Isolated Posterior Inferior Cerebellar Artery Dissection as a Cause of Ischemic Stroke: Clinical Features and Prognosis.
The purpose of this study was to clarify the incidence, clinical and radiological features and outcomes of isolated posterior inferior cerebellar artery (PICA) dissection in isolated PICA territory infarctions. We retrospectively reviewed consecutive inpatients with ischemic stroke secondary to isolated PICA dissection from our stroke database between January 2004 and December 2013 and reviewed the literature with regard to those patients. Of 167 consecutive patients with an isolated PICA territory infarction, a total of 10 patients (6.0%, 3 women, 48.1 ± 7.1 years) were diagnosed as having an isolated PICA dissection. Patients with PICA dissection were younger (p < 0.001), more commonly experienced headache at onset (p = 0.008), less commonly had hyperlipidemia (p = 0.044) and showed a lower modified Rankin Scale score at discharge (p = 0.002) when compared with patients without arterial dissection. In 6 of these 10 patients, PICA dissections had not been suspected on initial magnetic resonance angiography (MRA) and were confirmed by follow-up MRA or digital subtraction angiography. In the follow-up period (median 1.5 years, interquartile range 0.5-6.3 years), there were no recurrent ischemic or hemorrhagic stroke events. Isolated PICA dissection as an etiological mechanism in isolated PICA territory infarctions may be more common than was previously recognized to be. The diagnosis of PICA dissection is often difficult and requires close and repeated morphological evaluation. We should carefully identify PICA dissections as a possible cause of PICA territory infarctions.


Detection and sequence analysis of equine gammaherpesviruses from horses with respiratory tract disease in Turkey.
The equid herpesvirus 2 (EHV-2) and 5 (EHV-5), identified agents of respiratory infections and keratoconjunctivitis cases in some equids, comprise a high degree of antigenic heterogeneity. Prevalence and genetic characterization of EHV-2 and EHV-5 strains from Turkey were investigated in this study. A total of 73 nasal swabs and 54 blood specimens were sampled from horses with respiratory tract diseases characterized by mucopurulent nasal discharge and occasional coughing. Overall, EHV-2- and EHV-5-specific DNA amplicons were obtained from 19.2% (14/73) and 21.9% (16/73) of horses tested by multiplex nested PCR. Sequences of EHV-2 and EHV-5 glycoprotein B (gB) gene were used in a phylogenetic analysis that included six EHV-2 and three EHV-5 isolates, which showed that the Turkish EHV-2 and EHV-5 strains have marked sequence divergence from European strains and from each other. Turkish EHV-2 isolates were divided into two distinct subdivisions, and a few isolates were located on a separate branch. This study provides the first epidemiological and phylogenetical report about EHV-2 and EHV-5 infections in Turkey.


PEEK versus titanium cages in lateral lumbar interbody fusion: a comparative analysis of subsidence.
The authors have provided a review of radiographic subsidence after lateral lumbar interbody fusion (LLIF) as a comparative analysis between titanium and polyetheretherketone (PEEK) cages. Many authors describe a reluctance to use titanium cages in spinal fusion secondary to subsidence concerns due to the increased modulus of elasticity of metal cages. The authors intend for this report to provide observational data regarding the juxtaposition of these two materials in the LLIF domain. A retrospective review of a prospectively maintained database identified 113 consecutive patients undergoing lateral fusion for degenerative indications from January to December 2017. The surgeons performing the cage implantations were two orthopedic spine surgeons and two neurosurgeons. Plain standing radiographs were obtained at 1-2 weeks, 8-12 weeks, and 12 months postoperatively. Using a validated grading system, interbody subsidence into the endplates was graded at these time points on a scale of 0 to III. The primary outcome measure was subsidence between the two groups. Secondary outcomes were analyzed as well. Of the 113 patients in the sample, groups receiving PEEK and titanium implants were closely matched at 57 and 56 patients, respectively. Cumulatively, 156 cages were inserted and recombinant human bone morphogenetic protein-2 (rhBMP-2) was used in 38.1%. The average patient age was 60.4 years and average follow-up was 75.1 weeks. Subsidence in the titanium group in this study was less common than in the PEEK cage group. At early follow-up, groups had similar subsidence outcomes. Statistical significance was reached at the 8- to 12-week and 52-week follow-ups, demonstrating more subsidence in the PEEK cage group than the titanium cage group. rhBMP-2 usage was also highly correlated with higher subsidence rates at all 3 follow-up time points. Age was correlated with higher subsidence rates in univariate and multivariate analysis. Titanium cages were associated with lower subsidence rates than PEEK cages in this investigation. Usage of rhBMP-2 was also robustly associated with higher endplate subsidence. Each additional year of age correlated with an increased subsidence risk. Subsidence in LLIF is likely a response to a myriad of factors that include but are certainly not limited to cage material. Hence, the avoidance of titanium interbody implants secondary solely to concerns over a modulus of elasticity likely overlooks other variables of equal or greater importance.


In vivo single-molecule imaging identifies altered dynamics of calcium channels in dystrophin-mutant C. elegans.
Single-molecule (SM) fluorescence microscopy allows the imaging of biomolecules in cultured cells with a precision of a few nanometres but has yet to be implemented in living adult animals. Here we used split-GFP (green fluorescent protein) fusions and complementation-activated light microscopy (CALM) for subresolution imaging of individual membrane proteins in live Caenorhabditis elegans (C. elegans). In vivo tissue-specific SM tracking of transmembrane CD4 and voltage-dependent Ca(2+) channels (VDCC) was achieved with a precision of 30 nm within neuromuscular synapses and at the surface of muscle cells in normal and dystrophin-mutant worms. Through diffusion analyses, we reveal that dystrophin is involved in modulating the confinement of VDCC within sarcolemmal membrane nanodomains in response to varying tonus of C. elegans body-wall muscles. CALM expands the applications of SM imaging techniques beyond the petri dish and opens the possibility to explore the molecular basis of homeostatic and pathological cellular processes with subresolution precision, directly in live animals.


The diurnal variation of bone formation is attenuated in adult patients with type 2 diabetes.
Bone turnover has a diurnal variation influenced by food intake, incretin hormones, the sympathetic nervous system and osteocyte function. The aim of the study was to compare diurnal variation in bone turnover in patients with diabetes and controls. A clinical 24-h study with patients with type 1 diabetes (n = 5), patients with type 2 diabetes (n = 5) and controls (n = 5). Inclusion criterion: age >50 years. Exclusion criteria: diseases/medication that affect bone metabolism or recent use of incretin-based drugs. We drew blood samples hourly during the day and every 3 h during the night. We served an identical diet on all study days. We used repeated-measures one-way ANOVA to compare the levels of the investigated markers, and we quantified the effect of time by comparing group mean standard deviations. The bone formation marker procollagen type 1 N-terminal propeptide showed a significant interaction between time and group (P = 0.01), and the mean standard deviation was lower in patients with type 2 diabetes compared with controls (P = 0.04) and patients with type 1 diabetes (P = 0.02). Other markers of bone formation and resorption showed significant effect of time. Levels of glucagon-like peptide-2, glucose-dependent insulinotropic peptide and sclerostin only showed significant effect of time (all P values 0.01), but levels of sclerostin tended to being highest in type 2 diabetes and lowest in controls. The diurnal variation in bone formation is attenuated in patients with type 2 diabetes. This is not explained by changes in incretin hormone levels, but possibly mediated by sclerostin.


Direct observation of nanoparticle-cancer cell nucleus interactions.
We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype via nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultrafast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy.


Translational inhibition by microRNAs in plants.
MicroRNAs (miRNAs) are 21-24 nucleotide riboregulators, which selectively repress gene expression through transcript cleavage and/or translational inhibition. It was thought that most plant miRNAs act through target transcript cleavage due to the high degree of complementarity between miRNAs and their targets. However, recent studies have suggested widespread translational inhibition by miRNAs in plants. The mechanisms underlining translational inhibition by plant miRNAs are largely unknown, but existing evidence has indicated that plants and animals share some mechanistic similarity of translational inhibition. Translational inhibition by miRNAs has been shown to regulate floral patterning, floral timing, and stress responses. This chapter covers recent progress on plant miRNA-mediated translational control.


Pulmonary Artery Intimal Sarcoma versus Pulmonary Artery Thromboembolism: CT and Clinical Findings.
To describe CT and clinical findings of pulmonary artery intimal sarcoma (PAIS) compared with those of pulmonary thromboembolism (PTE), to investigate MRI and positron emission tomography (PET)-CT findings of PAIS, and to evaluate the effect of delayed diagnosis of PAIS on survival outcomes. Twenty-six patients with PAIS were retrospectively identified and matched for sex, with patients with PTE at a ratio of 1:2. CT and clinical findings of the two groups were compared using Student's t test or chi-square test. The effect of delayed diagnosis on survival was investigated using Kaplan-Meier analysis. The most common tumor pattern in PAIS was tumoral impaction. Heterogeneous attenuation, wall eclipse signs, intratumoral vessels, acute interphase angles, single location, presence of lung ischemia, and central location were significantly more common in PAIS than in PTE (all p < 0.01). Levels of D-dimers and brain natriuretic peptide were lower in PAIS than in PTE (p < 0.05). In three patients of PAIS, long inversion time sequence MRI showed intermingled dark signal intensity foci suggestive of intermingled thrombi. All nine patients who had undergone PET-CT displayed hypermetabolism. Diagnosis was delayed in 42.3% of the PAIS patients and those patients had a significantly shorter overall survival than patients whose diagnosis was not delayed (p < 0.05). The characteristic CT and clinical findings of PAIS may help achieve early diagnosis of PAIS and make better survival outcomes of patients. MRI and PET-CT can be used as second-line imaging modalities and could help distinguish PAIS from PTE and to plan clinical management.


Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition.
Experimental evidence suggests that the maintenance of an item in working memory is achieved through persistent activity in selective neural assemblies of the cortex. To understand the mechanisms underlying this phenomenon, it is essential to investigate how persistent activity is affected by external inputs or neuromodulation. We have addressed these questions using a recurrent network model of object working memory. Recurrence is dominated by inhibition, although persistent activity is generated through recurrent excitation in small subsets of excitatory neurons. Our main findings are as follows. (1) Because of the strong feedback inhibition, persistent activity shows an inverted U shape as a function of increased external drive to the network. (2) A transient external excitation can switch off a network from a selective persistent state to its spontaneous state. (3) The maintenance of the sample stimulus in working memory is not affected by intervening stimuli (distractors) during the delay period, provided the stimulation intensity is not large. On the other hand, if stimulation intensity is large enough, distractors disrupt sample-related persistent activity, and the network is able to maintain a memory only of the last shown stimulus. (4) A concerted modulation of GABA(A) and NMDA conductances leads to a decrease of spontaneous activity but an increase of persistent activity; the enhanced signal-to-noise ratio is shown to increase the resistance of the network to distractors. (5) Two mechanisms are identified that produce an inverted U shaped dependence of persistent activity on modulation. The present study therefore points to several mechanisms that enhance the signal-to-noise ratio in working memory states. These mechanisms could be implemented in the prefrontal cortex by dopaminergic projections from the midbrain.


Relative volume of the cerebellum in dolphins and comparison with anthropoid primates.
According to the 'developmental constraint hypothesis' of comparative mammalian neuroanatomy, brain growth follows predictable allometric trends. Therefore, brain structures should scale to the entire brain in the same way across mammals. Evidence for a departure from this pattern for cerebellum volume has recently been reported among the anthropoid primates. One of the mammalian groups that has been neglected in tests of the 'developmental constraint hypothesis' is the cetaceans (dolphins, whales, and porpoises). Because many cetaceans possess relative brain sizes in the range of primates comparative tests of the 'developmental constraint hypothesis' across these two groups could help to delineate the parameters of this hypothesis. In this paper, we compare relative cerebellum volumes in two cetacean species, the bottlenose dolphin (Tursiops truncatus) and the common dolphin (Delphinus delphis), with published data from anthropoid primates. We found that relative cerebellum size is significantly greater in the two dolphin species than in any of the primates, including humans. These results suggest that there is possibly expansion of brain structures independent of strictly allometric processes.


Rapid intramolecular hole hopping in meso-meso and meta-phenylene linked linear and cyclic multiporphyrin arrays.
A series of zinc porphyrin arrays comprised of a meso-meso linked porphyrin dimer, a meta-phenylene linked dimer, gable-like tetramers consisting of the meso-meso linked dimers bridged via a meta-phenylene linker, and a dodecameric ring composed of this alternating dimeric pattern were singly oxidized, and intramolecular hole hopping between the porphyrin moieties was probed using electron paramagnetic resonance (EPR) spectroscopy. Electron nuclear double resonance (ENDOR) spectroscopy was also used to probe hole hopping within the dimers. Rapid hole hopping occurs between both porphyrins within both dimers and among three porphyrins of the tetramers with rates >10(7) s(-1) at 290 K. Additionally, the hole hops among 8-12 porphyrins in the dodecameric ring with a rate that is >10(7) s(-1) at 290 K, but hopping is slow at 180 K. These results show that hole hopping is rapid even though the meta-phenyl bridges and direct meso-meso linkages do not provide optimal electronic coupling between the porphyrins within these multiporphyrin arrays. This greatly expands the scope of possible structures that can be employed to tailor the design of long distance charge transport systems.


Glutamine uptake by neurons: interaction of protons with system a transporters.
Astrocytes provide the glutamine required by neurons to synthesize glutamate and GABA. However, the mechanisms involved in glutamine transfer from glia to neurons have remained poorly understood. Recent work has implicated the System N transporter SN1 in the efflux of glutamine from astrocytes and the very closely related System A transporters SA1 and SA2 in glutamine uptake by neurons. To understand how these closely related proteins mediate flux in different directions, we have examined their ionic coupling. In contrast to the electroneutral exchange of H+ for Na+ and neutral amino acid catalyzed by SN1, we now show that SA1 and SA2 do not couple H+ movement to amino acid flux. As a result, SA1 and SA2 are electrogenic and do not mediate flux reversal as readily as SN1. Differences between System N and A transporters in coupling to H+ thus contribute to the delivery of glutamine from glia to neurons. Nonetheless, although they are not transported, H+ inhibit SA1 and SA2 by competing with Na+.


[Muscular sarcosporidiosis: report of a case].
A case of sarcosporidiosis in a 29 year-old woman is presented. The clinical picture showed a definitive myopathic pattern with symmetrical proximal weakness of shoulder and pelvic girdle and also weakness on neck flexors; the facial muscles were intact and she denied dysphagia. The histological findings after a muscle biopsy obtained from left deltoid muscle showed many round cysts within the muscle fibres without any surrounding inflammatory reaction. The cysts diameters varied from 30 to 500 micra and the length from 300 micra to 3 millimeter (Miescher's tube). The radially striated membrane could be seen in some cysts but there was some doubt because it could represent the remaining of the peripheral muscle fibre. We could not find spores inside the cysts. Besides the largest cysts there were muscle fibre hypertrophy. The authors concluded on the diagnosis of sarcosporidiosis because of the presence, diameter and length of cysts; some remarks are made on the only other parasite that could be confused with Sarcocystis sp: Toxoplasma gondii.


Sec72p contributes to the selective recognition of signal peptides by the secretory polypeptide translocation complex.
SEC72 encodes the 23-kD subunit of the Sec63p complex, an integral ER membrane protein complex that is required for translocation of presecretory proteins into the ER of Saccharomyces cerevisiae. DNA sequence analysis of SEC72 predicts a 21.6-kD protein with neither a signal peptide nor any transmembrane domains. Antibodies directed against a carboxyl-terminal peptide of Sec72p were used to confirm the membrane location of the protein. SEC72 is not essential for yeast cell growth, although an sec72 null mutant accumulates a subset of secretory precursors in vivo. Experiments using signal peptide chimeric proteins demonstrate that the sec72 translocation defect is associated with the signal peptide rather than with the mature region of the secretory precursor.


Investigating Thematic Roles through Implicit Learning: Evidence from Light Verb Constructions.
The syntactic structure of a sentence is usually a strong predictor of its meaning: Each argument noun phrase (i.e., Subject and Object) should map onto exactly one thematic role (i.e., Agent and Patient, respectively). Some constructions, however, are exceptions to this pattern. This paper investigates how the syntactic structure of an utterance contributes to its construal, using ditransitive English light verb constructions, such as "Nils gave a hug to his brother," as an example of such mismatches: Hugging is a two-role event, but the ditransitive syntactic structure suggests a three-role event. Data from an eye-tracking experiment and behavioral categorization data reveal that listeners learn to categorize sentences according to the number of thematic roles they convey, independent of their syntax. Light verb constructions, however, seem to form a category of their own, in which the syntactic structure leads listeners down an initial incorrect assignment of thematic roles, from which they only partly recover. These results suggest an automatic influence of syntactic argument structure on semantic interpretation and event construal, even in highly frequent constructions.


SUMO mediates interaction of Ebp2p, the yeast homolog of Epstein-Barr virus nuclear antigen 1-binding protein 2, with a RING finger protein Ris1p.
Ebp2p is essential for the assembly of 60S ribosomal subunits, and it interacts with other ribosome assembly factors in Saccharomyces cerevisiae. Two-hybrid screening exhibited that Ebp2p interacted with a small ubiquitin-related modifier (SUMO)-ligase Siz2p and SUMO-related proteins, Ris1p and Wss1p. Mutations of SUMO attachment sites of Ebp2p led to significantly weak interactions with Siz2p, Wss1p, and Ris1p, whereas they exhibited positive interactions with ribosome assembly factors. A SUMO-binding motif of Ris1p was required for interaction with Ebp2p. These results suggest that SUMO mediates the interaction between Ebp2p and SUMO related proteins and that Ebp2p switches its interaction partners via sumoylation.


Polychlorinated biphenyls (PCBs) as sentinels for the elucidation of Arctic environmental change processes: a comprehensive review combined with ArcRisk project results.
Polychlorinated biphenyls (PCBs) can be used as chemical sentinels for the assessment of anthropogenic influences on Arctic environmental change. We present an overview of studies on PCBs in the Arctic and combine these with the findings from ArcRisk-a major European Union-funded project aimed at examining the effects of climate change on the transport of contaminants to and their behaviour of in the Arctic-to provide a case study on the behaviour and impact of PCBs over time in the Arctic. PCBs in the Arctic have shown declining trends in the environment over the last few decades. Atmospheric long-range transport from secondary and primary sources is the major input of PCBs to the Arctic region. Modelling of the atmospheric PCB composition and behaviour showed some increases in environmental concentrations in a warmer Arctic, but the general decline in PCB levels is still the most prominent feature. 'Within-Arctic' processing of PCBs will be affected by climate change-related processes such as changing wet deposition. These in turn will influence biological exposure and uptake of PCBs. The pan-Arctic rivers draining large Arctic/sub-Arctic catchments provide a significant source of PCBs to the Arctic Ocean, although changes in hydrology/sediment transport combined with a changing marine environment remain areas of uncertainty with regard to PCB fate. Indirect effects of climate change on human exposure, such as a changing diet will influence and possibly reduce PCB exposure for indigenous peoples. Body burdens of PCBs have declined since the 1980s and are predicted to decline further.


