Presentation of a complex permittivity-meter with applications for sensing the moisture and salinity of a porous media.
This paper describes a sensor dedicated to measuring the vertical profile of the complex permittivity and the temperature of any medium in which sensor electrodes are inserted. Potential applications are the estimate of the humidity and salinity in a porous medium, such as a soil. It consists of vertically-stacked capacitors along two conductive parallel cylinders of 5 cm in diameter and at a 10-cm distance to scan a significant volume of the medium (~1 L). It measures their admittances owing to a self-balanced impedance bridge operating at a frequency in the range of 1-20 MHz, possibly 30 MHz. Thanks to accurate design and electronic circuit theory-based modeling, the determination of the admittances takes into account all distortions due to lead and bridge electromagnetic effects inside the sensor when working at high frequencies. Calibration procedures and uncertainties are presented. The article also describes developments to make the present sensor autonomous on digital acquisition, basic data treatment and energy, as well as able to transfer stored data by a radio link. These steps in progress are prerequisites for a wireless network of sensors.


Two widespread green Neottia species (Orchidaceae) show mycorrhizal preference for Sebacinales in various habitats and ontogenetic stages.
Plant dependence on fungal carbon (mycoheterotrophy) evolved repeatedly. In orchids, it is connected with a mycorrhizal shift from rhizoctonia to ectomycorrhizal fungi and a high natural (13)C and (15)N abundance. Some green relatives of mycoheterotrophic species show identical trends, but most of these remain unstudied, blurring our understanding of evolution to mycoheterotrophy. We analysed mycorrhizal associations and (13)C and (15)N biomass content in two green species, Neottia ovata and N. cordata (tribe Neottieae), from a genus comprising green and nongreen (mycoheterotrophic) species. Our study covered 41 European sites, including different meadow and forest habitats and orchid developmental stages. Fungal ITS barcoding and electron microscopy showed that both Neottia species associated mainly with nonectomycorrhizal Sebacinales Clade B, a group of rhizoctonia symbionts of green orchids, regardless of the habitat or growth stage. Few additional rhizoctonias from Ceratobasidiaceae and Tulasnellaceae, and ectomycorrhizal fungi were detected. Isotope abundances did not detect carbon gain from the ectomycorrhizal fungi, suggesting a usual nutrition of rhizoctonia-associated green orchids. Considering associations of related partially or fully mycoheterotrophic species such as Neottia camtschatea or N. nidus-avis with ectomycorrhizal Sebacinales Clade A, we propose that the genus Neottia displays a mycorrhizal preference for Sebacinales and that the association with nonectomycorrhizal Sebacinales Clade B is likely ancestral. Such a change in preference for mycorrhizal associates differing in ecology within the same fungal taxon is rare among orchids. Moreover, the existence of rhizoctonia-associated Neottia spp. challenges the shift to ectomycorrhizal fungi as an ancestral pre-adaptation to mycoheterotrophy in the whole Neottieae.


Development of an adaptive low-pass filtered speech test for the identification of auditory processing disorders.
One type of test commonly used to examine auditory processing disorders (APD) is the low-pass filtered speech test (LPFST), of which there are various versions. In LPFSTs, a monaural, low-redundancy speech sample is distorted by using filtering to modify its frequency content. Due to the richness of the neural pathways in the auditory system and the redundancy of acoustic information in spoken language, a normal listener is able to recognize speech even when parts of the signal are missing, whereas this ability is often impaired in listeners with APD. One limitation of the various versions of the LPFST is that they are carried out using a constant level of low-pass filtering (e.g. a fixed 1kHz corner frequency) which makes them prone to ceiling and floor effects. The purpose of this study was to counter these effects by modifying the LPFST using a computer-based adaptive procedure, and to evaluate the performance of normal-hearing participants of varying ages on the test. In this preliminary study, 33 adults and 30 children (aged 8-11 years) with no known history of listening difficulties were tested. The University of Canterbury Adaptive Speech Test (UCAST) platform was used to administer a four-alternative forced-choice adaptive test that altered a low-pass filter (LPF) to track the corner frequency at which participants correctly identified a certain percentage of the word stimuli. Findings on the University of Canterbury Adaptive Speech Test-Filtered Words (UCAST-FW) indicated a significant maturational effect. Adult participants performed significantly better on the UCAST-FW in comparison to the child participants. The UCAST-FW test was reliable over repeated administrations. An adaptive low-pass filtered speech test such as the UCAST-FW is sensitive to maturational changes in auditory processing ability.


TNFα signalling primes chromatin for NF-κB binding and induces rapid and widespread nucleosome repositioning.
The rearrangement of nucleosomes along the DNA fiber profoundly affects gene expression, but little is known about how signalling reshapes the chromatin landscape, in three-dimensional space and over time, to allow establishment of new transcriptional programs. Using micrococcal nuclease treatment and high-throughput sequencing, we map genome-wide changes in nucleosome positioning in primary human endothelial cells stimulated with tumour necrosis factor alpha (TNFα) - a proinflammatory cytokine that signals through nuclear factor kappa-B (NF-κB). Within 10 min, nucleosomes reposition at regions both proximal and distal to NF-κB binding sites, before the transcription factor quantitatively binds thereon. Similarly, in long TNFα-responsive genes, repositioning precedes transcription by pioneering elongating polymerases and appears to nucleate from intragenic enhancer clusters resembling super-enhancers. By 30 min, widespread repositioning throughout megabase pair-long chromosomal segments, with consequential effects on three-dimensional structure (detected using chromosome conformation capture), is seen. Whilst nucleosome repositioning is viewed as a local phenomenon, our results point to effects occurring over multiple scales. Here, we present data in support of a TNFα-induced priming mechanism, mostly independent of NF-κB binding and/or elongating RNA polymerases, leading to a plastic network of interactions that affects DNA accessibility over large domains.


Interactions of the pleckstrin homology domain with phosphatidylinositol phosphate and membranes: characterization via molecular dynamics simulations.
The mechanism of interaction of pleckstrin homology (PH) domains with phosphatidylinositol 4,5-bisphosphate (PIP 2)-containing lipid bilayers remains uncertain. While crystallographic studies have emphasized PH-inositol 1,4,5-trisphosphate (IP 3) interactions, biophysical studies indicate a degree of less specific protein-bilayer interactions. We have used molecular dynamics simulations to characterize the interactions of the PH domain from phospholipase C-delta1 with IP 3 and with PIP 2, the latter in lipid bilayers and in detergent micelles. Simulations of the PH domain in water reveal a reduction in protein flexibility when IP 3 is bound. Simulations of the PH domain bound to PIP 2 in lipid bilayers indicate a tightening of ligand-protein interactions relative to the PH-IP 3 complex, alongside formation of H-bonds between PH side chains and lipid (PC) headgroups, and a degree of penetration of hydrophobic side chains into the core of the bilayer. Comparison with simulations of the PH-bound domain to a PC bilayer in the absence of PIP 2 suggests that the presence of PIP 2 increases the extent of PH-membrane interactions. Thus, comparative molecular dynamics simulations reveal how a PI-binding domain undergoes changes in conformational dynamics on binding to a PIP 2-containing membrane and how interactions additional to those with the PI headgroup are formed.


Travel epidemiology--a global perspective.
In order to have a rational approach to necessary preventive measures it is essential to know the health risks. The 80 million travellers each year with destinations in Africa, Asia, Latin America, Pacific Islands and remote areas in Eastern Europe are exposed to a broad range of pathogens that are rarely encountered at home. The risk depends on the degree of endemicity in the area visited, the duration of stay, the individual behaviour and the preventive measures taken. Travellers' diarrhoea (TD) is the most frequent ailment of visitors to countries with poor hygiene. The incidence rate is 25-90% in the first 2 weeks abroad. The risk of TD is far less in travellers originating in a high risk country, as some immunity develops. Malaria is an important risk for travellers going to endemic areas. Without chemoprophylaxis, the monthly incidence is high in some destinations, among them frequently visited tropical Africa where 80-95% of the infections are due to Plasmodium falciparum. The incidence rates are lower in most endemic areas of Asia and Latin America where Plasmodium vivax predominates. The risk is nil in all capital cities of South America and SE Asia, as well as in many frequently visited tourist destinations. The diseases preventable by immunization will be discussed in a separate paper (Vaccination priorities; page 175). Sexually transmitted diseases occur frequently, as some travellers (5% of Europeans) engage in casual sex, approximately half of them without being protected by a condom. The prevalence for HIV-infection, syphilis, gonorrhoea, etc. often exceeds 50% in prostitutes. In some European countries, a major proportion of heterosexuals with newly acquired HIV-infection have acquired it while abroad.


Changes in the composition of ichthyoplankton assemblage and plastic debris in mangrove creeks relative to moon phases.
Lunar influence on the distribution of fish larvae, zooplankton and plastic debris in mangrove creeks of the Goiana Estuary, Brazil, was studied over a lunar cycle. Cetengraulis edentulus, Anchovia clupeoides and Rhinosardinia bahiensis were the most abundant fish larvae (56·6%), independent of the moon phase. The full moon had a positive influence on the abundance of Gobionellus oceanicus, Cynoscion acoupa and Atherinella brasiliensis, and the new moon on Ulaema lefroyi. The full and new moons also influenced the number of zoeae and megalopae of Ucides cordatus, protozoeae and larvae of caridean shrimps, and the number of hard and soft plastic debris, both <5 and >5 mm. Micro and macroplastics were present in samples from all 12 creeks studied, at densities similar to the third most abundant taxon, R. bahiensis. Cetengraulis edentulus and R. bahiensis showed a strong positive correlation with the last quarter moon, when there was less zooplankton available in the creeks and higher abundance of microplastic threads. Anchovia clupeoides, Diapterus rhombeus, U. lefroyi and hard microplastics were positively associated with different moon phases, when calanoid copepods, Caridean larvae and zoeae of U. cordatus were highly available in the creeks. Cynoscion acoupa, G. oceanicus and A. brasiliensis were strongly associated with the full moon, when protozoeae of caridean shrimps and megalopae of U. cordatus were also highly available, as were hard and soft macroplastics, paint chips (<5 mm) and soft microplastics. The results reinforce the role of mangrove creeks as nursery habitats. The moon phases influenced the distribution of fish larvae species, zooplankton and plastic debris by changing their compositions and abundances in the mangrove creeks of the Goiana Estuary when under the influence of different tidal current regimes.


