PMID- 26381835 TI - The broad orientation dependence of the motion streak aftereffect reveals interactions between form and motion neurons. AB - The extended integration time of visual neurons can lead to the production of the neural equivalent of an orientation cue along the axis of motion in response to fast-moving objects. The dominant model argues that these motion streaks resolve the inherent directional uncertainty arising from the small size of receptive fields in V1, by combining spatial orientation with motion signals in V1. This model was tested in humans using visual aftereffects, in which adapting to a static grating causes the perceived direction of a subsequently presented motion stimulus to be tilted away from the adapting orientation. We found that a much broader range of orientations produced aftereffects than predicted by the current model, suggesting that these orientation cues influence motion perception at a later stage than V1. We also found that varying the spatial frequency of the adaptor changed the aftereffect from repulsive to attractive for motion-test but not form-test stimuli. Finally, manipulations of V1 excitability, using transcranial stimulation, reduced the aftereffect, suggesting that the orientation cue is dependent on V1. These results can be accounted for if the orientation information from the motion streak, gathered in V1, enters the motion system at a later stage of motion processing, most likely V5. A computational model of motion direction is presented incorporating gain modifications of broadly tuned motion-selective neurons by narrowly tuned orientation-selective cells in V1, which successfully accounts for the extant data. These results reinforce the suggestion that orientation places strong constraints on motion processing but in a previously undescribed manner. PMID- 26381834 TI - Color constancy in a naturalistic, goal-directed task. AB - In daily life, we use color information to select objects that will best serve a particular goal (e.g., pick the best-tasting fruit or avoid spoiled food). This is challenging when judgments must be made across changes in illumination as the spectrum reflected from an object to the eye varies with the illumination. Color constancy mechanisms serve to partially stabilize object color appearance across illumination changes, but whether and to what degree constancy supports accurate cross-illumination object selection is not well understood. To get closer to understanding how constancy operates in real-life tasks, we developed a paradigm in which subjects engage in a goal-directed task for which color is instrumental. Specifically, in each trial, subjects re-created an arrangement of colored blocks (the model) across a change in illumination. By analyzing the re-creations, we were able to infer and quantify the degree of color constancy that mediated subjects' performance. In Experiments 1 and 2, we used our paradigm to characterize constancy for two different sets of block reflectances, two different illuminant changes, and two different groups of subjects. On average, constancy was good in our naturalistic task, but it varied considerably across subjects. In Experiment 3, we tested whether varying scene complexity and the validity of local contrast as a cue to the illumination change modulated constancy. Increasing complexity did not lead to improved constancy; silencing local contrast significantly reduced constancy. Our results establish a novel goal-directed task that enables us to approach color constancy as it emerges in real life. PMID- 26381836 TI - Allocentric kin recognition is not affected by facial inversion. AB - Typical judgments involving faces are disrupted by inversion, with the Thatcher illusion serving as a compelling example. In two experiments, we examined how inversion affects allocentric kin recognition-the ability to judge the degree of genetic relatedness of others. In the first experiment, participants judged whether pairs of photographs of children portrayed siblings or unrelated children. Half of the pairs were siblings, half were unrelated. In three experimental conditions, photographs were viewed in upright orientation, flipped around a horizontal axis, or rotated 180 degrees . Neither rotation nor flipping had any detectable effect on allocentric kin recognition. In the second experiment, participants judged pairs of photographs of adult women. Half of the pairs were sisters, half were unrelated. We again found no significant effect of facial inversion. Unlike almost all other face judgments, judgments of kinship from facial appearance do not rely on perceptual cues disrupted by inversion, suggesting that they rely more on spatially localized cues rather than "holistic" cues. We conclude that kin recognition is not simply a byproduct of other face perception abilities. We discuss the implications for cue combination models of other facial judgments that are affected by inversion. PMID- 26381837 TI - Distribution of independent components of binocular natural images. AB - An influential theory of the function of early processing in the visual cortex is that it forms an efficient coding of ecologically valid stimuli. In particular, correlations and differences between visual signals from the two eyes are believed to be of great importance in solving both depth from disparity and binocular fusion. Techniques such as independent-component analysis have been developed to learn efficient codings from natural images; these codings have been found to resemble receptive fields of simple cells in V1. However, the extent to which this approach provides an explanation of the functionality of the visual cortex is still an open question. We compared binocular independent components with physiological measurements and found a broad range of similarities along with a number of key differences. In common with physiological measurements, we found components with a broad range of both phase- and position-disparity tuning. However, we also found a larger population of binocularly anticorrelated components than have been found physiologically. We found components focused narrowly on detecting disparities proportional to half-integer multiples of wavelength rather than the range of disparities found physiologically. We present the results as a detailed analysis of phase and position disparities in Gabor like components generated by independent-component analysis trained on binocular natural images and compare these results to physiology. We find strong similarities between components learned from natural images, indicating that ecologically valid stimuli are important in understanding cortical function, but with significant differences that suggest that our current models are incomplete. PMID- 26381838 TI - Human optokinetic nystagmus and spatial frequency. AB - Optokinetic nystagmus (OKN) is a fundamental oculomotor response to retinal slip generated during natural movement through the environment. The timing and amplitude of the compensatory slow phases (SPs) alternating with saccadic quick phases (QPs) are remarkably variable, producing a characteristic irregular sawtooth waveform. We have previously found three stochastic processes that underlie OKN: the processes that determine QP and SP amplitude and the update dynamics of SP velocity. SP and QP parameters are interrelated and dependent on SP velocity such that changes in stimulus speed can have a seemingly complex effect on the nystagmus waveform. In this study we investigated the effect of stimulus spatial frequency on the stochastic processes of OKN. We found that increasing the spatial frequency of suprathreshold stimuli resulted in a significant increase in SP velocity with a corresponding reduction in retinal slip. However, retinal slip rarely reached values close to 0, indicating that the OKN system does not or cannot always minimize retinal slip. We deduce that OKN gain must be less than unity if extraretinal gain is lower than unity (as empirically observed), and that the difference between retinal and extraretinal gain determines the Markov properties of SP velocity. As retinal gain is reduced with stimuli of lower spatial frequency, the difference between retinal and extraretinal gain increases and the Markov properties of the system can be observed. PMID- 26381839 TI - The role of color in motion feature-binding errors. AB - Color-motion feature-binding errors occur in the periphery when half of the objects are red and move downward, and the other half are green and move upward. When red and green objects in the central visual field are similar but move in the opposite directions (red upward, green downward), peripheral objects often take on the perceived motion direction of the like-colored central objects (Wu, Kanai, & Shimojo, 2004). The present study determined whether color is essential to elicit these motion-binding errors, and tested two hypotheses that attempt to explain them. One hypothesis holds that binding errors occur because peripheral and central objects become linked if they have combinations of features in common. A peripheral object's link to central objects overwhelms its posited weak peripheral representation for motion feature binding, so the peripheral object appears to move in the direction of the linked central objects. Eliminating color by making all stimuli achromatic, therefore, should not increase peripheral binding errors. An alternative hypothesis is that binding errors depend on the overall feature correspondence among central and peripheral features represented at a preconjunctive level. In this case, binding errors may increase when all objects are changed to achromatic because chromatic central/peripheral correspondence is maximal (100%). Experiments showed more motion-binding errors with all-achromatic objects than with half red and half green objects. This and additional findings imply that peripheral motion-binding errors (a) can be elicited without color and (b) depend at least in part on the similarity of central and peripheral features represented preconjunctively. PMID- 26381840 TI - We make predictions about eye of origin of visual input: Visual mismatch negativity from binocular rivalry. AB - The visual mismatch negativity (vMMN) is a negative component of event-related potentials (ERPs). It occurs when an infrequent visual stimulus, a deviant, is randomly and unpredictably presented in a sequence of frequent visual stimuli, the standards, and is thought to reflect prediction and prediction error of visual input. We investigated the sensitivity of vMMN to eye of origin (utrocular) information as well as to orientation information. We presented 80% of binocular rivalry standards (one grating to one eye and an identical, orthogonally oriented grating to the other eye), and 20% of deviants, either by swapping the gratings between the eyes to change the eye of origin of the gratings (an eye-swap deviant) or by rotating the gratings by 45 degrees to change the orientation of the gratings (an orientation deviant). We found an orientation vMMN that was maximal at about 250 ms and an eye-swap vMMN that was maximal at about 380 ms. We also found deviance-related activity to both sorts of stimuli earlier than is traditionally defined as a vMMN. We used standardized low resolution brain electromagnetic tomography (sLORETA) to localize each vMMN component and found similar sources for both vMMNs in occipital and frontal areas of the brain but differences in parietal and temporal areas. We conclude that eye of origin information can be used to elicit vMMN, that eye-swap vMMN is different to orientation vMMN, and that vMMN can be generated from information of which observers are unaware. PMID- 26381841 TI - Space and time in masking and crowding. AB - Masking and crowding are major phenomena associated with contextual modulations, but the relationship between them remains unclear. We have recently shown that crowding is apparent in the fovea when the time available for processing is limited, pointing to the strong relationship between crowding in the spatial and temporal domains. Models of crowding emphasize the size (acuity) of the target and the spacing between the target and flankers as the main determinants that predict crowding. Our model, which is based on lateral interactions, posits that masking and crowding are related in the spatial and temporal domains at the fovea and periphery and that both can be explained by the increasing size of the human perceptive field (PF) with increasing eccentricity. We explored the relations between masking and crowding using letter identification and contrast detection by correlating the crowding effect with the estimated size of the PF and with masking under different spatiotemporal conditions. We found that there is a large variability in PF size and crowding effects across observers. Nevertheless, masking and crowding were both correlated with the estimated size of the PF in the fovea and periphery under a specific range of spatiotemporal parameters. Our results suggest that under certain conditions, crowding and masking share common neural mechanisms that underlie the spatiotemporal properties of these phenomena in both the fovea and periphery. These results could explain the transfer of training gains from spatiotemporal Gabor masking to letter acuity, reading, and reduced crowding. PMID- 26381842 TI - Analysis of gene mutations in PKD1/PKD2 by multiplex ligation-dependent probe amplification: some new findings. AB - Autosomal dominant polycystic kidney disease (ADPKD) is a serious genetic disorder that can lead to chronic renal disease. Protein dysfunction caused by mutations in the genes polycystic kidney disease 1 (PKD1) and polycystic kidney disease 2 (PKD2) is an important factor in the pathogenesis of ADPKD. In the present study, 30 Chinese patients with confirmed diagnosis of ADPKD, based on ultrasound or computerized tomography (CT) findings were selected, and the exon copy numbers of PKD1 and PKD2 were determined using multiplex ligation-dependent probe amplification (MLPA). MLPA identified exon deletion in 1 case, suspected exon deletion in 4 cases, and suspected duplications in 3 cases. One case of suspected exon deletion was confirmed using quantitative real-time polymerase chain reaction (q-PCR) and sequencing (PKD2 exon 8). A missense mutation was observed in 1 case of exon deletion using q-PCR and sequencing (PKD1 exon 40, c.11333 C>A). The cases of suspected duplications were verified by q-PCR, and the copy number of exon 6 of PKD1 in 1 case of suspected duplication was 3.8 times greater than that in normal controls. Our findings provide new insights into ADPKD screening and mark a possibly meaningful step toward improved diagnosis and treatment of patients with ADPKD. PMID- 26381844 TI - The association between second trimester estimated fetal weight and small for gestational age at birth. AB - OBJECTIVE: To analyze diagnostic accuracy of second trimester ultrasound fetal growth parameters as predictors of small for gestational age (SGA) birth weight. METHODS: We reviewed the fetal biometry from 714 consecutive patients with second trimester ultrasounds. The estimated fetal weight (EFW) and abdominal circumference (AC) percentiles were tested as predictors of SGA at birth (<100/00). RESULTS: 87 (12.2%) patients had an SGA baby. Patients with a second trimester EFW <=250/00 were significantly more likely to have SGA at birth (24.2% versus 10.3%, p < 0.001). Similar results were seen for women with second trimester AC <=250/00 (likelihood of SGA 21.9% versus 11.2%, p = 0.013). A second trimester EFW <=250/00 was a better predictor of SGA at birth than a second trimester EFW <= 100/00 (Positive likelihood ratio 2.30 versus 2.09). In the second trimester, only 9 (1.3%) patients had an EFW 0-100/00, only 43 (6%) patients had an EFW 11-200/00, and only 46 (6.4%) patients had an EFW 91-990/00. Each other EFW centile had more than 10% of the patients. CONCLUSIONS: The incidence of second trimester EFW or AC <=100/00 is less common than expected from standard tables. An EFW <=250/00 and an AC <=250/00 should be considered the second trimester marker for risk of SGA at birth. However, due to the low likelihood ratio of, it is not clear if second trimester ultrasound should be used as a predictor of SGA at birth. PMID- 26381843 TI - A systematic review of physical illness, functional disability, and suicidal behaviour among older adults. AB - OBJECTIVES: To conduct a systematic review of studies that examined associations between physical illness/functional disability and suicidal behaviour (including ideation, nonfatal and fatal suicidal behaviour) among individuals aged 65 and older. METHOD: Articles published through November 2014 were identified through electronic searches using the ERIC, Google Scholar, PsycINFO, PubMed, and Scopus databases. Search terms used were suicid* or death wishes or deliberate self harm. Studies about suicidal behaviour in individuals aged 65 and older with physical illness/functional disabilities were included in the review. RESULTS: Sixty-five articles (across 61 independent samples) met inclusion criteria. Results from 59 quantitative studies conducted in four continents suggest that suicidal behaviour is associated with functional disability and numerous specific conditions including malignant diseases, neurological disorders, pain, COPD, liver disease, male genital disorders, and arthritis/arthrosis. Six qualitative studies from three continents contextualized these findings, providing insights into the subjective experiences of suicidal individuals. Implications for interventions and future research are discussed. CONCLUSION: Functional disability, as well as a number of specific physical illnesses, was shown to be associated with suicidal behaviour in older adults. We need to learn more about what at-risk, physically ill patients want, and need, to inform prevention efforts for older adults. PMID- 26381846 TI - Age-related differences in hair trace elements: a cross-sectional study in Orenburg, Russia. AB - BACKGROUND: Age-related differences in the trace element content of hair have been reported. However, some discrepancies in the data exist. AIM: The primary objective of this study was to estimate the change in hair trace elements content in relation to age. SUBJECTS AND METHODS: Six hundred and eighteen women and 438 men aged from 10-59 years took part in the current cross-sectional study. RESULTS AND CONCLUSIONS: Hair Cr, Mn, Ni, Si, Al, As, Be, Cd and Pb tended to decrease with age in the female sample, whereas hair Cu, Fe, I, Se, Li and Sn were characterised by an age-associated increase. Hair levels of Cr, Cu, I, Mn, Ni, Si and Al in men decreased with age, whereas hair Co, Fe, Se, Cd, Li and Pb content tended to increase. Hair mercury increased in association with age in men and in women, whereas hair vanadium was characterised by a significant decrease in both sexes. The difference in hair trace element content between men and women decreased with age. These data suggest that age-related differences in trace element status may have a direct implication in the ageing process. PMID- 26381847 TI - Molecular Dynamics Study of Thermally Augmented Nanodroplet Motion on Chemical Energy Induced Wettability Gradient Surfaces. AB - Droplet motion on a surface with chemical energy induced wettability gradient has been simulated using molecular dynamics (MD) simulation to highlight the underlying physics of molecular movement near the solid-liquid interface including the contact line friction. The simulations mimic experiments in a comprehensive manner wherein microsized droplets are propelled by the surface wettability gradient against forces opposed to motion. The liquid-wall Lennard Jones interaction parameter and the substrate temperature are varied to explore their effects on the three-phase contact line friction coefficient. The contact line friction is observed to be a strong function of temperature at atomistic scales, confirming their experimentally observed inverse functionality. Additionally, the MD simulation results are successfully compared with those from an analytical model for self-propelled droplet motion on gradient surfaces. PMID- 26381850 TI - Lesion Activity Assessment (LAA) in Conjunction With International Caries Detection and Assessment System (ICDAS) for Occlusal Caries Diagnosis in Permanent Teeth. AB - OBJECTIVE: The aim of this study was to investigate the clinical performance and to validate the Lesion Activity Assessment (LAA) in conjunction with the International Caries Detection and Assessment System (ICDAS) for occlusal caries diagnosis in permanent teeth. METHODS: Patients with erupted or partially erupted third molars were recruited from the surgery clinic of the School of Dentistry of the Universidade Federal de Minas Gerais, Brazil. A calibrated examiner evaluated 49 teeth using the ICDAS-LAA criteria. The histologic criterion proposed by Ekstrand and others was used to validate severity at the thresholds D1 (outer half of the enamel), D2 (inner half of the enamel and outer third of the dentin), and D3 (inner or middle third of the dentin). Lesion activity was validated using 0.1% methyl red solution. RESULTS: The method demonstrated good reliability (weighted kappa for severity=0.60; unweighted kappa for activity=0.61). The ICDAS presented a higher performance for lesion detection (area under the receiver operating characteristic curve [Az]=0.79) using the threshold D3. At the thresholds D1 and D2, the results for Az were 0.57 and 0.74, respectively. Regarding the ICDAS-LAA, Az = 0.59. CONCLUSIONS: Clinical protocols can use ICDAS for the severity diagnosis of occlusal caries, but the LAA performance was poor. PMID- 26381851 TI - Urotensin II receptor on preoperative biopsy is associated with upstaging and upgrading in prostate cancer. AB - AIM: A higher Gleason score was associated with a lower tumor urotensin II receptor (UTII-R) expression in prostate cancer patients. METHODS: A retrospective review of formalin-fixed paraffin-embedded tumor tissue derived from those who had prostatectomy and matching biopsy specimens was conducted at six Institutions. UTII-R expression was evaluated on biopsy by immunohistochemistry. RESULTS: A total of 58 subjects undergoing radical prostatectomy were included. At multivariate analysis, low UTII-R expression was a significant predictor of Gleason upgrading, with an odds ratio of 10.3 (95% CI: 1.55-68.4), and of pathology upstaging, with an odds ratio of 11.1 (95% CI: 1.23 100.48). CONCLUSIONS: UTII-R expression on biopsy was associated with Gleason upgrading and pathology upstaging in prostate cancer patients. PMID- 26381853 TI - 2014 European Conference on Donor Health and Management. PMID- 26381852 TI - Development of human-like scFv-Fc antibodies neutralizing Botulinum toxin serotype B. AB - Botulinum neurotoxins (BoNTs) are responsible for human botulism, a life threatening disease characterized by flaccid muscle paralysis that occurs naturally by food poisoning or colonization of the gastrointestinal tract by BoNT producing clostridia. BoNTs have been classified as category A agents by the Centers for Disease Control and Prevention. To date, 7 subtypes of BoNT/B were identified showing that subtypes B1 (16 strains) and B2 (32 strains) constitute the vast majority of BoNT/B strains. Neutralizing antibodies are required for the development of anti-botulism drugs to deal with the potential risk. In this study, macaques (Macaca fascicularis) were immunized with recombinant light chain (LC) or heavy chain (HC) of BoNT/B2, followed by the construction of 2 hyper immune phage display libraries. The best single-chain variable fragments (scFvs) isolated from each library were selected according to their affinities and cross reactivity with BoNT/B1 toxin subtype. These scFvs against LC and HC were further analyzed by assessing the inhibition of in vitro endopeptidase activity of BoNT/B1 and B2 and neutralization of BoNT/B1 and B2 toxin-induced paralysis in the mouse ex vivo phrenic nerve assay. The antibodies B2-7 (against HC) and BLC3 (against LC) were produced as scFv-Fc, and, when tested individually, neutralized BoNT/B1 and BoNT/B2 in a mouse ex vivo phrenic nerve assay. Whereas only scFv-Fc BLC3 alone protected mice against BoNT/B2-induced paralysis in vivo, when B2-7 and BLC3 were combined they exhibited potent synergistic protection. The present study provided an opportunity to assess the extent of antibody-mediated neutralization of BoNT/B1 and BoNT/B2 subtypes in ex vivo and in vitro assays, and to confirm the benefit of the synergistic effect of antibodies targeting the 2 distinct functional domains of the toxin in vivo. Notably, the framework regions of the most promising antibodies (B2-7 and BLC3) are close to the human germline sequences, which suggest that they may be well tolerated in potential clinical development. PMID- 26381854 TI - Synthesis and characterization of a stable humic-urease complex: application to barley seed encapsulation for improving N uptake. AB - BACKGROUND: Most N fertilizers added to soil are not efficiently used by plants and are lost to the atmosphere or leached from the soil, causing environmental pollution and increasing cost. Barley seed encapsulation in calcium alginate gels containing free or immobilized urease to enhance plant utilization of soil N was investigated. RESULTS: Urease was immobilized with soil humic acids (HA). A central composite face-centered design was applied to optimize the immobilization process, reaching an immobilization yield of 127%. Soil stability of urease was enhanced after the immobilization. Seed encapsulation with free urease (FU) and humic-urease complex (HUC) resulted in a urease activity retention in the coating layer of 46% and 24%, and in germination rates of 87% and 92%, respectively. Under pot culture conditions, the pots planted with seeds encapsulated with FU and HUC showed higher ammonium N (NH4 (+) -N) (26% and 64%, respectively) than the control soil at 28 days after planting (DAP). Moreover, the seed encapsulation with FU and HUC increased the