emotions, and experiences commonly expressed by parents: 1) The Parent, 2) Impact on the Family, 3) Social Impact, and 4) Health and Educational Services. Findings revealed that parents who have a child with autism experienced multiple challenges in different aspects of care, impacting on parents' stress and adaptation. Health care provision should be family centered, addressing and supporting the needs of the whole family and not just the affected child, to ensure the family's well-being and quality of life in the face of a diagnosis of autism.


Eldecalcitol for the treatment of osteoporosis.
Eldecalcitol (1α, 25-dihydroxy-2β-[3-hydroxypropyloxy] vitamin D3; ED-71) is a new analog of the active form of vitamin D. Eldecalcitol has recently been approved for the treatment of osteoporosis in Japan. In addition to regulation of calcium metabolism carried out by conventional vitamin D analogs, eldecalcitol possesses a strong inhibitory effect on bone resorption and causes a significant increase in bone mineral density. A Phase III clinical trial on osteoporosis showed that eldecalcitol reduced the incidence of new vertebral fractures over 3 years by 26% compared with alfacalcidol. Although the overall risk of nonvertebral fractures was not reduced by eldecalcitol, the risk of wrist fracture was decreased significantly in the eldecalcitol group (71%) compared with the alfacalcidol group. The serum level of 25-hydroxyvitamin D (25[OH]D) was normalized by supplementation of native vitamin D in this trial, so the desirable effects on bone by eldecalcitol were considered to be derived from its distinctive pharmacological action. Increased blood calcium was observed in 21% of patients treated with eldecalcitol, and hypercalcemia (>11.5 mg/dL) occurred in 0.4% of eldecalcitol recipients, so serum calcium concentration should be monitored after starting eldecalcitol treatment. Eldecalcitol has dual effects on the metabolism of bone and calcium and is useful for the treatment of osteoporosis, especially for elderly patients (who frequently suffer from vitamin D deficiency). This article reviews the clinical efficacy and safety of eldecalcitol in the treatment of osteoporosis.


Endotracheal Intubation and In-Hospital Mortality after Intracerebral Hemorrhage.
Many patients with acute intracerebral hemorrhages (ICHs) undergo endotracheal intubation with subsequent mechanical ventilation (MV) for "airway protection" with the intent to prevent aspiration, pneumonias, and its related mortality. Conversely, these procedures may independently promote pneumonia, laryngeal trauma, dysphagia, and adversely affect patient outcomes. The net benefit of intubation and MV in this patient cohort has not been systematically investigated. We conducted a large single-center observational cohort study to examine the independent association between endotracheal intubation and MV, hospital-acquired pneumonia (HAP), and in-hospital mortality (HM) in patients with ICH. All consecutive patients admitted with a primary diagnosis of a spontaneous ICH to a tertiary care hospital in Boston, Massachusetts, from June 2000 through January 2014, who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Patients with pneumonia on admission, or those having brain or lung neoplasms were excluded. Our exposure of interest was endotracheal intubation and MV during hospitalization; our primary outcomes were incidence of HAP and HM, ascertained using International Classification of Diseases-9 and administrative discharge disposition codes, respectively, in patients who underwent endotracheal intubation and MV versus those who did not. Multivariable logistic regression was used to control for confounders. Of the 2,386 hospital admissions screened, 1,384 patients fulfilled study criteria and were included in the final analysis. A total of 507 (36.6%) patients were intubated. Overall 133 (26.23%) patients in the intubated group developed HAP versus 41 (4.67%) patients in the non-intubated group (p < 0.0001); 195 (38.5%) intubated patients died during hospitalization compared to 48 (5.5%) non-intubated patients (p < 0.0001). After confounder adjustments, OR for HAP and HM, were 4.23 (95% CI 2.48-7.22; p < 0.0001) and 4.32 (95% CI 2.5-7.49; p < 0.0001) with c-statistics of 0.79 and 0.89, in the intubated versus non-intubated patients, respectively. In this large hospital-based cohort of patients presenting with an acute spontaneous ICH, endotracheal intubation and MV were associated with increased odds of HAP and HM. These findings urge further examination of the practice of intubation in prospective studies.