Inhibition of stationary phase respiration impairs persister formation in E. coli.
Bacterial persisters are rare phenotypic variants that temporarily tolerate high antibiotic concentrations. Persisters have been hypothesized to underlie the recalcitrance of biofilm infections, and strategies to eliminate these cells have the potential to improve treatment outcomes for many hospital-treated infections. Here we investigate the role of stationary phase metabolism in generation of type I persisters in Escherichia coli, which are those that are formed by passage through stationary phase. We find that persisters are unlikely to derive from bacteria with low redox activity, and that inhibition of respiration during stationary phase reduces persister levels by up to ∼1,000-fold. Loss of stationary phase respiratory activity prevents digestion of endogenous proteins and RNA, which yields bacteria that are more capable of translation, replication and concomitantly cell death when exposed to antibiotics. These findings establish bacterial respiration as a prime target for reducing the number of persisters formed in nutrient-depleted, non-growing populations.


Aging and glucocorticoids: effects on cell signaling mediated through adenylyl cyclase.
Abnormalities of hypothalamus-pituitary-adrenal axis regulation are common in the elderly and excess glucocorticoids have been implicated in the loss of neural function in aging. In the current study, we examined cell signaling mediated through adenylyl cyclase in brain regions, heart and liver of young and aged rats given continuous infusions of dexamethasone (10 or 50 micrograms/kg/day) for 26 days. Aged control animals showed significant deficits in total adenylyl cyclase activity (assessed with forskolin-Mn++) in the brain regions and the heart; superimposed on this change, the striatum and the heart displayed interference with the response mediated either at the level of G-protein coupling to cyclase (striatum) or neurotransmitter receptor coupling to G-proteins (heart). Administration of dexamethasone to young rats did not reproduce the effects of aging on any of the measures of adenylyl cyclase, despite the fact that the higher dose produced Cushingoid effects. The same dexamethasone regimens given to aged rats produced alterations in G-protein coupling mechanisms in the cortex and in serotonergic-mediated cyclase responses in the striatum, and also decreased basal enzyme activity in the heart. In contrast to the brain regions and the heart, the liver showed unique effects of aging and dexamethasone. Total adenylyl cyclase activity, the enzymatic response to beta adrenergic stimulation and the number of beta adrenergic receptors were all elevated in aged animals as compared to the younger cohort. Dexamethasone decreased both hepatic beta receptor numbers and isoproterenol responsiveness in young animals, but increased receptor binding in aged animals. These data indicate that the defects associated with aging in the central nervous system and the cardiac cell signaling mediated through adenylyl cyclase are not a result of glucocorticoid excess; however, central and peripheral tissues respond differently to glucocorticoids in aged vs. young animals. Given the high incidence of hypothalamus-pituitary-adrenal axis dysregulation in the elderly, and particularly in elderly depression, effects of glucocorticoids on cell signaling may contribute to disruption of cell function and to hypo- or hyper-reactivity to drugs, such as antidepressants, that act by altering synaptic transmission.


Sonochemical degradation of organophosphorus pesticide in dilute aqueous solutions.
Ultrasonic irradiation was found to accelerate the rate of hydrolysis of omethoate in aqueous solution over the pH range of 2-12. Process parameters studied include pH, steady-state temperature, concentration, and the type of gases. Greater than 96% hydrolysis was observed in 30 minutes through this process and the rate of destruction increased with the help of more soluble and low thermal inert gas. So with Krypton, omethoate was found to undergo rapid destruction as compared with Argon. In the presence of ultrasound, the observed first-order rate of hydrolysis of omethoate is found to be independent of pH. The formation of transient supercritical water (SCW) appears to be an important factor in the acceleration of chemical reactions in the presence of ultrasound. A detailed chemical reaction mechanism for omethoate destruction in water was formulated. Experimental results and theoretical kinetic mechanism demonstrated that the most of the omethoate undergo destruction inside the cavitating holes. A very less effect of temperature on the degradation of omethoate within a temperature range of 20-70 degrees C proves that a small quantity of omethoate undergoes secondary destruction in the bulk liquid.


Structural and functional loss in restored wetland ecosystems.
Wetlands are among the most productive and economically valuable ecosystems in the world. However, because of human activities, over half of the wetland ecosystems existing in North America, Europe, Australia, and China in the early 20th century have been lost. Ecological restoration to recover critical ecosystem services has been widely attempted, but the degree of actual recovery of ecosystem functioning and structure from these efforts remains uncertain. Our results from a meta-analysis of 621 wetland sites from throughout the world show that even a century after restoration efforts, biological structure (driven mostly by plant assemblages), and biogeochemical functioning (driven primarily by the storage of carbon in wetland soils), remained on average 26% and 23% lower, respectively, than in reference sites. Either recovery has been very slow, or postdisturbance systems have moved towards alternative states that differ from reference conditions. We also found significant effects of environmental settings on the rate and degree of recovery. Large wetland areas (>100 ha) and wetlands restored in warm (temperate and tropical) climates recovered more rapidly than smaller wetlands and wetlands restored in cold climates. Also, wetlands experiencing more (riverine and tidal) hydrologic exchange recovered more rapidly than depressional wetlands. Restoration performance is limited: current restoration practice fails to recover original levels of wetland ecosystem functions, even after many decades. If restoration as currently practiced is used to justify further degradation, global loss of wetland ecosystem function and structure will spread.


Randomized clinical trial on the effect of coffee on postoperative ileus following elective colectomy.
Postoperative ileus is a common problem after abdominal surgery. It was postulated that coffee intake would decrease postoperative ileus after colectomy. This was a multicentre parallel open-label randomized trial. Patients with malignant or benign disease undergoing elective open or laparoscopic colectomy were assigned randomly before surgery to receive either coffee or water after the procedure (100 ml three times daily). The primary endpoint was time to first bowel movement; secondary endpoints were time to first flatus, time to tolerance of solid food, length of hospital stay and perioperative morbidity. A total of 80 patients were randomized, 40 to each group. One patient in the water arm was excluded owing to a change in surgical procedure. Patient characteristics were similar in both groups. In intention-to-treat analysis, the time to the first bowel movement was significantly shorter in the coffee arm than in the water arm (mean(s.d.) 60·4(21·3) versus 74·0(21·6) h; P = 0·006). The time to tolerance of solid food (49·2(21·3) versus 55·8(30·0) h; P = 0·276) and time to first flatus (40·6(16·1) versus 46·4(20·1) h; P = 0·214) showed a similar trend, but the differences were not significant. Length of hospital stay (10·8(4·4) versus 11·3(4·5) days; P = 0·497) and morbidity (8 of 40 versus 10 of 39 patients; P = 0·550) were comparable in the two groups. Coffee consumption after colectomy was safe and was associated with a reduced time to first bowel action.


A comprehensive analysis of deletions, multiplications, and copy number variations in PARK2.
To perform a comprehensive population genetic study of PARK2. PARK2 mutations are associated with juvenile parkinsonism, Alzheimer disease, cancer, leprosy, and diabetes mellitus, yet ironically, there has been no comprehensive study of PARK2 in control subjects; and to resolve controversial association of PARK2 heterozygous mutations with Parkinson disease (PD) in a well-powered study. We studied 1,686 control subjects (mean age 66.1 ± 13.1 years) and 2,091 patients with PD (mean onset age 58.3 ± 12.1 years). We tested for PARK2 deletions/multiplications/copy number variations (CNV) using semiquantitative PCR and multiplex ligation-dependent probe amplification, and validated the mutations by real-time quantitative PCR. Subjects were tested for point mutations previously. Association with PD was tested as PARK2 main effect, and in combination with known PD risk factors: SNCA, MAPT, APOE, smoking, and coffee intake. A total of 0.95% of control subjects and 0.86% of patients carried a heterozygous CNV mutation. CNV mutations found in 16 control subjects were all in exons 1-4, sparing exons that encode functionally critical protein domains. Thirteen patients had 2 CNV mutations, 5 had 1 CNV and 1 point mutation, and 18 had 1 CNV mutation. Mutations found in patients spanned exons 2-9. In whites, having 1 CNV was not associated with increased risk (odds ratio 1.05, p = 0.89) or earlier onset of PD (64.7 ± 8.6 heterozygous vs 58.5 ± 11.8 normal). This comprehensive population genetic study in control subjects fills the void for a PARK2 reference dataset. There is no compelling evidence for association of heterozygous PARK2 mutations, by themselves or in combination with known risk factors, with PD.


Heterotopic Ossification: Two Rare Forms and What They Can Teach Us.
Heterotopic ossification is characterized by the formation of normal bone at ectopic soft-tissue locations. Regardless of the etiology of heterotopic ossification, requisite pathogenetic conditions include an inductive signal capable of stimulating morphogenesis, a population of inducible osteoprogenitor cells, and a heterotopic environment conducive to osteogenesis. Two rare heritable and developmental forms of heterotopic ossification, fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, provide valuable clinical and pathogenetic insights into heterotopic ossification in humans. A fundamental understanding of the developmental and molecular pathology of these disorders may lead to more effective strategies for preventing and treating heterotopic ossification in humans.


Negative-pressure-induced enhancement in a freestanding ferroelectric.
Ferroelectrics are widespread in technology, being used in electronics and communications, medical diagnostics and industrial automation. However, extension of their operational temperature range and useful properties is desired. Recent developments have exploited ultrathin epitaxial films on lattice-mismatched substrates, imposing tensile or compressive biaxial strain, to enhance ferroelectric properties. Much larger hydrostatic compression can be achieved by diamond anvil cells, but hydrostatic tensile stress is regarded as unachievable. Theory and ab initio treatments predict enhanced properties for perovskite ferroelectrics under hydrostatic tensile stress. Here we report negative-pressure-driven enhancement of the tetragonality, Curie temperature and spontaneous polarization in freestanding PbTiO3 nanowires, driven by stress that develops during transformation of the material from a lower-density crystal structure to the perovskite phase. This study suggests a simple route to obtain negative pressure in other materials, potentially extending their exploitable properties beyond their present levels.