Xinfangfangia soli gen. nov., sp. nov., isolated from a diuron-polluted soil.
A novel Gram-staining-negative, non-motile and rod-shaped bacterial strain ZQBWT, which was isolated from a diuron-polluted soil collected near Nanjing, PR China, was investigated for its taxonomic position by a polyphasic approach. ZQBWT grew well at pH 6.0-12.0 (optimum, pH 7.0), 26-35 °C (optimum, 30 °C) and up to 0.5 % NaCl (optimally the absence of NaCl) in R2A broth. The major fatty acids of ZQBWT were C18 : 1ω7c (82.7 %) and C18 : 0 (5.3 %). The polar lipid profile included the major compounds phophatidylcholine, phosphatidylglycerol and phosphatidylmethylethanolamine. The only respiratory quinone was ubiquinone Q-10. The G+C content of genomic DNA was 67.0 mol%. Comparisons with 16S rRNA gene sequences revealed that ZQBWT has the highest sequence similarities with members of the genus Tabrizicola (≤95.97 %), followed by Rhodobacter(≤95.96 %) and Falsirhodobacter(95.95 %) which all belong to the family Rhodobacteraceaein the phylum Proteobacteria. Photosynthesis genes pufLM were not found and photosynthesis pigments were not formed in ZQBWT. On the basis of the results from chemotaxonomic, phenotypic and phylogenetic analysis, ZQBWT represents a novel species of a novel genus, for which the name Xinfangfangia soli gen. nov., sp. nov. is proposed. The type strain is ZQBWT (=KCTC 62102T=CCTCC AB 2017177T).


Therapy-related acute myeloid leukemia and myelodysplastic syndrome after hematopoietic cell transplantation for lymphoma.
Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, P<0.001). Significant risk factors for the development of t-AML/MDS after autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.


Everyday worry in adolescents with and without chronic pain: a diary study.
Young people report frequent worry, but we know little about the extent, character, or consequence of worry in adolescence, or individual differences associated with worry. Adolescents with chronic pain are one population that are known to have high levels of anxiety, which is associated with higher levels of disability and depression, impairing function. In this study we report a diary study: adolescents (N = 60; aged 16-18) recorded their worry over seven days. Our first aim was to describe the characteristics of adolescent worry and its consequences in a community sample. Our second aim was to compare the experience of girls to boys, and to compare the experience of those with and without chronic pain. Adolescents reported characteristics of each worry they had throughout the week, including content, frequency, strength, interference, emotion, and the strength of emotion associated with worry content. Adolescents reported the consequence for each content and the strength of the consequence. Worry content and consequences were categorised into four categories; health, relationship, personal competence, and other. Adolescents reported 675 unique episodes of worry over the seven-day period that were predominantly about personal competence. The strength of worry content was (M = 6.61, SD = 1.27) and the strength associated with the worry consequence was (M = 5.59, SD = 1.41). Worries were not reported as highly interfering (M = 4.14, SD = 1.61). Contrary to predictions, there were no differences in worry characteristics between adolescents with and without chronic pain. To conclude, worry is a frequent occurrence in older adolescents and the characteristics of worry are discussed. Adolescents worry mostly about personal competence. Adolescents with and without chronic pain reported similar worry characteristics.


Novel glaucoma procedures: a report by the American Academy of Ophthalmology.
To review the published literature and summarize clinically relevant information about novel, or emerging, surgical techniques for the treatment of open-angle glaucoma and to describe the devices and procedures in proper context of the appropriate patient population, theoretic effects, advantages, and disadvantages. Devices and procedures that have US Food and Drug Administration clearance or are currently in phase III clinical trials in the United States are included: the Fugo blade (Medisurg Ltd., Norristown, PA), Ex-PRESS mini glaucoma shunt (Alcon, Inc., Hunenberg, Switzerland), SOLX Gold Shunt (SOLX Ltd., Boston, MA), excimer laser trabeculotomy (AIDA, Glautec AG, Nurnberg, Germany), canaloplasty (iScience Interventional Corp., Menlo Park, CA), trabeculotomy by internal approach (Trabectome, NeoMedix, Inc., Tustin, CA), and trabecular micro-bypass stent (iStent, Glaukos Corporation, Laguna Hills, CA). Literature searches of the PubMed and the Cochrane Library databases were conducted up to October 2009 with no date or language restrictions. These searches retrieved 192 citations, of which 23 were deemed topically relevant and rated for quality of evidence by the panel methodologist. All studies but one, which was rated as level II evidence, were rated as level III evidence. All of the devices studied showed a statistically significant reduction in intraocular pressure and, in some cases, glaucoma medication use. The success and failure definitions varied among studies, as did the calculated rates. Various types and rates of complications were reported depending on the surgical technique. On the basis of the review of the literature and mechanism of action, the authors also summarized theoretic advantages and disadvantages of each surgery. The novel glaucoma surgeries studied all show some promise as alternative treatments to lower intraocular pressure in the treatment of open-angle glaucoma. It is not possible to conclude whether these novel procedures are superior, equal to, or inferior to surgery such as trabeculectomy or to one another. The studies provide the basis for future comparative or randomized trials of existing glaucoma surgical techniques and other novel procedures.


Ureteric stents: investigating flow and encrustation.
Blockages of the ureter, e.g. due to calculi (kidney stones), can result in an increase in renal pelvic pressure. This may be relieved by inserting a stent (essentially a permeable hollow tube). However, a number of complications are associated with stent use. Stents can result in reflux (backflow of urine along the ureter), which will promote recurrent urinary infection and possible renal parenchymal damage. Furthermore, long-term stent use is associated with infection and precipitation of salts from the urine, which can lead to a build-up of crystalline deposits on the stent surface, making stent removal difficult and painful. This paper examines factors governing urine flow in a stented ureter, the implications for reflux, and the processes by which the stent surface encrusts, in particular focusing on the influence of bacterial infection. An interdisciplinary approach is adopted, involving a combination of theoretical investigations and novel experiments.


Solid-state 23Na NMR study of sodium lariat ether receptors exhibiting cation-pi interactions.
Noncovalent cation-pi interactions are important in a variety of supramolecular and biochemical systems. We present a 23Na solid-state nuclear magnetic resonance (SSNMR) study of two sodium lariat ether complexes, 1 and 2, in which a sodium cation interacts with an indolyl group that models the side chain of tryptophan. Sodium-23 SSNMR spectra of magic-angle spinning (MAS) and stationary powdered samples have been acquired at three magnetic field strengths (9.4, 11.75, 21.1 T) and analyzed to provide key information on the sodium electric field gradient and chemical shift (CS) tensors which are representative of the cation-pi binding environment. Triple-quantum MAS NMR spectra acquired at 21.1 T clearly reveal two crystallographically distinct sites in both 1 and 2. The quadrupolar coupling constants, CQ(23Na), range from 2.92 +/- 0.05 MHz for site A of 1 to 3.33 +/- 0.05 MHz for site B of 2; these values are somewhat larger than those reported previously by Wong et al. (Wong, A.; Whitehead, R. D.; Gan, Z.; Wu, G. J. Phys. Chem. A 2004, 108, 10551) for NaBPh4, but very similar to the values obtained for sodium metallocenes by Willans and Schurko (Willans, M. J.; Schurko, R. W. J. Phys. Chem. B 2003, 107, 5144). We conclude from the 21.1 T data that the spans of the sodium CS tensors are less than 20 ppm for 1 and 2 and that the largest components of the EFG and CS tensors are non-coincident. Quantum chemical calculations of the NMR parameters substantiate the experimental findings and provide additional insight into the dependence of CQ(23Na) on the proximity of the indole ring to Na+. Taken together, this work has provided novel information on the NMR interaction tensors characteristic of a sodium cation interacting with a biologically important arene.


Onset patterns prior to 36 months in autism spectrum disorders.
The present study investigated differences among children with three different patterns of autism symptom onset: regression, plateau, and no loss and no plateau. Cross-sectional data were collected from parents of children aged 3-17 years with an autism spectrum disorder (n = 2,720) who were recruited through a US-based online research database. Parental report of developmental characteristics was assessed through a parent questionnaire, and current autism symptoms were measured via the Social Responsiveness Scale and Social Communication Questionnaire. Multivariate analyses indicated that children with regression had a distinct developmental pattern marked by less delayed early development. However, following regression, these children evinced elevated autism symptom scores and an increased risk for poorer outcomes when compared with the other onset groups.


Changes in pain intensity after discontinuation of long-term opioid therapy for chronic noncancer pain.
Little is known about changes in pain intensity that may occur after discontinuation of long-term opioid therapy (LTOT). The objective of this study was to characterize pain intensity after opioid discontinuation over 12 months. This retrospective U.S. Department of Veterans Affairs (VA) administrative data study identified N = 551 patients nationally who discontinued LTOT. Data over 24 months (12 months before and after discontinuation) were abstracted from VA administrative records. Random-effects regression analyses examined changes in 0 to 10 pain numeric rating scale scores over time, whereas growth mixture models delineated pain trajectory subgroups. Mean estimated pain at the time of opioid discontinuation was 4.9. Changes in pain after discontinuation were characterized by slight but statistically nonsignificant declines in pain intensity over 12 months after discontinuation (B = -0.20, P = 0.14). Follow-up growth mixture models identified 4 pain trajectory classes characterized by the following postdiscontinuation pain levels: no pain (average pain at discontinuation = 0.37), mild clinically significant pain (average pain = 3.90), moderate clinically significant pain (average pain = 6.33), and severe clinically significant pain (average pain = 8.23). Similar to the overall sample, pain trajectories in each of the 4 classes were characterized by slight reductions in pain over time, with patients in the mild and moderate pain trajectory categories experiencing the greatest pain reductions after discontinuation (B = -0.11, P = 0.05 and B = -0.11, P = 0.04, respectively). Pain intensity after discontinuation of LTOT does not, on average, worsen for patients and may slightly improve, particularly for patients with mild-to-moderate pain at the time of discontinuation. Clinicians should consider these findings when discussing risks of opioid therapy and potential benefits of opioid taper with patients.


G-quadruplex-binding benzo[a]phenoxazines down-regulate c-KIT expression in human gastric carcinoma cells.
There is considerable interest in the structure and function of G-quadruplex nucleic acid secondary structures, their cellular functions, and their potential as therapeutic targets. G-Quadruplex sequence motifs are prevalent in gene promoter regions and it has been hypothesized that G-quadruplex structure formation is associated with the transcriptional status of the downstream gene. Using a functional cell-based assay, we have identified two novel G-quadruplex ligands that reduce the transcription of a luciferase reporter driven from the G-quadruplex-containing c-KIT promoter. We have further shown that endogenous c-KIT expression in a human gastric carcinoma cell line is also reduced on treatment with these molecules. Biophysical analysis using surface plasmon resonance has shown that these molecules preferentially bind with high affinity to one of the two G-quadruplex sequences in the c-KIT promoter over double-stranded DNA. This work highlights the utility of cell-based reporter assays to identify new G-quadruplex binding molecules that modulate transcription and identifies benzo[a]phenoxazine derivatives as potential antitumor agents.