N uptake 83% and 97%, respectively, at 35 DAP. CONCLUSION: Seed encapsulation with urease could substantially contribute to enhancing plant N nutrition in the early stages of seedling establishment. (c) 2015 Society of Chemical Industry. PMID- 26381855 TI - A Quantitative Framework Classifying the Palliative Care Workforce into Specialist and Generalist Components. AB - BACKGROUND: Early referral to palliative care (PC) services has been shown to improve quality of life in advanced cancer. However, limitations in trained PC workforce raise issues with the sustainability of delivering PC with early PC referral. Classifying PC into generalist and specialist components could be one approach to sustainable PC delivery models but a quantitative guide for this classification is presently lacking in the literature. OBJECTIVE: To undertake a retrospective examination of clinical data obtained from a PC benchmarking project to develop a quantitative framework guiding classification of PC services into specialist and generalist components. DESIGN: A descriptive retrospective study of data from 2726 hospitalized inpatients under the care of a tertiary consultative PC service over a 2-year period was conducted. Daily categorical symptom, overall psychological and social distress scores at the start and end of 3392 palliative care episodes as well as the number of visits made by the PC team to patients were extracted for analysis. RESULTS: More than 50% of patients had symptom, overall psychological or social distress scores of nil or mild severity at episode start and end. Approximately 20% of all 2726 patients accounted for approximately half of all visits made by the team regardless of the reasons for review. This patient percentage minority had more PC episodes starting with moderate or severe pain. These findings suggest a Pareto-like distribution in the occurrence of moderate/severe PC problems and the intensity of PC input. CONCLUSIONS: Large-scale clinical data supports the use of a Pareto-based quantitative framework for a workforce comprising of mainly generalist PC staff supported by smaller numbers of PC specialists. PMID- 26381856 TI - Effect of OnabotulinumtoxinA Injection on Depression in Chronic Migraine. AB - OBJECTIVE: The current study retrospectively evaluated patient reported outcomes (PROs) collected before and after at least 2 sessions of onabotulinumtoxinA (onabot) injections for chronic migraine. Depression was assessed by the Patient Health Questionnaire-9. METHOD: Chronic migraineurs receiving onabot were identified. In addition to the Patient Health Questionnaire-9 (PHQ9), the European Quality of Life (QOL), 5-Dimension (EQ-5D) (QOL), Headache Impact Test (HIT6), and Pain Disability Index (PDI) were reviewed across >=2 consecutive onabot injections for 6-12 months. Paired t-tests on patient's questionnaire scores before and after treatment were performed. Analysis of the PHQ9 was restricted to patients with pretreatment scores >= 10 (moderate to severe depression). Change in PHQ9 was the primary outcome, and other PROs were also evaluated. RESULTS: Four hundred twenty-nine patients met the inclusion criteria, and data were gathered from 2010 to 2014. Average age was 45 years, with 85.5% female, and 92.1% Caucasian. There were 127 patients with PHQ9 scores >=10 at baseline. Their PHQ9 scores improved from 14.4 (high-moderate) pre-onabot to 11.3 (low-moderate) post-onabot (P <.0001, 95% CI = -4.2 to -2.1); PDI improved from 4.3 to 3.8 (P = .0078, 95% CI = -0.7 to -0.1); EQ-5D improved from 0.74 to 0.77 (P = .0078; 95%CI = 0.01 to 0.04); HIT6 improved from 63.3 to 60.5 (P <.0001, 95%CI = -3.4 to -2.2). For comparison, in the PREEMPT onabot regulatory trials, HIT6 changed from 66 to 61.2 after 5 onabot injections at 24 weeks, P < .001. CONCLUSION: Onabot injections in chronic migraine patients statistically improved depression scores in patients beginning with at least moderate depression and improved scores in headache and quality of life. Onabot injections also decreased impact of headache on daily life. PMID- 26381857 TI - Fracture resistance of simulated immature teeth filled with Biodentine and white mineral trioxide aggregate - an in vitro study. AB - BACKGROUND: The purpose of this study was to evaluate the long-term fracture resistance of simulated immature teeth filled with Biodentine (BD) and white mineral trioxide aggregate (WMTA) as pulp space barriers for regenerative endodontic procedures (REPs). MATERIALS AND METHODS: Sixty extracted human maxillary anterior teeth were divided into four groups of 15 teeth each. Positive control teeth received no treatment. The remaining teeth were prepared until a size 6 Peeso (1.7 mm) could be passed 1 mm beyond the apex. Then, an engineering twist drill of 3 mm diameter was used to extend the preparation of the canal 3 mm below CEJ. The root canals were irrigated and disinfected according to AAE considerations for REPs. The canals were filled with either BD or WMTA. The negative control canals were left unfilled. The coronal access cavities were restored with glass ionomer followed by composite resin. The teeth were placed in phosphate-buffered saline solution and stored for 12 months. Each specimen was then subjected to fracture testing using a universal testing machine. The peak load to fracture and the fracture resistance were recorded, and the data were analysed statistically. RESULTS: The positive control group had the highest fracture resistance and differed significantly (P < 0.05) from the other experimental groups. No significant difference was found between BD and WMTA (P > 0.05). CONCLUSIONS: Considering the risk of cervical root fracture for pulpless infected immature teeth treated with REPs, after 12 months, there was no difference between WMTA and BD regarding the resistance to root fracture. PMID- 26381858 TI - Will models of genetic evaluation and genomic selection 'converge'? PMID- 26381859 TI - Borderline personality disorder and neuropsychological measures of executive function: A systematic review. AB - The notion that neurocognitive deficits may be core to the development of borderline personality disorder (BPD) has received considerable attention in recent years, with growing evidence pointing to cognitive deficits in executive function (EF). A relationship between EF and BPD has long been suggested by evidence of high comorbidity between BPD and disorders characterized by poor EF (e.g. attention-deficit/hyperactivity disorder); however, despite a marked increase in studies of EF and BPD in recent years, the precise nature of this relationship remains unclear. We provide a systematic review of this emerging evidence base, with respect to (1) studies of participants diagnosed with BPD in which EF has been indexed in isolation from broader cognitive processes; (2) the specific domains of EF that have been most robustly associated with BPD; and (3) whether deficits in EF are uniquely associated with BPD, independent of comorbid psychopathology. Key directions for future research are discussed with respect to strategies for measuring EF and the need for research designs that control for phenotypic overlap between BPD and related forms of psychopathology. PMID- 26381860 TI - Using elliptical best fits to characterize dental shapes. AB - A variety of geometric morphometric methods have recently been used to describe dental shape variation in human evolutionary studies. However, the applicability of these methods is limited when teeth are worn or are difficult to orient accurately. Here we show that elliptical best fits on outlines of dental tissues below the crown provide basic size- and orientation-free shape descriptors. Using the dm(2) and M(3) as examples, we demonstrate that these descriptors can be used for taxonomic purposes, such as distinguishing between Neanderthal and recent modern human teeth. We propose that this approach can be a useful alternative to existing methodology. PMID- 26381861 TI - The Evolution of Individual Maternity Care Providers to Delayed Cord Clamping: Is It the Evidence? AB - INTRODUCTION: Studies of organizational strategies to incorporate evidence into practice and change provider behavior have shown limited success. The majority of existing research centers on influencing participants to change practice versus understanding what occurs when providers have successfully shifted to an evidence based practice on their own. This study sought to explore the dynamics involved when individual midwives and physicians transitioned from a practice less based on the evidence to one with more scientific support. Delayed cord clamping was selected as the exemplar practice for the study. METHODS: A qualitative grounded theory approach was used. Seventeen providers were interviewed throughout the United States. This included 5 physicians and 12 midwives from a variety of practice configurations and birth settings including the home, birth center, and hospital. RESULTS: Five themes arose from the stories of the participants: 1) trusting colleagues, 2) believing the evidence, 3) honoring mothers and families, 4) knowing personal certainty, and 5) protecting the integrity of the mother and the baby. The themes served as drivers of change for the providers in what emerged as an evolution toward change rather than a decision to change. From the themes, the model for individual evolution to evidence-based practice was developed. DISCUSSION: Important findings included the significant role that colleagues play in an individual's journey toward a new practice, the fact that the evidence alone was never a sole driver of change, and the emergence of a discourse: Who owns the baby? The model developed as a result of this study provides a new framework for both future research and potential strategies to support the incorporation of evidence into practice. PMID- 26381862 TI - Erratum: A flavanone from Baccharis retusa (Asteraceae) prevents elastase-induced emphysema in mice by regulating NF-kappaB, oxidative stress and metalloproteinases. PMID- 26381863 TI - Erratum to: 'Ventilator-associated Pneumonia caused by commensal oropharyngeal a retrospective Analysis of a prospectively collected Database'. PMID- 26381864 TI - Ichthyosis with confetti: clinics, molecular genetics and management. AB - Ichthyosis with confetti (IWC) is an autosomal dominant congenital ichthyosis also known as ichthyosis variegata or congenital reticular ichthyosiform erythroderma. It manifests at birth with generalized ichthyosiform erythroderma or with a collodion baby picture. The erythrodermic and ichthyotic phenotype persists during life and its severity may modify. However, the hallmark of the disease is the appearance, in childhood or later in life, of healthy skin confetti-like spots, which increase in number and size with time. IWC is a very rare genodermatosis, with a prevalence <1/1,000,000 and only 40 cases reported worldwide. The most important associated clinical features include ear deformities, mammillae hypoplasia, palmoplantar keratoderma, hypertrichosis and ectropion. IWC is due to dominant negative mutations in the KRT10 and KRT1 genes, encoding for keratins 10 and keratin 1, respectively. In this context, healthy skin confetti-like spots represent "repaired" skin due to independent events of reversion of keratin gene mutations via mitotic recombination. In most cases, IWC clinical suspicion is delayed until the detection of white skin spots. Clinical features, which may represent hint to the diagnosis of IWC even before appearance of confetti-like spots, include ear and mammillae hypoplasia, the progressive development of hypertrichosis and, in some patients, of adherent verrucous plaques of hyperkeratosis. Altogether the histopathological finding of keratinocyte vacuolization and the nuclear staining for keratin 10 and keratin 1 by immunofluorescence are pathognomonic. Nevertheless, mutational analysis of KRT10 or KRT1 genes is at present the gold standard to confirm the diagnosis. IWC has to be differentiated mainly from congenital ichthyosiform erythroderma. Differential diagnosis also includes syndromic ichthyoses, in particular Netherton syndrome, and the keratinopathic ichthyoses. Most of reported IWC cases are sporadic, but familial cases with autosomal dominant mode of inheritance have been also described. Therefore, knowledge of the mutation is the only way to properly counsel the couples. No specific and satisfactory therapy is currently available for IWC. Like for other congenital ichthyoses, topical treatments (mainly emollients and keratolytics) are symptomatic and offer only temporary relief. Among systemic treatments, retinoids, in particular acitretin, improve disease symptoms in most patients. Although at present there is no curative therapy for ichthyoses, treatments have improved considerably over the years and the best therapy for each patient is always the result of both physician and patient efforts. PMID- 26381865 TI - A Radiation Dose Reduction Technology to Improve Patient Safety During Cardiac Catheterization Interventions. AB - OBJECTIVES: A novel radiation dose reduction technology was evaluated in a cardiac catheterization laboratory during routine clinical care to determine if it could reduce radiation dose to patients undergoing coronary angiography and percutaneous coronary intervention. These results were compared to patients undergoing similar procedures in a cardiac catheterization laboratory without this technology. BACKGROUND: There is a safety priority in clinical care to reduce X-ray radiation dose to patients in order to lower the risk of deterministic and stochastic effects. Dose reduction technologies must be verified in clinical settings to prove if they reduce X-ray radiation dose and to what extent. METHODS: Radiation dose data and procedure characteristics of 268 consecutive patients were collected and analyzed from a cardiac catheterization laboratory with dose reduction technology installed (referred to as Lab A, n = 135) and from a cardiac catheterization laboratory without this technology (referred as Lab B, n = 133). RESULTS: For diagnostic procedures, the median total dose-area product in Lab A was reduced by 46% (P < 0.0001) compared to Lab B, with no differences in terms of body mass index (P = 0.180), total fluoroscopy times (P = 1), number of acquired images (P = 0.920), and contrast medium (P = 0.660). For interventional procedures, the median total dose-area product in Lab A was reduced by 34% (P = 0.015) compared to Lab B, with no differences in terms of body mass index (P = 0.665), total fluoroscopy times (P = 0.765), number of acquired images (P = 0.923), and contrast medium (P = 0.969). CONCLUSIONS: This new dose reduction technology significantly reduces X-ray radiation dose without affecting fluoroscopy time, number of images, and contrast medium used during diagnostic and interventional coronary procedures. PMID- 26381867 TI - Developmental attenuation of N-methyl-D-aspartate receptor subunit expression by microRNAs. AB - BACKGROUND: N-methyl-D-aspartate receptors (NMDARs) are a subtype of ionotropic glutamate receptors and are expressed throughout the central nervous system (CNS). Their activity is required for excitatory synaptic transmission, the developmental refinement of neural circuits and for the expression of many forms of synaptic plasticity. NMDARs are obligate heterotetramers and the expression of their constituent subunits is developmentally and anatomically regulated. In rodent cortex and hippocampus, the GluN2B subunit is expressed at high levels early in development and decreases to plateau levels later while expression of the GluN2A subunit has a concomitant increase. Regulation of GluN2A and GluN2B expressions are incompletely understood. Here, we showed the influence of miRNAs in this process. FINDINGS: Two miRNAs, miR-19a and miR-539 can influence the levels of NMDARs subunits, as they target the mRNAs encoding GluN2A and GluN2B respectively. MiR-539 also modified the expression of the transcription factor REST, a known regulator of NMDAR subunit expression. CONCLUSIONS: miR-19a and miR 539, in collaboration with REST, serve to set the levels of GluN2A and GluN2B precisely during development. These miRNAs offer an entry point for interventions that affect plasticity and a novel approach to treat neurodegenerative diseases. PMID- 26381868 TI - Inhibition of Diaphanous Formin Signaling In Vivo Impairs Cardiovascular Development and Alters Smooth Muscle Cell Phenotype. AB - OBJECTIVE: We and others have previously shown that RhoA-dependent stimulation of myocardin-related transcription factor nuclear localization promotes smooth muscle cell (SMC) marker gene expression. The goal of this study was to provide direct in vivo evidence that actin polymerization by the diaphanous-related formins contributes to the regulation of SMC differentiation and phenotype. APPROACH AND RESULTS: Conditional Cre-based genetic approaches were used to overexpress a well-characterized dominant-negative variant of mDia1 (DNmDia) in SMC. DNmDia expression in SM22-expressing cells resulted in embryonic and perinatal lethality in ~20% of mice because of defects in myocardial development and SMC investment of peripheral vessels. Although most DNmDia(+)/SM22Cre(+) mice exhibited no overt phenotype, the re-expression of SMC differentiation marker gene expression that occurs after carotid artery ligation was delayed, and this effect was accompanied by a significant decrease in myocardin-related transcription factor-A nuclear localization. Interestingly, neointima growth was inhibited by expression of DNmDia in SMC and this was likely because of a defect in directional SMC migration and not to defects in SMC proliferation or survival. Finally, by using the tamoxifen-inducible SM MHC-CreER(T2) line, we showed that SMC-specific induction of DNmDia in adult mice decreased SMC marker gene expression. CONCLUSIONS: Our demonstration that diaphanous-related formin signaling plays a role in heart and vascular development and the maintenance of SMC phenotype provides important new evidence that Rho/actin/myocardin-related transcription factor signaling plays a critical role in cardiovascular function. PMID- 26381870 TI - Therapeutic Angiogenesis by Ultrasound-Mediated MicroRNA-126-3p Delivery. AB - OBJECTIVE: MicroRNAs are involved in many critical functions, including angiogenesis. Ultrasound-targeted microbubble destruction (UTMD) is a noninvasive technique for targeted vascular transfection of plasmid DNA and may be well suited for proangiogenic microRNA delivery. We aimed to investigate UTMD of miR 126-3p for therapeutic angiogenesis in chronic ischemia. APPROACH AND RESULTS: The angiogenic potential of miR-126-3p was tested in human umbilical vein endothelial cells in vitro. UTMD of miR-126-3p was tested in vivo in Fischer-344 rats before and after chronic left femoral artery ligation, evaluating target knockdown, miR-126-3p and miR-126-5p expression, phosphorylated Tie2 levels, microvascular perfusion, and vessel density. In vitro, miR-126-3p-transfected human umbilical vein endothelial cells showed repression of sprouty-related protein-1 and phosphatidylinositol-3-kinase regulatory subunit 2, negative regulators of vascular endothelial growth factor and angiopoietin-1 signaling, increased phosphorylated Tie2 mediated by knockdown of phosphatidylinositol-3 kinase regulatory subunit 2 and greater angiogenic potential mediated by both vascular endothelial growth factor/vascular endothelial growth factor R2 and angiopoietin-1 /Tie2 effects. UTMD of miR-126-3p resulted in targeted vascular transfection, peaking early after delivery and lasting for >3 days, and resulting in inhibition of sprouty-related protein-1 and phosphatidylinositol-3-kinase regulatory subunit 2, with minimal uptake in remote organs. Finally, UTMD of miR 126-3p to chronic ischemic hindlimb muscle resulted in improved perfusion, vessel density, enhanced arteriolar formation, pericyte coverage, and phosphorylated Tie2 levels, without affecting miR-126-5p or delta-like 1 homolog levels. CONCLUSIONS: UTMD of miR-126 results in improved tissue perfusion and vascular density in the setting of chronic ischemia by repressing sprouty-related protein 1 and phosphatidylinositol-3-kinase regulatory subunit 2 and enhancing vascular endothelial growth factor and angiopoietin-1 signaling, with no effect on miR-126 5p. UTMD is a promising platform for microRNA delivery, with applications for therapeutic angiogenesis. PMID- 26381869 TI - Endothelial Nitric Oxide Synthase-Derived Nitric Oxide Prevents Dihydrofolate Reductase Degradation via Promoting S-Nitrosylation. AB - OBJECTIVE: Dihydrofolate reductase (DHFR) is a key protein involved in tetrahydrobiopterin (BH4) regeneration from 7,8-dihydrobiopterin (BH2). Dysfunctional DHFR may induce endothelial nitric oxide (NO) synthase (eNOS) uncoupling resulting in enzyme production of superoxide anions instead of NO. The mechanism by which DHFR is regulated is unknown. Here, we investigate whether eNOS-derived NO maintains DHFR stability. APPROACH AND RESULTS: DHFR activity, BH4 content, eNOS activity, and S-nitrosylation were assessed in human umbilical vein endothelial cells and in aortas isolated from wild-type and eNOS knockout mice. In human umbilical vein endothelial cells, depletion of intracellular NO by transfection with eNOS-specific siRNA or by the NO scavenger 2-(4-carboxyphenyl) 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO)-both of which had no effect on DHFR mRNA levels-markedly reduced DHFR protein levels in parallel with increased DHFR polyubiquitination. Supplementation of S-nitroso-l-glutathione (GSNO), a NO donor, or MG132, a potent inhibitor of the 26S proteasome, prevented eNOS silencing and PTIO-induced DHFR reduction in human umbilical vein endothelial cells. PTIO suppressed S-nitrosylation of DHFR, whereas GSNO promoted DHFR S-nitrosylation. Mutational analysis confirmed that cysteine 7 of DHFR was S nitrosylated. Cysteine 7 S-nitrosylation stabilized DHFR from ubiquitination and degradation. Experiments performed in aortas confirmed that PTIO or eNOS deficiency reduces endothelial DHFR, which can be abolished by MG132 supplementation. CONCLUSIONS: We conclude that S-nitrosylation of DHFR at cysteine 7 by eNOS-derived NO is crucial for DHFR stability. We also conclude that NO-induced stabilization of DHFR prevents eNOS uncoupling via regeneration of BH4, an essential eNOS cofactor. PMID- 26381873 TI - Errata. PMID- 26381871 TI - Vitamin D Protects Against Atherosclerosis via Regulation of Cholesterol Efflux and Macrophage Polarization in Hypercholesterolemic Swine. AB - OBJECTIVE: Prevalence of vitamin D (VD) deficiency and its association with the risk of cardiovascular disease prompted us to evaluate the effect of VD status on lipid metabolism and atherosclerosis in hypercholesterolemic microswine. APPROACH AND RESULTS: Yucatan microswine were fed with VD-deficient (0 IU/d), VD sufficient (1000 IU/d), or VD-supplemented (3000 IU/d) high-cholesterol diet for 48 weeks. Serum lipids and 25(OH)-cholecalciferol levels were measured biweekly. Histology and biochemical parameters of liver and arteries were analyzed. Effect of 1,25(OH)2D3 on cholesterol metabolism was examined in human hepatocyte carcinoma cell line (HepG2) and human monocytic cell line (THP-1) macrophage derived foam cells. VD deficiency decreased plasma high-density lipoprotein levels, expression of liver X receptors, ATP-binding membrane cassette transporter A1, and ATP-binding membrane cassette transporter G1 and promoted cholesterol accumulation and atherosclerosis in hypercholesterolemic microswine. VD promoted nascent high-density lipoprotein formation in HepG2 cells via ATP binding membrane cassette transporter A1-mediated cholesterol efflux. Cytochrome P450 (CYP)27B1 and VD receptor were predominantly present in the CD206(+) M2 macrophage foam cell-accumulated cores in coronary artery plaques. 1,25(OH)2D3 increased the expression of liver X receptors, ATP-binding membrane cassette transporter A1, and ATP-binding membrane cassette transporter G1 and promoted cholesterol efflux in THP-1 macrophage-derived foam cells. 1,25(OH)2D3 decreased intracellular free cholesterol and polarized macrophages to M2 phenotype with decreased expression of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 under lipopolysaccharide stimulation. 