T-Cell Immunoglobulin and ITIM Domain (TIGIT) Associates with CD8+ T-Cell Exhaustion and Poor Clinical Outcome in AML Patients.
T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is a recently identified T-cell coinhibitory receptor. In this study, we aimed to determine the clinical impact of TIGIT in patients with acute myelogenous leukemia (AML) and dissect the role of TIGIT in the pathogenesis of leukemia progression. TIGIT expression on T cells from peripheral blood collected from patients with AML was examined by flow cytometry. The correlation of TIGIT expression to clinical outcomes, including rate of complete remission and relapse post-allogeneic stem cell transplantation (alloSCT) in AML patients, was analyzed. Phenotypic and functional study (cytokine release, proliferation, killing, and apoptosis) of TIGIT-expressing T cells were performed. Using siRNA to silence TIGIT, we further elucidated the regulatory role of TIGIT in the T-cell immune response by dissecting the effect of TIGIT knockdown on cytokine release and apoptosis of T cells from AML patients. TIGIT expression on CD8(+) T cells is elevated in AML patients and high-TIGIT correlates with primary refractory disease and leukemia relapse post-alloSCT. TIGIT(+) CD8(+) T cells display phenotypic features of exhaustion and exhibit functional impairment manifested by low production of cytokines and high susceptibility to apoptosis. Importantly, their functional defects are reversed by TIGIT knockdown. TIGIT contributes to functional T-cell impairment and associates with poor clinical outcome in AML. Our study suggests that blockade of TIGIT to restore T-cell function and antitumor immunity may represent a novel effective leukemia therapeutic. Clin Cancer Res; 22(12); 3057-66. ©2016 AACR.


Beyond the dinner table: who's having breakfast, lunch and dinner family meals and which meals are associated with better diet quality and BMI in pre-school children?
Having frequent family dinners is associated with better diet quality in children; however, it is unknown whether the frequency of certain family meal types (i.e. dinner) is more strongly associated with better child weight and diet quality compared with other meal types (i.e. breakfast, lunch). Thus, the current study examined the frequency of eating breakfast, lunch or dinner family meals and associations with pre-school children's overall diet quality (HEI-2010) and BMI percentile. Cross-sectional baseline data (2012-2014) from two randomized controlled childhood obesity prevention trials, NET-Works and GROW, were analysed together. Studies were carried out in community and in-home settings in urban areas of Minnesota and Tennessee, USA. Parent-child (ages 2-5 years) pairs from Minnesota (n 222 non-Hispanics; n 312 Hispanics) and Tennessee (n 545 Hispanics; n 55 non-Hispanics) participated in the study. Over 80 % of families ate breakfast or lunch family meals at least once per week. Over 65 % of families ate dinner family meals ≥5 times/week. Frequency of breakfast family meals and total weekly family meals were significantly associated with healthier diet quality for non-Hispanic pre-school children (P<0·05), but not for Hispanic children. Family meal frequency by meal type was not associated with BMI percentile for non-Hispanic or Hispanic pre-school children. Breakfast family meal frequency and total weekly family meal frequency were associated with healthier diet quality in non-Hispanic pre-school children but not in Hispanic children. Longitudinal research is needed to clarify the association between family meal type and child diet quality and BMI percentile.


Controlling epithelial sodium channels with light using photoswitchable amilorides.
Amiloride is a widely used diuretic that blocks epithelial sodium channels (ENaCs). These heterotrimeric transmembrane proteins, assembled from β, γ and α or δ subunits, effectively control water transport across epithelia and sodium influx into non-epithelial cells. The functional role of δβγENaC in various organs, including the human brain, is still poorly understood and no pharmacological tools are available for the functional differentiation between α- and δ-containing ENaCs. Here we report several photoswitchable versions of amiloride. One compound, termed PA1, enables the optical control of ENaC channels, in particular the δβγ isoform, by switching between blue and green light, or by turning on and off blue light. PA1 was used to modify functionally δβγENaC in amphibian and mammalian cells. We also show that PA1 can be used to differentiate between δβγENaC and αβγENaC in a model for the human lung epithelium.


Acute effects of ambient particulate matter on blood pressure: differential effects across urban communities.
Recent studies have suggested a link between exposure to ambient particulate matter <2.5 microm in diameter (PM(2.5)) and adverse cardiovascular outcomes. The objective of this study was to examine the effects of differing community-level exposure to PM(2.5) on daily measures of blood pressure (BP) among an adult population. During the period May 2002 through April 2003, BP was examined at 2 time points for 347 adults residing in 3 distinct communities of Detroit, Michigan. Exposure to PM(2.5) was assessed in each community during this period, along with multivariate associations between PM(2.5) and BP. In models combining all 3 of the communities, PM(2.5) was significantly associated with systolic blood pressure; a 10-microg/m(3) increase in daily PM(2.5) was associated with a 3.2-mm Hg increase in systolic blood pressure (P=0.05). However, in models that added a location interaction, larger effects were observed for systolic blood pressure within the community with highest PM(2.5) levels; a 10-microg/m(3) increase in daily PM(2.5) was associated with a 8.6-mm Hg increase in systolic blood pressure (P=0.01). We also found young age (<55 years) and not taking BP medications to be significant predictors of increased BP effects. Among those taking BP medications, the PM(2.5) effect on BP appeared to be mitigated, partially explaining the age effect, because those participants <55 years of age were less likely to take BP medications. Short-term increases in exposure to ambient PM(2.5) are associated with acute increases in BP in adults, especially within communities with elevated levels of exposure.


Comparative effects of enalapril, atenolol and chlorthalidone on blood pressure and kidney function of diabetic patients affected by arterial hypertension and persistent proteinuria.
Arterial hypertension and proteinuric nephropathy are common features in diabetic patients. In streptozotocin-diabetic rats, it has been possible to reduce the blood pressure and proteinuria by converting enzyme inhibitors, and so slowing the decline of kidney function. These results have been confirmed in diabetic patients affected by arterial hypertension and persistent proteinuria. However, up to now it has not been clear if these favorable renal effects are related specifically to converting enzyme inhibition. In the attempt to clarify this last point, from a practical as well as from a speculative point of view, 12 type 2 diabetic outpatients affected by mild to moderate arterial hypertension and persistent macroalbuminuria (greater than 250 mg/daily, at least on three consecutive occasions) without any other signs of renal diseases were studied. In a randomized sequence and in a double blind fashion, after a washout period of 3 weeks, the patients underwent pharmacological treatment which consisted of enalapril 20 mg o.d., chlorthalidone 12.5 mg o.d., atenolol 50 mg o.d. and placebo o.d. Each treatment lasted 45 days. Kidney function, blood pressure and heart rate were checked at the beginning and at the end of each treatment, while urinary albumin excretion was measured at the end of the 4th, 5th, and 6th week of each treatment. Blood pressure significantly decreased in a similar fashion after each active treatment, while kidney function did not change significantly. Urinary albumin excretion rate significantly decreased after enalapril and atenolol, but did not change after chlorthalidone. According to these results we can hypothesize that the inhibition of tissue angiotensin formation and its related change on the glomerular permeability, rather than renal and systemic hemodynamic features, seem to be the common mechanisms by which both enalapril as well as atenolol decrease the albuminuria in our patients.


Analysing reduced tillage practices within a bio-economic modelling framework.
Sustainable intensification of agricultural production systems will require changes in farm practice. Within arable cropping systems, reducing the intensity of tillage practices (e.g. reduced tillage) potentially offers one such sustainable intensification approach. Previous researchers have tended to examine the impact of reduced tillage on specific factors such as yield or weed burden, whilst, by definition, sustainable intensification necessitates a system-based analysis approach. Drawing upon a bio-economic optimisation model, 'MEETA', we quantify trade-off implications between potential yield reductions, reduced cultivation costs and increased crop protection costs. We extend the MEETA model to quantify farm-level net margin, in addition to quantifying farm-level gross margin, net energy, and greenhouse gas emissions. For the lowest intensity tillage system, zero tillage, results demonstrate financial benefits over a conventional tillage system even when the zero tillage system includes yield penalties of 0-14.2% (across all crops). Average yield reductions from zero tillage literature range from 0 to 8.5%, demonstrating that reduced tillage offers a realistic and attainable sustainable intensification intervention, given the financial and environmental benefits, albeit that yield reductions will require more land to compensate for loss of calories produced, negating environmental benefits observed at farm-level. However, increasing uptake of reduced tillage from current levels will probably require policy intervention; an extension of the recent changes to the CAP ('Greening') provides an opportunity to do this.


Evidence, appropriateness, and technology assessment in cardiology: a case study of computed tomography.
As the volume, complexity, and cost of new medical technology increase, the need for evaluating benefits and risks becomes increasingly important. Once the formal requirements for Food and Drug Administration approval and insurance coverage are met, however, few systematic criteria are applied to ensure patient benefit. A more systematic policy approach regarding new technologies is needed, with input from balanced groups reviewing evidence of clinical outcomes data to determine patient benefit. This paper examines cardiac computed tomography angiography as a case study; it proposes procedures designed to ensure that the benefits of new technologies justify their costs.


Does Dark-Spot Syndrome Experimentally Transmit among Caribbean Corals?
Over the last half-century, coral diseases have contributed to the rapid decline of coral populations throughout the Caribbean region. Some coral diseases appear to be potentially infectious, yet little is known about their modes of transmission. This study experimentally tested whether dark-spot syndrome on Siderastrea siderea was directly or indirectly transmissible to neighboring coral colonies. We also tested whether open wounds were necessary to facilitate disease transmission. At the completion of the experiments, we sampled bacterial communities on diseased, exposed, and healthy coral colonies to determine whether bacterial pathogens had transmitted to the susceptible colonies. We saw no evidence of either direct or waterborne transmission of dark-spot syndrome, and corals that received lesions by direct contact with diseased tissue, healed and showed no signs of infection. There were no significant differences among bacterial communities on healthy, exposed, and diseased colonies, although nine individual ribotypes were significantly higher in diseased corals compared with healthy and exposed corals, indicating a lack of transmission. Although our experiments do not fully refute the possibility that dark-spot syndrome is infectious and transmissible, our results suggest that in situ macroscopic signs of dark-spot syndrome are not always contagious.