Identification of proteins and protein domains that contact DNA within adenovirus nucleoprotein cores by ultraviolet light crosslinking of oligonucleotides 32P-labelled in vivo.
A new approach to the identification of DNA binding proteins has been developed and used to study the DNA-protein interactions within the nucleoprotein core of subgroup C adenoviruses. Virions labelled in vivo with [32P]orthophosphate were exposed to ultraviolet light and the DNA digested by chemical or enzymatic methods. Labelled phosphoamino acids of the virion phosphoproteins were selectively hydrolysed by alkali, permitting proteins crosslinked to DNA to be identified by virtue of their covalently attached, 32P-labelled nucleotides. In parallel experiments, [3H]arginine-labelled virions were crosslinked by exposure to ultraviolet light and analysed by more conventional methods. The results indicate that proteins VII and V lie in close contact with viral DNA within the core. The compact arrangement of the nucleoprotein core appears to be capable of trapping protein VII molecules that are not covalently attached to DNA after exposure to ultraviolet light, suggesting that viral DNA might be wrapped around clusters of protein VII molecules. The domains of protein VII that lie in contact with DNA were identified by partial proteolytic mapping of the sites of covalent-attachment of the 32P-labelled oligonucleotides. The implications of these data for the nature of the interactions that mediate the packaging of viral DNA within the nucleoprotein core of adenovirions are discussed.


The psychological development of children from Belarus exposed in the prenatal period to radiation from the Chernobyl atomic power plant.
This study examined psychological development in 138 children at the age of 6-7 and 10-11 years, who had suffered prenatal radiation exposure at the time of the Chernobyl accident in 1986. These children were compared to a control group of 122 children of the same age from noncontaminated areas of Belarus. The examination included neurological and psychiatric examination, intellectual assessment, and clinical psychological investigation of parents as well as the estimation of thyroid exposure in utero. The exposed group manifested a relative increase in psychological impairment compared with the control group, with increased prevalence in cases of specific developmental speech-language disorders (18.1% vs. 8.2% at 6-7 years; 10.1% vs. 3.3% at 10-11 years) and emotional disorders (20.3% vs. 7.4% at 6-7 years; 18.1 vs. 7.4% at 10-11 years). The mean IQ of the exposed group was lower than that of the control group, and there were more cases of borderline IQ (IQ = 70-79) (15.9% vs. 5.7% at 6-7 years; and 10.1% vs. 3.3% at 10-11 years). The mean value of thyroid doses from 131I 0.4 Gy was estimated for children exposed in utero. No correlation was found between individual thyroid doses and IQ at age 6-7 years or 10-11 years. We notice a positive moderate correlation between IQ of children and the educational level of their parents. There was a moderate correlation between high personal anxiety in parents and emotional disorders in children. We conclude that a significant role in the genesis of borderline intellectual functioning, specific developmental disorders of speech, language and scholastic skills, as well as emotional disorders in the exposed group of children was played by unfavourable social-psychological and social-cultural factors such as a low educational level of parents, the break of microsocial contacts, and adaptational difficulties, which appear following the evacuation and relocation from the contaminated areas.


Prosocial Behavior and Subjective Insecurity in Violent Contexts: Field Experiments.
Subjective insecurity is a key determinant of different forms of prosocial behavior. In Study 1, we used field experiments with farmers in Colombian villages exposed to different levels of violence to investigate how individual perceptions of insecurity affect cooperation, trust, reciprocity and altruism. To do so, we developed a cognitive-affective measure of subjective insecurity. We found that subjective insecurity has a negative effect on cooperation but influences trust and altruism positively. In Study 2, carried out three years after Study 1, we repeated the initial design with additional measures of victimization. Our goal was to relate subjective insecurity with actual victimization. The findings of Study 2 support the initial results, and are robust and consistent for cooperative behavior and trust when including victimization as a mediator. Different indicators of victimization are positively correlated with subjective insecurity and an aggregate index of victimization has a negative direct effect on cooperation and trust.


Krill oil, vitamin D and Lactobacillus reuteri cooperate to reduce gut inflammation.
Current research into original therapies to treat intestinal inflammation is focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to assess in vitro and in vivo the potential cooperative effects of KLD in reducing gut inflammation. Colorectal adenocarcinoma cell lines, CACO2 and HT29, and C57BL/6 mice were used for in vitro and in vivo analyses, respectively. Cells were exposed to cytomix (interferon gamma + tumour necrosis factor alpha (TNF-α)) to induce inflammation or co-exposed to cytomix and KO, LR and VitD3 alone or to cytomix and KLD. Animals were treated for 7 days with dextran sodium sulphate (DSS) to induce colitis or with DSS and KLD. In vitro assays: F-actin expression was analysed by immunofluorescence; scratch test and trans-epithelial electric resistance test were performed to measure wound healing; adhesion/invasion assays of adhesive and invasive Escherichia coli (AIEC) bacteria were made; mRNA expression of TNF-α, interleukin (IL)-8 and vitamin D receptor (VDR) was detected by quantitative PCR. In vivo assays: body weight, clinical score, histological score and large intestine weight and length were estimated; mRNA expression of TNF-α, IL-1β, IL-6, IL-10 by quantitative PCR; VDR expression was detected by quantitative PCR and immunohistochemistry. In vitro: KLD restores epithelial cell-cell adhesion and mucosal healing during inflammation, while decreases the adhesiveness and invasiveness of AIEC bacteria and TNF-α and IL-8 mRNA expression and increases VDR expression. In vivo: KLD significantly improves body weight, clinical score, histological score and large intestine length of mice with DSS-induced colitis and reduces TNF-α, IL-1β and IL-6 mRNA levels, while increases IL-10 mRNA and VDR levels. KLD has significant effects on the intestinal mucosa, strongly decreasing inflammation, increasing epithelial restitution and reducing pathogenicity of harmful commensal bacteria.


Genetic variability of the common Snook Centropomus undecimalis (Perciformes: Centropomidae) in connected marine and riverine environments.
The Common Snook, Centropomus undecimalis, inhabits riverine and marine areas of Southern Gulf of Mexico, where it is subject to intense use and exploitation. It has been reported that the genetic identification of fish stocks constitutes a valuable tool for wild population management; nevertheless, there is no available information on the genetic identification on fish stocks of this species in the region. The aim of this study was to determine the genetic relationship between C. undecimalis captured in marine and freshwater environments of the Gulf of Mexico and the San Pedro River. For this, muscle tissue samples of 79 specimens were obtained from areas located more than 300km apart. The genotype of each individual was determined using seven microsatellite primer pairs. Five primers amplified efficiently presenting between six and 28 alleles per locus. High levels of heterozygosis were observed in samples from both environments. Deviation from HWE due to an excess of heterozygotes was observed. The values of genetic difference indicate an absence of population structure (F(ST) = 0.0075 and R(ST) = (0.016, p = 0.051) and similarity in the allele frequencies, defined by Nei's index (0.805). Data showed the existence of a high gene flow due to the number of migrants (Nm = 18.7). Our results suggest that individuals living in these environments belong to the same genetic population. We suggest the development of management and protection plans for this fish species population in the wild.


Metabolic adaptation in Cryptococcus neoformans during early murine pulmonary infection.
The pathogenic fungus Cryptococcus neoformans generally initiates infection in mammalian lung tissue and subsequently disseminates to the brain. We performed serial analysis of gene expression (SAGE) on C. neoformans cells recovered from the lungs of mice and found elevated expression of genes for central carbon metabolism including functions for acetyl-CoA production and utilization. Deletion of the highly expressed ACS1 gene encoding acetyl-CoA synthetase revealed a requirement for growth on acetate and for full virulence. Transcripts for transporters (e.g. for monosaccharides, iron, copper and acetate) and for stress-response proteins were also elevated thus indicating a nutrient-limited and hostile host environment. The pattern of regulation was reminiscent of the control of alternative carbon source utilization and stress response by the Snf1 protein kinase in Saccharomyces cerevisiae. A snf1 mutant of C. neoformans showed defects in alternative carbon source utilization, the response to nitrosative stress, melanin production and virulence. However, loss of Snf1 did not influence the expression of a set of genes for carbon metabolism that were elevated upon lung infection. Taken together, the results reveal specific metabolic adaptations of C. neoformans during pulmonary infection and indicate a role for ACS1 and SNF1 in virulence.


Is there Still a Place for Vacuum Extraction (Ventouse) in Modern Obstetric Practice in Nigeria.
There has been a decline in operative vaginal delivery world-wide. Vacuum extraction has largely replaced forceps delivery in our low resource setting and in the developed countries, but the teaching and exposure of this procedure is still on the decline. There is a need for enhanced teaching and exposure of operative vaginal delivery and mastering of the procedure in our centers by the residents in training. Review of the pertinent literature and studies on operative vaginal delivery, selected references, internet services on operative vaginal delivery. Earlier studies on operative vaginal delivery showed that vacuum extraction has been the procedure of choice. The rates reported from developed countries were much higher than the rates reported from Nigeria. Vacuum extraction rates of 1.5% from Zaria, 1.7% from Maiduguri, 1.6% from Ilorin and 3.5% from Benin City all in Nigeria. At the University of Nigeria Teaching Hospital, Enugu-Nigeria, ventouse is popular with rates of 3.1% in 1980, 3.5% in 2001, and 1.5% in 2006, but still on the decline. Vacuum extraction is safe and effective practice in our poor resource setting. There is a need for enhanced teaching and exposure of residents in training because widely divergent situation can exist; facilities and adequate back up for caesarean section may not always be available in our poor resource setting.