1,25(OH)2D3 markedly induced CYP27A1 expression via a VD receptor-dependent c-Jun N-terminal kinase (JNK) 1/2 signaling pathway and increased 27-hydroxycholesterol levels, which induced liver X receptors, ATP-binding membrane cassette transporter A1, and ATP-binding membrane cassette transporter G1 expression and stimulated cholesterol efflux that was inhibited by VD receptor antagonist and JNK1/2 signaling inhibitor in THP-1 macrophage-derived foam cell. CONCLUSIONS: VD protects against atherosclerosis in hypercholesterolemic swine via controlling cholesterol efflux and macrophage polarization via increased CYP27A1 activation. PMID- 26381872 TI - Vascular and plaque imaging with ultrasmall superparamagnetic particles of iron oxide. AB - Cardiovascular Magnetic Resonance (CMR) has become a primary tool for non invasive assessment of cardiovascular anatomy, pathology and function. Existing contrast agents have been utilised for the identification of infarction, fibrosis, perfusion deficits and for angiography. Novel ultrasmall superparamagnetic particles of iron oxide (USPIO) contrast agents that are taken up by inflammatory cells can detect cellular inflammation non-invasively using CMR, potentially aiding the diagnosis of inflammatory medical conditions, guiding their treatment and giving insight into their pathophysiology. In this review we describe the utilization of USPIO as a novel contrast agent in vascular disease. PMID- 26381875 TI - The influence of prophylactic proton pump inhibitor treatment on the development of symptomatic marginal ulceration in Roux-en-Y gastric bypass patients: a historic cohort study. AB - BACKGROUND: Marginal ulceration at the gastrojejunostomy is a serious complication after laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) and occurs in 1%-16% of patients. Proton pump inhibitors (PPIs) might lower the occurrence of these ulcers. OBJECTIVES: The aim of the present study was to evaluate the effect of 6 months prophylactic usage of PPIs on the development of marginal ulceration and compare this with a historic patient control group. SETTING: A single institution cohort at a bariatric center of excellence, The Sint Lucas Andreas Zienkenhuis, Amsterdam METHODS: A consecutive database of patients who underwent LRYGB from November 2007 to September 2012 in a single institution was retrospectively reviewed. From August 2011, patients received a standard dose of pantozol 40 mg once daily directly postoperatively for 6 months. No standard PPI prophylaxis was administered before August 2011, and the patients not using PPIs in this historic cohort served as the control group. RESULTS: A total of 610 patients underwent LRYGB, of which 128 patients (21.0%) underwent revisional surgery. Postoperative PPIs were administered in the intervention group of 337 patients, compared with the historic control group consisting of 273 patients. Six patients (1.2%) who received postoperative PPIs versus 20 patients (7.3 %) in the historic control group developed marginal ulceration (P = .001). Patients using proton pump inhibitors developed fewer gastrointestinal complaints postoperatively (P< .001). CONCLUSIONS: Routine usage of PPIs reduced the occurrence of marginal ulceration after LRYGB. PMID- 26381876 TI - The long-term impact of biliopancreatic diversion on glycemic control in the severely obese with type 2 diabetes mellitus in relation to preoperative duration of diabetes. AB - BACKGROUND: Bariatric surgery has been shown to be effective in severely obese patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: Evaluate the long-term efficacy of biliopancreatic diversion (BPD) for the treatment of T2DM depending on the preoperative duration of T2DM. SETTING: University Hospital. METHODS: Retrospective analysis investigating 2 subsets of severely obese patients who had undergone BPD from 1984 to 1995. The first included 52 patients with a preoperative T2DM duration of ~1 year (SD group - 49 on oral agents and 3 on insulin), and the second included 68 patients who had been diabetic for>5 years before BPD (LD group - 52 on oral agents and 16 on insulin). Postoperatively, T2DM was regarded as in remission when fasting serum glucose (FSG) was lower than 100 mg/dL on regular diet and without antidiabetic therapy. RESULTS: In the SD patients, the number of individuals without T2DM remission were lower both at 5 10 (0/31, 0% of patients, versus 8/54, 15% of patients, p<.04) and at>15 years (1/28, 3% of patients, versus 10/41, 24% of patients, p<.0012). Furthermore, after BPD, the number of patients with dyslipidemia strongly reduced (p<.001) in both groups, values at 5-10 years remaining very similar to those observed at>15 years. CONCLUSION: These results indicate that severely obese patients with longer T2DM duration have a worse metabolic outcome maintained at long and very long term following BPD. PMID- 26381877 TI - RNA-seq analyses of changes in the Anopheles gambiae transcriptome associated with resistance to pyrethroids in Kenya: identification of candidate-resistance genes and candidate-resistance SNPs. AB - BACKGROUND: The extensive use of pyrethroids for control of malaria vectors, driven by their cost, efficacy and safety, has led to widespread resistance. To favor their sustainable use, the World Health Organization (WHO) formulated an insecticide resistance management plan, which includes the identification of the mechanisms of resistance and resistance surveillance. Recognized physiological mechanisms of resistance include target site mutations in the para voltage-gated sodium channel, metabolic detoxification and penetration resistance. Such understanding of resistance mechanisms has allowed the development of resistance monitoring tools, including genotyping of the kdr mutation L1014F/S in the para gene. METHODS: The sequence-based technique RNA-seq was applied to study changes in the transcriptome of deltamethrin-resistant and -susceptible Anopheles gambiae mosquitoes from the Western Province of Kenya. The resulting gene expression profiles were compared to data in the most recent literature to derive a list of candidate resistance genes. RNA-seq data were analyzed also to identify sequence polymorphisms linked to resistance. RESULTS: A total of five candidate-resistance genes (AGAP04177, AGAP004572, AGAP008840, AGAP007530 and AGAP013036) were identified with altered expression between resistant and susceptible mosquitoes from West and East Africa. A change from G to C at position 36043997 of chromosome 3R resulting in A101G of the sulfotransferase gene AGAP009551 was significantly associated with the resistance phenotype (odds ratio: 5.10). The kdr L1014S mutation was detected at similar frequencies in both phenotypically resistant and susceptible mosquitoes, suggesting it is no longer fully predictive of the resistant phenotype. CONCLUSIONS: Overall, these results support the conclusion that resistance to pyrethroids is a complex and evolving phenotype, dependent on multiple gene functions including, but not limited to, metabolic detoxification. Functional convergence among metabolic detoxification genes may exist, with the role of each gene being modulated by the life history and selection pressure on mosquito populations. As a consequence, biochemical assays that quantify overall enzyme activity may be a more suitable method for predicting metabolic resistance than gene-based assays. PMID- 26381878 TI - Health and economic consequences of different options for timing the coordinated global cessation of the three oral poliovirus vaccine serotypes. AB - BACKGROUND: World leaders remain committed to globally-coordinated oral poliovirus vaccine (OPV) cessation following successful eradication of wild polioviruses, but the best timing and strategy for implementation depend on existing and emerging conditions. METHODS: Using an existing integrated global poliovirus risk management model, we explore alternatives to the current timing plan of coordinated cessation of each OPV serotype (i.e., OPV1, OPV2, and OPV3 cessation for serotypes 1, 2, and 3, respectively). We assume the current timing plan involves OPV2 cessation in 2016 followed by OPV1 and OPV3 cessation in 2019 and we compare this to alternative timing options, including cessation of all three serotypes in 2018 or 2019, and cessation of both OPV2 and OPV3 in 2017 followed by OPV1 in 2019. RESULTS: If Supplemtal Immunization Activity frequency remains sufficiently high through cessation of the last OPV serotype, then all OPV cessation timing options prevent circulating vaccine-derived poliovirus (cVDPV) outbreaks after OPV cessation of any serotype. The various OPV cessation timing options result in relatively modest differences in expected vaccine associated paralytic poliomyelitis cases and expected total of approximately 10 13 billion polio vaccine doses used. However, the expected amounts of vaccine of different OPV formulations needed changes dramatically with each OPV cessation timing option. Overall health economic impacts remain limited for timing options that only change the OPV formulation but preserve the currently planned year for cessation of the last OPV serotype and the global introduction of inactivated poliovirus vaccine (IPV) introduction. Earlier cessation of the last OPV serotype or later global IPV introduction yield approximately $1 billion in incremental net benefits due to saved vaccination costs, although the logistics of implementation of OPV cessation remain uncertain and challenging. CONCLUSIONS: All countries should maintain the highest possible levels of population immunity to transmission for each poliovirus serotype prior to the coordinated cessation of the OPV serotype to manage cVDPV risks. If OPV2 cessation gets delayed, then global health leaders should consider other OPV cessation timing options. PMID- 26381879 TI - Effect of Chondroitin Sulphate on Pro-Inflammatory Mediators and Disease Activity in Patients with Inflammatory Bowel Disease. AB - BACKGROUND/AIMS: To evaluate the incidence rate of relapse in patients with inflammatory bowel disease (IBD) undergoing chondroitin sulphate (CS) treatment and its effect on the concentrations of several pro-inflammatory proteins. METHODS: Prospective, observational, 12-month follow-up study in patients with IBD in remission, starting CS (Condrosan(r), Bioiberica S.A.) treatment for osteoarthritis (OA). Crohn's Disease Activity Index and modified Truelove-Witts severity index were calculated for Crohn's disease and ulcerative colitis (UC) respectively. Levels of vascular endothelial growth factor (VEGFA), -C, fibroblast growth factor 2, hepatocyte growth factor, angiopoietin (Ang)-1, Ang 2, transforming growth factor beta, tumour necrosis factor alpha, interleukin (IL)-1beta, IL-6, IL-12, IL-17, IL-23, intracellular adhesion molecule-1, vascular adhesion molecule-1, matrix metalloproteinase-3 and PGE2 were quantified by ELISA. OA joint pain was evaluated using a visual analogue scale. RESULTS: A total of 37 patients (19 UC and 18 Crohn's disease) were included. The mean values for OA joint pain decreased after 12 months from 5.9 +/- 2.8 to 3.0 +/- 2.3 (p < 0.05). Only 1 patient (with UC) flared during follow-up. The incidence rate of relapse was 3.4% per patient-year of follow-up. Mean serum VEGFA levels increased between baseline (492 pg/ml) and 12-month treatment (799 pg/ml; p < 0.05). CONCLUSION: The incidence of IBD relapse in patients under CS treatment was lower than that generally reported. This treatment might modulate VEGFA. CS decreases OA-related pain in patients with IBD. PMID- 26381881 TI - Silencing of ATPase Inhibitory Factor 1 Inhibits Cell Growth via Cell Cycle Arrest in Bladder Cancer. AB - OBJECTIVE: The role of the ATPase inhibitory factor 1 (IF1) is inhibit the hydrolase activity of F1Fo-ATPase when oxidative phosphorylation is impaired. It has been demonstrated that IF1 is overexpressed in various carcinomas and mediates tumor cell activities, but the detailed mechanisms of IF1-mediated tumor progression and the link between IF1 and cell cycle progression remain unclear. Herein, we aimed to investigate the potential role of IF1 in cell cycle progression of human bladder cancer (BCa). METHODS: The expression of IF1 was analyzed by immunohistochemistry in tumor tissues. Western blot was used to detect protein expression in the cells. Cell proliferation was determined by MTT and colony formation assays. The cell cycle was analyzed using flow cytometry. RESULTS: We firstly showed IF1 was overexpressed in BCa. Silencing of IF1 by small interfering RNA led to a significant decrease in cell proliferation and migration in T24 and UM-UC-3 cells. Importantly, IF1 knockdown caused cell cycle arrest at G0/G1 stage and decreased the protein level of cyclin E/cyclin dependent kinases (cdk) 2 and/or cyclin D/cdk4/cdk6. CONCLUSION: These results suggest the inhibitory effect of IF1 knockdown on BCa cell proliferation is via the suppression of cyclins and cdks related to G1/S transition and then induction of G0/G1 arrest, and firstly indicate IF1 mediates the tumor cell cycle. We concluded that IF1 may be a novel therapeutic target for BCa. PMID- 26381880 TI - Zinc and diabetes mellitus: understanding molecular mechanisms and clinical implications. AB - BACKGROUND: Diabetes mellitus is a leading cause of morbidity and mortality worldwide. Studies have shown that Zinc has numerous beneficial effects in both type-1 and type-2 diabetes. We aim to evaluate the literature on the mechanisms and molecular level effects of Zinc on glycaemic control, beta-cell function, pathogenesis of diabetes and its complications. METHODS: A review of published studies reporting mechanisms of action of Zinc in diabetes was undertaken in PubMed and SciVerse Scopus medical databases using the following search terms in article title, abstract or keywords; ("Zinc" or "Zn") and ("mechanism" or "mechanism of action" or "action" or "effect" or "pathogenesis" or "pathology" or "physiology" or "metabolism") and ("diabetes" or "prediabetes" or "sugar" or "glucose" or "insulin"). RESULTS: The literature search identified the following number of articles in the two databases; PubMed (n = 1799) and SciVerse Scopus (n = 1879). After removing duplicates the total number of articles included in the present review is 111. Our results show that Zinc plays an important role in beta cell function, insulin action, glucose homeostasis and the pathogenesis of diabetes and its complications. CONCLUSION: Numerous in-vitro and in-vivo studies have shown that Zinc has beneficial effects in both type-1 and type-2 diabetes. However further randomized double-blinded placebo-controlled clinical trials conducted for an adequate duration, are required to establish therapeutic safety in humans. PMID- 26381882 TI - Transcriptome Analysis Reveals the Mechanism Underlying the Production of a High Quantity of Chlorogenic Acid in Young Leaves of Lonicera macranthoides Hand. Mazz. AB - Lonicera macranthoides Hand.-Mazz (L. macranthoides) is a medicinal herb that is widely distributed in southern China. The biosynthetic and metabolic pathways for a core secondary metabolite in L. macranthoides, chlorogenic acid (CGA), have been elucidated in many species. However, the mechanisms of CGA biosynthesis and the related gene regulatory network in L. macranthoides are still not well understood. In this study, CGA content was quantified by high performance liquid chromatography (HPLC), and CGA levels differed significantly among three tissues; specifically, the CGA content in young leaves (YL) was greater than that in young stems (YS), which was greater than that in mature flowers (MF). Transcriptome analysis of L. macranthoides yielded a total of 53,533,014 clean reads (average length 90 bp) and 76,453 unigenes (average length 703 bp). A total of 3,767 unigenes were involved in biosynthesis pathways of secondary metabolites. Of these unigenes, 80 were possibly related to CGA biosynthesis. Furthermore, differentially expressed genes (DEGs) were screened in different tissues including YL, MF and YS. In these tissues, 24 DEGs were found to be associated with CGA biosynthesis, including six phenylalanine ammonia lyase (PAL) genes, six 4-coumarate coenzyme A ligase (4CL) genes, four cinnamate 4-Hydroxylase (C4H) genes, seven hydroxycinnamoyl transferase/hydroxycinnamoyl-CoA quinate transferase HCT/HQT genes and one coumarate 3-hydroxylase (C3H) gene.These results further the understanding of CGA biosynthesis and the related regulatory network in L. macranthoides. PMID- 26381883 TI - Future Discounting in Congo Basin Hunter-Gatherers Declines with Socio-Economic Transitions. AB - Humans have a tendency to discount the future; that is we value small, short-term rewards over larger, long-term rewards. The degree of future discounting, however, changes in response to socio-ecological factors. Here, we study Mbendjele BaYaka hunter-gatherers of northern Congo and their farmer neighbours to investigate adaptations in inter-temporal preferences in humans. We argue that in immediate-return systems, where food storage is absent and egalitarianism is enforced through levelling mechanisms, future discounting is an adaptive strategy to prevent wealth accumulation and the emergence of hierarchies. This ensures food sharing and allows for survival in unpredictable environments where there is risk of an energy shortfall. On the other hand, when food storage is made possible by the emergence of agriculture or as seen in some delayed-return hunter gatherer populations, wealth accumulation, hierarchies and lower discount rates become the adaptive strategy. Therefore, individuals in immediate-return, egalitarian societies will discount the future more than those in non egalitarian, delayed-return societies. Consistent with the predictions we found that market integration and socio-economic transitions decrease the future discounting in Mbendjele hunter-gatherers. Our measures of socio-economic differences marked this transition in hunter-gatherers living in a logging town. The degree of future-discounting was the same between more market-integrated hunter-gatherers and their farmer neighbours. PMID- 26381884 TI - Hypocholesterolemia predicts relapses in patients with Takayasu arteritis. AB - OBJECTIVES: The aim of this study is to identify variables at diagnosis to predict the subsequent relapse in patients with Takayasu arteritis (TA). METHODS: We retrospectively analyzed 33 patients with TA in our hospitals from April 2000 to July 2015. We collected baseline variables at diagnosis including clinical symptoms and laboratory data using medical records and investigated associations of these indices with subsequent relapses. RESULTS: The patients included two males and 31 females (94%). The median age at diagnosis was 39 years old, and the median follow-up duration was 90 months. Relapse was noted in 18 patients (55%). Only lower total cholesterol (Tcho) [median, 117 mg/dL (relapse) vs. 182 mg/dL (nonrelapse)] was preferentially distributed in the relapse group as compared with the non-relapse group. Multivariable logistic analysis showed that hypocholesterolemia (<150 mg/dL) at diagnosis was the only predictor of subsequent relapse (odds ratio: 5.43, 95% confidence interval: 1.13-30.19; p = 0.035). The nonrelapse survival rate was significantly lower in the group with a Tcho level <150 mg/dL by Kaplan-Meier estimate (p < 0.001). CONCLUSIONS: We found that hypocholesterolemia at diagnosis is a predictor of subsequent relapse in patients with TA. PMID- 26381885 TI - Determining Ultrasonic Vocalization Preferences in Mice using a Two-choice Playback Test. AB - Mice emit ultrasonic vocalizations (USVs) during a variety of conditions, such as pup isolation and adult social interactions. These USVs differ with age, sex, condition, and genetic background of the emitting animal. Although many studies have characterized these differences, whether receiver mice can discriminate among objectively different USVs and show preferences for particular sound traits remains to be elucidated. To determine whether mice can discriminate between different characteristics of USVs, a playback experiment was developed recently, in which preference responses of mice to two different USVs could be evaluated in the form of a place preference. First, USVs from mice were recorded. Then, the recorded USVs were edited, trimmed accordingly, and exported as stereophonic sound files. Next, the USV amplitudes generated by the two ultrasound emitters used in the experiment were adjusted to the same sound pressure level. Nanocrystalline silicon thermo-acoustic emitters were used to play the USVs back. Finally, to investigate the preference of subject mice to selected USVs, pairs of two differing USV signals were played back simultaneously in a two-choice test box. By repeatedly entering a defined zone near an ultrasound emitter and searching the wire mesh in front of the emitter, the mouse reveals its preference for one sound over another. This model allows comparing the attractiveness of the various features of mouse USVs, in various contexts. PMID- 26381886 TI - Axillary Cystic Hygroma. PMID- 26381887 TI - A Risk Score to Guide Cystatin C Testing to Detect Occult-Reduced Estimated Glomerular Filtration Rate. AB - BACKGROUND/AIMS: Persons with occult-reduced estimated glomerular filtration rate (eGFR<60 ml/min/1.73 m2 detected by serum cystatin C but missed by creatinine) have high risk for complications. Among persons with preserved kidney function by creatinine-based eGFR (eGFRcreat>60 ml/min/1.73 m2), tools to guide cystatin C testing are needed. METHODS: We developed a risk score to estimate an individual's probability of reduced eGFR by cystatin C (eGFRcys<60 ml/min/1.73 m2) in The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and externally validated in the Third National Health and Nutrition Examination Survey (NHANES III). We used logistic regression with Bayesian model averaging and variables available in practice. We assessed performance characteristics using calibration and discrimination measures. RESULTS: Among 24,877 adults with preserved kidney function by creatinine, 13.5% had reduced eGFRcys. Older and Black participants, current smokers and those with higher body mass index, lower eGFRcreat, diabetes, hypertension and history of cardiovascular disease were more likely to have occult-reduced eGFR (p<0.001). The final risk function had a c-statistic of 0.87 in REGARDS and 0.84 in NHANES. By risk score, 72% of occult-reduced eGFR cases were detected by screening only 22% of participants. CONCLUSIONS: A risk score using characteristics readily accessible in clinical practice can identify the majority of persons with reduced eGFRcys, which is missed by creatinine. PMID- 26381888 TI - Exploring Biological Motion Processing in Parkinson's Disease Using Temporal Dilation. AB - Biological motion (BM) perception is the compelling ability of the visual system to perceive complex animated movements effortlessly and promptly. A recent study has shown that BM can automatically lengthen perceived temporal duration independent of global configuration. The present study aimed mainly to investigate this temporal dilation effect of BM signals in Parkinson's disease (PD) patients. We used the temporal dilation effect as an implicit measure of visual processing of BM. In all, 32 PD patients (under off-therapy conditions) and 32 healthy controls (HCs) participated in our study. In each trial, an upright BM sequence and an inverted BM sequence were presented within an interval in the center of the screen. We tested both canonical and scrambled BM sequences; the scrambled ones were generated by disturbing the global configuration of the canonical ones but preserving exactly the same local motion components. Observers were required to make a verbal two-alternative forced choice response to indicate which interval (the first or the second) appeared longer. Statistical analyses were conducted on the points of subjective equality (PSEs). We found that the temporal dilation effect was significantly reduced for PD patients compared with HCs in both canonical and scrambled BM conditions. Moreover, no temporal dilation effects of scrambled BM were shown in both early- and late-stage PD patients, while the temporal dilation effect of canonical BM was relatively preserved in the early stages. PMID- 26381889 TI - Genetic Diversity in Lens Species Revealed by EST and Genomic Simple Sequence Repeat Analysis. AB - Low productivity of pilosae type lentils grown in South Asia is attributed to narrow genetic base of the released cultivars which results in susceptibility to biotic and abiotic stresses. For enhancement of productivity and production, broadening of genetic base is essentially required. The genetic base of released cultivars can be broadened by using diverse types including bold seeded and early maturing lentils from Mediterranean region and related wild species. Genetic diversity in eighty six accessions of three species of genus Lens was assessed based on twelve genomic and thirty one EST-SSR markers. The evaluated set of genotypes included diverse lentil varieties and advanced breeding lines from Indian programme, two early maturing ICARDA lines and five related wild subspecies/species endemic to the Mediterranean region. Genomic SSRs exhibited higher polymorphism in comparison to EST SSRs. GLLC 598 produced 5 alleles with highest gene diversity value of 0.80. Among the studied subspecies/species 43 SSRs detected maximum number of alleles in L. orientalis. Based on Nei's genetic distance cultivated lentil L. culinaris subsp. culinaris was found to be close to its wild progenitor L. culinaris subsp. orientalis. The Prichard's structure of 86 genotypes distinguished different subspecies/species. Higher variability was recorded among individuals within population than among populations. PMID- 26381890 TI - Ramped hybrid encoding for improved ultrashort echo time imaging. AB - PURPOSE: We propose a new acquisition to minimize the per-excitation encoding duration and improve the imaging capability for short T2 * species. METHODS: In the proposed ramped hybrid encoding (RHE) technique, gradients are applied before the radiofrequency (RF) pulse as in pointwise encoding time reduction with radial acquisition (PETRA) and zero echo time (ZTE) imaging. However, in RHE, gradients are rapidly ramped after RF excitation to the maximum amplitude to minimize encoding duration. To acquire central k-space data not measured during RF deadtime, RHE uses a hybrid encoding scheme similar to PETRA. A new gradient calibration method based on single-point imaging was developed to estimate the k space trajectory and enable robust and high quality reconstruction. RESULTS: RHE enables a shorter per-excitation encoding time and provides the highest spatial resolution among ultrashort T2 * imaging methods. In phantom and in vivo experiments, RHE exhibited robust imaging with negligible chemical shift or blurriness caused by T2 * decay and unwanted slice selection. CONCLUSION: RHE allows the shortest per-excitation encoding time for ultrashort T2 * imaging, which alleviates the impact of fast T2 * decay occurring during encoding, and enables improved spatial resolution. Magn Reson Med 76:814-825, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26381891 TI - Source-Related Effects of Wastewater on Transcription Factor (AhR, CAR and PXR) Mediated Induction of Gene Expression in Cultured Rat Hepatocytes and Their Association with the Prevalence of Antimicrobial-Resistant Escherichia coli. AB - Extracts of wastewater collected from 4 sewage treatment plants (STPs) receiving effluents from different sources in South India were investigated for their levels of transcription factor-mediated gene induction in primary cultured rat hepatocytes. In addition, the relation between gene induction