Knowledge of risk of developing diabetes mellitus among siblings of Type 2 diabetic patients.
We set out to investigate the extent to which siblings of diabetic subjects perceived themselves likely to develop Type 2 diabetes mellitus (DM) when offered screening tests. Nondiabetic siblings, aged 35-74 years, of Type 2 diabetic patients who were more than 35 years old at diagnosis had fasting plasma glucose measured in a study to determine heritability of diabetes. Questionnaires assessing perceived likelihood of developing, seriousness and knowledge about diabetes were completed. Logistic regression assessed factors predicting perceptions of diabetes risk. Factors predicting diabetes on screening were male sex, increasing age and body mass index (BMI) > or = 30. Eighty-nine per cent of 540 eligible siblings completed questionnaires. Thirty-eight per cent saw themselves at increased risk of diabetes and 34% thought diabetes a serious problem. Predictors of perceiving an increased likelihood of developing diabetes were female sex, age 35-54 years vs. 55-74 years and having a parent with diabetes. BMI did not affect perceptions of likelihood. A perception of reduced vulnerability to diabetes may occur due to unawareness of risk or minimization of risk. Feelings of invulnerability may affect emotional response to a subsequent result. It is not known whether providing more information about the risk of developing diabetes prior to screening would affect outcomes


Error self-regulation following traumatic brain injury: a single case study evaluation of metacognitive skills training and behavioural practice interventions.
The objective of the study was to evaluate the effects of metacognitive skills training (MST) and behavioural practice on error self-regulation during a naturalistic task after traumatic brain injury (TBI). A single-case study design was used and three participants (two males, one female) aged 26-43 years with severe TBI were included in the study. In the first study, after a four-session baseline of behavioural practice, two participants received eight MST sessions followed by four maintenance sessions. In the second study, a third participant received 16 sessions of behavioural practice to assess the extent to which error self-regulation improves through long-term task practice and therapist corrections. Participants prepared two different meals with a novel meal introduced later to examine skills generalisation. Behavioural outcomes included error frequency, checking and self-corrections. Data analysis involved a combination of visual analysis and two standard deviation (2-SD) band analysis. In the MST study, the two participants demonstrated a 38% and 76% reduction in error frequency (p < .05), a significant decrease in checks (p < .05), and a significant increase in self-corrections (p < .05) relative to baseline. In the behavioural practice study, the participant demonstrated reduced errors (25%), although this was not statistically significant, and a significant increase in checks (p < .05), but self-corrections did not significantly change (p > .05). This exploratory research suggests that, firstly, by targeting error self-regulation MST can potentially promote independence on complex everyday tasks; and secondly, although behavioural practice alone may facilitate some functional gains, it fails to promote more independent self-regulatory behaviours.


Comparative evaluation of antifungal action of tea tree oil, chlorhexidine gluconate and fluconazole on heat polymerized acrylic denture base resin - an in vitro study.
Candida albicans-associated denture stomatitis is the most common type of denture stomatitis seen in denture wearers. This study evaluates and compares the antifungal action of fluconazole, chlorhexidine gluconate and tea tree oil on heat-polymerised denture base resin, which has been previously contaminated with C. albicans grown in BHI broth. Seventy-five specimens were immersed in BHI broth previously inoculated with C. albicans and stored for 3 h at 37°C. They were divided into five groups (n = 15): G1: 2% chlorhexidine solution; G2: 100% pure pharmaceutical grade tea tree oil; G3: 65 μg/ml fluconazole solution; C1: specimens not disinfected; C2: specimens not contaminated with Candida. Each specimen was then transferred to individual tubes containing BHI broth and incubated for 24 h. Culture media turbidity was evaluated for absorbance over a period of 14 days using a microplate reader. It was observed that the lower the absorbance, the stronger the antimicrobial action. Statistical analysis was performed (two-way anova and Bonferroni test, p < 0.001). Chlorhexidine and tea tree oil inhibited Candida up to the 14th day, whereas antifungal effect of fluconazole was not significant after the 7th day. Tea tree oil and chlorhexidine gluconate are more effective than fluconazole in inhibiting C. albicans growth on heat-polymerised acrylic resin.


Central pattern generator interneurons are targets for the modulatory serotonergic cerebral giant cells in the feeding system of Lymnaea.
1. The objective of the experiments was to explore the modulatory functions of the serotonergic cerebral giant cells (CGCs) of the Lymnaea feeding system by examining their synaptic connections with the central pattern generator (CPG) interneurons and the modulatory slow oscillator (SO) interneuron. 2. One type of modulatory function, "gating," requires that the CGCs fire tonically at a minimum of 7 spikes/min. Above this minimum level the CGCs control the frequency of CPG interneuron oscillation-- "frequency control," a second type of modulation. In an SO-driven fictive feeding rhythm, an increase in the frequency of the rhythm, with increased CGC firing rate, resulted from a reduction in the duration of the N1 (protraction) and N2 (rasp) phases of the feeding cycle with little effect on the N3 (swallow) phase. 3. The CGCs excited the N1 phase interneurons SO and N1M (N1 medial) cells but had no consistent effects on the N1 lateral cells. The CGC-->SO postsynaptic response was probably monosynaptic (< or = 200 ms in duration) with unitary 1:1 excitatory postsynaptic potentials (EPSPs) following each CGC spike. The CGC-->N1M excitatory response was slow and nonunitary, and a burst of CGC spikes evoked a depolarization of the N1M cells that lasted up to 10 s and triggered N1M cell bursts. Both CGC-->SO and CGC-->N1M excitatory responses could be mimicked by the focal application of serotonin (5-HT). 4. Both CGC-->SO and CGC-->N1M excitatory connections systematically increased the N1M cell firing rate within the CGCs' physiological firing range (0-40 spikes/min). This was due to both the direct (CGC-->N1M) and indirect (CGC-->SO-->N1M) excitatory synaptic pathways. The CGC-induced increase in N1M cell firing rate probably accounted for the reduced duration of the N1M cell feeding burst by causing a more rapid reversal of the feeding cycle from the N1 phase to the N2 phase. This phase reversal was due to the previously described recurrent inhibitory pathway (N1-->N2 excitation followed by N2-->N1 inhibition). 5. The CGCs' ability to provide a depolarizing drive to the N1M cells meant that this excitatory connection was also likely to be important for gating. 6. Activity in the CGCs produced nonunitary, long-lasting, excitatory postsynaptic responses on the N2 ventral (N2v) CPG interneurons, and these were likely to be involved in both the gating and the frequency control by the CGCs on the N2 phase of the feeding rhythm. Suppressing CGC tonic firing initially increased the duration of the N2v plateau (which determines the duration of the N2 phase of the feeding cycle, frequency function) but eventually led to a loss of N2v plateauing (gating function). 7. Nonunitary, weakly inhibitory CGC-->N2 dorsal responses were recorded that could be mimicked by the application of 5-HT. 8. Spikes in the CGCs evoked 1:1 monosynaptic EPSPs in the N3 tonic (N3t) CPG interneurons. This excitatory effect could be mimicked by the application of 5-HT. Within the physiological range of CGC firing, this excitation did not appear to influence the firing rate of the N3t cells. 9. N3 phasic (N3p) CPG interneurons showed biphasic (hyperpolarizing followed by depolarizing) unitary responses to spikes evoked in the CGCs. The inhibitory synaptic response was maintained in a high-Ca2+/high-Mg2+ (Hi-Di) saline and was mimicked by the focal application of 5-HT, indicating that it was probably monosynaptic. The excitatory component was, however, reduced in a Hi-Di saline, indicating that it was probably polysynaptic. Suppressing the CGCs during an SO-driven feeding rhythm caused the N3p cells to fire less, suggesting that the removal of the excitatory component of the response might be significant. 10. We conclude that the general depolarizing effects of the CGCs on a number of the CP


CSF complement 3 and factor H are staging biomarkers in Alzheimer's disease.
CSF levels of established Alzheimer's disease (AD) biomarkers remain stable despite disease progression, and non-amyloid non-tau biomarkers have the potential of informing disease stage and progression. We previously identified complement 3 (C3) to be decreased in AD dementia, but this change was not found by others in earlier AD stages. We hypothesized that levels of C3 and associated factor H (FH) can potentially distinguish between mild cognitive impairment (MCI) and dementia stages of AD, but we also found their levels to be influenced by age and disease status. We developed a biochemical/bioinformatics pipeline to optimize the handling of complex interactions between variables in validating biochemical markers of disease. We used data from the Alzheimer's Disease Neuro-imaging Initiative (ADNI, n = 230) to build parallel machine learning models, and objectively tested the models in a test cohort (n = 73) of MCI and mild AD patients independently recruited from Emory University. Whereas models incorporating age, gender, APOE ε4 status, and CSF amyloid and tau levels failed to reliably distinguish between MCI and mild AD in ADNI, introduction of CSF C3 and FH levels reproducibly improved the distinction between the two AD stages in ADNI (p < 0.05) and the Emory cohort (p = 0.014). Within each AD stage, the final model also distinguished between fast vs. slower decliners (p < 0.001 for MCI, p = 0.007 for mild AD), with lower C3 and FH levels associated with more advanced disease and faster progression. We propose that CSF C3 and FH alterations may reflect stage-associated biomarker changes in AD, and can complement clinician diagnosis in diagnosing and staging AD using the publically available ADNI database as reference.


Dietary quercetin, quercetin-gene interaction, metabolic gene expression in lung tissue and lung cancer risk.
Epidemiological and mechanistic evidence on the association of quercetin-rich food intake with lung cancer risk and carcinogenesis are inconclusive. We investigated the role of dietary quercetin and the interaction between quercetin and P450 and glutathione S-transferase (GST) polymorphisms on lung cancer risk in 1822 incident lung cancer cases and 1991 frequency-matched controls from the Environment And Genetics in Lung cancer Etiology study. In non-tumor lung tissue from 38 adenocarcinoma patients, we assessed the correlation between quercetin intake and messenger RNA expression of the same P450 and GST metabolic genes. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific quintiles of intake were calculated using unconditional logistic regression adjusting for putative risk factors. Frequent intake of quercetin-rich foods was inversely associated with lung cancer risk (OR = 0.49; 95% CI: 0.37-0.67; P-trend < 0.001) and did not differ by P450 or GST genotypes, gender or histological subtypes. The association was stronger in subjects who smoked >20 cigarettes per day (OR = 0.35; 95% CI: 0.19-0.66; P-trend = 0.003). Based on a two-sample t-test, we compared gene expression and high versus low consumption of quercetin-rich foods and observed an overall upregulation of GSTM1, GSTM2, GSTT2, and GSTP1 as well as a downregulation of specific P450 genes (P-values < 0.05, adjusted for age and smoking status). In conclusion, we observed an inverse association of quercetin-rich food with lung cancer risk and identified a possible mechanism of quercetin-related changes in the expression of genes involved in the metabolism of tobacco carcinogens in humans. Our findings suggest an interplay between quercetin intake, tobacco smoking, and lung cancer risk. Further research on this relationship is warranted.