Evidence of an emerging digital divide among hospitals that care for the poor.
Some hospitals that disproportionately care for poor patients are falling behind in adopting electronic health records (EHRs). Data from a national survey indicate early evidence of an emerging digital divide: U.S. hospitals that provide care to large numbers of poor patients also had minimal use of EHRs. These same hospitals lagged others in quality performance as well, but those with EHR systems seemed to have eliminated the quality gap. These findings suggest that adopting EHRs should be a major policy goal of health reform measures targeting hospitals that serve large populations of poor patients.


Direct visual internal urethrotomy: Is it a durable treatment option?
To evaluate the long-term success rate of direct vision internal urethrotomy as a treatment for anterior urethral strictures. We retrospectively analyzed the results for patients who underwent internal urethrotomy from January 2009 to January 2014 for anterior urethral strictures. Patients were followed till January 2016. Patients with complicated urethral strictures with a history of previous urethroplasty, hypospadias repair, or previous radiation were excluded from the study, as anticipated low success rate of direct visual internal urethrotomy (DVIU) in these patients. The Kaplan-Meier method was used to analyze stricture-free probability after the first, second, and third urethrotomy. A total of 186 patients were included in this study. Stricture-free rates after first, second, and third urethrotomy were 29.66%, 22.64%, and 13.33%, respectively. Although DVIU may be a management option for anterior urethral stricture disease, it seems that long-term results are disappointing.


The relationship between cyberloafing levels and social media addiction among nursing students.
The study was conducted to examine the relationship between cyberloafing levels and social media addiction among nursing students in different cities (Erzurum, Istanbul, and Van) in Turkey. This study was comparative and descriptive in design, and the sample included 518 nursing students. The average Cyberloafing Scale (CLS) total score of the students was 87.71 ± 18.55, while the average Social Media Addiction Scale (SMAS) total score was 71.30 ± 19.85. A positive and moderately significant relationship was found between the CLS and SMAS scores (p < 0.01). The cyberloafing and social media addiction levels of nursing students were found to be high. It was also found that the cyberloafing levels of the students increased as their social media addiction levels increased.


Indirect Effects of Japanese Barberry Infestations on White-Footed Mice Exposure to Borrelia burgdorferi.
Japanese barberry (Berberis thunbergii de Candolle; Ranunculales: Berberidaceae) is an exotic shrub that has invaded woodland understories in the northeastern United States. It forms dense thickets providing ideal structure and microclimate for questing blacklegged ticks (Ixodes scapularis Say; Acari: Ixodidae). While there have been studies on the favorable habitat barberry provides blacklegged ticks, little has been studied on the relationship between barberry, vectors (ticks), and reservoirs (white-footed mice; Peromyscus leucopus Rafinesque; Rodentia: Cricetidae); specifically, the influence Japanese barberry has on the abundance of blacklegged ticks and Borrelia burgdorferi infection (Johnson, Schmid, Hyde, Steigerwalt, and Brenner; Spirochaetales: Spirochaetaceae) in mice. We studied the impacts of barberry treatment over the course of 6 yr to determine influence on encounter abundance with white-footed mice, encounter abundance with B. burgdorferi-infected mice, and juvenile blacklegged ticks parasitizing mice. Results from our study suggest that while both white-footed mouse and B. burgdorferi-infected mouse encounters remained similar between barberry treatment areas, juvenile tick attachment to mice was significantly greater in intact barberry stands (X¯ = 4.4 ticks per mouse ± 0.23 SEM) compared with managed (X¯ = 2.8 ± 0.17; P < 0.001) or absent (X¯ = 2.2 ± 0.16; P < 0.001) stands. Results of this study indicated that management of barberry stands reduced contact opportunities between blacklegged ticks and white-footed mice. Continued efforts to manage Japanese barberry will not only allow for reestablishment of native plant species, but will also reduce the number of B. burgdorferi-infected blacklegged ticks on the landscape.


Synthesis of bright red-emissive dicyanoetheno-bridged hexa-peri-hexabenzocoronene dimers.
The introduction of a dicyanomethyl anion group to hexa-peri-hexabenzocoronene (HBC) substantially enhanced the emission properties of HBC due to a large perturbation of its electronic structure. In addition, dicyanoetheno-bridged HBC dimers obtained from oxidation of a dicyanomethyl HBC anion exhibited bright red emission in solution and solid states. Intramolecular charge transfer interactions between the HBC units and the dicyanoethene bridge induced solvatochromic behaviour in their emission spectra. Dicyanoetheno-bridged HBC dimers exhibited cis-trans photoisomerization behaviour in the solution, affording the mixture in cis-isomer dominance in the photostationary state. Theoretical calculations revealed that the cis-isomer is more thermodynamically stable than the trans-isomer.


Shape saliency modulates contextual processing in the human lateral occipital complex.
Visual context influences our perception of target objects in natural scenes. However, little is known about the analysis of context information and its role in shape perception in the human brain. We investigated whether the human lateral occipital complex (LOC), known to be involved in the visual analysis of shapes, also processes information about the context of shapes within cluttered scenes. We employed an fMRI adaptation paradigm in which fMRI responses are lower for two identical than for two different stimuli presented consecutively. The stimuli consisted of closed target contours defined by aligned Gabor elements embedded in a background of randomly oriented Gabors. We measured fMRI adaptation in the LOC across changes in the context of the target shapes by manipulating the position and orientation of the background elements. No adaptation was observed across context changes when the background elements were presented in the same plane as the target elements. However, adaptation was observed when the grouping of the target elements was enhanced in a bottom-up (i.e., grouping by disparity or motion) or top-down (i.e., shape priming) manner and thus the saliency of the target shape increased. These findings suggest that the LOC processes information not only about shapes, but also about their context. This processing of context information in the LOC is modulated by figure-ground segmentation and grouping processes. That is, neural populations in the LOC encode context information when relevant to the perception of target shapes, but represent salient targets independent of context changes.


Delivery of focused short pulses through a multimode fiber.
Light propagation through multimode fibers suffers from spatial distortions that lead to a scrambled intensity profile. In previous work, the correction of such distortions using various wavefront control methods has been demonstrated in the continuous wave case. However, in the ultra-fast pulse regime, modal dispersion temporally broadens a pulse after propagation. Here, we present a method that compensates for spatial distortions and mitigates temporal broadening due to modal dispersion by a selective phase conjugation process in which only modes of similar group velocities are excited. The selectively excited modes are forced to follow certain paths through the multimode fiber and interfere constructively at the distal tip to form a focused spot with minimal temporal broadening. We demonstrate the delivery of focused 500 fs pulses through a 30 cm long step-index multimode fiber. The achieved pulse duration corresponds to approximately 1/30th of the duration obtained if modal dispersion was not controlled. Moreover, we measured a detailed two-dimensional map of the pulse duration at the output of the fiber and confirmed that the focused spot produces a two-photon absorption effect. This work opens new possibilities for ultra-thin multiphoton imaging through multimode fibers.


Second generation registry framework.
Information management systems are essential to capture data be it for public health and human disease, sustainable agriculture, or plant and animal biosecurity. In public health, the term patient registry is often used to describe information management systems that are used to record and track phenotypic data of patients. Appropriate design, implementation and deployment of patient registries enables rapid decision making and ongoing data mining ultimately leading to improved patient outcomes. A major bottleneck encountered is the static nature of these registries. That is, software developers are required to work with stakeholders to determine requirements, design the system, implement the required data fields and functionality for each patient registry. Additionally, software developer time is required for ongoing maintenance and customisation. It is desirable to deploy a sophisticated registry framework that can allow scientists and registry curators possessing standard computing skills to dynamically construct a complete patient registry from scratch and customise it for their specific needs with little or no need to engage a software developer at any stage. This paper introduces our second generation open source registry framework which builds on our previous rare disease registry framework (RDRF). This second generation RDRF is a new approach as it empowers registry administrators to construct one or more patient registries without software developer effort. New data elements for a diverse range of phenotypic and genotypic measurements can be defined at any time. Defined data elements can then be utilised in any of the created registries. Fine grained, multi-level user and workgroup access can be applied to each data element to ensure appropriate access and data privacy. We introduce the concept of derived data elements to assist the data element standards communities on how they might be best categorised. We introduce the second generation RDRF that enables the user-driven dynamic creation of patient registries. We believe this second generation RDRF is a novel approach to patient registry design, implementation and deployment and a significant advance on existing registry systems.


Persistence of social jetlag and sleep disruption in healthy young adults.
Sleep disruption has been associated with increased risks for several major chronic diseases that develop over decades. Differences in sleep/wake timing between work and free days can result in the development of social jetlag (SJL), a chronic misalignment between a person's preferred sleep/wake schedule and sleep/wake timing imposed by his/her work schedule. Only a few studies have examined the persistence of SJL or sleep disruption over time. This prospective investigation examined SJL and sleep characteristics over a 2-year period to evaluate whether SJL or poor sleep were chronic conditions during the study period. SJL and sleep measures (total sleep time [TST], sleep onset latency [SOL], wake after sleep onset [WASO]), and sleep efficiency [SE]), were derived from armband monitoring among 390 healthy men and women 21-35 years old. Participants wore the armband for periods of 4-10 days at 6-month intervals during the follow-up period (N = 1431 repeated observations). The consistency of SJL or sleep disruption over time was analyzed using generalized linear mixed models (GLMMs) for repeated measures. Repeated measures latent class analysis (RMLCA) was then used to identify subgroups among the study participants with different sleep trajectories over time. Individuals in each latent group were compared using GLMMs to identify personal characteristics that differed among the latent groups. Minor changes in mean SJL, chronotype, or TST were observed over time, whereas no statistically significant changes in SOL, WASO, or SE were observed during the study period. The RMLCA identified two groups of SJL that remained consistent throughout the study (low SJL, mean ± SE: 0.4 ± 0.04 h, 42% of the study population; and high SJL, 1.4 ± 0.03 h, 58%). Those in the SJL group with higher values tended to be employed and have an evening chronotype. Similarly, two distinct subgroups were observed for SOL, WASO, and SE; one group with a pattern suggesting disrupted sleep over time, and another with a consistently normal sleep pattern. Analyses of TST identified three latent groups with relatively short (5.6 ± 1.0 h, 21%), intermediate (6.5 ± 1.0 h, 44%), and long (7.3 ± 1.0 h, 36%) sleep durations, all with temporally stable, linear trajectories. The results from this study suggest that sleep disturbances among young adults can persist over a 2 year period. Latent groups with poor sleep tended to be male, African American, lower income, and have an evening chronotype relative to those with more normal sleep characteristics. Characterizing the persistence of sleep disruption over time and its contributing factors could be important for understanding the role of poor sleep as a chronic disease risk factor.