levels and the prevalence of antimicrobial-resistant Escherichia coli (E. coli) in wastewater was examined. STP-3, which treats only hospital wastewater, exhibited significantly greater induction potency of all 6 drug metabolizing cytochrome P450 (CYP) genes examined, CYP1A1, 1A2, 1B1, 2B15, 3A1, and 3A2, whereas the wastewater at STP-1, which exclusively receives domestic sewage, showed significantly diminished levels of induction of 3 CYP genes when compared to the levels of CYP induction at STP-2, which receives mixed wastewater. Samples collected during the monsoon season showed a significantly altered gene induction capacity compared to that of samples from the pre-monsoon period. The data suggest that the toxicity of wastewater in STPs was not significantly diminished during the treatment process. The chemical-gene interaction data predicted that a vast number of chemicals present in the wastewater would stimulate the genes studied in the rat hepatocytes. The multivariable logistic regression analysis demonstrated that the prevalence of isolates resistant to cefotaxime, imipenem and streptomycin was significantly correlated with the levels of induction of at least three CYP-isozymes in STP wastewater. In addition, the resistance of isolates in treatment plants was not altered by the treatment steps, whereas the sampling season did have an impact on the resistance to specific antimicrobials. The identification of receptor-mediated gene regulation capacities offers important data not limited to the (synergistic) physiological role of chemicals in biological systems but may provide new insight into the link between the effects of known/unknown drugs and prevalence of antimicrobial-resistant bacteria in wastewater. PMID- 26381892 TI - Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease. AB - Little is known about the optimal duration of therapy with an anti-tumor necrosis factor (TNF) agent and/or an immunomodulator for patients with inflammatory bowel disease (IBD). We performed a systematic search of the literature to identify studies reporting after de-escalation (drug cessation or dose reduction) of anti TNF agents and/or immunomodulators in patients in remission from IBD. Studies were reviewed according to the type of IBD and drug. Rates of relapse, factors associated with relapse, and response to re-treatment were determined. Our search yielded 6315 unique citations; we analyzed findings from 69 studies (18 on de escalation [drug cessation or dose reduction] of immunomodulator monotherapy, 8 on immunomodulator de-escalation from combination therapy, and 43 on de escalation of anti-TNF agents, including 3 during pregnancy) comprising 4672 patients. Stopping immunomodulator monotherapy after a period of remission was associated with high rates of relapse in patients with Crohn's disease or ulcerative colitis (approximately 75% of patients experienced a relapse within 5 years after therapy was stopped). Most studies of patients with Crohn's disease who discontinued an immunomodulator after combination therapy found that rates of relapse did not differ from those of patients who continued taking the drug (55% 60% had disease relapse 24 months after they stopped taking the immunomodulator). The only study in patients with ulcerative colitis supported continued immunomodulator use. Approximately 50% of patients who discontinued anti-TNF agents after combination therapy maintained remission 24 months later, but the proportion in remission decreased with time. Markers of disease activity, poor prognostic factors, and complicated or relapsing disease course were associated with future relapse. In conclusion, based on a systematic review, 50% or more of patients with IBD who cease therapy have a disease relapse. Further studies are required to accurately identify subgroups of patients who are good candidates for discontinuation of treatment. The decision to withdraw a drug should be made for each individual based on patient preference, disease markers, consequences of relapse, safety, and cost. PMID- 26381893 TI - Assessments of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in Korean patients with psoriasis vulgaris and psoriatic arthritis. AB - The objective of this retrospective study is to assess neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as inflammatory markers in patients with psoriasis and psoriatic arthritis (PsA). A hundred and eleven psoriasis patients and 25 PsA patients were compared with 94 healthy controls. Demographic, clinical and laboratory information were collected and analyzed. NLR and PLR were calculated. White blood cell (WBC), neutrophils, eosinophils and NLR were increased in psoriasis patients compared with controls. WBC, neutrophils, NLR, monocytes, platelets and PLR were increased in PsA patients compared with both controls and psoriasis patients. Erythrocyte sedimentation rate (ESR) and C reactive protein were significantly higher in PsA patients compared with psoriasis patients. Among psoriasis patients, Psoriasis Area and Severity Index (PASI) score correlated positively with platelets, NLR and PLR. These parameters were all significantly higher in moderate to severe psoriasis patients (PASI >= 10) compared with mild patients (PASI < 10). Elevated platelets, NLR and PLR were significantly associated with the increased PASI scores in multivariate analysis. NLR, PLR and ESR were statistically significant predictors for the presence of PsA in psoriasis patients. NLR was the strongest predictor (odds ratio = 3.351, P = 0.005). In conclusion, elevated NLR and PLR were significantly associated with psoriasis and PsA. Both NLR and PLR were strong predictors for the presence of PsA among psoriasis patients. PMID- 26381894 TI - A novel manual therapy programme during radiation therapy for head and neck cancer - our clinical experience with five patients. PMID- 26381895 TI - Gene Expression Profiling and Molecular Signaling of Dental Pulp Cells in Response to Tricalcium Silicate Cements: A Systematic Review. AB - INTRODUCTION: Signaling molecules and responding dental pulp stem cells are the 2 main control keys of dentin regeneration/dentinogenesis. The aim of this study was to present a systematic review investigating the gene expression of various dental pulp cells in response to different variants of tricalcium silicate cements. METHODS: A systematic search of the literature was performed by 2 independent reviewers followed by article selection and data extraction. Studies analyzing all sorts of dental pulp cells (DPCs) and any variant of tricalcium silicate cement either as the experimental or as the control group were included. RESULTS: A total of 39 articles were included in the review. Among the included studies, ProRoot MTA (Dentsply, Tulsa Dental, OK) was the most commonly used tricalcium silicate cement variant. The extracellular signal regulated kinase/mitogen-activated protein kinase pathway was the most commonly activated pathway to be identified, and similarly, dentin sialophosphoprotein osteocalcin dentin matrix acidic phosphoprotein 1, alkaline phosphatase, bone sialoprotein, osteopontin, type I collagen, and Runx2 were the most commonly expressed genes in that order of frequency. CONCLUSIONS: Biodentine (Septodont Ltd, Saint Maur des Fausses, France), Bioaggregate (Innovative Bioceramix, Vancouver, BC, Canada), and mineral trioxide aggregate stimulate the osteogenic/odontogenic capacity of DPCs by proliferation, angiogenesis, and biomineralization through the activation of the extracellular signal regulated kinase 1/2, nuclear factor E2 related factor 2, p38, c-Jun N-terminal kinase mitogen-activated protein kinase, p42/p44 mitogen-activated protein kinase, nuclear factor kappa B, and fibroblast growth factor receptor pathways. When DPCs are placed into direct contact with tricalcium silicate cements, they show higher levels of gene activation, which in turn could translate into more effective pulpal repair and faster and more predictable formation of reparative dentin. PMID- 26381896 TI - The Human-Baited Double Net Trap: An Alternative to Human Landing Catches for Collecting Outdoor Biting Mosquitoes in Lao PDR. AB - Estimating the exposure of individuals to mosquito-borne diseases is a key measure used to evaluate the success of vector control operations. The gold standard is to use human landing catches where mosquitoes are collected off the exposed limbs of human collectors. This is however an unsatisfactory method since it potentially exposes individuals to a range of mosquito-borne diseases. In this study several sampling methods were compared to find a method that is representative of the human-biting rate outdoors, but which does not expose collectors to mosquito-borne infections. The sampling efficiency of four odour baited traps were compared outdoors in rural Lao PDR; the human-baited double net (HDN) trap, CDC light trap, BG sentinel trap and Suna trap. Subsequently the HDN, the best performing trap, was compared directly with human landing catches (HLC), the 'gold standard', for estimating human-biting rates. HDNs collected 11-44 times more mosquitoes than the other traps, with the exception of the HLC. The HDN collected similar numbers of Anopheles (Rate Ratio, RR = 1.16, 95% Confidence Intervals, 95% CI = 0.61-2.20) and Culex mosquitoes (RR = 1.26, 95% CI = 0.74 2.17) as HLC, but under-estimated the numbers of Aedes albopictus (RR = 0.45, 95% CI = 0.27-0.77). Simpson's index of diversity was 0.845 (95% CI 0.836-0.854) for the HDN trap and 0.778 (95% CI 0.769-0.787) for HLC, indicating that the HDN collected a greater diversity of mosquito species than HLC. Both HLC and HDN can distinguish between low and high biting rates and are crude ways to measure human biting rate. The HDN is a simple and cheap method to estimate the human-biting rate outdoors without exposing collectors to mosquito bites. PMID- 26381897 TI - Functionalized biocompatible WO3 nanoparticles for triggered and targeted in vitro and in vivo photothermal therapy. AB - We report on dopamine-conjugated hyaluronic acid (HA-D), a mussel-inspired facile capping material that can modify tungsten oxide (WO3) nanoparticles to be both biocompatible and targetable, allowing precise delivery (WO3-HA) to a tumor site. Near-infrared (NIR) irradiated WO3-HA showed a rapid and substantial rise in photothermal heat to complete in vitro thermolysis of malignant MDAMB and A549 cancer cellsbut was found to be relatively less sensitive to normal MDCK cells. A long-term in vivo investigation of ~10 nm HA thickness on WO3 (WO3-HA) nanoparticles demonstrated efficient photo-thermal conversion with time-dependent tumor target accumulation. This long-termin vivo survival study ofWO3-HA showed promising biocompatibility, with a complete recovery from malignant tumor. Due to the importance of keeping simplicity in the design of therapeutic nanoparticles, we therefore expect that this facile scheme (HA-D) would contribute to the biocompatible development of versatile metallic nanoparticles for photothermal applications. PMID- 26381898 TI - Improved oral absorption of exenatide using an original nanoencapsulation and microencapsulation approach. AB - Oral delivery is the most convenient and favorable route for chronic administration of peptides and proteins to patients. However, many obstacles are faced when developing such a delivery route. Nanoparticles (NPs) are among the leading innovative solutions for delivery of these drugs. Exenatide is a peptidic drug administered subcutaneously (SC) twice a day chronically as an add-on therapy for the worldwide pandemic disease, diabetes. Many attempts to develop oral nanocarriers for this drug have been unsuccessful due to the inability to retain this hydrophilic macromolecule under sink conditions or to find a suitable cross-linker which does not harm the chemical integrity of the peptide. In this study, we report about an original oral delivery solution based on a mixture of albumin and dextran NPs cross-linked using sodium trimetaphosphate (STMP). Moreover, we suggest a second defense line of gastro-resistant microparticles (MPs) composed of an appropriate ratio of Eudragit(r) L100-55 (Eudragit L) and hydroxypropylmethylcellulose (HPMC), for additional protection to these NPs presumably allowing them to be absorbed in the intestine intact. Our results demonstrate that such a system indeed improves the relative oral bioavailability of exenatide to a level of about 77% compared to subcutaneous injection due to the presence of dextran in the coating wall of the NPs which apparently promotes the lymphatic uptake in the enterocytes. This technology may be a milestone on the way to deliver other peptides and proteins orally. PMID- 26381899 TI - RAGE siRNA-mediated gene silencing provides cardioprotection against ventricular arrhythmias in acute ischemia and reperfusion. AB - Expression of receptor for advanced glycation end-products (RAGE) is suggested to play a crucial role in mediating cardiac ischemia/reperfusion (IR) injury, and the blockade of RAGE signaling has been considered as a potential therapeutic strategy for the treatment of IR-induced cardiac damage. In this study, we primarily investigated the effects of RAGE suppression particularly on IR-induced ventricular arrhythmia. To inhibit the IR-induced upregulation of RAGE, siRNA targeting RAGE (siRAGE) was delivered to myocardium by using deoxycholic acid modified polyethylenimine (PEI-DA) as a non-viral gene carrier. The resultant PEI DA/siRAGE nanocomplexes successfully silenced the expression of RAGE and attenuated the inflammation and apoptosis in the ischemic-reperfused myocardium. According to our results, the electrophysiological properties (e.g., action potential propagation, action potential duration, and conduction velocity), disrupted by IR injury, were restored to normal level and the induction of ventricular tachycardia was abolished by RAGE silencing. We further found that RAGE suppression led to the activation of Wnt signaling, followed by the expression of gap junction protein, connexin43. Thus it could be concluded that successful siRAGE delivery is protective against IR-induced ventricular arrhythmia. PMID- 26381900 TI - Red blood cells affect the margination of microparticles in synthetic microcapillaries and intravital microcirculation as a function of their size and shape. AB - A key step in particle-based drug delivery throughmicrocirculation is particlemigration from blood flow to vesselwalls, also known as "margination",which promotes particle contact and adhesion to the vesselwall. Margination and adhesion should be independently addressed as two distinct phenomena, considering that the former is a fundamental prerequisite to achieve particle adhesion and subsequent extravasation. Although margination has beenmodeled by numerical simulations and investigated inmodel systems in vitro, experimental studies including red blood cells (RBCs) are lacking. Here, we evaluate the effect of RBCs on margination through microfluidic studies in vitro and by intravital microscopy in vivo.We showthatmargination,which is almost absent when particles are suspended in a cell-free medium, is drastically enhanced by RBCs. This effect is size- and shape-dependent, larger spherical/discoid particles being more effectively marginated both in vitro and in vivo. Our findings can be explained by the collision of particles with RBCs that induces the drifting of the particles towards the vessel walls where they become trapped in the cell-free layer. These results are relevant for the design of drug delivery strategies based on systemically administered carriers. PMID- 26381901 TI - Delivery of tumor-homing TRAIL sensitizer with long-acting TRAIL as a therapy for TRAIL-resistant tumors. AB - Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has attracted great interest as a cancer therapy because it selectively induces death receptor (DR)-mediated apoptosis in cancer cells while sparing normal tissue. However, recombinant human TRAIL demonstrates limited therapeutic efficacy in clinical trials, possibly due to TRAIL-resistance of primary cancers and its inherent short half-life. Here we introduce drug delivery approaches to maximize in vivo potency of TRAIL in TRAIL-resistant tumor xenografts by (1) extending the half life of the ligand with PEGylated TRAIL (TRAILPEG) and (2) concentrating a TRAIL sensitizer, selected from in vitro screening, in tumors via tumor-homing nanoparticles. Antitumor efficacy of TRAILPEG with tumor-homing sensitizer was evaluated in HCT116 and HT-29 colon xenografts. Western blot, real-time PCR, immunohistochemistry and cell viability assays were employed to investigate mechanisms of action and antitumor efficacy of the combination. We discovered that doxorubicin (DOX) sensitizes TRAIL-resistant HT-29 colon cancer cells to TRAIL by upregulating mRNA expression of DR5 by 60% in vitro. Intravenously administered free DOX does not effectively upregulate DR5 in tumor tissues nor demonstrate synergy with TRAILPEG in HT-29 xenografts, but rather introduces significant systemic toxicity. Alternatively, when DOX was encapsulated in hyaluronic acid-based nanoparticles (HAC/DOX) and intravenously administered with TRAILPEG, DR-mediated apoptosis was potentiated in HT-29 tumors by upregulating DR5 protein expression by 70% and initiating both extrinsic and intrinsic apoptotic pathways with reduced systemic toxicity compared to HAC/DOX or free DOX combined with TRAILPEG (80% vs. 40% survival rate; 75% vs. 34% tumor growth inhibition). This study demonstrates a unique approach to overcome TRAIL-based therapy drawbacks using sequential administration of a tumor-homing TRAIL sensitizer and long-acting TRAILPEG. PMID- 26381902 TI - Targeted delivery of platinum-taxane combination therapy in ovarian cancer. AB - Biodegradable polypeptide-based nanogels have been developed from amphiphilic block copolymers, poly(ethylene glycol)-b-poly(L-glutamic acid)-b-poly(L phenylalanine), which effectively co-incorporate cisplatin and paclitaxel, the clinically used drug combination for the treatment of advanced ovarian cancer. In order to target both drugs selectively to the tumor cells, we explored the benefits of ligand-mediated drug delivery by targeting folate receptors, which are overexpressed in most ovarian cancers. Drug-loaded nanogels were surface functionalized with folic acid (FA) with the help of a PEG spacer without affecting the ligand binding affinity and maintaining the stability of the carrier system. FA-decorated nanogels significantly suppressed the growth of intraperitoneal ovarian tumor xenografts outperforming their nontargeted counterparts without extending their cytotoxicity to the normal tissues. We also confirmed that synchronized co-delivery of the platinum-taxane drug combination via single carrier to the same targeted cells is more advantageous than a combination of targeted single drug formulations administered at the same drug ratio. Lastly, we demonstrated that the same platform can also be used for localized chemotherapy. Our data indicate that intraperitoneal administration can be more effective in the context of targeted combination therapy. Our findings suggest that multifunctional nanogels are promising drug delivery carriers for improvement of current treatment for ovarian cancer. PMID- 26381903 TI - Analysis of the Mycoplasma genitalium MgpB Adhesin to Predict Membrane Topology, Investigate Antibody Accessibility, Characterize Amino Acid Diversity, and Identify Functional and Immunogenic Epitopes. AB - Mycoplasma genitalium is a sexually transmitted pathogen and is associated with reproductive tract disease that can be chronic in nature despite the induction of a strong antibody response. Persistent infection exacerbates the likelihood of transmission, increases the risk of ascension to the upper tract, and suggests that M. genitalium may possess immune evasion mechanism(s). Antibodies from infected patients predominantly target the MgpB adhesin, which is encoded by a gene that recombines with homologous donor sequences, thereby generating sequence variation within and among strains. We have previously characterized mgpB heterogeneity over the course of persistent infection and have correlated the induction of variant-specific antibodies with the loss of that particular variant from the infected host. In the current study, we examined the membrane topology, antibody accessibility, distribution of amino acid diversity, and the location of functional and antigenic epitopes within the MgpB adhesin. Our results indicate that MgpB contains a single transmembrane domain, that the majority of the protein is surface exposed and antibody accessible, and that the attachment domain is located within the extracellular C-terminus. Not unexpectedly, amino acid diversity was concentrated within and around the three previously defined variable regions (B, EF, and G) of MgpB; while nonsynonymous mutations were twice as frequent as synonymous mutations in regions B and G, region EF had equal numbers of nonsynonymous and synonymous mutations. Interestingly, antibodies produced during persistent infection reacted predominantly with the conserved C terminus and variable region B. In contrast, infection-induced antibodies reacted poorly with the N-terminus, variable regions EF and G, and intervening conserved regions despite the presence of predicted B cell epitopes. Overall, this study provides an important foundation to define how different segments of the MgpB adhesin contribute to functionality, variability, and immunogenicity during persistent M. genitalium infection. PMID- 26381904 TI - Microshear bond strength of preheated silorane- and methacrylate-based composite resins to dentin. AB - The aim of this study was to investigate the effect of preheating on microshear bond strength (MSBS) of silorane and methacrylate-based composite resins to human dentin. The teeth were randomly divided into three main groups: (1) composite resins were heated upto 68 degrees C; (2) cooled to 4 degrees C; and (3) control [room temperature (RT)]. Each group was then randomly subdivided into four subgroups according to adhesive system used [Solobond M (Voco), All Bond SE (Bisco), Clearfil SE Bond (CSE) (Kuraray), Silorane adhesive system (SAS) (3M ESPE)]. Resin composite cylinders were formed (0.9 mm diameter * 0.7 mm length) and MSBS of each specimen was tested. The preheated groups exhibited the highest MSBS (p < 0.001) and the groups cooled to 4 degrees C exhibited the lowest MSBS (p < 0.001). The CSE showed higher MSBS than the other adhesives (p < 0.001). This study concludes that preheating of composite resins may be an alternative way to increase the MSBS of composites on dentin. PMID- 26381905 TI - Safety and vaccine efficacy of an attenuated Vibrio vulnificus strain with deletions in major cytotoxin genes. AB - Vibrio vulnificus is a human pathogen causing a rapidly progressing fatal septicemia. We have previously reported that a V. vulnificus large toxin RtxA1 causes programmed necrotic cell death through calcium-mediated mitochondrial dysfunction. Here we developed a live attenuated vaccine strain (CMM781) having deletions in three genes encoding major virulence factors: RTX cytotoxin (rtxA1), hemolysin/cytolysin (vvhA) and metalloprotease (vvpE) of a clinical isolate strain CMCP6. The CMM781 strain showed significant attenuation in cytotoxicity and mouse lethality. The safety of CMM781 was also confirmed by measuring the transepithelial electric resistance of Caco-2 cell monolayers. Intragastric immunization of mice with the live attenuated V. vulnificus strain resulted in induction of systemic and mucosal antibodies specific to the pathogen. Moreover, the vaccinated mice were protected from challenges with high doses of the virulent strain through various injection routes. These results suggest that CMM781 appears to be a safe and effective vaccine candidate that would provide significant protection against V. vulnificus infection. PMID- 26381906 TI - Oxidative Stress-Dependent Coronary Endothelial Dysfunction in Obese Mice. AB - Obesity is involved in several cardiovascular diseases including coronary artery disease and endothelial dysfunction. Endothelial Endothelium vasodilator and vasoconstrictor agonists play a key role in regulation of vascular tone. In this study, we evaluated coronary vascular response in an 8 weeks diet-induced obese C57BL/6 mice model. Coronary perfusion pressure in response to acetylcholine in isolated hearts from obese mice showed increased vasoconstriction and reduced vasodilation responses compared with control mice. Vascular nitric oxide assessed in situ with DAF-2 DA showed diminished levels in coronary arteries from obese mice in both basal and acetylcholine-stimulated conditions. Also, released prostacyclin was decreased in heart perfusates from obese mice, along with plasma tetrahydrobiopterin level and endothelium nitric oxide synthase dimer/monomer ratio. Obesity increased thromboxane A2 synthesis and oxidative stress evaluated by superoxide and peroxynitrite levels, compared with control mice. Obese mice treated with apocynin, a NADPH oxidase inhibitor, reversed all parameters to normal levels. These results suggest that after 8 weeks on a high-fat diet, the increase in oxidative stress lead to imbalance in vasoactive substances and consequently to endothelial dysfunction in coronary arteries. PMID- 26381907 TI - Effect of humeral stem design on humeral position and range of motion in reverse shoulder arthroplasty. AB - PURPOSE: The impacts of humeral offset and stem design after reverse shoulder arthroplasty (RSA) have not been well-studied, particularly with regard to newer stems which have a lower humeral inclination. The purpose of this study was to analyze the effect of different humeral stem designs on range of motion and humeral position following RSA. METHODS: Using a three-dimensional computer model of RSA, a traditional inlay Grammont stem was compared to a short curved onlay stem with different inclinations (155 degrees , 145 degrees , 135 degrees ) and offset (lateralised vs medialised). Humeral offset, the