Adrenergic differentiation and Ret expression in rat pheochromocytomas.
Pheochromocytomas are catecholamine-producing tumors of the adult adrenal medulla. They are rare in humans and most other species but common in laboratory rats. However, the relevance of rat pheochromocytomas as a model for their human counterparts is uncertain. Previous studies of spontaneous and drug-induced rat pheochromocytomas and the PC12 pheochromocytoma cell line suggested a distinctive noradrenergic phenotype, possibly reflecting origin from a progenitor not present in the adult human adrenal. In this study, we studied 31 pheochromocytomas derived from test and control male and female rats in toxicologic studies for expression of the epinephrine-synthesizing enzyme phenylethanolamine-N-methyltransferase (PNMT) and the receptor tyrosine kinase Ret. PNMT, which defines adrenergic chromaffin cells, is frequently expressed in human pheochromocytomas, often in tumors that also overexpress RET. We also tested for the expression of the cell cycle checkpoint protein p27(Kip1), which recently was reported absent in pheochromocytomas from a strain of rats with a hereditary mixed multiple endocrine neoplasia (MEN)-like syndrome. Using immunoblots, we demonstrated PNMT expression in almost 50% of the 31 tumors, although often at lower levels than in normal rat adrenal medulla. The majority of tumors overexpressed Ret. There was no apparent correlation between PNMT and Ret. However, in this study, PNMT expression was strongly associated with tumors arising in female rats, while overexpression of Ret did not show a sex predilection. Robust expression of p27(Kip1) was seen in all tumors from the toxicologic studies and also in a small sample of pheochromocytomas from Long-Evans rats, which were reported to have a mixed MEN-like syndrome in the 1980s. The present results show that rat pheochromocytomas have greater phenotypic diversity than previously believed and greater similarity to their human counterparts with respect to these two important markers. Loss of p27(Kip1) does not appear to account for the high frequency of pheochromocytomas in commonly utilized rat strains.


Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: a Canadian experience.
Congenital cystic adenomatoid malformation of the lung (CCAM) is diagnosed by prenatal ultrasonography with an increasing frequency but controversy persists as to its prognosis and prenatal management. A multi-institutional study of cases of CCAM diagnosed antenatally identified by ultrasonographers and by a review of hospital charts. We obtained 48 cases from five centers. We estimate the incidence of CCAM at 1:25,000 to 1:35,000 pregnancies. The incidence of voluntary abortions was 15% (7/48), of spontaneous abortions 2% (1/41) and of postnatal death 10% (4/40). One of the postnatal deaths was from trisomy 18. Of the 7 aborted fetuses, 2 had multiple malformations and 1 had severe hydrops and oligohydramnios; the other 4 had a large mass with mediastinal displacement but without hydrops. When pregnancy was allowed to continue, 56% of the lesions regressed spontaneously, even though one third of these had initial progression. In 17 cases (42%) the mediastinal shift corrected itself, sometimes by simple growth of the fetus but most often by a decrease in the size of the lung mass. In 1 fetus, repeated needle decompressions followed by double-pigtail catheter drainage of large cysts allowed regression of hydrops. Despite this, neonatal death occurred from pulmonary hypoplasia. CCAM can lead to fetal or neonatal demise from hydrops, lung hypoplasia, prematurity or severe associated malformations, but has a good prognosis in the majority of cases.


Identification of a mutant PfCRT-mediated chloroquine tolerance phenotype in Plasmodium falciparum.
Mutant forms of the Plasmodium falciparum transporter PfCRT constitute the key determinant of parasite resistance to chloroquine (CQ), the former first-line antimalarial, and are ubiquitous to infections that fail CQ treatment. However, treatment can often be successful in individuals harboring mutant pfcrt alleles, raising questions about the role of host immunity or pharmacokinetics vs. the parasite genetic background in contributing to treatment outcomes. To examine whether the parasite genetic background dictates the degree of mutant pfcrt-mediated CQ resistance, we replaced the wild type pfcrt allele in three CQ-sensitive strains with mutant pfcrt of the 7G8 allelic type prevalent in South America, the Oceanic region and India. Recombinant clones exhibited strain-dependent CQ responses that ranged from high-level resistance to an incremental shift that did not meet CQ resistance criteria. Nonetheless, even in the most susceptible clones, 7G8 mutant pfcrt enabled parasites to tolerate CQ pressure and recrudesce in vitro after treatment with high concentrations of CQ. 7G8 mutant pfcrt was found to significantly impact parasite responses to other antimalarials used in artemisinin-based combination therapies, in a strain-dependent manner. We also report clinical isolates from French Guiana that harbor mutant pfcrt, identical or related to the 7G8 haplotype, and manifest a CQ tolerance phenotype. One isolate, H209, harbored a novel PfCRT C350R mutation and demonstrated reduced quinine and artemisinin susceptibility. Our data: 1) suggest that high-level CQR is a complex biological process dependent on the presence of mutant pfcrt; 2) implicate a role for variant pfcrt alleles in modulating parasite susceptibility to other clinically important antimalarials; and 3) uncover the existence of a phenotype of CQ tolerance in some strains harboring mutant pfcrt.


Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients.
"T50," shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant. The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORIT) cohort is a completed, large, multiethnic controlled clinical trial cohort of chronic, stable kidney transplant recipients (KTRs). We conducted a longitudinal case-cohort analysis using a randomly selected subcohort of patients, and all individual cases who developed CVD. Serum T50 and fetuin-A were determined in this total of n = 685 FAVORIT trial participants at randomization. During a median surveillance of 2.18-years, 311 incident or recurrent CVD events occurred. Shorter T50 (minutes) or reduced fetuin-A concentrations (g/L) were associated with CVD after adjustment for treatment assignment, systolic blood pressure, age, sex, race, preexisting CVD and diabetes, smoking, body mass index, total cholesterol/HDL cholesterol, kidney allograft vintage and type, calcineurin inhibitor, or lipid-lowering drug use, estimated glomerular filtration rate, and urinary albumin/creatinine: tertile 1 (lowest) to tertile 3 (highest) comparisons, T50, (hazard ratio [HR] 1.86; 95% CI 1.20-2.89); fetuin-A, (HR 2.25; 95% CI 1.38-3.69). Elevated high sensitivity c-reactive protein (hsCRP) was an effect modifier of both these associations. Shortened T50, as well as reduced fetuin-A levels, ostensible promoters of vascular calcification, remained associated with greater risk for CVD outcomes, after adjustment for major CVD risk factors, measures of kidney function and damage, and KTR clinical characteristics and demographics, in a large, multiethnic cohort of long-term KTRs. Increased hsCRP was an effect modifier of these CVD risk associations.


Discriminability metric based on human contrast sensitivity.
We evaluated a metric for predicting the discriminability of different digitized versions of alphanumeric characters. The metric is based on the assumption that there exists a visual filter such that discriminability is monotonic with the contrast energy in the visually filtered difference between stimuli. To test this hypothesis, we presented two same or different digital versions of a master character and asked subjects to indicate whether the characters were the same or different in a forced-choice procedure with feedback. The filtered contrast energy difference was calculated by convolving the difference between stimulus pairs with filters derived from published human contrast sensitivity functions, following an initial nonlinear transformation of stimulus intensity, and summing the squared result. For some types of stimulus difference, such as contrast quantization errors and Gaussian blurring, performance on discrimination tasks is monotonically related to the contrast energy of the filtered difference vector. The results are consistent with the hypothesis that there exists a single psychometric function that can predict the discriminability of different digitized versions of characters when displayed on various devices.


Interdisciplinary expert consensus on management of type B intramural haematoma and penetrating aortic ulcer.
An expert panel on the treatment of type B intramural haematoma (IMH) and penetrating atherosclerotic ulcer (PAU) consisting of cardiologists, cardiothoracic surgeons, vascular surgeons and interventional radiologists reviewed the literature to develop treatment algorithms using a consensus method. Data from 46 studies considered relevant were retrieved for a total of 1386 patients consisting of 925 with IMH, and 461 with PAU. The weighted mean 30-day mortality from IMH was 3.9%, 3-year aortic event-related mortality with medical treatment 5.4%, open surgery 23.2% and endovascular therapy 7.1%. In patients with PAU early and 3-year aortic event-mortality rates with open surgery were 15.9 and 25.0%, respectively, and with TEVAR were 7.2 and 10.4%, respectively. According to panel consensus statements, haemodynamic instability, persistent pain, signs of impending rupture and progressive periaortic haemorrhage in two successive imaging studies require immediate surgical or endovascular treatment. In the absence of these complications, medical treatment is warranted, with imaging control at 7 days, 3 and 6 months and annually thereafter. In the chronic phase, aortic diameter >55 mm or a yearly increase ≥ 5 mm should be considered indications for open surgery or thoracic endovascular treatment, with the latter being preferred. In complicated type B aortic PAU and IMH, endovascular repair is the best treatment option in the presence of suitable anatomy.