Diagnostic accuracy of clinical examination features for identifying large rotator cuff tears in primary health care.
Rotator cuff tears are a common and disabling complaint. The early diagnosis of medium and large size rotator cuff tears can enhance the prognosis of the patient. The aim of this study was to identify clinical features with the strongest ability to accurately predict the presence of a medium, large or multitendon (MLM) rotator cuff tear in a primary care cohort. Participants were consecutively recruited from primary health care practices (n = 203). All participants underwent a standardized history and physical examination, followed by a standardized X-ray series and diagnostic ultrasound scan. Clinical features associated with the presence of a MLM rotator cuff tear were identified (P<0.200), a logistic multiple regression model was derived for identifying a MLM rotator cuff tear and thereafter diagnostic accuracy was calculated. A MLM rotator cuff tear was identified in 24 participants (11.8%). Constant pain and a painful arc in abduction were the strongest predictors of a MLM tear (adjusted odds ratio 3.04 and 13.97 respectively). Combinations of ten history and physical examination variables demonstrated highest levels of sensitivity when five or fewer were positive [100%, 95% confidence interval (CI): 0.86-1.00; negative likelihood ratio: 0.00, 95% CI: 0.00-0.28], and highest specificity when eight or more were positive (0.91, 95% CI: 0.86-0.95; positive likelihood ratio 4.66, 95% CI: 2.34-8.74). Combinations of patient history and physical examination findings were able to accurately detect the presence of a MLM rotator cuff tear. These findings may aid the primary care clinician in more efficient and accurate identification of rotator cuff tears that may require further investigation or orthopedic consultation.


Genomic Characterisation of a Highly Divergent Siadenovirus (Psittacine Siadenovirus F) from the Critically Endangered Orange-Bellied Parrot (Neophema chrysogaster).
Siadenoviruses have been detected in wild and captive birds worldwide. Only nine siadenoviruses have been fully sequenced; however, partial sequences for 30 others, many of these from wild Australian birds, are also described. Some siadenoviruses, e.g., the turkey siadenovirus A, can cause disease; however, most cause subclinical infections. An example of a siadenovirus causing predominately subclinical infections is psittacine siadenovirus 2, proposed name psittacine siadenovirus F (PsSiAdV-F), which is enzootic in the captive breeding population of the critically endangered orange-bellied parrot (OBP, Neophema chrysogaster). Here, we have fully characterised PsSiAdV-F from an OBP. The PsSiAdV-F genome is 25,392 bp in length and contained 25 putative genes. The genome architecture of PsSiAdV-F exhibited characteristics similar to members within the genus Siadenovirus; however, the novel PsSiAdV-F genome was highly divergent, showing highest and lowest sequence similarity to skua siadenovirus A (57.1%) and psittacine siadenovirus D (31.1%), respectively. Subsequent phylogenetic analyses of the novel PsSiAdV-F genome positioned the virus into a phylogenetically distinct sub-clade with all other siadenoviruses and did not show any obvious close evolutionary relationship. Importantly, the resulted tress continually demonstrated that novel PsSiAdV-F evolved prior to all known members except the frog siadenovirus A in the evolution and possibly the ancestor of the avian siadenoviruses. To date, PsSiAdV-F has not been detected in wild parrots, so further studies screening PsSiAdV-F in wild Australian parrots and generating whole genome sequences of siadenoviruses of Australian native passerine species is recommended to fill the siadenovirus evolutionary gaps.


Gene-based polymorphisms reveal limited genomic divergence in a species with a heritable life-history dimorphism.
Understanding the genetic basis of life-history traits is a long-standing goal of evolutionary biology. Many closely related species have contrasting life-history strategies, suggesting that the switches in early development that lead to divergent life-histories evolve quickly and frequently. Life-history changes that originate in early development have profound downstream effects on a species' morphology, ecology, genetic diversity, and even speciation rate. How do such transitions in development mode occur, and what is the underlying genetic architecture? To begin to address these questions, we investigated genetic variation in an emerging model in developmental evolution, the polychaete Streblospio benedicti, which has two contrasting and highly heritable offspring types. We compare transcript-based SNP genotypes of individuals of the two development modes to determine the extent of genomic differentiation between them. We find that there is extensive allele sharing across the two types, and minimal fixed differences. We use the site frequency spectrum to fit demographic models to our data and determine that there is recent gene flow between developmental morphs. Our data suggest that the evolution of a genetic developmental dimorphism is not associated with longstanding genetic isolation or genomically extensive divergence. Rather, differences at developmentally important loci, or modest allele-frequency differences at many loci, may be responsible for the drastic life-history differences.


Single-agent therapy for women with acute polymicrobial pelvic infections.
Pathogens that cause acute polymicrobial female pelvic infections usually do not differ from those that compose the normal flora of the lower reproductive tract. Accurate identification of these bacteria is difficult because cultures obtained via the lower tract can easily be contaminated. Although use of a double-lumen catheter-protected brush culture cannot completely eliminate the risk of contamination, it is the least invasive method for obtaining culture material from the upper reproductive tract. Compounding the problem of accurately identifying pathogens that cause acute upper tract infections is the fact that bacteria appear to be present in the upper tracts of asymptomatic women with normal examinations. Because of these problems and because of the polymicrobial nature of these infections, empiric therapy frequently includes more than one antimicrobial agent. Newer, semisynthetic penicillins and cephalosporins have expanded spectrums of in vitro activity against most of the bacteria frequently recovered from pelvic infection sites. Comparative clinical trials have shown these agents to be as effective when used alone as is combination therapy. With few exceptions, empiric monotherapy with one of these newer antimicrobials will be curative for women with acute upper tract infection, will have less potential toxicity, will require less space, materials, and manpower to administer, and will be less expensive.


Mid-infrared emission characteristic and energy transfer of Ho3+-doped tellurite glass sensitized by Tm 3+.
We report on 2.0-microm emission characteristic and energy transfer of Ho3+-doped tellurite glass sensitized by Tm3+ upon excitation of a conventional 808 nm laser diode. The Judd-Ofelt strength parameters, spontaneous radiative transition probabilities and radiative lifetime of Ho3+ have been calculated from the absorption spectra by using the Judd-Ofelt theory. Significant enhancement of 2.0-microm emission of Ho3+ has been observed with increasing Tm3+ doping up to 0.7 mol%. The energy transfer coefficient of the forward Tm3+-->Ho3+ is approximately 17 times larger than that of the backward Tm3+<--Ho3+ energy transfer. Our result indicates that the maximum gain of 2.0-microm emission, assigned to the transition of (5)I7-->(5)I8 of Ho3+, might be achieved from the tellurite glass at the concentration of 0.5 mol% of Tm2O3 and 0.15 mol% of Ho2O3. The high gain coefficient and quantum efficiency (1.16) along with the large value of the product of the stimulated emission cross-section and the measured radiative lifetime (4.12 x 10(-27) m(2)s) of the Ho3+/Tm3+-codoped tellurite glasses might find potential applications in efficient 2.0-microm laser.


The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review.
This article describes a comprehensive meta-analysis that was conducted to estimate the prevalence of attention-deficit/hyperactivity disorder (ADHD), as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). A systematic literature review identified 86 studies of children and adolescents (N = 163,688 individuals) and 11 studies of adults (N = 14,112 individuals) that met inclusion criteria for the meta-analysis, more than half of which were published after the only previous meta-analysis of the prevalence of ADHD was completed. Although prevalence estimates reported by individual studies varied widely, pooled results suggest that the prevalence of DSM-IV ADHD is similar, whether ADHD is defined by parent ratings, teacher ratings, or a best estimate diagnostic procedure in children and adolescents (5.9-7.1 %), or by self-report measures in young adults (5.0 %). Analyses of diagnostic subtypes indicated that the predominantly inattentive type is the most common subtype in the population, but individuals with the combined type are more likely to be referred for clinical services. Additional research is needed to determine the etiology of the higher prevalence of ADHD in males than females and to clarify whether the prevalence of ADHD varies as a function of socioeconomic status or ethnicity. Finally, there were no significant prevalent differences between countries or regions of the world after controlling for differences in the diagnostic algorithms used to define ADHD. These results provide important support for the diagnostic validity of ADHD, and argue against the hypothesis that ADHD is a cultural construct that is restricted to the United States or any other specific culture.


Requirements for the cytoplasmic domain of the alphaPS1, alphaPS2 and betaPS integrin subunits during Drosophila development.
The integrins are a family of transmembrane heterodimeric proteins that mediate adhesive interactions and participate in signaling across the plasma membrane. In this study we examine the functional significance of the cytoplasmic domains of the alphaPS1, alphaPS2 and betaPS subunits of the Drosophila Position Specific (PS) integrin family by analyzing the relationship between cytoplasmic domain structure and function in the context of a developing organism. By examining the ability of ssPS molecules lacking the cytoplasmic domain to rescue embryonic abnormalities associated with PS integrin loss, we find that although many embryonic events require the betaPS cytoplasmic domain, this portion of the molecule is not required for at least two processes requiring PS integrins: formation of midgut constrictions and maintaining germband integrity. Furthermore, our studies demonstrate that mutant proteins affecting four highly conserved amino acid residues in the cytoplasmic tail function with different efficiencies during embryonic development, suggesting that interaction of PS integrins with cytoplasmic ligands is developmentally modulated during embryogenesis. We have also examined the ability of alphaPS1 and alphaPS2 to function without their cytoplasmic domains. By analyzing the ability of transgenes producing truncated alphaPS molecules to rescue abnormalities associated with integrin loss, we find that the cytoplasmic tail of alphaPS2 is essential for both embryonic and postembryonic processes, while this portion of alphaPS1 is not required for function in the wing and in the retina. Furthermore, temperature-shift experiments suggest roles for the alphaPS2 cytoplasmic domain in signaling events occurring in the developing wing.