acromiohumeral distance (AHD), and range of motion were evaluated for each configuration. RESULTS: Altering stem design led to a nearly 7-mm change in humeral offset and 4 mm in the AHD. Different inclinations of the onlay stems had little influence on humeral offset and larger influence on decreasing the AHD. There was a 10 degrees decrease in abduction and a 5 degrees increase in adduction between an inlay Grammont design and an onlay design with the same inclination. Compared to the 155 degrees model, the 135 degrees model improved adduction by 28 degrees , extension by 24 degrees and external rotation of the elbow at the side by 15 degrees , but led to a decrease in abduction of 9 degrees . When the tray was placed medially, on the 145 degrees model, a 9 degrees loss of abduction was observed. CONCLUSIONS: With varus inclination prostheses (135 degrees and 145 degrees ), elevation remains unchanged, abduction slightly decreases, but a dramatic improvement in adduction, extension and external rotation with the elbow at the side are observed. PMID- 26381908 TI - Prosthetic joint infection following hip fracture and degenerative hip disorder: a cohort study of three thousand, eight hundred and seven consecutive hip arthroplasties with a minimum follow-up of five years. AB - PURPOSE: Prosthetic joint infections (PJIs) occur on a regular basis and with an increasing incidence. Under reporting of complications to national registries and unreliable ICD-10 coding increases the risk of under estimating the true rate of PJIs after hip arthroplasty. Also, the microbiology and final outcome is less well described, especially for hip-fracture patients operated upon with primary and secondary fracture prostheses. Our aim was to analyse re-operation rate, outcome and microbiology of PJIs following hip arthroplasty in patients operated upon due to hip fractures and degenerative hip disorders. METHODS: This was a single-centre cohort study of 3807 consecutive hip arthroplasties performed between 1996 and 2005. The primary study outcome was to compare the incidence of PJIs. The secondary outcome was to analyse the microbiology and outcome of PJIs. RESULTS: We identified 62 PJIs: seven surgical-site PJIs were found in patients operated upon for a degenerative hip disorder, 22 [hazard ratio (HR) 4.3] were found in patients operated upon for a primary fracture and prosthesis and 25 (HR 6.1) in patients operated upon with a secondary fracture and prosthesis. Outcome treatment was unfavourable for hip fracture patients with a high rate of Girdlestone operation performed (22 of 27). Staphylococcal infections dominated in the fracture group, whereas polybacterial infections were more common in patients with degenerative hip disorder. CONCLUSIONS: Patients with a displaced femoral neck fracture treated primary or secondary with arthroplasties have a greater risk of PJIs and display worse outcomes compared with patients with a total hip replacement due to degenerative hip disorders. PMID- 26381909 TI - Erratum to: Genome-wide association study of reproductive traits in Nellore heifers using Bayesian inference. PMID- 26381910 TI - Protein folding optimization based on 3D off-lattice model via an improved artificial bee colony algorithm. AB - Protein folding is a fundamental topic in molecular biology. Conventional experimental techniques for protein structure identification or protein folding recognition require strict laboratory requirements and heavy operating burdens, which have largely limited their applications. Alternatively, computer-aided techniques have been developed to optimize protein structures or to predict the protein folding process. In this paper, we utilize a 3D off-lattice model to describe the original protein folding scheme as a simplified energy-optimal numerical problem, where all types of amino acid residues are binarized into hydrophobic and hydrophilic ones. We apply a balance-evolution artificial bee colony (BE-ABC) algorithm as the minimization solver, which is featured by the adaptive adjustment of search intensity to cater for the varying needs during the entire optimization process. In this work, we establish a benchmark case set with 13 real protein sequences from the Protein Data Bank database and evaluate the convergence performance of BE-ABC algorithm through strict comparisons with several state-of-the-art ABC variants in short-term numerical experiments. Besides that, our obtained best-so-far protein structures are compared to the ones in comprehensive previous literature. This study also provides preliminary insights into how artificial intelligence techniques can be applied to reveal the dynamics of protein folding. Graphical Abstract Protein folding optimization using 3D off-lattice model and advanced optimization techniques. PMID- 26381911 TI - Impact sensitivity and the maximum heat of detonation. AB - We demonstrate that a large heat of detonation is undesirable from the standpoint of the impact sensitivity of an explosive and also unnecessary from the standpoints of its detonation velocity and detonation pressure. High values of the latter properties can be achieved even with a moderate heat of detonation, and this in turn enhances the likelihood of relatively low sensitivity. PMID- 26381912 TI - Molecular modeling of amorphous, non-woven polymer networks. AB - We outline a simple and efficient approach to generating molecular models of amorphous polymer networks. Similar to established techniques of preparing woven polymer networks from quenching high-temperature molecular simulation runs, we use a molecular dynamics simulations of a generic melt as starting points. This generic melt is however only used to describe parts of the polymers, namely the cross-linker units which positions are adopted from particle positions of the quenched melt. Specific degrees of network connectivity are tuned by geometric criteria for linker-linker connections and by suitable multi-body interaction potentials applied to the generic melt simulations. Using this technique we demonstrate adjusting fourfold linker coordination in amorphous polymer networks comprising 10-20% under-coordinated linkers. Graphical Abstract Molecular modeling of amorphous, non-woven polymer networks. PMID- 26381913 TI - Pharmacokinetic Evaluation of Improved Oral Bioavailability of Valsartan: Proliposomes Versus Self-Nanoemulsifying Drug Delivery System. AB - The objective of this study was to develop proliposomes and self-nanoemulsifying drug delivery system (SNEDDS) for a poorly bioavailable drug, valsartan, and to compare their in vivo pharmacokinetics. Proliposomes were prepared by thin-film hydration method using different lipids such as soy phosphatidylcholine (SPC), hydrogenated soy phosphatidylcholine (HSPC), distearyl phosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoyl phosphatidylglycerol sodium (DMPG) and cholesterol in various ratios. SNEDDS formulations were prepared using varying concentrations of capmul MCM, labrafil M 2125, and Tween 80. Both proliposomes and SNEDDS were evaluated for particle size, zeta potential, in vitro drug release, in vitro permeability, and in vivo pharmacokinetics. In vitro drug release was carried out in purified water and 0.1 N HCl using USP type II dissolution apparatus. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA) and everted rat intestinal permeation techniques. Among the formulations, the proliposomes with drug/DMPG/cholesterol in the ratio of 1:1:0.5 and SNEDDS with capmul MCM (16.0% w/w), labrafil M 2125 (64.0% w/w), and Tween 80 (18.0% w/w) showed the desired particle size and zeta potential. Enhanced drug release was observed with proliposomes and SNEDDS as compared to pure valsartan. Valsartan permeability across PAMPA and everted rat intestinal permeation models was significantly higher with proliposomes and SNEDDS. Following single oral administration of proliposomes and SNEDDS, a relative bioavailability of 202.36 and 196.87%, respectively, was achieved compared to pure valsartan suspension. The study results indicated that both proliposomes and SNEDDS formulations are comparable in improving the oral bioavailability of valsartan. PMID- 26381914 TI - The Effect of Local Delivery Doxycycline and Alendronate on Bone Repair. AB - The aim of the present study was to investigate the local effect of 10% doxycycline and 1% alendronate combined with poly(lactic-co-glycolic acid) (PLGA) on bone repair. Thirty rats were divided into three groups, as follows: control group (CG), drug group (DG), and vehicle-PLGA group (VG). Bone defect was created in the right femur and filled with the following: blood clot (CG); PLGA gel, 10% doxycycline and 1% alendronate (DG); or vehicle-PLGA (VG). The animals were euthanized 7 or 15 days after surgery. Bone density, bone matrix and number of osteoclasts were quantified. At 7 days, the findings showed increased density in DG (177.75 +/- 76.5) compared with CG (80.37 +/- 27.4), but no difference compared with VG (147.1 +/- 41.5); no statistical difference in bone neoformation CG (25.6 +/- 4.8), VG (27.8 +/- 4), and DG (18.9 +/- 7.8); and decrease osteoclasts in DG (4.6 +/- 1.9) compared with CG (26.7 +/- 7.4) and VG (17.3 +/- 2.7). At 15 days, DG (405.1 +/- 63.1) presented higher density than CG (213.2 +/- 60.9) and VG (283.4 +/- 85.8); there was a significant increase in percentage of bone neoformation in DG (31.5 +/- 4.2) compared with CG (23 +/- 4), but no difference compared with VG (25.1 +/- 2.9). There was a decreased number of osteoclasts in DG (20.7 +/- 4.7) and VG (29.5 +/- 5.4) compared with CG (40 +/- 9.4). The results suggest that the association of 10% doxycycline and 1% alendronate with PLGA-accelerated bone repair. PMID- 26381915 TI - Nanoencapsulation of Rose-Hip Oil Prevents Oil Oxidation and Allows Obtainment of Gel and Film Topical Formulations. AB - The rose-hip oil holds skin regenerating properties with applications in the dermatological and cosmetic area. Its nanoencapsulation might favor the oil stability and its incorporation into hydrophilic formulations, besides increasing the contact with the skin and prolonging its effect. The aim of the present investigation was to develop suitable rose-hip-oil-loaded nanocapsules, to verify the nanocapsule effect on the UV-induced oxidation of the oil and to obtain topical formulations by the incorporation of the nanocapsules into chitosan gel and film. The rose-hip oil (500 or 600 MUL), polymer (Eudragit RS100(r), 100 or 200 mg), and acetone (50 or 100 mL) contents were separately varied aiming to obtain an adequate size distribution. The results led to a combination of the factors acetone and oil. The developed formulation showed average diameter of 158 +/- 6 nm with low polydispersity, pH of 5.8 +/- 0.9, zeta potential of +9.8 +/- 1.5 mV, rose-hip oil content of 54 +/- 1 MUL/mL and tendency to reversible creaming. No differences were observed in the nanocapsules properties after storage. The nanoencapsulation of rose-hip oil decreased the UVA and UVC oxidation of the oil. The chitosan gel and film containing rose-hip-oil-loaded nanocapsules showed suitable properties for cutaneous use. In conclusion, it was possible to successfully obtain rose-hip-oil-loaded nanocapsules and to confirm the nanocapsules effect in protecting the oil from the UV rays. The chitosan gel and film were considered interesting alternatives for incorporating the nanoencapsulated rose-hip oil, combining the advantages of the nanoparticles to the advantages of chitosan. PMID- 26381916 TI - Magnetic Control of Macromolecular Conformations in Supramolecular Anionic Polysaccharide-Iron Complexes. AB - The anionic iota carrageenan polysaccharide is enriched with Fe(II) and Fe(III) by ion exchange against FeSO4 and FeCl3 . With divalent iron, portions of polymer chains undergo a secondary structure transition from random coils to single helices. The single-chain macromolecular conformations can be manipulated by an external magnetic field: upon exposure to 1.1 T, the helical portions exhibit 1.5 fold stiffening and 1.1-fold stretching, whereas the coil conformations respond much less as a result of lower contents of condensed iron ions. Along with the coil-helix transition, the trivalent iron triggers the formation of superstructures. The applicability of iron-enriched iota carrageenan as functional ingredient for food fortification is tested by free Fe(2+) and Fe(3+) contents, respectively, with the most promising iota-Fe(III) yielding 53% of bound iron, which is due to the superstructures, where the ferric ions are chelated by the supramolecularly self-assembled polymer host. PMID- 26381918 TI - Improving the Implementation of Evidence-Based Clinical Practices in Adolescent Reproductive Health Care Services. AB - PURPOSE: The purposes of the study were to describe baseline data in the implementation of evidence-based clinical practices among health center partners as part of a community-wide teen pregnancy prevention initiative and to identify opportunities for health center improvement. METHODS: Health center partner baseline data were collected in the first year (2011) and before program implementation of a 5-year community-wide teen pregnancy prevention initiative. A needs assessment on health center capacity and implementation of evidence-based clinical practices was administered with 51 health centers partners in 10 communities in the United States with high rates of teen pregnancy. RESULTS: Health centers reported inconsistent implementation of evidence-based clinical practices in providing reproductive health services to adolescents. Approximately 94.1% offered same-day appointments, 91.1% had infrastructure to reduce cost barriers, 90.2% offered after-school appointments, and 80.4% prescribed hormonal contraception without prerequisite examinations or testing. Approximately three quarters provided visual and audio privacy in examination rooms (76.5%) and counseling areas (74.5%). Fewer offered a wide range of contraceptive methods (67.8%) and took a sexual health history at every visit (54.9%). Only 45.1% reported Quick Start initiation of hormonal contraception, emergency contraception (43.1%), or intrauterine devices (12.5%) were "always" available to adolescents. CONCLUSIONS: The assessment highlighted opportunities for health center improvement. Strategies to build capacity of health center partners to implement evidence-based clinical practices may lead to accessibility and quality of reproductive health services for adolescents in the funded communities. PMID- 26381919 TI - Sociodemographic Differences in Human Papillomavirus Vaccine Initiation by Adolescent Males. AB - PURPOSE: The purpose of this study was to describe patterns of human papillomavirus (HPV) vaccine initiation by males and characterize sociodemographic differences. METHODS: We conducted a retrospective cohort study of 11- to 18-year-old males in a large primary care network who had a preventive or acute visit between October 2009 and December 2013. Outcomes measured were HPV vaccine series initiation and initiation at the first eligible visit. Logistic regression measured independent associations between outcomes and sociodemographic characteristics, adjusting for potential confounders including visit frequency, insurance changes, and the presence of complex medical conditions. RESULTS: Of 58,757 eligible patients, most were white (57%) with private insurance (77%). During the study period, 39% of the cohort initiated the vaccine series, and 7% initiated at their first eligible visit. Black patients with private (adjusted odds ratio [aOR], 1.99; 95% confidence interval [CI], 1.73 2.30) and Medicaid insurance (aOR, 2.90; 95% CI, 2.56-3.30) had significantly higher odds of HPV vaccine initiation compared with white patients with private insurance. A similar trend was found for Hispanic patients with private (aOR, 1.45; 95% CI, 1.26-1.67) and Medicaid insurance (aOR, 2.15; 95% CI, 1.78-2.60). These differences were present both in the preroutine recommendation period (2009 2011) and the postroutine recommendation period (2012-2013). CONCLUSIONS: Traditionally marginalized populations have higher odds of HPV vaccine initiation, both at the first eligible visit and overall. Although the true mechanism underlying these differences remains unknown, potential candidates include provider recommendation patterns and differential vaccine acceptance within these groups. PMID- 26381920 TI - Real-Time Elastography Visualization and Histopathological Characterization of Rabbit Atherosclerotic Carotid Arteries. AB - To evaluate the feasibility of non-invasive vascular real-time elastography imaging (RTE) in visualizing the composition of rabbit carotid atherosclerotic plaque as determined by histopathology, a rabbit model of accelerated carotid atherosclerosis was used. Thirty rabbits were randomly divided into two groups of 15 rabbits each. The first group was fed a cholesterol-rich diet and received balloon-induced injury the left common carotid artery endothelium, whereas the second group only received a cholesterol-rich diet. The rabbits were all examined in vivo with HITACHI non-invasive vascular real-time elastography (Hi-RTE) at baseline and 12 wk, and results from the elastography were compared with American Heart Association histologic classifications. Hi-RTE and the American Heart Association histologic classifications had good agreement, with weighted Cohen's kappa (95% confidence internal) of 0.785 (0.649-0.920). Strains of segmented plaques that were stained in different colors were statistically different (p < 0.0001). The sensitivity and specificity of elastograms for detecting a lipid core were 95.5% and 61.5%, respectively, and the area under the receiver operating characteristic curve was 0.789, with a 95% confidence interval of 0.679 to 0.876. This study is the first to indicate the feasibility of utilizing Hi-RTE in visualizing normal and atherosclerotic rabbit carotid arteries non-invasively. This affordable and reliable method can be widely applied in research of both animal and human peripheral artery atherosclerosis. PMID- 26381917 TI - Redox control of protein degradation. AB - Intracellular proteolysis is critical to maintain timely degradation of altered proteins including oxidized proteins. This review attempts to summarize the most relevant findings about oxidant protein modification, as well as the impact of reactive oxygen species on the proteolytic systems that regulate cell response to an oxidant environment: the ubiquitin-proteasome system (UPS), autophagy and the unfolded protein response (UPR). In the presence of an oxidant environment, these systems are critical to ensure proteostasis and cell survival. An example of altered degradation of oxidized proteins in pathology is provided for neurodegenerative diseases. Future work will determine if protein oxidation is a valid target to combat proteinopathies. PMID- 26381921 TI - Effects of endurance, circuit, and relaxing training on cardiovascular risk factors in hypertensive elderly patients. AB - Recommendations for prevention of cardiovascular diseases (CVDs) risk factors among older adults highlighted the importance of exercise-based interventions, including endurance training (ET). However, the evidence of efficacy of other interventions based on short-bouts of exercise (circuit training, CT), and the practice of breath-control and meditation (relaxing training, RT) is growing. The aim of this study was to elucidate if CT or RT are equally effective in CVD risk factors reduction compared to ET. To this purpose, in 40 elderly participants, with clinically diagnosed grade 1 hypertension, resting blood pressure, blood glucose, and cholesterol levels, peak oxygen uptake ([Formula: see text]), mechanical efficiency and quality of life were evaluated before and after 12 weeks of ET, CT, and RT treatments. Resting blood pressure reduced significantly in all groups by ~11 %. In ET, blood cholesterol levels (-18 %), [Formula: see text] (+8 %), mechanical efficiency (+9 %), and quality of life scores (+36 %) ameliorated. In CT blood glucose levels (-11 %), [Formula: see text] (+7 %) and quality of life scores (+35 %) were bettered. Conversely, in RT, the lower blood pressure went along only with an improvement in the mental component of quality of life (+42 %). ET and CT were both appropriate interventions to reduce CVDs risk factors, because blood pressure reduction was accompanied by decreases in blood glucose and cholesterol levels, increases in [Formula: see text], mechanical efficiency, and quality of life. Although RT influenced only blood pressure and quality of life, this approach would be an attractive alternative for old individuals unable or reluctant to carry out ET or CT. PMID- 26381922 TI - Diet and identity: being a good parent in the face of contradictions presented by the ketogenic diet. AB - The ketogenic diet is a high-fat diet used to treat drug-resistant childhood epilepsy. Given that negative meanings tend to be attached to fatty foods and children's food consumption is seen to be the responsibility of parents, the ketogenic diet may be problematic for parenting identity. This article draws upon in-depth semi-structured interviews with 12 parents from 10 families that have a child whose epilepsy is being treated with the ketogenic diet. The main focus of the article is the meanings these parents attached to foods and how they were drawn upon or altered to overcome some of the contradictions presented by the diet. It will be argued that the diet was medicalised and parents came to view food as medicine. When viewing food in this way, negative associations with fat were reversed. Furthermore, parents also used food as a symbol of inclusion and prioritised portion size or the child's enjoyment of food in order to use food as a symbol of love. In turn this enabled parents to feel they were being good parents. Overall, it seems that diet can be medicalised and the identity of the good parent maintained if dietary treatment is successful. PMID- 26381923 TI - Tandem vaginoscopy with colonoscopy: a diagnostic technique for the assessment of colovaginal fistula. AB - AIM: Colovaginal fistula (CVF) has a negative impact on quality of life. Identifying the fistula track is a critical step in its management. In a subset of patients, localizing the fistula preoperatively can be difficult. The purpose of this report is to describe the technique and results of tandem vaginoscopy with colonoscopy (TVC). METHOD: A retrospective analysis was conducted of all patients referred to a tertiary centre with symptoms suggestive of CVF but no prior successful localization of a fistula. TVC was performed by one colorectal surgeon in the endoscopy suite under intravenous sedation. RESULTS: Between 2003 and 2013, 18 patients (median age 58 years) underwent TVC. CVF was ruled out in three patients. In the remaining 15 patients, TVC documented the fistula in 13. In eight cases a wire was passed through the fistulous track from the vagina to the colon, in three the track was large enough to be traversed with the endoscope and in two a fistulous opening was noted on the vaginal side but passage of a wire to localize the opening on the colonic side was not possible due to extensive scarring. No TVC-related complications were recorded. The sensitivity, specificity, positive predictive value and negative predictive value for TVC in detecting CVF were 86.7%, 100%, 100% and 60%, respectively. CONCLUSION: TVC is a useful technique that can localize the fistulous track in most patients with CVF. PMID- 26381924 TI - Milestones: The Road to Faculty Development. AB - PURPOSE: Milestones for the assessment of residents in graduate medical education mark a change in our evaluation paradigms. The Accreditation Council for Graduate Medical Education has created milestones and defined them as significant points in development of a resident based on the 6 competencies. We propose that a similar approach be taken for resident assessment of teaching faculty. We believe this will establish parity and objectivity for faculty evaluation, provide improved data about attending surgeons' teaching, and standardize faculty evaluations by residents. METHODS: A small group of advanced surgery educators determined appropriate educational characteristics, resulting in creation of 11 milestones (Fig. 2) that were reviewed by faculty and residents. The residents have historically answered 16 questions, developed by our surgical education committee (Fig. 3), on a 5-point Likert score (never to very often). Three weeks after completing this Likert-type evaluation, the residents were asked to again evaluate attending faculty using the Faculty Milestones evaluation. The residents then completed a survey of 7 questions (scale of 1-9-disagree to strongly agree, neutral = 5), assessing the new milestones and compared with the previous Likert evaluation system. RESULTS: Of 32 surgery residents, 13 completed the Likert evaluations (3760 data points) and 13 completed the milestones evaluations (1800 data points). The number completing both or neither is not known, as the responses are anonymous when used for faculty feedback. The Faculty Milestones attending physicians' scores have far fewer top of range scores (21% vs 42%) and have a wider spread of data giving better indication of areas for improvement in teaching skills. The residents completed 17 surveys (116 responses) to evaluate the new milestones system. Surveys indicated that milestones were easier to use (average rating 6.13 +/- 0.42 Standard Error (SE)), effective (6.82 +/- 0.39) and efficient (6.11 +/- 0.53), and more objective (6.69 +/- 0.39/6.75 +/- 0.38) than the Likert evaluations are. Average response was 6.47 +/- 0.46 for overall satisfaction with the Faculty Milestones evaluation. More surveys were completed than evaluations, as all residents had an opportunity to review both evaluation systems. CONCLUSIONS: Faculty Milestones are more objective in evaluating surgical faculty and mirror the new paradigm in resident evaluations. Residents found this was an easier, more effective, efficient, and objective