The vaccine efficacy of recombinant duck enteritis virus expressing secreted E with or without PrM proteins of duck tembusu virus.
A newly emerged tembusu virus that causes egg-drop has been affecting ducks in China since 2010. Currently, no vaccine is available for this disease. A live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine has been used routinely to control lethal DEV in ducks since the 1960s. Here, we constructed two recombinant DEVs by transfecting overlapping fosmid DNAs. One virus, rDEV-TE, expresses the truncated form of the envelope glycoprotein (TE) of duck tembusu virus (DTMUV), and the other virus, rDEV-PrM/TE, expresses both the TE and pre-membrane proteins (PrM). Animal study demonstrated that both recombinant viruses induced measurable anti-DTMUV neutralizing antibodies in ducks. After two doses of recombinant virus, rDEV-PrM/TE completely protected ducks from DTMUV challenge, whereas rDEV-TE only conferred partial protection. These results demonstrate that recombinant DEV expressing the TE and pre-membrane proteins is protective and can serve as a potential candidate vaccine to prevent DTMUV infection in ducks.


Effect of Planting Date, Cultivar, and Stage of Plant Development on Incidence of Fusarium Wilt of Lettuce in Desert Production Fields.
Fusarium wilt of lettuce, first recognized in Japan in 1955, has since been discovered in the United States (California in 1990, Arizona in 2001), Iran (1995), Taiwan (1998), and Italy (2001). In Arizona, the causal agent, Fusarium oxysporum f. sp. lactucae, has been recovered from lettuce plants in 27 different lettuce fields during the 2001 to 2003 production seasons. Studies were initiated to examine the impact of planting date, cultivar, and stage of plant development on the incidence of disease in the field. In 2002 and 2003, tested lettuce cultivars were sown in at least one of the following planting windows; early-season (September), mid-season (October), and late-season (December). Within each planting window, significant differences in disease incidence among lettuce cultivars were noted at plant maturity. The mean incidence of Fusarium wilt on cultivars sown in September, October, and December was 92.3, 15.1, and 2.0%, respectively, in 2002 and 74.2, 5.1, and 0.7%, respectively, in 2003. The mean soil temperatures at the10-cm depth during the September, October, and December plantings for both years were 26, 14, and 14°C, respectively. Initial symptoms of Fusarium wilt were apparent as early as 14 days after seeding, with increasing incidence of disease noted as the crop developed and reached maturity. Among all lettuce cultivars planted in September, only one and two cultivars of romaine in 2002 and 2003, respectively, reached maturity with ≤5% incidence of Fusarium wilt, whereas the lowest incidence of disease among crisphead, green leaf, red leaf, or butterhead cultivars was 73.7, 27.0, 20.2, and 65.7%, respectively, in 2002 and 62.1, 29.0, 100, and 100%, respectively, in 2003. For October plantings, all romaine cultivars had ≤5% incidence of Fusarium wilt at maturity, whereas disease incidence among tested cultivars of crisphead lettuce in 2002 and 2003 ranged from 0.8 to 66.8% and 0.3 to 43.3%, respectively. When planted in December, 82 and 88% of tested cultivars, including all romaine entries, reached maturity with ≤1% incidence of Fusarium wilt. Selection of appropriate lettuce cultivars and planting times should allow successful production of lettuce in the southwestern Arizona production region with minimal or no incidence of disease in fields infested with F. oxysporum f. sp. lactucae. On the other hand, successful production of lettuce in infested fields when temperatures favor disease development will not be possible until lettuce cultivars are developed that possess high tolerance or resistance to the pathogen.