SU-E-T-267: Construction and Evaluation of a Neutron Wall to Shield a 15 MV Linac in a Low-Energy Vault.
To design and quantify the shielding efficacy of an inner Borated Polyethylene (BPE)wall for a 15 MV linac in a low energy vault. A Varian TrueBeam linac with a maximum photon energy of 15 MV was installed in asmaller, preexisting vault. This vault originally housed a low-energy machine and did not havesufficient maze length recommended for neutron attenuation. Effective dose rate calculationswere performed using the Modified Kersey's Method as detailed in NCRP Report No. 151 andfound to be unacceptably high. An initial survey following the machine installation confirmedthese calculations. Rather than restrict the linac beam energy to 10 MV, BPE was investigatedas a neutron moderating addition. An inner wall and door were planned and constructed using4'×8'×1″ thick 5% BPE sheets. The resulting door and wall had 2″ of BPE; conduits and ductwork were also redesigned and shielded. A survey was conducted following construction of thewall. The vault modification reduced the expected effective dose at the vault door from 36.23to 0.010 mSv/week. As specific guidelines for vault modification are lacking, this project quantitativelydemonstrates the potential use of BPE for vault modification. Such modifications may provide alow-cost shielding solution to allow for the use of high energy modes in smaller treatment vaults.


Robustness and Ruggedness of Isoelectric Focusing and Superficially Porous Liquid Chromatography with Fourier Transform Mass Spectrometry.
An investigation of a multidimensional proteomics workflow composed of off-gel isoelectric focusing (IEF) and superficially porous liquid chromatography (SPLC) with Fourier transform mass spectrometry (FTMS) was completed in order to assess various figures of merit associated with intact protein measurements. Triplicate analysis performed at both high and low FTMS resolutions on the E. coli proteome resulted in ∼900 redundant proteoforms from 3 to 95 kDa. Normalization of the chromatographic axis to identified proteoforms enabled reproducible physicochemical property measurements between proteome replicates with inter-replicate variances of ±3 ppm mass error for proteoforms <30 kDa, ±1.1 Da for proteins >30 kDa, ±12 s retention time error, and ±0.21 pI units. The results for E. coli and standard proteins revealed a correlation between pI precision and proteoform abundance with species detected in multiple IEF fractions exhibiting pI precisions less than the theoretical resolution of the off-gel system (±0.05 vs ±0.17, respectively). Evaluation of differentially modified proteoforms of standard proteins revealed that high sample loads (100s μgrams) change the IEF pH gradient profile, leading to sample broadening that facilitates resolution of charged post-translational modifications (e.g., phosphorylation, sialylation). Despite the impact of sample load on IEF resolution, results on standard proteins measured directly or after being spiked into E. coli demonstrated that the reproducibility of the workflow permitted recombination of the MS signal across IEF fractions in a manner supporting the evaluation of three label-free quantitation metrics for intact protein studies (proteoforms, proteoform ratios, and protein) over 102-103 sample amount with low femtomole detection limits.


Study protocol for the development of a European measure of best practice for people with long term mental health problems in institutional care (DEMoBinc).
This study aims to build a measure for assessing and reviewing the living conditions, care and human rights of people with longer term mental health problems in psychiatric and social care institutions. Protection of their human rights is imperative since impaired mental capacity secondary to mental illness can make them vulnerable to abuse and exploitation from others. They also constitute a major resource pressure for mental health services, social services, informal carers and society as a whole. This study uses an iterative methodology to develop a toolkit to assess internationally agreed domains of care that are considered most important for recovery. These domains are identified by collating results from: i) a systematic review of the literature on institutional care for this service user group; ii) a review of the relevant care standards in each participating country; iii) Delphi exercises in partner countries with mental health professionals, service users, carers and advocates. Common domains and cross-cutting themes are agreed by the principal researchers and an international expert panel. Items are developed to assess these domains and incorporated into the toolkit which is designed to be administered through a face to face interview with the institution's manager. The toolkit is refined in response to inter-rater reliability testing, feedback from interviewers and interviewees regarding its utility, and feedback from key stakeholders in each country about its ability to deliver information that can be used within each country's established systems for quality assessment and review. Cross-validation of the toolkit ratings against service users' quality of life, autonomy and markers of recovery tests whether it can deliver a proxy-measure of the service users' experiences of care and the institution's promotion of their human rights and recovery. The ability of the toolkit to assess the "value for money" delivered by institutions is investigated by comparing toolkit ratings and service costs. The study will deliver the first international tool for the assessment of the quality of institutional care for people with longer term mental health problems that is accurate, reliable, informative, useful and easy to use.


Approach to a tremor patient.
Tremors are commonly encountered in clinical practice and are the most common movement disorders seen. It is defined as a rhythmic, involuntary oscillatory movement of a body part around one or more joints. In the majority of the population, tremor tends to be mild. They have varying etiology; hence, classifying them appropriately helps in identifying the underlying cause. Clinically, tremor is classified as occurring at rest or action. They can also be classified based on their frequency, amplitude, and body part involved. Parkinsonian tremor is the most common cause of rest tremor. Essential tremor (ET) and enhanced physiological tremor are the most common causes of action tremor. Isolated head tremor is more likely to be dystonic rather than ET. Isolated voice tremor could be considered to be a spectrum of ET. Psychogenic tremor is not a diagnosis of exclusion; rather, demonstration of various clinical signs is needed to establish the diagnosis. Severity of tremor and response to treatment can be assessed using clinical rating scales as well as using electrophysiological measurements. The treatment of tremor is symptomatic. Medications are effective in half the cases of essential hand tremor and in refractory patients; deep brain stimulation is an alternative therapy. Midline tremors benefit from botulinum toxin injections. It is also the treatment of choice in dystonic tremor and primary writing tremor.


Who Supports Health Reform?
In this article, we report results from a new study that surveyed a large, national sample of American adults about their willingness to pay for health reform. As in previous work, we find that self-identified Republicans, older Americans, and high-income Americans are less supportive of reform. However, these basic findings mask three important features of public opinion. First, income has a substantial effect on support for reform, even holding political affiliation constant. Indeed, income is the most important determinant of support for reform. Second, the negative effects of income on support for reform begin early in the income distribution, at annual family income levels of $25,000 to $50,000. Third, although older Americans have a less favorable view of reform than the young, much of their opposition is due to dislike of large policy changes than to reform per se.


Vasoconstriction to hypoxia of the human internal mammary artery.
Experiments were designed to determine the role of the endothelium in response to hypoxia in the human internal mammary artery (IMA). Segments of IMA were harvested during coronary artery bypass surgery. Rings (4 mm in length) of IMA, with and without endothelium, were suspended to force transducers in organ baths containing a physiologic salt solution (37 degrees C, 95% O2/5% CO2, and pH = 7.4). The rings were contracted with norepinephrine (NE, 1 x 10(-7) M, initial tension), and then exposed to hypoxia (95% N2/5% CO2, PO2 = 35 +/- 5 mmHg). In IMA segments with endothelium, hypoxia caused an initial, transient relaxation (hypoxic inhibition) to 52 +/- 9% of the initial tension, followed by contraction of the blood vessel (hypoxic potentiation; 178 +/- 10% of initial tension). In vessels without endothelium, hypoxia only induced relaxation (to 10 +/- 2% of initial tension). In vessels with endothelium, reoxygenation induced transient rapid relaxation (to 31 +/- 12%; post-hypoxic inhibition) which then stabilized to 50 +/- 14% of the initial tension. However, segments without endothelium returned to their initial tension. Indomethacin (1 x 10(-5) M) reduced the endothelium-dependent hypoxic contraction and abolished the hypoxic and post-hypoxic inhibition. Free radical scavengers (superoxide dismutase plus catalase and deferoxamine) did not modify the responses to hypoxia and reoxygenation. These experiments indicate that hypoxia induces the release of an endothelium-derived constricting cyclooxygenase product from the human IMA endothelium, and that reoxygenation causes release of a cyclooxygenase-dependent endothelium-derived relaxing factor. The release of endothelium-derived constricting factor(s) could induce vasospasm and cause cardiovascular collapse if IMA grafts are exposed to hypoxia perioperatively.


Are Payers Ready, Willing, and Able to Provide Access to New Durable Gene Therapies?
To explore payer feedback regarding awareness of new gene therapies, sustainability of current financing mechanisms, unique challenges by payer segment, and need and preference for new financial models. Qualitative interview with standardized interview guide. Sixty-minute telephone interviews were conducted with financial decision makers from 15 US payers between August and September 2017. One-third of payers interviewed (n = 5) were newly aware and learning about new gene therapies, 40% (n = 6) described watchful waiting, whereas 26.7% (n = 4) were engaged in active management. New payment models-specifically, performance-based agreements and risk-pooling-were supported by 47% (n = 7) of payers, whereas the current payment model was supported by 53% (n = 8). Major challenges included uncertainty related to utilization, cost, and duration of cure. Payers cited regulation, plan turnover, and ability to track long-term outcomes as barriers to implementation of new models. Access to new gene therapies may be impacted by payer ability to absorb the cost of coverage. Variation exists in awareness of new gene therapies and level of incorporation of new costs into future plan coverage. The sustainability of current financing mechanisms varies by payer segment, profitability, and size; smaller plans and Medicaid are likely to be impacted first. Government reinsurance, commercial reinsurance, and stop-loss insurance backstop current reimbursement models, dampening the need for urgent action. The tipping point for action may be severe premium inflation in stop loss and reinsurance. Payers are open to innovative financing models that improve financial predictability and reward clinical performance.