Incorporating Voluntary Medical Male Circumcision Into Traditional Circumcision Contexts: Experiences of a Local Consortium in Zimbabwe Collaborating With an Ethnic Group.
Employing voluntary medical male circumcision (VMMC) within traditional settings may increase patient safety and help scale up male circumcision efforts in sub-Saharan Africa. In Zimbabwe, the VaRemba are among the few ethnic groups that practice traditional male circumcision, often in suboptimal hygienic environments. ZAZIC, a local consortium, and the Zimbabwe Ministry of Health and Child Care (MoHCC) established a successful, culturally sensitive partnership with the VaRemba to provide safe, standardized male circumcision procedures and reduce adverse events (AEs) during traditional male circumcision initiation camps. The foundation for the VaRemba Camp Collaborative (VCC) was established over a 4-year period, between 2013 and 2017, with support from a wide group of stakeholders. Initially, ZAZIC supported VaRemba traditional male circumcisions by providing key commodities and transport to help ensure patient safety. Subsequently, 2 male VaRemba nurses were trained in VMMC according to national MoHCC guidelines to enable medical male circumcision within the camp. To increase awareness and uptake of VMMC at the upcoming August-September 2017 camp, ZAZIC then worked closely with a trained team of circumcised VaRemba men to create demand for VMMC. Non-VaRemba ZAZIC doctors were granted permission by VaRemba leaders to provide oversight of VMMC procedures and postoperative treatment for all moderate and severe AEs within the camp setting. Of 672 male camp residents ages 10 and older, 657 (98%) chose VMMC. Only 3 (0.5%) moderate infections occurred among VMMC clients; all were promptly treated and healed well. Although the successful collaboration required many years of investment to build trust with community leaders and members, it ultimately resulted in a successful model that paired traditional circumcision practices with modern VMMC, suggesting potential for replicability in other similar sub-Saharan African communities.


Brownian dynamics simulations with hard-body interactions: spherical particles.
A novel approach to account for hard-body interactions in (overdamped) Brownian dynamics simulations is proposed for systems with non-vanishing force fields. The scheme exploits the analytically known transition probability for a Brownian particle on a one-dimensional half-line. The motion of a Brownian particle is decomposed into a component that is affected by hard-body interactions and into components that are unaffected. The hard-body interactions are incorporated by replacing the "affected" component of motion by the evolution on a half-line. It is discussed under which circumstances this approach is justified. In particular, the algorithm is developed and formulated for systems with space-fixed obstacles and for systems comprising spherical particles. The validity and justification of the algorithm is investigated numerically by looking at exemplary model systems of soft matter, namely at colloids in flow fields and at protein interactions. Furthermore, a thorough discussion of properties of other heuristic algorithms is carried out.


Audiovisual distraction reduces pain perception during shockwave lithotripsy.
Lithotripsy is an established method to fragment kidney stones that can be performed without general anesthesia in the outpatient setting. Discomfort and/or noise, however, may deter some patients. It has been demonstrated that audiovisual distraction (AV) can reduce sedoanalgesic requirements and improve patient satisfaction in nonurologic settings, but to our knowledge, this has not been investigated with lithotripsy. This randomized controlled trial was designed to test the hypothesis that AV distraction can reduce perceived pain during lithotripsy. All patients in the study received identical analgesia before a complete session of lithotripsy on a fixed-site Storz Modulith SLX F2 lithotripter. Patients were randomized to two groups: One group (n=61) received AV distraction via a wall-mounted 32″ (82 cm) television with wireless headphones; the other group (n=57) received no AV distraction. The mean intensity of treatment was comparable in both groups. Patients used a visual analogue scale (0-10) to record independent pain and distress scores and a nonverbal pain score was documented by the radiographer during the procedure (0-4). In the group that received AV distraction, all measures of pain perception were statistically lower. The patient-reported pain score was reduced from a mean of 6.1 to 2.4 (P<0.0001), and the distress score was reduced from a mean of 4.4 to 1.0 (P=0.0001). The mean nonverbal score recorded by the radiographer was reduced from 1.5 to 0.5 (<0.0001). AV distraction significantly lowered patients' reported pain and distress scores. This correlated with the nonverbal scores reported by the radiographer. We conclude that AV distraction is a simple method of improving acceptance of lithotripsy and optimizing treatment.


Reliable phase unwrapping algorithm based on rotational and direct compensators.
Phase unwrapping still plays an important role in many data-processing chains based on phase information. Here, we introduce a new phase unwrapping approach for noisy wrapped phase maps of continuous objects to improve the accuracy and computational time requirements of phase unwrapping using a rotational compensator (RC) method. The proposed algorithm is based on compensating the singularity of discontinuity sources. It uses direct compensation for adjoining singular point (SP) pairs and uses RC for other SP pairs. The performance of the proposed method is tested through both simulated and real wrapped phase data. The proposed algorithm is faster than the original algorithm with the RC and has proved efficiency compared to other phase unwrapping methods.


Specific residues of RUNX2 are obligatory for formation of BMP2-induced RUNX2-SMAD complex to promote osteoblast differentiation.
BMP2 signaling and RUNX2 regulatory pathways converge for transcriptional control of bone formation in vivo. SMAD proteins are recruited to RUNX2 regulatory complexes via an overlapping nuclear matrix targeting signal/Smad interacting domain sequence (391-432) in Runx2. To establish the contribution of RUNX2-SMAD interaction to osteoblastogenesis, we characterized a number of point mutants. Only a triple mutation of amino acids 426-428 (HTY-AAA) results in loss of RUNX2 interactions with either BMP2- or TGF-beta- responsive SMADs and fails to integrate the BMP2/TGF-beta signal on target gene promoters. In a Runx2 null cell reconstitution assay, the HTY mutant did not activate the program of osteoblast differentiation (alkaline phosphatase, collagen type 1, osteopontin, bone sialoprotein and osteocalcin) in response to BMP2 signaling. Thus, subnuclear targeting function and formation of a RUNX2-SMAD osteogenic complex are functionally inseparable. Taken together, these studies provide direct evidence that RUNX2 is essential for execution and completion of BMP2 signaling for osteoblast differentiation.


Syncrip/hnRNP Q is required for activity-induced Msp300/Nesprin-1 expression and new synapse formation.
Memory and learning involve activity-driven expression of proteins and cytoskeletal reorganization at new synapses, requiring posttranscriptional regulation of localized mRNA a long distance from corresponding nuclei. A key factor expressed early in synapse formation is Msp300/Nesprin-1, which organizes actin filaments around the new synapse. How Msp300 expression is regulated during synaptic plasticity is poorly understood. Here, we show that activity-dependent accumulation of Msp300 in the postsynaptic compartment of the Drosophila larval neuromuscular junction is regulated by the conserved RNA binding protein Syncrip/hnRNP Q. Syncrip (Syp) binds to msp300 transcripts and is essential for plasticity. Single-molecule imaging shows that msp300 is associated with Syp in vivo and forms ribosome-rich granules that contain the translation factor eIF4E. Elevated neural activity alters the dynamics of Syp and the number of msp300:Syp:eIF4E RNP granules at the synapse, suggesting that these particles facilitate translation. These results introduce Syp as an important early acting activity-dependent regulator of a plasticity gene that is strongly associated with human ataxias.


Divorce and women's risk of health insurance loss.
This article bridges the literatures on the economic consequences of divorce for women with that on marital transitions and health by focusing on women's health insurance. Using a monthly calendar of marital status and health insurance coverage from 1,442 women in the Survey of Income and Program Participation, we examine how women's health insurance changes after divorce. Our estimates suggest that roughly 115,000 American women lose private health insurance annually in the months following divorce and that roughly 65,000 of these women become uninsured. The loss of insurance coverage we observe is not just a short-term disruption. Women's rates of insurance coverage remain depressed for more than two years after divorce. Insurance loss may compound the economic losses women experience after divorce and contribute to as well as compound previously documented health declines following divorce.


Validation of a novel real-time PCR for detecting Rasamsonia argillacea species complex in respiratory secretions from cystic fibrosis patients.
Members of the recently introduced fungal genus Rasamsonia (formerly included in the Geosmithia genus) have been described as emerging pathogens in immunosuppressed hosts or patients with cystic fibrosis (CF). Rasamsonia species have often been misidentified as Penicillium or Paecilomyces because of similar morphological characteristics. We validated a commercially available real-time PCR assay (Primerdesign™, UK) for accurate detection of species from the Rasamsonia argillacea complex. First, we tested this assay with a collection of 74 reference strains and clinical isolates and then compared the PCR with cultures of 234 respiratory samples from 152 patients with CF from two University Hospitals in Germany and France. The assay reliably detected the three main species within the Rasamsonia argillacea species complex (R. argillacea, R. piperina, R. aegroticola), which are typically encountered in CF patients. The limit of DNA detection was between 0.01 and 1 pg/μL. Analysis of the DNA extracts from respiratory specimens of CF patients revealed that four out of the 153 patients studied (2.6%) were colonized with R. argillacea species complex. Two species from the R. argillacea complex grew in the parallel cultures from the same patients. In one patient the PCR was positive 5 months before culture. The real-time PCR assay is a sensitive and specific method for detecting the three most important species of the R. argillacea species complex encountered in the CF context. Detection of these emerging pathogens in respiratory secretions from CF patients by this novel assay may increase our understanding of the occurrence and epidemiology of the R. argillacea species complex.


PRIMROSE: a computer program for generating and estimating the phylogenetic range of 16S rRNA oligonucleotide probes and primers in conjunction with the RDP-II database.
We describe PRIMROSE, a computer program for identifying 16S rRNA probes and PCR primers for use as phylogenetic and ecological tools in the identification and enumeration of bacteria. PRIMROSE is designed to use data from the Ribosomal Database Project (RDP) to find potentially useful oligonucleotides with up to two degenerate positions. The taxonomic range of these, and other existing oligonucleotides, can then be explored, allowing for the rapid identification of suitable oligonucleotides. PRIMROSE includes features to allow user-defined sequence databases to be used. An in silico trial of the program using the RDP database identified oligonucleotides that described their target taxa with a degree of accuracy far greater than that of equivalent currently used oligonucleotides. We identify oligonucleotides for subdivisions of the Proteobacteria and for the Cytophaga-Flexibacter-Bacteroides (CFB) division. These oligonucleotides describe up to 94.7% of their target taxon with fewer than 50 non-target hits, and the authors recommend that they be investigated further. A comparison with PROBE DESIGN within the ARB software package shows that PRIMROSE is capable of identifying oligonucleotides with a higher specificity. PRIMROSE has an intuitive graphical user interface and runs on the Microsoft Windows 95/NT/2000 operating systems. It is open source and is freely available from the authors.