evaluation of our faculty. Although our Faculty Milestones are designed for surgical educators, they are likely to be applicable with appropriate modifications to other medical educators as well. PMID- 26381925 TI - General Surgery Residents can Be a Reliable Resource in the Evaluation of Residency Applications. AB - OBJECTIVE: Surgical residents' ability to screen general surgery (GS) applicants has not been previously investigated. The objective of this study was to compare surgical residents' evaluation of Electronic Residency Application Service (ERAS) applicants to that of faculty using a standardized assessment instrument. DESIGN: A prospective analysis of ERAS applications using a standardized assessment tool. SETTING: A university-affiliated, academic, county GS residency program. PARTICIPANTS: Before the interview day, 51 ERAS (2013-2014) applications were reviewed by 10 different assessors (6 GS faculty, including the program director, and 4 GS residents), who evaluated applicants on 10 characteristics (subjective and objective) using a 5-point Likert scale, a total score, and a Global Rating Scale that ranked candidates into deciles. RESULTS: There were a total of 510 assessments. In 8 of 10 individual domains the interrater reliability (IRR) between residents and faculty was good. The IRRs of the total score and global score were excellent. The Spearman rho between the total score and final rank list were similar for faculty (-0.558) and residents (-0.592). CONCLUSIONS: The excellent IRR score between the total and global scores of faculty and residents demonstrates the reliability of GS residents in evaluating ERAS applications. The low correlations between the total score and final rank are consistent with those in previous studies, in which the interview has been demonstrated to be the most important factor in determining final selection. PMID- 26381926 TI - Neurophysiological correlates of attention behavior in early infancy: Implications for emotion regulation during early childhood. AB - Current theoretical conceptualizations of regulatory development suggest that attention processes and emotion regulation processes share common neurophysiological underpinnings and behavioral antecedents such that emotion regulation abilities may build on early attentional skills. To further elucidate this proposed relationship, we tested whether early neurophysiological processes measured during an attention task in infancy predicted in-task attention behavior and whether infants' attention behavior was subsequently associated with their ability to regulate emotion during early childhood (N=388). Results indicated that greater electroencephalogram (EEG) power change (from baseline to task) at medial frontal locations (F3 and F4) during an attention task at 10months of age was associated with concurrent observed behavioral attention. Specifically, greater change in EEG power at the right frontal location (F4) was associated with more attention and greater EEG power at the left frontal location (F3) was associated with less attention, indicating a potential right hemisphere specialization for attention processes already present during the first year of life. In addition, after controlling for 5-month attention behavior, increased behavioral attention at 10months was negatively associated with children's observed frustration to emotional challenge at 3years of age. Finally, the indirect effects from 10-month EEG power change at F3 and F4 to 3-year emotion regulation via infants' 10-month behavioral attention were significant, suggesting that infants' attention behavior is one mechanism through which early neurophysiological activity is related to emotion regulation abilities during childhood. PMID- 26381927 TI - Toxoplasma gondii Toc75 Functions in Import of Stromal but not Peripheral Apicoplast Proteins. AB - Apicomplexa are unicellular parasites causing important human and animal diseases, including malaria and toxoplasmosis. Most of these pathogens possess a relict but essential plastid, the apicoplast. The apicoplast was acquired by secondary endosymbiosis between a red alga and a flagellated eukaryotic protist. As a result the apicoplast is surrounded by four membranes. This complex structure necessitates a system of transport signals and translocons allowing nuclear encoded proteins to find their way to specific apicoplast sub compartments. Previous studies identified translocons traversing two of the four apicoplast membranes. Here we provide functional support for the role of an apicomplexan Toc75 homolog in apicoplast protein transport. We identify two apicomplexan genes encoding Toc75 and Sam50, both members of the Omp85 protein family. We localize the respective proteins to the apicoplast and the mitochondrion of Toxoplasma and Plasmodium. We show that the Toxoplasma Toc75 is essential for parasite growth and that its depletion results in a rapid defect in the import of apicoplast stromal proteins while the import of proteins of the outer compartments is affected only as the secondary consequence of organelle loss. These observations along with the homology to Toc75 suggest a potential role in transport through the second innermost membrane. PMID- 26381928 TI - Clinical outcomes after interruption of entecavir therapy in HBeAg-negative chronic hepatitis B patients with compensated cirrhosis. AB - BACKGROUND: Long-term nucleos(t)ide analogues therapy may reduce hepatocellular carcinoma (HCC) in chronic hepatitis B patients with advanced fibrosis or cirrhosis. AIM: To investigate in a retrospective-prospective study whether this beneficial effect would be reduced in cirrhotic patients who discontinued a successful course of entecavir (ETV) therapy. METHODS: The study included 586 hepatitis B e antigen (HBeAg)-negative patients with compensated cirrhosis, mean age of 53.8 +/- 10 years and 81% males, treated with ETV for at least 12 months. After ETV therapy for 46.5 +/- 22.9 months, 205 patients who achieved hepatitis B virus (HBV) DNA suppression discontinued therapy. The clinical outcomes were assessed and HCC incidence was compared between propensity score (PS)-matched patients who continued and patients who discontinued ETV therapy by Asian Pacific Association for the Study of Liver stopping rule. RESULTS: During a mean duration of 59.3 +/- 19 months after start of ETV therapy, nine and six HCC developed in an estimated annual incidence of 2.3% and 1.6% in 154 PS-matched patients who continued and who discontinued ETV therapy, respectively (P = 0.587). Multivariate Cox proportional hazards regression analyses showed that age (HR 1.065, P < 0.001) and HBV DNA (HR 1.216, P = 0.048) were the significant factors for HCC development. The rates of adverse clinical outcomes were comparable. CONCLUSIONS: The clinical outcomes, including HCC, after cessation of a successful course of entecavir therapy in patients with compensated cirrhosis were comparable to those who continued therapy. The results suggest that this strategy of finite therapy is safe and a feasible alternative to indefinite therapy, especially in a low resources setting. PMID- 26381929 TI - An Examination of the Workflow Processes of the Screening, Brief Intervention, and Referral to Treatment (SBIRT) Program in Health Care Settings. AB - INTRODUCTION: Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a public health program used to identify, reduce, and prevent problematic use, abuse, and dependence on alcohol and illicit drugs that has been adapted for implementation in emergency departments and ambulatory clinics nationwide. METHODS: This study used a combination of observational, timing, and descriptive analyses from a multisite evaluation to understand the workflow processes implemented in 21 treatment settings. Direct observations of 59 SBIRT practitioners and semi-structured interviews with 170 stakeholders, program administrators, practitioners, and program evaluators provided information about workflow in different medical care settings. RESULTS: The SBIRT workflow processes are presented at three levels: service delivery, information storage, and information sharing. Analyses suggest limited variation in the overall workflow processes across settings, although performance sites tailored the program to fit with existing clinical processes, health information technology, and patient characteristics. Strategies for successful integration include co locating SBIRT providers in the medical care setting and integrating SBIRT data into electronic health records. CONCLUSIONS: Provisions within the Patient Protection and Affordable Care Act of 2010 call for the integration of behavioral health and medical care services. SBIRT is being adapted in different types of medical care settings, and the workflow processes are being adapted to ensure efficient delivery, illustrating the successful integration of behavioral health and medical care. PMID- 26381930 TI - [Oncoplastic breast surgery for the management of ductal carcinoma in situ]. AB - DCIS (Ductal carcinoma in situ) constitutes 15,2% of breast cancers. Conservative surgery coupled with adjuvant radiotherapy is often recommended. The rate of revision surgery is high, from 30 to 60%. The concern is a high quality resection within clear margins with a satisfactory aesthetic result. The objective of this review is to precise the place of oncoplastic surgery in DCIS care. Among risk factors of recurrence, tumoral invasion of surgical margins is capital. In histology, clear margins usually adopted for DCIS are 2mm, even though there is no international consensus. Recent studies show that a 10mm limit would be better. Aesthetic damage caused by surgery, often increased by radiotherapy, has a negative impact on women quality of life: oncoplastic surgery may minimize it. Techniques of plastic surgery, arranged into level 1 and 2, allow pushing back conservative treatment limits by removing a larger tumor with clear margins. Often used in invasive cancers, few data exist regarding oncoplastic surgery and DCIS. It allows to increase the dimensions of surgical resection by 20% and to decrease positive margins significantly therefore the rate of revision surgeries. Patients are satisfied with it. Specific indications need to be clarified according to age, size and "comedonecrosis" presence. Oncoplastic surgery should be developed in DCIS specific care. PMID- 26381931 TI - Characterization of NLR-A subfamily members in miiuy croaker and comparative genomics revealed NLRX1 underwent duplication and lose in actinopterygii. AB - The NOD-like receptors (NLRs, nucleotide-binding domain and leucine-rich repeat containing receptors) are a recently identified family of intracellular pathogen recognition receptors in vertebrates. Several subfamilies of NLRs have been characterized in mammals and implicated in immunity and apoptosis, but studies of NLRs in teleost species have been lacking. Here we analyzed three NLR-A subfamily members from miiuy croaker: NLRC3, NLRC5, and NLRX1. Structural analysis showed that miiuy croaker NLR-A subfamily members own the feature of 5'UTR intron which may influence their role in enhancing translation level. Comparative analysis revealed NLRX1 duplicated into NLRX1a and NLRX1b, then NLRX1a was lost in actinopterygii and NLRX1b formed NLRX1 that now we called. Simultaneously, molecular evolutionary analysis indicated that the ancestral lineages of NLRX1 in tetrapod and actinopterygii under positive selection pressure. The positively sites in actinopterygii are mainly located in NACHT domain which was the critical region for signal transduction, suggesting that the evolution of NLRX1 gene in the ancestor of actinopterygii is beneficial in immune response. Pathogens challenge demonstrated that the expressions of NLRC3 and NLRC5 in miiuy croaker were induced not only by Vibrio anguillarum but also by poly (I:C), whereas NLRX1 exhibited more sensitive response to bacteria than virus. PMID- 26381932 TI - Folic acid deficiency impairs the gill health status associated with the NF kappaB, MLCK and Nrf2 signaling pathways in the gills of young grass carp (Ctenopharyngodon idella). AB - The aim of this study was to investigate the effect of dietary folic acid on fish growth, the immune and barrier functions of fish gills, and the potential mechanisms of these effects. Young grass carp (Ctenopharyngodon idella) were fed diets containing graded levels of folic acid at 0.10 (basal diet), 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results showed that acid phosphatase and lysozyme activities and the complement component 3 content in fish gills decreased with folic acid deficiency (P < 0.05). Folic acid deficiency up-regulated liver-expressed antimicrobial peptide 1, interleukin 1beta, interleukin 8, tumor necrosis factor alpha, nuclear factor kappaB p65, IkappaB kinase alpha (IKK-alpha), IKK-beta and IKK-gamma gene expression. Folic acid deficiency down-regulated interleukin 10, transforming growth factor beta, IkappaB and target of rapamycin gene expression in fish gills (P < 0.05). These results showed that limited folic acid decreased fish gill immune status. Furthermore, folic acid deficiency down-regulated claudin-b, claudin-c, claudin 3, occludin and zonula occludens 1 gene expression, whereas folic acid deficiency up-regulated claudin-12, claudin-15, myosin light chain kinase and p38 mitogen activated protein kinase gene expression in fish gills (P < 0.05). These results suggested that folic acid deficiency disrupted tight junction-mediated fish gill barrier function. Additionally, folic acid deficiency increased the content of reactive oxygen species, protein carbonyl and malondialdehyde (MDA); Mn superoxide dismutase activity and gene expression; and Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b gene expression (P < 0.05). Conversely, folic acid deficiency decreased Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferases and glutathione reductase activities and gene expression as well as NF-E2-related factor 2 gene expression in fish gills (P < 0.05). All of these results indicated that folic acid deficiency impaired fish gill health status via regulating gene expression of cytokines, tight junction proteins, antioxidant enzymes, NF-kappaB p65, MLCK and Nrf2. Based on percent weight gain, LZ activity and MDA content in the gills, the dietary folic acid requirements for young grass carp were 1.60, 2.07 and 2.08 mg kg(-1), respectively. PMID- 26381933 TI - Low level laser therapy reduces acute lung inflammation without impairing lung function. AB - Acute lung injury is a condition characterized by exacerbate inflammatory reaction in distal airways and lung dysfunction. Here we investigate the treatment of acute lung injury (ALI) by low level laser therapy (LLLT), an effective therapy used for the treatment of patients with inflammatory disorders or traumatic injuries, due to its ability to reduce inflammation and promote tissue regeneration. However, studies in internal viscera remains unclear. C57BL/6 mice were treated with intratracheal lipopolysaccharide (LPS) (5 mg/kg) or phosphate buffer saline (PBS). Six hours after instillation, two groups were irradiated with laser at 660 nm and radiant exposure of 10 J/cm2 . Intratracheal LPS inoculation induced a marked increase in the number of inflammatory cells in perivascular and alveolar spaces. There was also an increase in the expression and secretion of cytokines (TNF-alpha, IL-1beta, IL-6,) and chemokine (MCP-1). The LLLT application induced a significant decrease in both inflammatory cells influx and inflammatory mediators secretion. These effects did not affect lung mechanical properties, since no change was observed in tissue resistance or elastance. In conclusion LLLT is able to reduce inflammatory reaction in lungs exposed to LPS without affecting the pulmonary function and recovery. PMID- 26381934 TI - A comprehensive theoretical model for on-chip microring-based photonic fractional differentiators. AB - Microring-based photonic fractional differentiators play an important role in the on-chip all-optical signal processing. Unfortunately, the previous works do not consider the time-reversal and the time delay characteristics of the microring based fractional differentiator. They also do not include the effect of input pulse width on the output. In particular, it cannot explain why the microring based differentiator with the differentiation order n > 1 has larger output deviation than that with n < 1, and why the microring-based differentiator cannot reproduce the three-peak output waveform of an ideal differentiator with n > 1. In this paper, a comprehensive theoretical model is proposed. The critically coupled microring resonator is modeled as an ideal first-order differentiator, while the under-coupled and over-coupled resonators are modeled as the time reversed ideal fractional differentiators. Traditionally, the over-coupled microring resonators are used to form the differentiators with 1 < n < 2. However, we demonstrate that smaller fitting error can be obtained if the over coupled microring resonator is fitted by an ideal differentiator with n < 1. The time delay of the differentiator is also considered. Finally, the influences of some key factors on the output waveform and deviation are discussed. The proposed theoretical model is beneficial for the design and application of the microring based fractional differentiators. PMID- 26381935 TI - Hypothalamic PKA regulates leptin sensitivity and adiposity. AB - Mice lacking the RIIbeta regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) display reduced adiposity and resistance to diet-induced obesity. Here we show that RIIbeta knockout (KO) mice have enhanced sensitivity to leptin's effects on both feeding and energy metabolism. After administration of a low dose of leptin, the duration of hypothalamic JAK/STAT3 signalling is increased, resulting in enhanced POMC mRNA induction. Consistent with the extended JAK/STAT3 activation, we find that the negative feedback regulator of leptin receptor signalling, Socs3, is inhibited in the hypothalamus of RIIbeta KO mice. During fasting, RIIbeta-PKA is activated and this correlates with an increase in CREB phosphorylation. The increase in CREB phosphorylation is absent in the fasted RIIbeta KO hypothalamus. Selective inhibition of PKA activity in AgRP neurons partially recapitulates the leanness and resistance to diet-induced obesity of RIIbeta KO mice. Our findings suggest that RIIbeta-PKA modulates the duration of leptin receptor signalling and therefore the magnitude of the catabolic response to leptin. PMID- 26381937 TI - Introduction: Applying Chemical Biology to Ion Channels. AB - Ion channels are membrane-spanning proteins that control the flow of ions across biological membranes through an aqueous pathway. The opening or closing of this pore can be controlled by a myriad of physiological inputs (voltage, ligands, temperature, metabolites, pH), which in turn allow for the controlled flux of ions across membranes, resulting in the generation of minute electrical signals. The functional implications of ion channel function on physiological processes are vast. Electrical impulses, in the form of action potentials or diverse chemo electrical signals, coordinate the syncytium of the heart beat, support a myriad of neuronal communication pathways, insulin secretion, and are central to the immune response, with more roles being discovered virtually everyday. Thus, ion channel function is a biophysical process that is central to biological life at many levels. And with over 500 channel-forming subunits known today in humans, this large class of proteins is also increasingly recognised as important drug targets, as inherited or acquired ion channel dysfunction are known causes of disease. PMID- 26381936 TI - RACK1 antagonizes TNF-alpha-induced cell death by promoting p38 activation. AB - p38 mitogen-activated protein kinase (MAPK) activity has been reported to either promote or suppress cell death, which depends on cell type and stimulus. Our previous report indicates that p38 exerts a protective role in tumor necrosis factor (TNF)-alpha-induced cell death in L929 fibroblastoma cells. However, key molecules regulating p38 activation remain unclear. Here, we show that ectopic expression of scaffold protein receptor for activated C kinase 1 (RACK1) suppressed TNF-alpha-induced cell death in L929 cells, which was associated with enhanced p38 activation. Knockdown of endogenous RACK1 expression exhibited opposite effects. The protective role of RACK1 in TNF-alpha-induced cell death diminished upon blockade of p38 activation. Therefore, RACK1 antagonizes TNF alpha-induced cell death through, at least partially, augmenting p38 activation. Further exploration revealed that RACK1 directly bound to MKK3/6 and enhanced the kinase activity of MKK3/6 without affecting MKK3/6 phosphorylation. Similar effects of RACK1 were also observed in primary murine hepatocytes, another cell type sensitive to TNF-alpha-induced cell death. Taken together, our data suggest that RACK1 is a key factor involved in p38 activation as well as TNF-alpha induced cell death. PMID- 26381939 TI - Cysteine Modification: Probing Channel Structure, Function and Conformational Change. AB - Cysteine substitution has been a powerful tool to investigate the structure and function of proteins. It has been particularly useful for studies of membrane proteins in their native environment, embedded in phospholipid membranes. Among the 20 amino acids, cysteine is uniquely reactive. This reactivity has motivated the synthesis of a wide array of sulfhydryl reactive chemicals. The commercially available array of sulfhydryl reactive reagents has allowed investigators to probe the local steric and electrostatic environment around engineered cysteines and to position fluorescent, paramagnetic and mass probes at specific sites within proteins and for distance measurements between pairs of sites. Probing the reactivity and accessibility of engineered cysteines has been extensively used in Substituted Cysteine Accessibility Method (SCAM) investigations of ion channels, membrane transporters and receptors. These studies have successfully identified the residues lining ion channels, agonist/antagonist and allosteric modulator binding sites, and regions whose conformation changes as proteins transition between different functional states. The thousands of cysteine-substitution mutants reported in the literature demonstrate that, in general, mutation to cysteine is well tolerated. This has allowed systematic studies of residues in transmembrane segments and in other parts of membrane proteins. Finally, by inserting pairs of cysteines and assaying their ability to form disulfide bonds, changes in proximity and mobility relationships between specific positions within a protein can be inferred. Thus, cysteine mutagenesis has provided a wealth of data on the structure of membrane proteins in their functional environment. This data can complement the structural insights obtained from the burgeoning number of crystal structures of detergent solubilized membrane proteins whose functional state is often uncertain. This article will review the use of cysteine mutagenesis to probe structure-function relationships in ion channels focusing mainly on Cys-loop receptors. PMID- 26381938 TI - Engineered Ionizable Side Chains. AB - One of the great challenges of mechanistic ion-channel biology is to obtain structural information from well-defined functional states. In the case of neurotransmitter-gated ion channels, the open-channel conformation is particularly elusive owing to its transient nature and brief mean lifetime. In this Chapter, we show how the analysis of single-channel currents recorded from mutants engineered to contain single ionizable side chains in the transmembrane region can provide specific information about the open-channel conformation without any interference from the closed or desensitized conformations. The method takes advantage of the fact that the alternate binding and unbinding of protons to and from an ionizable side chain causes the charge of the protein to fluctuate by 1 unit. We show that, in mutant muscle acetylcholine nicotinic receptors (AChRs), this fluctuating charge affects the rate of ion conduction in such a way that individual proton-transfer events can be identified in a most straightforward manner. From the extent to which the single-channel current amplitude is reduced every time a proton binds, we can learn about the proximity of the engineered side chain to the lumen of the pore. And from the kinetics of proton binding and unbinding, we can calculate the side-chain's affinity for protons (pK a), and hence, we can learn about the electrostatic properties of the microenvironment around the introduced ionizable group. The application of this method to systematically mutated AChRs allowed us to identify unambiguously the stripes of the M1, M2 and M3 transmembrane alpha-helices that face the pore's lumen in the open-channel conformation in the context of a native membrane. PMID- 26381940 TI - Functional Site-Directed Fluorometry. AB - Initially developed in the mid-1990s to examine the conformational changes of the canonical Shaker voltage-gated potassium channel, functional site-directed fluorometry has since been expanded to numerous other voltage-gated and ligand gated ion channels as well as transporters, pumps, and other integral membrane proteins. The power of functional site-directed fluorometry, also known as voltage-clamp fluorometry, lies in its ability to provide information on the conformational changes in a protein in response to changes in its environment with high temporal resolution while simultaneously monitoring the function of that protein. Over time, applications of site-directed fluorometry have expanded to examine the interactions of ion channels with modulators ranging from membrane potential to ligands to accessory protein subunits to lipids. In the future, the range of questions answerable by functional site-directed fluorometry and its interpretive power should continue to improve, making