Retroviral gene transfer to primitive normal and leukemic hematopoietic cells using clinically applicable procedures.
Clinical uses of gene transfer to bone marrow transplants require the establishment of a reproducible method for infecting large numbers of very primitive hematopoietic cells at high efficiency using cell-free retrovirus-containing media. In this study we report the results of experiments with preparations of a high-titer (2-5 x 10(7)/ml) helper-free recombinant neo(r) retrovirus that indicate this goal can now be achieved based on measurements of gene transfer efficiencies to cells referred to as long-term culture initiating cells (LTC-IC) because they give rise to clonogenic cells after greater than or equal to 5 wk in long-term culture (LTC). Intermittent, repeated exposure of normal human marrow mononuclear cells to virus-containing supernatant over a 3-d period of cell maintenance on an IL-3/granulocyte colony-stimulating factor (G-CSF) producing stromal layer resulted in gene transfer efficiencies to LTC-IC of 41%; a level previously obtainable only using co-cultivation infection techniques. Marrow cells enriched greater than or equal to 500-fold for LTC-IC (1-2% pure) by flow cytometry showed gene transfer efficiencies of 27% when infected in a similar fashion over a shorter period (24 h), but in the presence of added soluble IL-3 and G-CSF without stromal feeders, and this increased to 61% when Steel factor was also present during the infection period. By using a less highly enriched population of LTC-IC obtained by a bulk immunoselection technique applicable to large-scale clinical marrow harvests, gene transfer efficiencies to LTC-IC of 40% were achieved and this was increased to 60% by short-term preselection in G418. Southern analysis of DNA from the nonadherent cells produced by these LTC over a 6-wk period provided evidence of clonal evolution of LTC-IC in vitro. Leukemic chronic myelogenous leukemia LTC-IC were also infected at high efficiency using the same supernatant infection strategy with growth factor supplementation. These data demonstrate the feasibility of using cell-free virus preparations for infecting clinical marrow samples suitable for transplantation, as well as for further analysis of human marrow stem cell dynamics in vitro.


Smooth pursuit in twins before and after alcohol ingestion.
The influence of genetic factors on characteristics of smooth pursuit were evaluated in young adult monozygotic (MZ) and dizygotic (DZ) twins before and after the administration of a single dose of ethanol. Sinusoidal pursuit was recorded using a scleral search coil at frequencies of 0.25 and 0.5 Hz before and after alcohol consumption. Pursuit gain, interval between saccades, saccadic accuracy, and saccadic amplitude were quantified. Alcohol consumption reduced pursuit gain and saccadic accuracy and increased the rate and amplitude of saccades. Before and after alcohol consumption, the intraclass correlations for MZ twins (rMZ) were highly significant for pursuit gain, interval between saccades, and saccade amplitude. Corresponding correlations for DZ twins (rDZ) were not significant. Heritability values were similar before and after alcohol ingestion. The disparity between rMZ and rDZ suggests either multiple gene interactions or common environmental influences for MZ twins, greater than those for DZ twins.


Influence of the meteorological conditions and some pollutants on PM10 concentrations in Lamphun, Thailand.
Particulate matter (PM) has been occurring regularly during the dry season in the upper north of Thailand including Lamphun Province that might be influenced by various factors including climatologic and other pollutants. This paper aims to investigate the climatologic and gaseous factors influencing the occurrence of PM10 concentration using Pollution Control Department (PCD) data. The secondary data of 2009 to 2017 obtained from the PCD was used for analysis. We used descriptive statistics, Pearson's correlation coefficient, multiple regression and graphic presentation using R program (R packages of 'open air' and 'ncdf4') and Microsoft Excel Spreadsheet®. In addition, the periodic measurement of PM2.5 and PM10 were investigated to determine the ratio of PM2.5/PM10. The results indicated that haze episodes (daily PM10 concentration always over the PCD standard) normally occur during the dry season from February to April. The maximum concentration was always found in March. The PM10 concentration was negatively associated with relative humidity and temperature while the PM10 concentration showed a strongly positive association with CO and NO2 concentration with correlation values of 0.70 and 0.57, respectively. Furthermore, we found CO and PM10 concentration was associated with ozone concentration. This finding will benefit local communities and the public health sector to provide a warning system for preparation and response plans to react to PM10 episodes in their responsible areas.