PUX10 Is a Lipid Droplet-Localized Scaffold Protein That Interacts with CELL DIVISION CYCLE48 and Is Involved in the Degradation of Lipid Droplet Proteins.
The number of known proteins associated with plant lipid droplets (LDs) is small compared with other organelles. Many aspects of LD biosynthesis and degradation are unknown, and identifying and characterizing candidate LD proteins could help elucidate these processes. Here, we analyzed the proteome of LD-enriched fractions isolated from tobacco (Nicotiana tabacum) pollen tubes. Proteins that were highly enriched in comparison with the total or cytosolic fraction were further tested for LD localization via transient expression in pollen tubes. One of these proteins, PLANT UBX DOMAIN-CONTAINING PROTEIN10 (PUX10), is a member of the plant UBX domain-containing (PUX) protein family. This protein localizes to LDs via a unique hydrophobic polypeptide sequence and can recruit the AAA-type ATPase CELL DIVISION CYCLE48 (CDC48) protein via its UBX domain. PUX10 is conserved in Arabidopsis thaliana and expressed in embryos, pollen tubes, and seedlings. In pux10 knockout mutants in Arabidopsis, LD size is significantly increased. Proteomic analysis of pux10 mutants revealed a delayed degradation of known LD proteins, some of which possessed ubiquitination sites. We propose that PUX10 is involved in a protein degradation pathway at LDs, mediating an interaction between polyubiquitinated proteins targeted for degradation and downstream effectors such as CDC48.


How does age affect baseline screening mammography performance measures? A decision model.
In order to promote consumer-oriented informed medical decision-making regarding screening mammography, we created a decision model to predict the age dependence of the cancer detection rate, the recall rate and the secondary performance measures (positive predictive values, total intervention rate, and positive biopsy fraction) for a baseline mammogram. We constructed a decision tree to model the possible outcomes of a baseline screening mammogram in women ages 35 to 65. We compared the single baseline screening mammogram decision with the no screening alternative. We used the Surveillance Epidemiology and End Results national cancer database as the primary input to estimate cancer prevalence. For other probabilities, the model used population-based estimates for screening mammography accuracy and diagnostic mammography outcomes specific to baseline exams. We varied radiologist performance for screening accuracy. The cancer detection rate increases from 1.9/1000 at age 40 to 7.2/1000 at age 50 to 15.1/1000 at age 60. The recall rate remains relatively stable at 142-157/1000, which varies from 73-236/1000 at age 50 depending on radiologist performance. The positive predictive value of a screening mammogram increases from 1.3% at age 40 to 9.8% at age 60, while the positive predictive value of a diagnostic mammogram varies from 2.9% at age 40 to 19.2% at age 60. The model predicts the total intervention rate = 0.013*AGE2 - 0.67*AGE + 40, or 34/1000 at age 40 to 47/1000 at age 60. Therefore, the positive biopsy (intervention) fraction varies from 6% at age 40 to 32% at age 60. Breast cancer prevalence, the cancer detection rate, and all secondary screening mammography performance measures increase substantially with age.


Natural history of cerebral arteriovenous malformations: a meta-analysis.
The purpose of this report was to provide overall arteriovenous malformation (AVM) hemorrhage rates and, with enhanced statistical power, to elucidate significant risk factors for hemorrhage. The authors performed a meta-analysis via the PubMed database through January 2012 using the terms "AVM," "arteriovenous malformation," "natural history," "bleed," and "hemorrhage." Additional studies were identified through reference searches in each reviewed article. English language studies providing annual hemorrhage rates for AVMs were included. Data extraction, performed independently by the authors, included demographic data, hemorrhage rates, and hazard ratios for hemorrhage risk factors. The analysis was performed using a random effects model. Nine natural history studies with 3923 patients and 18,423 patient-years of follow-up were identified for analysis. The overall annual hemorrhage rate was 3.0% (95% CI 2.7%-3.4%). The rate of hemorrhage was 2.2% (95% CI 1.7%-2.7%) for unruptured AVMs and 4.5% (95% CI 3.7%-5.5%) for ruptured AVMs. Prior hemorrhage (HR 3.2, 95% CI 2.1-4.3), deep AVM location (HR 2.4, 95% CI 1.4-3.4), exclusively deep venous drainage (HR 2.4, 95% CI 1.1-3.8), and associated aneurysms (HR 1.8, 95% CI 1.6-2.0) were statistically significant risk factors for hemorrhage. Any deep venous drainage (HR 1.3, 95% CI 0.9-1.75) and female sex (HR 1.4, 95% CI 0.6-2.1) demonstrated a trend toward an increased risk of hemorrhage that was not statistically significant. Small AVM size and older patient age were not significant risk factors for hemorrhage. Arteriovenous malformations with prior hemorrhage, deep location, exclusively deep venous drainage, and associated aneurysms have greater annual hemorrhage rates than their counterparts, influencing surgical decision making and the selection of radiosurgery for these lesions.


Targeting of the Fun30 nucleosome remodeller by the Dpb11 scaffold facilitates cell cycle-regulated DNA end resection.
DNA double strand breaks (DSBs) can be repaired by either recombination-based or direct ligation-based mechanisms. Pathway choice is made at the level of DNA end resection, a nucleolytic processing step, which primes DSBs for repair by recombination. Resection is thus under cell cycle control, but additionally regulated by chromatin and nucleosome remodellers. Here, we show that both layers of control converge in the regulation of resection by the evolutionarily conserved Fun30/SMARCAD1 remodeller. Budding yeast Fun30 and human SMARCAD1 are cell cycle-regulated by interaction with the DSB-localized scaffold protein Dpb11/TOPBP1, respectively. In yeast, this protein assembly additionally comprises the 9-1-1 damage sensor, is involved in localizing Fun30 to damaged chromatin, and thus is required for efficient long-range resection of DSBs. Notably, artificial targeting of Fun30 to DSBs is sufficient to bypass the cell cycle regulation of long-range resection, indicating that chromatin remodelling during resection is underlying DSB repair pathway choice.


Poleward microtubule flux mitotic spindles assembled in vitro.
In the preceding paper we described pathways of mitotic spindle assembly in cell-free extracts prepared from eggs of Xenopus laevis. Here we demonstrate the poleward flux of microtubules in spindles assembled in vitro, using a photoactivatable fluorescein covalently coupled to tubulin and multi-channel fluorescence videomicroscopy. After local photoactivation of fluorescence by UV microbeam, we observed poleward movement of fluorescein-marked microtubules at a rate of 3 microns/min, similar to rates of chromosome movement and spindle elongation during prometaphase and anaphase. This movement could be blocked by the addition of millimolar AMP-PNP but was not affected by concentrations of vanadate up to 150 microM, suggesting that poleward flux may be driven by a microtubule motor similar to kinesin. In contrast to previous results obtained in vivo (Mitchison, T. J. 1989. J. Cell Biol. 109:637-652), poleward flux in vitro appears to occur independently of kinetochores or kinetochore microtubules, and therefore may be a general property of relatively stable microtubules within the spindle. We find that microtubules moving towards poles are dynamic structures, and we have estimated the average half-life of fluxing microtubules in vitro to be between approximately 75 and 100 s. We discuss these results with regard to the function of poleward flux in spindle movements in anaphase and prometaphase.


Evaluation of hepatoprotective activity of Cissus quadrangularis stem extract against isoniazid-induced liver damage in rats.
The study was designed to investigate the hepatoprotective activity of methanol extract of Cissus quadrangularis (CQ) against isoniazid-induced hepatotoxicity in rats. The successive petroleum ether (60-80°C) and methanol extracts of C. quadrangularis were used. Hepatic damage was induced in Wistar rats by administering isoniazid (54 mg/kg, p.o.) once daily for 30 days. Simultaneously, CQ (500 mg/kg p.o) was administered 1 h prior to the administration of isoniazid (54 mg/kg, p.o.) once daily for 30 days. Silymarin (50 mg/kg p.o) was used as a reference drug. Elevated levels of aspartate transaminase, alanine transaminase, alkaline posphatase, and bilirubin following isoniazid administration were significantly lowered due to pretreatment with CQ. Isoniazid administration significantly increased lipid peroxidation (LPO) and decreased antioxidant activities such as reduced glutathione, superoxide dismutase, and catalase. Pretreatment of rats with CQ significantly decreased LPO and increased the antioxidant activities. The results of this study indicated that the hepatoprotective effect of CQ might be attributed to its antioxidant property.


Adverse events in cardiovascular-related training programs in people with spinal cord injury: a systematic review.
There are anecdotal reports of adverse events (AEs) associated with exercise in people with spinal cord injury (SCI) and consequent concern by people with SCI and their providers about potential risks of exercise. Enumeration of specific events has never been performed and the extent of risk of exercise to people with SCI is not understood. To systematically review published evidence to identify and enumerate reports of adverse events or AEs associated with training in persons with SCI. Review was limited to peer-reviewed studies published in English from 1970 to 2011: (1) in adults with SCI, (2) evaluating training protocols consisting of repeated sessions over at least 4 weeks to maintain or improve cardiovascular health, (3) including volitional exercise modalities and functional electrical stimulation (FES)-enhanced exercise modalities, and (4) including a specific statement about AEs. Trained reviewers initially identified a total of 145 studies. After further screening, 38 studies were included in the review. Quality of evidence was evaluated using established procedures. There were no serious AEs reported. There were no common AEs reported across most types of interventions, except for musculoskeletal AEs related to FES walking. There were few AEs in volitional exercise studies. There is no evidence to suggest that cardiovascular exercise done according to guidelines and established safety precautions is harmful. To improve the strength of these conclusions, future publications should include definition of AEs, information about pre-intervention screening, and statements of the nature and extent of AEs.