it an even more powerful technique for dissecting the conformational dynamics of ion channels and other membrane proteins. PMID- 26381941 TI - Bioreactive Tethers. AB - Ion channel complexes are challenging to study by traditional biochemical methods due to their membranous lipid environment and large size. Bioreactive tethers are specialized chemical probes that have been used in electrophysiological experiments to provide unique insight into ion channel structure and function. Because bioreactive tethers are small molecular probes, they can be used to manipulate ion channel function in heterologous expression systems, native cells and animal models. This chapter covers three classes of tethers: photoswitchable, molecular rulers, and chemically reactive. The modular nature of bioreactive tethers enables the facile synthesis of next generation reagents with enhanced functionalities to interrogate and control ion channels in novel and multifarious ways. PMID- 26381942 TI - Flipping the Photoswitch: Ion Channels Under Light Control. AB - Nature has incorporated small photochromic molecules, colloquially termed 'photoswitches', in photoreceptor proteins to sense optical cues in phototaxis and vision. While Nature's ability to employ light-responsive functionalities has long been recognized, it was not until recently that scientists designed, synthesized and applied synthetic photochromes to manipulate many of which open rapidly and locally in their native cell types, biological processes with the temporal and spatial resolution of light. Ion channels in particular have come to the forefront of proteins that can be put under the designer control of synthetic photochromes. Photochromic ion channel controllers are comprised of three classes, photochromic soluble ligands (PCLs), photochromic tethered ligands (PTLs) and photochromic crosslinkers (PXs), and in each class ion channel functionality is controlled through reversible changes in photochrome structure. By acting as light-dependent ion channel agonists, antagonist or modulators, photochromic controllers effectively converted a wide range of ion channels, including voltage-gated ion channels, 'leak channels', tri-, tetra- and pentameric ligand-gated ion channels, and temperature-sensitive ion channels, into man-made photoreceptors. Control by photochromes can be reversible, unlike in the case of 'caged' compounds, and non-invasive with high spatial precision, unlike pharmacology and electrical manipulation. Here, we introduce design principles of emerging photochromic molecules that act on ion channels and discuss the impact that these molecules are beginning to have on ion channel biophysics and neuronal physiology. PMID- 26381945 TI - Too close for comfort? PMID- 26381944 TI - Genetic Variants in the Insulin-like Growth Factor Pathway and Colorectal Cancer Risk in the Netherlands Cohort Study. AB - Interrelationships between insulin-like growth factors (IGFs), hyperinsulinaemia, diabetes, and colorectal cancer (CRC) indicate involvement of IGFs in colorectal tumorigenesis. We investigated the CRC risk associated with 24 single nucleotide polymorphisms (SNPs) in 9 genes related to the IGF pathway and an IGF1 19-CA repeat polymorphism. Variants were selected from literature and genotyped in toenail DNA from 3,768 subcohort members and 2,580 CRC cases from the Netherlands Cohort Study, which has a case-cohort design (n = 120,852). We used the follow-up period 1986-2002. Eighteen SNPs were unequivocally associated with selected endpoints in the literature and unfavorable alleles were aggregated into a genetic sum score. Cox regression showed that a higher genetic sum score significantly increased CRC risk at all subsites, except the rectum, in men (highest vs. lowest tertile: HR for CRC = 1.36, 95% CI: 1.11, 1.65; P-trend = 0.002). Single SNPs (except the IGF1 SNP rs5742694) were not associated with risk. Models including the total number of IGF1 19-CA repeats showed CRC risk was halved at all subsites in women carrying < 38 repeats but not > 38 repeats (<= 36 versus 38 repeats: HR for CRC = 0.44; 95% CI: 0.33, 0.58; P-trend < 0.001). These findings support a role for variants in IGF-related genes in colorectal tumorigenesis. PMID- 26381946 TI - Mind meld. PMID- 26381947 TI - Protection priority. PMID- 26381943 TI - Incorporation of Non-Canonical Amino Acids. AB - In this chapter we discuss the strengths, caveats and technical considerations of three approaches for reprogramming the chemical composition of selected amino acids within a membrane protein. In vivo nonsense suppression in the Xenopus laevis oocyte, evolved orthogonal tRNA and aminoacyl-tRNA synthetase pairs and protein ligation for biochemical production of semisynthetic proteins have been used successfully for ion channel and receptor studies. The level of difficulty for the application of each approach ranges from trivial to technically demanding, yet all have untapped potential in their application to membrane proteins. PMID- 26381948 TI - Integration of social science into research is crucial. PMID- 26381960 TI - Crowdsourcing digs up an early human species. PMID- 26381961 TI - Africa braced for snakebite crisis. PMID- 26381963 TI - Hunt for gravitational waves to resume after massive upgrade. PMID- 26381962 TI - NIH disclosure rules falter. PMID- 26381964 TI - Newfound meteor showers expand astronomical calendar. PMID- 26381965 TI - Corrections. PMID- 26381966 TI - Why interdisciplinary research matters. PMID- 26381967 TI - Interdisciplinary research by the numbers. PMID- 26381968 TI - How to solve the world's biggest problems. PMID- 26381969 TI - Grant giving: Global funders to focus on interdisciplinarity. PMID- 26381970 TI - Interdisciplinarity: How to catalyse collaboration. PMID- 26381971 TI - Interdisciplinarity: Inside Manchester's 'arts lab'. PMID- 26381972 TI - Anthropology: One-man multidisciplinarian. PMID- 26381973 TI - Undergraduate teaching: Education reforms ring true 50 years on. PMID- 26381974 TI - Surgery: Tailor checklists to clinical teams. PMID- 26381975 TI - Italy: Lack of help stymied community care. PMID- 26381976 TI - Seafood: Mining shell waste will not be easy. PMID- 26381977 TI - China: New environment law shows its fangs. PMID- 26381978 TI - Pacific islands: Seal of approval for ocean observations. PMID- 26381979 TI - Catalysis: Tens of thousands of atoms replaced by one. PMID- 26381980 TI - Condensed-matter physics: Charge topology in superconductors. PMID- 26381981 TI - Atmospheric science: The death toll from air-pollution sources. PMID- 26381982 TI - Relativistic boost as the cause of periodicity in a massive black-hole binary candidate. AB - Because most large galaxies contain a central black hole, and galaxies often merge, black-hole binaries are expected to be common in galactic nuclei. Although they cannot be imaged, periodicities in the light curves of quasars have been interpreted as evidence for binaries, most recently in PG 1302-102, which has a short rest-frame optical period of four years (ref. 6). If the orbital period of the black-hole binary matches this value, then for the range of estimated black hole masses, the components would be separated by 0.007-0.017 parsecs, implying relativistic orbital speeds. There has been much debate over whether black-hole orbits could be smaller than one parsec (ref. 7). Here we report that the amplitude and the sinusoid-like shape of the variability of the light curve of PG 1302-102 can be fitted by relativistic Doppler boosting of emission from a compact, steadily accreting, unequal-mass binary. We predict that brightness variations in the ultraviolet light curve track those in the optical, but with a two to three times larger amplitude. This prediction is relatively insensitive to the details of the emission process, and is consistent with archival ultraviolet data. Follow-up ultraviolet and optical observations in the next few years can further test this prediction and confirm the existence of a binary black hole in the relativistic regime. PMID- 26381983 TI - Inhomogeneity of charge-density-wave order and quenched disorder in a high-Tc superconductor. AB - It has recently been established that the high-transition-temperature (high-Tc) superconducting state coexists with short-range charge-density-wave order and quenched disorder arising from dopants and strain. This complex, multiscale phase separation invites the development of theories of high-temperature superconductivity that include complexity. The nature of the spatial interplay between charge and dopant order that provides a basis for nanoscale phase separation remains a key open question, because experiments have yet to probe the unknown spatial distribution at both the nanoscale and mesoscale (between atomic and macroscopic scale). Here we report micro X-ray diffraction imaging of the spatial distribution of both short-range charge-density-wave 'puddles' (domains with only a few wavelengths) and quenched disorder in HgBa2CuO4 + y, the single layer cuprate with the highest Tc, 95 kelvin (refs 26-28). We found that the charge-density-wave puddles, like the steam bubbles in boiling water, have a fat tailed size distribution that is typical of self-organization near a critical point. However, the quenched disorder, which arises from oxygen interstitials, has a distribution that is contrary to the usually assumed random, uncorrelated distribution. The interstitial-oxygen-rich domains are spatially anticorrelated with the charge-density-wave domains, because higher doping does not favour the stripy charge-density-wave puddles, leading to a complex emergent geometry of the spatial landscape for superconductivity. PMID- 26381984 TI - Designing switchable polarization and magnetization at room temperature in an oxide. AB - Ferroelectric and ferromagnetic materials exhibit long-range order of atomic scale electric or magnetic dipoles that can be switched by applying an appropriate electric or magnetic field, respectively. Both switching phenomena form the basis of non-volatile random access memory, but in the ferroelectric case, this involves destructive electrical reading and in the magnetic case, a high writing energy is required. In principle, low-power and high-density information storage that combines fast electrical writing and magnetic reading can be realized with magnetoelectric multiferroic materials. These materials not only simultaneously display ferroelectricity and ferromagnetism, but also enable magnetic moments to be induced by an external electric field, or electric polarization by a magnetic field. However, synthesizing bulk materials with both long-range orders at room temperature in a single crystalline structure is challenging because conventional ferroelectricity requires closed-shell d(0) or s(2) cations, whereas ferromagnetic order requires open-shell d(n) configurations with unpaired electrons. These opposing requirements pose considerable difficulties for atomic-scale design strategies such as magnetic ion substitution into ferroelectrics. One material that exhibits both ferroelectric and magnetic order is BiFeO3, but its cycloidal magnetic structure precludes bulk magnetization and linear magnetoelectric coupling. A solid solution of a ferroelectric and a spin-glass perovskite combines switchable polarization with glassy magnetization, although it lacks long-range magnetic order. Crystal engineering of a layered perovskite has recently resulted in room-temperature polar ferromagnets, but the electrical polarization has not been switchable. Here we combine ferroelectricity and ferromagnetism at room temperature in a bulk perovskite oxide, by constructing a percolating network of magnetic ions with strong superexchange interactions within a structural scaffold exhibiting polar lattice symmetries at a morphotropic phase boundary (the compositional boundary between two polar phases with different polarization directions, exemplified by the PbZrO3-PbTiO3 system) that both enhances polarization switching and permits canting of the ordered magnetic moments. We expect this strategy to allow the generation of a range of tunable multiferroic materials. PMID- 26381985 TI - The contribution of outdoor air pollution sources to premature mortality on a global scale. AB - Assessment of the global burden of disease is based on epidemiological cohort studies that connect premature mortality to a wide range of causes, including the long-term health impacts of ozone and fine particulate matter with a diameter smaller than 2.5 micrometres (PM2.5). It has proved difficult to quantify premature mortality related to air pollution, notably in regions where air quality is not monitored, and also because the toxicity of particles from various sources may vary. Here we use a global atmospheric chemistry model to investigate the link between premature mortality and seven emission source categories in urban and rural environments. In accord with the global burden of disease for 2010 (ref. 5), we calculate that outdoor air pollution, mostly by PM2.5, leads to 3.3 (95 per cent confidence interval 1.61-4.81) million premature deaths per year worldwide, predominantly in Asia. We primarily assume that all particles are equally toxic, but also include a sensitivity study that accounts for differential toxicity. We find that emissions from residential energy use such as heating and cooking, prevalent in India and China, have the largest impact on premature mortality globally, being even more dominant if carbonaceous particles are assumed to be most toxic. Whereas in much of the USA and in a few other countries emissions from traffic and power generation are important, in eastern USA, Europe, Russia and East Asia agricultural emissions make the largest relative contribution to PM2.5, with the estimate of overall health impact depending on assumptions regarding particle toxicity. Model projections based on a business-as-usual emission scenario indicate that the contribution of outdoor air pollution to premature mortality could double by 2050. PMID- 26381986 TI - The cell menagerie: human immune profiling. PMID- 26381988 TI - Decompensated cirrhosis and microbiome interpretation. PMID- 26381989 TI - Qin et al. reply. PMID- 26381991 TI - Biotransformation of magnetic nanoparticles as a function of coating in a rat model. AB - Long-term in vivo studies in murine models have shown that DMSA-coated nanoparticles accumulate in spleen, liver and lung tissues during extended periods of time (at least up to 3 months) without any significant signs of toxicity detected. During that time, nanoparticles undergo a process of biotransformation either by reducing the size or the particle aggregation or both. Using a rat model, we have evaluated the transformations of magnetic nanoparticles injected at low doses. Particles with two different coatings, dimercaptosuccinic acid (NP-DMSA) and polyethylene glycol (NP-PEG-(NH2)2) have been administered to animals, to evaluate the role of coating in the degradation of the particles. We have found that low doses of magnetic nanoparticles are quickly metabolized by the animals. In fact, using a nanoparticle dose four times lower than in previous experiments, NP-DMSA were not observed 24 h after the administration either in the liver or in the lungs. Interestingly, an increased amount of ferritin, the iron storage protein, was observed in liver tissues from rats that were treated with the low dose of NP-DMSA in comparison with the control ones, suggesting a rapid metabolization of the particles into ferritin iron. On the other side we have found that, NP-PEG-(NH2)2 are still detectable in several organs 24 h after their administration at low doses. Probably, due to the longer circulation times of the NP-PEG-(NH2)2, there is a delay in the arrival of the particles to the tissue and this is the reason why we are able to see the particles 24 h post-administration. PEG coating could also be protecting the nanoparticles from rapid degradation of the reticuloendothelial system. Knowledge on the biodistribution, circulation time and degradation processes is required to gain a better understanding of the safety evaluation of this kind of nanomaterial for biomedical applications. PMID- 26381992 TI - Absolute configuration and chiral self-assembly of rubrene on Bi(111). AB - We investigated the chiral self-assembly of rubrene molecules on a semi-metallic Bi(111) surface using low-temperature scanning tunneling microscopy. The absolute configuration of isolated rubrene enantiomers was identified from high-resolution images. Two types of homochiral domains of rubrene monomers and hexamers were observed, respectively. For rubrene monomers, chiral separation was spontaneous with each chiral monomer appearing in their respective domain. For rubrene hexamers, two levels of organization chirality were recorded: one is six heterochiral rubrene molecules arranged alternatively in a rubrene hexamer; and the other is a homochiral arrangement of individual hexamers. After annealing at 350 K, a large area of supramolecular self-assembled L- and R-type triangular heterochiral hexamers was obtained at the narrow terrace of Bi(111). Moreover, a molecular chiral inversion from the L-(R-) type to the R-(L-) type occurs during the formation of the hexamer domain structure and can be attributed to the enhanced intermolecular interactions governed by the intensive intermolecular extrusion at the narrow terrace. PMID- 26381993 TI - Instillation and Fixation Methods Useful in Mouse Lung Cancer Research. AB - The ability to instill live agents, cells, or chemicals directly into the lung without injuring or killing the mice is an important tool in lung cancer research. Although there are a number of methods that have been published showing how to intubate mice for pulmonary function measurements, none are without potential problems for rapid tracheal instillation in large cohorts of mice. In the present paper, a simple and quick method is described that enables an investigator to carry out such instillations in an efficient manner. The method does not require any special tools or lighting and can be learned with very little practice. It involves anesthetizing a mouse, making a small incision in the neck to visualize the trachea, and then inserting an intravenous catheter directly. The small incision is quickly closed with tissue adhesive, and the mice are allowed to recover. A skilled student or technician can do instillations at an average rate of 2 min/mouse. Once the cancer is established, there is frequently a need for quantitative histologic analysis of the lungs. Traditionally pathologists usually do not bother to standardize lung inflation during fixation, and analyses are often based on a scoring system that can be quite subjective. While this may sometime be sufficiently adequate for gross estimates of the size of a lung tumor, any proper stereological quantification of lung structure or cells requires a reproducible fixation procedure and subsequent lung volume measurement. Here we describe simple reliable procedures for both fixing the lungs under pressure and then accurately measuring the fixed lung volume. The only requirement is a laboratory balance that is accurate over a range of 1 mg-300 g. The procedures presented here thus could greatly improve the ability to create, treat, and analyze lung cancers in mice. PMID- 26381994 TI - Synthesis of E-Alkyl Alkenes from Terminal Alkynes via Ni-Catalyzed Cross Coupling of Alkyl Halides with B-Alkenyl-9-borabicyclo[3.3.1]nonanes. AB - The first Ni-catalyzed Suzuki-Miyaura coupling of alkyl halides with alkenyl-(9 BBN) reagents is reported. Both primary and secondary alkyl halides including alkyl chlorides can be coupled. The coupling method can be combined with hydroboration of terminal alkynes, allowing the expedited synthesis of functionalized alkyl alkenes from readily available alkynes with complete (E) selectivity in one pot. The method was applied to the total synthesis of (+/-) Recifeiolide, a natural macrolide. PMID- 26381995 TI - Gelation and mechanical response of patchy rods. AB - We perform Brownian dynamics simulations to study the gelation of suspensions of attractive, rod-like particles. We show that in detail the rod-rod surface interactions can dramatically affect the dynamics of gelation and the structure and mechanics of the networks that form. If the attraction between the rods is perfectly smooth along their length, they will collapse into compact bundles. If the attraction is sufficiently corrugated or patchy, over time, a rigid space spanning network will form. We study the structure and mechanical properties of the networks that form as a function of the fraction of the surface, f, that is allowed to bind. Surprisingly, the structural and mechanical properties are non monotonic in f. At low f, there are not a sufficient number of cross-linking sites to form networks. At high f, rods bundle and form disconnected clusters. At intermediate f, robust networks form. The elastic modulus and yield stress are both non-monotonic in the surface coverage. The stiffest and strongest networks show an essentially homogeneous deformation under strain with rods re-orienting along the extensional axis. Weaker, more clumpy networks at high f re-orient relatively little with strong non-affine deformation. These results suggest design strategies for tailoring surface interactions between rods to yield rigid networks with optimal mechanical properties. PMID- 26381996 TI - Antifungal prophylaxis in pediatric patients undergoing therapy for cancer: drugs and dosing. AB - PURPOSE OF REVIEW: Invasive fungal disease (IFD) is an important cause of morbidity and mortality in immunocompromised patients. In contrast to adults, detailed information of pharmacokinetics and pharmacodynamics of many antifungal compounds is lacking in pediatric patients, and antifungal agents that have been proven to be effective in adults have not been licensed for children. We therefore review the current literature on drugs and dosing for antifungal prophylaxis in the pediatric age group. RECENT FINDINGS: Although there are only few compounds approved for antifungal prophylaxis in children, an increasing number of reports describe safety and suggest efficacy of agents given to prevent IFD in the pediatric population. Owing to the small number of children included in most studies, however, evidence for efficacy has to be extrapolated from studies in adults. In addition, most studies do not address the optimal dosage of a compound to prevent IFD (optimal balance between efficacy and toxicity). SUMMARY: Although there is a wide use of prophylactic antifungal agents in children, future studies need to establish the optimal dosing of each compound. PMID- 26381997 TI - Management of fever and neutropenia in paediatric cancer patients: room for improvement? AB - PURPOSE OF REVIEW: Fever and neutropenia is the most common complication in the treatment of childhood cancer. This review will summarize recent publications that focus on improving the management of this condition as well as those that seek to optimize translational research efforts. RECENT FINDINGS: A number of clinical decision rules are available to assist in the identification of low-risk fever and neutropenia however few have undergone external validation and formal impact analysis. Emerging evidence suggests acute fever and neutropenia management strategies should include time to antibiotic recommendations, and quality improvement initiatives have focused on eliminating barriers to early antibiotic administration. Despite reported increases in antimicrobial resistance, few studies have focused on the prediction, prevention, and optimal treatment of these infections and the effect on risk stratification remains unknown. A consensus guideline for paediatric fever and neutropenia research is now available and may help reduce some of the heterogeneity between studies that have previously limited the translation of evidence into clinical practice. SUMMARY: Risk stratification is recommended for children with cancer and fever and neutropenia. Further research is required to quantify the overall impact of this approach and to refine exactly which children will benefit from early antibiotic administration as well as modifications to empiric regimens to cover antibiotic-resistant organisms. PMID- 26381998 TI - Hepatitis B: encouraging the use of interferon. AB - PURPOSE OF REVIEW: Hepatitis B is a major cause of hepatocellular carcinoma and liver cirrhosis. Interferon (IFN)-based therapies provide the highest likelihood of achieving off-treatment virological and serological control although their use is often avoided because of the side-effect profile. We review recent developments regarding the use of IFN in the treatment of chronic hepatitis B, including proposed strategies to enhance efficacy while limiting treatment exposure for patients who are unlikely to achieve acceptable treatment endpoints. RECENT FINDINGS: The utility of host genetics (human leukocyte antigen associations and interleukin 28B) is yet to be defined. In hepatitis B e antigen (HBeAg)-positive disease, add-on IFN therapy to patients on entecavir may allow curtailment of nucleos(t)ide analogue treatment. In HBeAg-negative disease, an on treatment stopping rule that measures decline of hepatitis B surface antigen and hepatitis B virus DNA at 12 and 24 weeks may identify up to two-thirds of poor responders. Prolonging IFN therapy to 96 weeks in patients with HBeAg-negative disease may improve virological and serological response rates. The combination of telbivudine and IFN therapy is contraindicated because of high rates of peripheral neuropathy. SUMMARY: These findings need to be confirmed in larger trials before they can be instituted into routine clinical practice. PMID- 26381999 TI - Treatment of adult T-cell leukaemia/lymphoma: is the virus a target? AB - PURPOSE OF REVIEW: To discuss current understanding of the mechanisms of human T lymphotropic virus type-1 (HTLV-1) tumorigenesis and current and potential treatment strategies for adult T-cell leukaemia/lymphoma (ATL), an aggressive malignant