High-pressure studies of aggregation of recombinant human interleukin-1 receptor antagonist: thermodynamics, kinetics, and application to accelerated formulation studies.
Recombinant human interleukin-1 receptor antagonist (IL-1ra) in aqueous solutions unfolds and aggregates when subjected to hydrostatic pressures greater than about 180 MPa. This study examined the mechanism and thermodynamics of pressure-induced unfolding and aggregation of IL-1ra. The activation free energy for growth of aggregates (DeltaG-/+(aggregation)) was found to be 37 +/- 3 kJ/mol, whereas the activation volume (DeltaV-/+(aggregation)) was -120 +/- 20 mL/mol. These values compare closely with equilibrium values for denaturation: The free energy for denaturation, DeltaG(denaturation), was 20 +/- 5 kJ/mol, whereas the partial specific volume change for denaturation, DeltaV(denaturation), was -110 +/- 30 mL/mol. When IL-1ra begins to denature at pressures near 140 MPa, cysteines that are normally buried in the native state become exposed. Under oxidizing conditions, this results in the formation of covalently cross-linked aggregates containing nonnative, intermolecular disulfide bonds. The apparent activation free energy for nucleation of aggregates, DeltaG-/+(nuc), was 42 +/- 4 kJ/mol, and the activation volume for nucleation, DeltaV-/+(nuc),was -175 +/- 37 mL/mol, suggesting that a highly solvent-exposed conformation is needed for nucleation. We hypothesize that the large specific volume of IL-1ra, 0.752 +/- 0.004 mL/g, coupled with its relatively low conformational stability, leads to its susceptibility to denaturation at relatively low pressures. The positive partial specific adiabatic compressibility of IL-1ra, 4.5 +/- 0.7 +/- 10(-12) cm2/dyn, suggests that a significant component of the DeltaV(denaturation) is attributable to the elimination of solvent-free cavities. Lastly, we propose that hydrostatic pressure is a useful variable to conduct accelerated formulation studies of therapeutic proteins.


Interaction between the 90-kDa heat shock protein and soluble guanylyl cyclase: physiological significance and mapping of the domains mediating binding.
The 90-kDa heat shock protein (hsp90) regulates the stability and function of many client proteins, including members of the NO-cGMP signaling pathway. Soluble guanylyl cyclase (sGC), an NO receptor, was recently reported to be an hsp90-interacting partner. In the present study, we show that hsp90 binds to both subunits of the most common sGC form (alpha(1)beta(1)) when these are expressed individually but only interacts with beta(1) in the heterodimeric form of the enzyme. Characterization of the region of hsp90 required to bind each subunit in immunoprecipitation experiments revealed that residues 310 to 456 of hsp90 interact with the sGC subunits. The region of beta(1) responsible for binding to hsp90beta was mapped using in vitro binding assays and immunoprecipitation experiments and was found to lie in the regulatory domain. The physiological importance of the hsp90/sGC interaction was investigated by treating rat smooth muscle cells with the hsp90 inhibitors radicicol and geldanamycin (GA) and determining both sGC activity and protein levels. Long-term (24 or 48 h) inhibition of hsp90 resulted in a strong decrease of both alpha(1) and beta(1) protein levels and sGC activity. Moreover, incubation of smooth muscle cells with the proteasome inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) blocked the GA-induced down-regulation of sGC. We conclude that the N-terminal region of the beta(1) subunit mediates binding of the heterodimeric form of sGC to hsp90 and that this interaction involves the M domain of hsp90. Hsp90 binding to sGC regulates the pool of active enzymes by affecting the protein levels of the two subunits.


A cross-sectional exploration of the personality traits of dietitians.
Personality traits refer to habitual patterns of behaviour, thought and emotions, and have been shown to influence health professionals' career decisions, career development, job satisfaction and retention. There is an opportunity to better understand and support the career pathways of dietitians by exploring their personality traits. The two primary aspects of personality are: (i) temperament traits, which determine automatic emotional responses to experiences, and are generally stable over lifetime, and (ii) character traits, which reflect personal goals and values, and tend to develop with life experience. The present study explored the levels of temperament and character traits of dietitians, as well as their relationship to demographic variables. The study comprised a cross-sectional online survey of 346 Australian dietitians [95% female; mean (SD) age 32 (10) years; mean (SD) time since graduation 7 (9) years]. Temperament and character traits were measured by the Temperament and Character Inventory. Key demographic variables were measured to describe career decisions and pathways of dietitians. Multivariate analyses of variance was used to investigate the relationship between demographic variables and personality traits. Levels of several traits were significantly associated with gender, age and highest level of education. In comparison to the general population, the dietitians displayed average levels of Novelty Seeking; high levels of Harm Avoidance, Reward Dependence, Persistence, Self-Directedness and Cooperativeness; and low levels of Self-Transcendence. The dietitians in the present study displayed levels of personality traits that were similar to other health professionals, although they differed from the general population. These findings are the precursor to further work that may inform recruitment strategies and career counselling in dietetics.