Radiological emergency preparedness: a survey of nuclear medicine technologists in the United States.
Because of the increasing risk of radiological emergencies, public health agencies and first-response organizations are working to increase their capability of responding. Nuclear medicine technologists (NMTs) have expertise in certain areas, such as radiation safety, radiobiology, decontamination, and the use of radiation detection and monitoring equipment, that could be useful during the response to events that involve radiological materials. To better understand the potential role that NMTs may have in response efforts, a cross-sectional survey was conducted. The survey was sent electronically to the 7,000 members of the Technology Section of the Society of Nuclear Medicine and Molecular Imaging. Eight hundred fifty NMTs responded to the survey, for a response rate of 12.14%. The study queried NMTs across the United States on their knowledge of using radiation detection and monitoring equipment, such as a scintillation γ-cameras, Geiger counters, thyroid probes, well counters, and portal monitors; willingness to participate in response efforts during a nuclear reactor accident, nuclear weapon detonation, or dirty bomb detonation; access to radiation detection and monitoring equipment within their work setting; familiarity with current preparedness guidance and tools provided by the Centers for Disease Control and Prevention and U.S. Department of Health and Human Services; and registration in volunteer initiatives such as the Emergency System for Advance Registration of Volunteer Health Professionals, Metropolitan Medical Response System, and Medical Reserve Corps. Survey results suggest that NMTs are knowledgeable and willing to respond to radiological emergencies, regardless of number of years of work experience. Radiological preparedness training within the last 5 y significantly increases NMTs' willingness to respond and familiarity with current guidance and tools provided by the Centers for Disease Control and Prevention and Department of Health and Human Services. Respondents reported a low participation level in volunteer programs, and most agreed that continuing education should include radiological emergency preparedness. NMTs should be considered an untapped resource and should be strategically recruited for involvement in radiological emergency preparedness planning and training. NMTs should also consider becoming involved in local volunteer initiatives because they have the knowledge and willingness to provide assistance during a radiological emergency.


Aedesin: structure and antimicrobial activity against multidrug resistant bacterial strains.
Multidrug resistance, which is acquired by both Gram-positive and Gram-negative bacteria, causes infections that are associated with significant morbidity and mortality in many clinical settings around the world. Because of the rapidly increasing incidence of pathogens that have become resistant to all or nearly all available antibiotics, there is a need for a new generation of antimicrobials with a broad therapeutic range for specific applications against infections. Aedesin is a cecropin-like anti-microbial peptide that was recently isolated from dengue virus-infected salivary glands of the Aedes aegypti mosquito. In the present study, we have refined the analysis of its structural characteristics and have determined its antimicrobial effects against a large panel of multidrug resistant bacterial strains, directly isolated from infected patients. Based the results from nuclear magnetic resonance spectroscopy analysis, Aedesin has a helix-bend-helix structure typical for a member of the family of α-helix anti-microbial peptides. Aedesin efficiently killed Gram-negative bacterial strains that display the most worrisome resistance mechanisms encountered in the clinic, including resistance to carbapenems, aminoglycosides, cephalosporins, 4th generation fluoroquinolones, folate inhibitors and monobactams. In contrast, Gram-positive strains were insensitive to the lytic effects of the peptide. The anti-bacterial activity of Aedesin was found to be salt-resistant, indicating that it is active under physiological conditions encountered in body fluids characterized by ionic salt concentrations. In conclusion, because of its strong lytic activity against multidrug resistant Gram-negative bacterial strains displaying all types of clinically relevant resistance mechanisms known today, Aedesin might be an interesting candidate for the development of alternative treatment for infections caused by these types of bacteria.


Genome-Wide Analysis Reveals Ancestral Lack of Seventeen Different tRNAs and Clade-Specific Loss of tRNA-CNNs in Archaea.
Transfer RNA (tRNA) is a category of RNAs that specifically decode messenger RNAs (mRNAs) into proteins by recognizing a set of 61 codons commonly adopted by different life domains. The composition and abundance of tRNAs play critical roles in shaping codon usage and pairing bias, which subsequently modulate mRNA translation efficiency and accuracy. Over the past few decades, effort has been concentrated on evaluating the specificity and redundancy of different tRNA families. However, the mechanism and processes underlying tRNA evolution have only rarely been investigated. In this study, by surveying tRNA genes in 167 completely sequenced genomes, we systematically investigated the composition and evolution of tRNAs in Archaea from a phylogenetic perspective. Our data revealed that archaeal genomes are compact in both tRNA types and copy number. Generally, no more than 44 different types of tRNA are present in archaeal genomes to decode the 61 canonical codons, and most of them have only one gene copy per genome. Among them, tRNA-Met was significantly overrepresented, with an average of three copies per genome. In contrast, the tRNA-UAU and 16 tRNAs with A-starting anticodons (tRNA-ANNs) were rarely detected in all archaeal genomes. The conspicuous absence of these tRNAs across the archaeal phylogeny suggests they might have not been evolved in the common ancestor of Archaea, rather than have lost independently from different clades. Furthermore, widespread absence of tRNA-CNNs in the Methanococcales and Methanobacteriales genomes indicates convergent loss of these tRNAs in the two clades. This clade-specific tRNA loss may be attributing to the reductive evolution of their genomes. Our data suggest that the current tRNA profiles in Archaea are contributed not only by the ancestral tRNA composition, but also by differential maintenance and loss of redundant tRNAs.


Prevalence of chronic pain after traumatic brain injury: a systematic review.
The Centers for Disease Control and Prevention estimates that approximately 1.4 million US individuals sustain traumatic brain injuries (TBIs) per year. Previous reports suggest an association between TBI and chronic pain syndromes (eg, headache) thought to be more common in patients with mild TBI and in those who have sustained brain injury from violent rather than unintentional trauma. Comorbid psychiatric disorders such as posttraumatic stress disorder (PTSD) may also mediate chronic pain symptoms. To determine the prevalence of chronic pain as an underdiagnosed consequence of TBI and to review the interaction between chronic pain and severity of TBI as well as the characteristics of pain after TBI among civilians and combatants. The Ovid/MEDLINE database was searched for articles published between 1951 and February 2008 using any combination of the terms brain injury, pain, headache, blast injury, and combat (combat disorders, war, military medicine, wounds and injuries, military personnel, veterans). The PubMed and MD Consult databases were searched in a similar fashion. The Cochrane Collaboration, National Institutes of Health Clinical Trials Database, Meta-Register of Current Controlled Trials, and CRISP databases were searched using the keyword brain injury. All articles in peer-reviewed journals reporting original data on pain syndromes in adult patients with TBI with regard to pain prevalence, pain category, risk factors, pathogenesis, and clinical course were selected, and manual searches were performed of their reference lists. The data were pooled and prevalence rates calculated. Twenty-three studies (15 cross-sectional, 5 prospective, and 3 retrospective) including 4206 patients were identified. Twelve studies assessed headache pain in 1670 patients. Of these, 966 complained of chronic headache, yielding a prevalence of 57.8% (95% confidence interval [CI], 55.5%-60.2%). Among civilians, the prevalence of chronic pain was greater in patients with mild TBI (75.3% [95% CI, 72.7%-77.9%]) compared with moderate or severe TBI (32.1% [95% CI, 29.3%-34.9%]). Twenty studies including 3289 civilian patients with TBI yielded a chronic pain prevalence of 51.5% (95% CI, 49.8%-53.2%). Three studies assessed TBI among 917 veterans and yielded a pain prevalence of 43.1% (95% CI, 39.9%-46.3%). PTSD may mediate chronic pain, but brain injury appears to have an independent correlation with chronic pain. Chronic pain is a common complication of TBI. It is independent of psychologic disorders such as PTSD and depression and is common even among patients with apparently minor injuries to the brain.


Structure of HIV-1 reverse transcriptase with the inhibitor beta-Thujaplicinol bound at the RNase H active site.
Novel inhibitors are needed to counteract the rapid emergence of drug-resistant HIV variants. HIV-1 reverse transcriptase (RT) has both DNA polymerase and RNase H (RNH) enzymatic activities, but approved drugs that inhibit RT target the polymerase. Inhibitors that act against new targets, such as RNH, should be effective against all of the current drug-resistant variants. Here, we present 2.80 A and 2.04 A resolution crystal structures of an RNH inhibitor, beta-thujaplicinol, bound at the RNH active site of both HIV-1 RT and an isolated RNH domain. beta-thujaplicinol chelates two divalent metal ions at the RNH active site. We provide biochemical evidence that beta-thujaplicinol is a slow-binding RNH inhibitor with noncompetitive kinetics and suggest that it forms a tropylium ion that interacts favorably with RT and the RNA:DNA substrate.


Female gender, estrogen loss, and Sub-RPE deposit formation in aged mice.
Estrogen status influences the incidence and severity of many diseases in women. Because women with early menopause appear at risk for worse ARMD, estrogen deficiency may also contribute to the onset or severity of ARMD in women. It has been observed that aged male C57BL/6 mice fed a high-fat diet and briefly exposed to blue-green light exhibit development of significant sub-RPE deposits and mild Bruch's membrane (BrM) thickening. This model was used in an attempt to delineate the role of gender and estrogen status in this model. C57BL/6 male and female mice of 9 or 16 months were fed a high-fat diet for 4.5 months. Several groups of 9-month-old female mice underwent estrogen depletion by ovariectomy, with or without supplementation with exogenous 17beta-estradiol. After 4 weeks of a high-fat diet, the eyes were exposed to seven 5-second doses of nonphototoxic levels of blue-green light over 2 weeks. Three and a half months after cessation of blue light treatment, transmission electron microscopy was performed to assess severity of deposits, BrM changes, and choriocapillaris endothelial morphology. In some mice, gelatin zymography and Western blot analyses were performed on protein extracts of freshly isolated RPE to determine the effect of estrogen on matrix metalloproteinase (MMP)-2 activity in the RPE. Both male and female 16-month-old mice showed qualitatively similar basal laminar deposit morphology, but the severity of thickness, continuity, and content was significantly greater in female mice. Aged female mice also demonstrated a trend toward more severe endothelial changes and increased BrM thickening compared with age-matched male mice. Ovariectomized middle-aged mice showed more severe deposits than sham-surgery control animals. However, ovariectomized mice that received high-dose estrogen supplementation also showed significant deposits, although they had thinner BrMs than did the estrogen-deficient mice. Loss of RPE MMP-2 activity correlated with deposit severity, with estrogen-deficient mice expressing less MMP-2 than ovary-intact control mice. Female gender in aged mice and estrogen deficiency in middle-aged mice appears to increase the severity of sub-RPE deposit formation. Estrogen deficiency may increase susceptibility to formation of sub-RPE deposits by dysregulating turnover of BrM, contributing to collagenous thickening and endothelial changes. Estrogen supplementation at the dosages used in this study does not appear to protect against formation of sub-RPE deposits.