Blood Pressure Measurement Training Program and Adherence of Public Health Nurses to BP Measurement Guidelines.
To compare the level of adherence of public health nurses to BP measurement guidelines based on their knowledge if the guidelines and skills in BP measurement before and after Blood Pressure Measurement Training Program (BPMTP). An experimental pre- and post-test design using two-staged cluster randomization was conducted. 118 PHNs (mean age ± 38.45 years, mean years of experience ± 13.45 years; 84.1% women) from six districts in Manila were equally assigned to either the BPMTP group or control group. Structured instruments were used. Demographic characteristics, current BP measurement practices, and level of adherence to BP measurement guidelines based on knowledge of the guidelines and skills in BP measurement were equivalent in both groups at baseline. Nurses in the BPMTP group showed improved adherence (p=<0.05) compared to nurses in the control group. Both groups did not show significant change in their skill on recording, interpretation, and referral (p=1.000). This study showed that Blood Pressure Measurement Training Package is feasible in improving adherence of nurses based on their increased knowledge of the BP measurement guidelines and skills in BP measurement. A larger-scale study is warranted to show that BPMTP can potentially improve clinical management of hypertension in public health clinics globally.


Host-adaptive antigenic variation in Bunyaviruses.
Bunyamwera virus and snowshoe have virus (family Bunyaviridae) were passaged up to six times through mosquito cells in culture and the resultant viruses were compared to the input, mammalian cell-passed virus using monoclonal antibodies raised against the input virus. The mosquito cell-adapted virus population consisted of mutants which were better adapted to replication in the new host than was the input mammalian cell-passed virus and were differentially susceptible to neutralization by antibody.


Effects of etiological agent and bather shedding of pathogens on interpretation of epidemiological data used to establish recreational water quality standards.
The overall goal of the study reported herein was to use techniques in the field of risk assessment (specifically a state-space population dynamic model of disease transmission within recreational waters) to explore the relative significance of (1) active shedding of microorganisms from bathers themselves, and (2) the type and concentration of etiological agent on the observed heterogeneity of the incidence of illness in epidemiological studies that have been used to develop ambient water quality criteria. The etiological agent and corresponding dose ingested during recreational contact was found to significantly impact the observed incidence of illness in an epidemiological study conducted in recreational water. In addition, the observed incidence of illness was found not to necessarily reflect background concentrations of indicator organisms, but rather microorganisms shed during recreational contact. Future revisions to ambient water quality criteria should address the etiological agent, dose, and the significance of microbial shedding relative to background concentrations of pathogens and indicator organisms in addition to the incidence of illness and concentration of indicator organisms. Without a quantitative assessment of these additional variables, study findings may potentially be site specific and not representative of the health risks associated with specific indicator concentrations in all recreational waters.


The role of health-related behavioural factors in accounting for inequalities in coronary heart disease risk by education and area deprivation: prospective study of 1.2 million UK women.
Some recent research has suggested that health-related behaviours, such as smoking, might explain much of the socio-economic inequalities in coronary heart disease (CHD) risk. In a large prospective study of UK women, we investigated the associations between education and area deprivation and CHD risk and assessed the contributions of smoking, alcohol consumption, physical activity and body mass index (BMI) to these inequalities. After excluding women with heart disease, stroke or cancer at recruitment, 1,202,983 women aged 56 years (SD 5 years) on average, were followed for first coronary event (hospital admission or death) and for CHD mortality. Relative risks of CHD were estimated by Cox regression, and the extent to which any association could be accounted for by smoking, alcohol, physical inactivity, and BMI was assessed by calculating the percentage reduction in the relevant likelihood-ratio (LR) statistic after adjustment for these factors, separately and together. A total of 71,897 women had a first CHD event (hospital admission or death) and 6032 died from CHD during 12 years follow-up. In analyses adjusted by age, birth cohort and region of residence only, lower levels of education and greater deprivation were associated with higher risks of CHD (P heterogeneity < 0.0001 for each); associations for education were found within every level of deprivation and for deprivation were found within every level of education. Smoking, alcohol consumption, physical inactivity and BMI accounted for most of the associations (adjustment for all four factors together reduced the LR statistics for education and for deprivation by 76 % and 71 %, respectively, for first CHD event; and by 87 % and 79 %, respectively, for CHD mortality). Of these four factors, adjustment for smoking resulted in the largest reduction in the LR statistic. Given the large reduction in the predictive values of education and deprivation after adjustment for only four health-related behavioural factors recorded just at recruitment, residual confounding might plausibly account for the remaining associations. Most of the association between CHD risk and education and area deprivation in UK women is accounted for by health-related behaviours, particularly by smoking and to a lesser extent by alcohol consumption, physical inactivity and BMI.


Assessment of knowledge and attitudes regarding automated external defibrillators and cardiopulmonary resuscitation among American University students.
We sought to quantify knowledge and attitudes regarding automated external defibrillators (AEDs) and cardiopulmonary resuscitation (CPR) among university students. We also aimed to determine awareness of the location of an actual AED on campus. We performed an online survey of undergraduate and graduate students at a mid-sized, private university that has 37 AEDs located throughout its two campuses. 267 students responded to the survey. Almost all respondents could identify CPR (98.5%) and an AED (88.4%) from images, but only 46.1% and 18.4%, respectively, could indicate the basic mechanism of CPR and AEDs. About a quarter (28.1%) of respondents were comfortable using an AED without assistance, compared with 65.5% when offered assistance. Of those who did not feel comfortable, 87.7% indicated that they were 'afraid of doing something wrong.' One out of 6 (17.6%) respondents knew that a student centre had an AED, and only 2% could recall its precise location within the building. Most (66.3%) respondents indicated they would look for an AED near fire extinguishers, followed by the entrance of a building (19.6%). This study found that most students at an American university can identify CPR and AEDs, but do not understand their basic mechanisms of action or are willing to perform CPR or use AEDs unassisted. Recent CPR/AED training and 9-1-1 assistance increases comfort. The most common fear reported was incorrect CPR or AED use. Almost all students could not recall where an AED was located in a student centre.


Characterization of two genes, glpQ and ugpQ, encoding glycerophosphoryl diester phosphodiesterases of Escherichia coli.
The nucleotide sequences of the glpQ and ugpQ genes of Escherichia coli, which both encode glycerophosphoryl diester phosphodiesterases, were determined. The glpQ gene encodes a periplasmic enzyme of 333 amino acids, produced initially with a 25 residue long signal sequence, while ugpQ codes for a cytoplasmic protein of 247 amino acids. Despite differences in size and cellular location, significant similarity in the primary structures of the two enzymes was found suggesting a common evolutionary origin. The 3' end of the ugpQ gene overlaps an open reading frame that is transcribed in the opposite direction. This open reading frame encodes a polypeptide with an unusual composition, i.e., 46 of the 146 amino acids are Gln or Asn. This polypeptide and the UgpQ protein were identified in an in vitro transcription/translation system as proteins with apparent molecular weights of 19.5 and 27 kDa, respectively.


Nickel(ii) inhibits the oxidation of DNA 5-methylcytosine in mammalian somatic cells and embryonic stem cells.
Nickel is found widely in the environment. It is an essential microelement but also toxic. However, nickel displays only weak genotoxicity and mutagenicity. Exploration of the epigenetic toxicity of nickel is extremely interesting. Iron(ii)- and 2-oxoglutarate-dependent Tet dioxygenases are a class of epigenetic enzymes that catalyze the oxidation of DNA 5-methylcytosine (5mC). Thus, they are critical for DNA demethylation and, importantly, are involved with nuclear reprogramming, embryonic development, and regulation of gene expression. Here, we demonstrated that nickel(ii) dramatically inhibits Tet proteins-mediated oxidation of DNA 5mC in cells ranging from somatic cell lines to embryonic stem cells, as manifested by the consistent observation of a significant decrease in 5-hydroxymethylcytosine, a critical intermediate resulting from the oxidation of 5mC. The inhibitory effects of nickel(ii) were concentration- and time-dependent. Using HEK293T cells overexpressing Tet proteins and ascorbic acid-stimulated Tet-proficient ES cells, we observed that nickel(ii) significantly reduced DNA demethylation at the global level. Interestingly, we also showed that nickel(ii) might affect the naïve or ground state of pluripotent embryonic stem cells. Here we show, for the first time, that nickel(ii) represses the oxidation of DNA 5mC and potentially alters the Tet proteins-regulated DNA methylation landscape in human cells. These findings provide new insights into the epigenetic toxicology of nickel.


Molecular mechanism of preQ1 riboswitch action: a molecular dynamics study.
Riboswitches often occur in the 5'-untranslated regions of bacterial mRNA where they regulate gene expression. The preQ(1) riboswitch controls the biosynthesis of a hypermodified nucleoside queuosine in response to binding the queuosine metabolic intermediate. Structures of the ligand-bound and ligand-free states of the preQ(1) riboswitch from Thermoanaerobacter tengcongensis were determined recently by X-ray crystallography. We used multiple, microsecond-long molecular dynamics simulations (29 μs in total) to characterize the structural dynamics of preQ(1) riboswitches in both states. We observed different stabilities of the stem in the bound and free states, resulting in different accessibilities of the ribosome-binding site. These differences are related to different stacking interactions between nucleotides of the stem and the associated loop, which itself adopts different conformations in the bound and free states. We suggest that the loop not only serves to bind preQ(1) but also transmits information about ligand binding from the ligand-binding pocket to the stem, which has implications for mRNA accessibility to the ribosome. We explain functional results obscured by a high salt crystallization medium and help to refine regions of disordered electron density, which demonstrates the predictive power of our approach. Besides investigating the functional dynamics of the riboswitch, we have also utilized this unique small folded RNA system for analysis of performance of the RNA force field on the μs time scale. The latest AMBER parmbsc0χ(OL3) RNA force field is capable of providing stable trajectories of the folded molecule on the μs time scale. On the other hand, force fields that are not properly balanced lead to significant structural perturbations on the sub-μs time scale, which could easily lead to inappropriate interpretation of the simulation data.