disease of CD4 cells caused by HTLV-1. RECENT FINDINGS: Treatment of the aggressive subtypes of ATL remains inadequate, with little improvement in overall survival in the 30 years since HTLV-1 was discovered. Detailed analysis of the clonal expansion of HTLV-1 has provided new insight into pathogenesis. Most HTLV-1-infected cells, including ATL, express CCR4 which can be targeted. Reports of antitumour effects with allogeneic bone marrow transplantation provide a rationale for novel immunotherapy approaches. Progress has been made in the indolent subtypes of ATL with the use of 'antiviral' therapies. SUMMARY: ATL has poor prognosis. There is a major, urgent, unmet clinical need to identify HTLV carriers who will develop ATL to develop biomarkers of transforming disease and disease progression and to provide novel treatment approaches within the context of clinical trials. Several strategies now include putative or actual antiviral therapy. Potentially, the risk of ATL would be reduced by eliminating some or all infected clones. HTLV-1 infection, and hence ATL, can be prevented by antenatal HTLV-1 screening. PMID- 26382000 TI - Optimizing dosing of antibiotics in critically ill patients. AB - PURPOSE OF REVIEW: Recent studies suggest that contemporary antibiotic dosing is unlikely to achieve best outcomes for critically ill patients because of extensive pharmacokinetic variability and altered pharmacodynamics. Dose adaptation is considered quite challenging because of unpredictable dose-exposure relationships. Consequently, individualization of antibiotic dosing has been advocated. Herein, we describe recent developments in the optimization of antibiotic dosing in the critically ill. RECENT FINDINGS: Conventional doses of many antibiotics frequently result in sub or supratherapeutic exposures in the critically ill. Clinical studies continue to illustrate that dose-exposure relationships are highly variable in severely ill patients. Dose optimization based on pharmacokinetic/pharmacodynamic principles can effectively improve antibiotic exposure. Therapeutic drug monitoring (TDM) with adaptive feedback is likely to be the most robust approach to optimize dosing for individual patients. This more accurate approach to dosing is made possible with the user-friendly dosing software that is emerging. SUMMARY: The scope of TDM is broadening from the traditional focus on prevention of toxicity, to include optimization of antibiotic exposure thereby improving patient outcomes. However, the evidence relating TDM practice with improved clinical outcome remains limited. Well designed, multicentre, randomized controlled studies are warranted. PMID- 26382001 TI - High mobility group box 1 (HMGB1) is upregulated by the Epstein-Barr virus infection and promotes the proliferation of human nasopharyngeal carcinoma cells. AB - CONCLUSION: The current study confirmed the significant high mobility group box 1 (HMGB1) was promoted in human nasopharyngeal carcinoma (NPC) tissues by Epstein Barr virus (EBV) infection, in association with the malignant status of NPC, and promoted the proliferation NPC cells RAGE-dependently. OBJECTIVES: The present study was to examine the association of HMGB1 over-expression in human NPC with the EBV-positivity and to determine the regulatory role of HMGB1 on the proliferation of NPC cells in vitro. METHODS: Real-time PCR and Western blotting were utilized to examine the HMGB1 expression. EBV infection in CNE-2 cells was performed to investigate the HMGB1 promotion by EBV infection. RNA interference technology was utilized for the RAGE knockout. RESULTS: It was demonstrated that HMGB1 was significantly higher in both mRNA and protein levels in the EBV positive NPC tissues, in marked association with the malignant status of NPC, and with the LMP1 DNA level in EBV-positive NPC samples. In addition, the MTT assay, growth curve, and the colony forming assay confirmed the promotion by HMGB1 to the proliferation of CNE-2 cells, depending on RAGE. PMID- 26382002 TI - Reduced perceptual exclusivity during object and grating rivalry in autism. AB - The dynamics of binocular rivalry may be a behavioral footprint of excitatory and inhibitory neural transmission in visual cortex. Given the presence of atypical visual features in Autism Spectrum Conditions (ASC), and the growing evidence in support of the idea of an imbalance in excitatory/inhibitory neural transmission in animal and genetic models of ASC, we hypothesized that binocular rivalry might prove a simple behavioral marker of such a transmission imbalance in the autistic brain. In support of this hypothesis, we previously reported a slower rate of rivalry in ASC, driven by longer transitional states between dominant percepts. We tested whether atypical dynamics of binocular rivalry in ASC are specific to certain stimulus features. 53 participants (26 with ASC, matched for age, sex, and IQ) participated in a binocular rivalry experiment in which the dynamics of rivalry were measured at two levels of stimulus complexity, low (grayscale gratings) and high (colored objects). Individuals with ASC experienced a slower rate of binocular rivalry, driven by longer transitional states between dominant percepts. These exaggerated transitional states were present at both low and high levels of stimulus complexity (gratings and objects), suggesting that atypical binocular dynamics in autism are robust with respect to stimulus choice. Interactions between stimulus properties and rivalry dynamics in autism indicate that achromatic grating stimuli produce stronger group differences. These results confirm the finding of atypical dynamics of binocular rivalry in ASC. These dynamics were present for stimuli of both low and high levels of visual complexity, suggesting a pervasive imbalance in competitive interactions throughout the visual system of individuals with ASC. PMID- 26382003 TI - Initial eye movements during face identification are optimal and similar across cultures. AB - Culture influences not only human high-level cognitive processes but also low level perceptual operations. Some perceptual operations, such as initial eye movements to faces, are critical for extraction of information supporting evolutionarily important tasks such as face identification. The extent of cultural effects on these crucial perceptual processes is unknown. Here, we report that the first gaze location for face identification was similar across East Asian and Western Caucasian cultural groups: Both fixated a featureless point between the eyes and the nose, with smaller between-group than within-group differences and with a small horizontal difference across cultures (8% of the interocular distance). We also show that individuals of both cultural groups initially fixated at a slightly higher point on Asian faces than on Caucasian faces. The initial fixations were found to be both fundamental in acquiring the majority of information for face identification and optimal, as accuracy deteriorated when observers held their gaze away from their preferred fixations. An ideal observer that integrated facial information with the human visual system's varying spatial resolution across the visual field showed a similar information distribution across faces of both races and predicted initial human fixations. The model consistently replicated the small vertical difference between human fixations to Asian and Caucasian faces but did not predict the small horizontal leftward bias of Caucasian observers. Together, the results suggest that initial eye movements during face identification may be driven by brain mechanisms aimed at maximizing accuracy, and less influenced by culture. The findings increase our understanding of the interplay between the brain's aims to optimally accomplish basic perceptual functions and to respond to sociocultural influences. PMID- 26382004 TI - The preview benefit in single-feature and conjunction search: Constraints of visual marking. AB - Previewing distracters enhances the efficiency of visual search. Watson and Humphreys (1997) proposed that the preview benefit rests on visual marking, a mechanism which actively encodes distracter locations at preview and inhibits them afterwards at search. As Watson and Humphreys did, we used a letter-color search task to study constraints of visual marking in conjunction search and near efficient single-feature search with single-colored and homogeneous distracter letters. Search performance was measured for fixed target and distracter features (block design) and for randomly changed features across trials (random design). In single-feature search there was a full preview benefit for both block and random designs. In conjunction search a full preview benefit was obtained only for the block design; randomly changing target and distracter features disrupted the preview benefit. However, the preview benefit was restored when the distracters were organized in spatially coherent blocks. These findings imply that the temporal segregation of old and new items is sufficient for visual marking in near-efficient single-feature search, while in conjunction search it is not. We propose a supplanting grouping principle for the preview benefit: When the new items add a new color, conjunction search is initialized and attentional resources are withdrawn from the marking mechanism. Visual marking can be restored by a second grouping principle that joins with temporal asynchrony. This principle can be either spatial or feature based. In the case of the latter, repetition priming is necessary to establish joint grouping by color and temporal asynchrony. PMID- 26382005 TI - Stream specificity and asymmetries in feature binding and content-addressable access in visual encoding and memory. AB - Human memory is content addressable-i.e., contents of the memory can be accessed using partial information about the bound features of a stored item. In this study, we used a cross-feature cuing technique to examine how the human visual system encodes, binds, and retains information about multiple stimulus features within a set of moving objects. We sought to characterize the roles of three different features (position, color, and direction of motion, the latter two of which are processed preferentially within the ventral and dorsal visual streams, respectively) in the construction and maintenance of object representations. We investigated the extent to which these features are bound together across the following processing stages: during stimulus encoding, sensory (iconic) memory, and visual short-term memory. Whereas all features examined here can serve as cues for addressing content, their effectiveness shows asymmetries and varies according to cue-report pairings and the stage of information processing and storage. Position-based indexing theories predict that position should be more effective as a cue compared to other features. While we found a privileged role for position as a cue at the stimulus-encoding stage, position was not the privileged cue at the sensory and visual short-term memory stages. Instead, the pattern that emerged from our findings is one that mirrors the parallel processing streams in the visual system. This stream-specific binding and cuing effectiveness manifests itself in all three stages of information processing examined here. Finally, we find that the Leaky Flask model proposed in our previous study is applicable to all three features. PMID- 26382007 TI - Object-based spatial attention when objects have sufficient depth cues. AB - Attention directed to a part of an object tends to obligatorily spread over all of the spatial regions that belong to the object, which may be critical for rapid object-recognition in cluttered visual scenes. Previous studies have generally used simple rectangles as objects and have shown that attention spreading is reflected by amplitude modulation in the posterior N1 component (150-200 ms poststimulus) of event-related potentials, while other interpretations (i.e., rectangular holes) may arise implicitly in early visual processing stages. By using modified Kanizsa-type stimuli that provided less ambiguity of depth ordering, the present study examined early event-related potential spatial attention effects for connected and separated objects, both of which were perceived in front of (Experiment 1) and in back of (Experiment 2) the surroundings. Typical P1 (100-140 ms) and N1 (150-220 ms) attention effects of ERP in response to unilateral probes were observed in both experiments. Importantly, the P1 attention effect was decreased for connected objects compared to separated objects only in Experiment 1, and the typical object-based modulations of N1 were not observed in either experiment. These results suggest that spatial attention spreads over a figural object at earlier stages of processing than previously indicated, in three-dimensional visual scenes with multiple depth cues. PMID- 26382006 TI - Spatial selectivity in the temporoparietal junction, inferior frontal sulcus, and inferior parietal lobule. AB - Spatial selectivity, as measured by functional magnetic resonance imaging (fMRI) activity patterns that vary consistently with the location of visual stimuli, has been documented in many human brain regions, notably the occipital visual cortex and the frontal and parietal regions that are active during endogenous, goal directed attention. We hypothesized that spatial selectivity also exists in regions that are active during exogenous, stimulus-driven attention. To test this hypothesis, we acquired fMRI data while subjects maintained passive fixation. At jittered time intervals, a briefly presented wedge-shaped array of rapidly expanding circles appeared at one of three contralateral or one of three ipsilateral locations. Positive fMRI activations were identified in multiple brain regions commonly associated with exogenous attention, including the temporoparietal junction, the inferior parietal lobule, and the inferior frontal sulcus. These activations were not organized as a map across the cortical surface. However, multivoxel pattern analysis of the fMRI activity correctly classified every pair of stimulus locations, demonstrating that patterns of fMRI activity were correlated with spatial location. These observations held for both contralateral and ipsilateral stimulus pairs as well as for stimuli of different textures (radial checkerboard) and shapes (squares and rings). Permutation testing verified that the obtained accuracies were not due to systematic biases and demonstrated that the findings were statistically significant. PMID- 26382008 TI - MCP-1 and soluble TWEAK levels are independently associated with coronary artery disease severity in patients with chronic kidney disease. AB - PURPOSE: Patients diagnosed with chronic kidney disease (CKD) have a greater rate of cardiovascular mortality when compared with the general population. The soluble form of TNF-like weak inducer of apoptosis (TWEAK) and monocyte chemoattractan protein 1 (MCP-1) play important roles in cellular proliferation, migration and apoptosis. The current study aimed to analyze whether soluble TWEAK (sTWEAK) and MCP-1 levels are associated with the severity of coronary arterial disease (CAD) in CKD patients. METHODS: Ninety-seven patients diagnosed with CKD stages 2-3 according to their estimated glomerular filtration rate and the presence of kidney injury were included in the study. Plasma sTWEAK and MCP-1 concentrations were determined using commercially available ELISA kits. Coronary angiographies were performed through femoral artery access using the Judkins technique. RESULTS: Correlation analysis of sTWEAK and Gensini scores showed significant association (p < 0.01, r(2) = 0.287). Also significant correlation has been found in MCP-1 levels and Gensini scores (p < 0.01, r(2) = 0.414). When patients were divided into two groups with a limit of 17 according to their Gensini score, sTWEAK levels indicated a statistically significant difference (p < 0.01). CONCLUSIONS: Our findings support a relationship between sTWEAK and MCP 1 levels and CAD in CKD stages 2-3 patients. PMID- 26382010 TI - Omega-3 long-chain polyunsaturated fatty acids and fish oil supplementation during pregnancy: which evidence? AB - OBJECTIVE: The aim of this study was to provide evidence-based recommendations for omega-3 supplementation during pregnancy through a systematic review of level 1 data published on this topic. METHODS: We reviewed all randomized-controlled trials (RCTs) including women who were randomized to treatment with either omega 3 supplementation or control (placebo or no treatment) during pregnancy and analyzed all the outcomes reported in the trials, separately. We planned to evaluate the effect of omega-3 on: preterm birth (PTB); pre-eclampsia (PE) and intrauterine growth restriction (IUGR); gestational diabetes; perinatal mortality; small for gestational age (SGA) and birth weight; infant eye and brain development; and postpartum depression. RESULTS: We identified 34 RCTs including 14 106 singletons and 2578 twins. These level-1 data showed that omega-3 was not associated with prevention of PTB, PE, IUGR, gestational diabetes, SGA, post partum depression or better children development. Data about birth weight, perinatal mortality and childhood cognitive outcome were limited. Women with gestational diabetes who received omega-3 had significantly lower serum C reactive protein concentrations, low incidence of hyperbilirubinemia in newborns and decreased newborns' hospitalization rate. CONCLUSIONS: There was not enough evidence to support the routine use of omega-3 supplementation during pregnancy. Given the 73% significant decrease in perinatal death in the singleton gestations who started omega-3 supplementation <= 20 weeks, further research is needed. Large RCTs in multiple gestations and longer follow-up are also required. PMID- 26382009 TI - Enhanced EJ Cell Killing of (125)I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter. AB - AIM: To investigate the enhancing effect of radionuclide therapy by the therapeutic gene placed under the control of radio-responsive promoter. METHODS: The recombinant lentivirus E8-codA-GFP, including a synthetic radiation-sensitive promoter E8, cytosine deaminase (CD) gene, and green fluorescent protein gene, was constructed. The gene expression activated by (125)I radiation was assessed by observation of green fluorescence. The ability of converting 5-fluorocytosine (5-FC) to 5-fluorourial (5-FU) by CD enzyme was assessed by high-performance liquid chromatography. The viability of the infected cells exposed to (125)I in the presence of 5-FC was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay, and the infected cells exposed to (125)I alone served as negative control and 5-FU as positive control. RESULTS: The recombinant lentiviral vector was constructed successfully. On exposure of infected cells to (125)I, green fluorescence can be observed and 5-FU can be detected. MTT assay showed that the survival rate for infected cells treated with (125)I was lower compared with the (125)I control group, but higher than the positive control group. CONCLUSION: The synthetic promoter E8 can induce the expression of downstream CD gene under (125)I radiation, and the tumor killing effect of (125)I can be enhanced by combining CD gene therapy with radiosensitive promoter. PMID- 26382011 TI - Synthesis, antitumor activity evaluation of some new N-aroyl-alpha,beta unsaturated piperidones with fluorescence. AB - Novel N-aroyl-alpha,beta-unsaturated piperidones, series 1, series 2 and series 3 (featuring 2-bromo-4,5-dimethoxybenzylidene, 4-dimethylaminobenzylidene and 4 trifluoromethylbenzylidene, respectively), were synthesized as candidate cytotoxins. Most of the compounds displayed potent cytotoxicity against the human neoplastic cell lines SK-BR-3, PG-BE1, NCI-H460, MIA PaCa-2 and SW1990 in vitro, and approximately 64% of the IC50 values were lower than 5 MUM. Among those tested, compound 1b of series 1, 3a, 3d and 3e of series 3 proved to be the most active. Importantly, 1b displayed marked inhibitory effects on tumor growth in vivo and had no apparent toxicity to mice; this was evaluated by a nude mouse PG BE1 xenograft model. In addition, the fluorescent properties of compounds series 1-3 were investigated. The interesting fluorescence exhibited by these compounds could be useful for their visualization in tumor cells, permitting further studies on these alpha,beta-unsaturated piperidones as candidates for novel fluorescent antitumor agents. PMID- 26382012 TI - Single nucleotide polymorphism in the SEPS1 gene may contribute to the risk of various human diseases: a meta-analysis. AB - BACKGROUND: Recently the G-105A promoter polymorphism in SEPS1 has been shown to increase pro-inflammatory cytokine expression and, thus, to be correlated with various types of human cancers and diseases. AIMS: This study examined whether this functional polymorphism was related to the risks of several human diseases by performing a meta-analysis. SUBJECTS AND METHODS: This study identified all published studies in MEDLINE, Science Citation Index, the Cochrane Library, PubMed, Embase, Current Contents Index and three Chinese databases. RESULTS AND CONCLUSIONS: Eleven case-control studies were incorporated into this meta analysis. The results showed that carriers of the rs28665122 G > A polymorphism in the SEPS1 gene are at increased risk of developing diseases under five genetic models. According to the ethnicity-stratified sub-group analysis, SEPS1 rs28665122 polymorphism is significantly linked to increased risk of developing related diseases in Europeans under five genetic models; but not among Asians. This data indicates a statistical association between SEPS1 rs28665122 G > A variants and the development of various human diseases. Such findings suggest that SEPS1 may be a potential gene marker for disease diagnosis and prognosis. PMID- 26382013 TI - Targeted Tuning of Interactive Forces by Engineering of Molecular Bonds in Series and Parallel Using Peptide-Based Adhesives. AB - Polymer-mediated adhesion plays a major role for both technical glues and biological processes like self-assembly or biorecognition. In contrast to engineering systems, adhesive strength in biological systems is precisely tuned via well-adjusted arrangement of individual bonds. How adhesion may be engineered by arrangement of individual bonds is however not yet well-understood. Here we show how the number of bonds in series and parallel can significantly influence adhesion forces using specifically designed surface-bridging peptides. We directly measure how adhesion forces between -COOH and -NH2 functionalized surfaces across aqueous media vary as a function of the number of bonds in parallel. We also introduce surface bridging peptide sequences that are similarly end-functionalized with amines and carboxylic acid. Compared to single molecular junctions, adhesive strength mediated by these surface bridging peptides decreases by a factor of 2 for adhesive junctions that consist of two acid/base bonds in series. Furthermore, adhesive strength varies with the density of bonds in parallel. For dense systems, we observe that the formation of a bridging peptide monolayer is sterically hindered and therefore adhesion is further reduced significantly by 20%. Our results unravel how the arrangement of individual bonds in an adhesive junction allows for a wide tuning of adhesive strength on the basis of utilizing just one single specific bond. As such, for peptide adhesives it is essential to consider bonds in parallel in a wide range of applications where both high adhesion and triggered release of adhesive bonds is essential. PMID- 26382014 TI - Common Variants Associated with Type 2 Diabetes in a Black South African Population of Setswana Descent: African Populations Diverge. AB - The increasing worldwide prevalence of type 2 diabetes mellitus (T2D) is a serious global health concern. Although T2D has a strong genetic etiology, limited knowledge exists about the common variants associated with it in the black South African population. This study set out to evaluate the association of previously reported common variants in other world populations with T2D susceptibility in a black South African population of Setswana descent. A case control study design of 178 cases and 178 controls nested in the Prospective Urban Rural Epidemiology (PURE) study was conducted wherein we genotyped for 77 single nucleotide polymorphisms (SNPs). PLINK software was used to evaluate the standard genetic models of disease penetrance for the association of the common variants with impaired glucose tolerance (IGT) while adjusting for age, sex, and body mass index. Only rs1436955 significantly associated with an increase in T2D risk; three other variants, rs831571, rs8050136, and rs7542900, significantly associated with decreased risk of T2D. However, none of the four SNPs had significant associations after correcting for multiple testing (p<0.05). Although further studies are required to confirm these observations, the common variants associated with T2D risk among the Black South Africans of Setswana descent might likely be different than those in the Asian and European populations. This study supports the broader thesis that the genetic background of Africans is diverse and cannot be directly extrapolated using genetic variants from other ethnicities. Therefore there is a need to identify the population-specific variants linked with T2D in Africa. PMID- 26382015 TI - Acceptability and Applicability of an American Health Videogame with Story for Childhood Obesity Prevention Among Hong Kong Chinese Children. AB - OBJECTIVE: Positive changes in diet have been observed in research carried out in the United States from the use of "Escape from Diab" (Diab), a health videogame designed to lower the risk of obesity and type 2 diabetes. Whether the American story and characters in Diab might be perceived by Hong Kong Chinese children as interesting has not been explored. This study assessed the acceptability and applicability of Diab among Hong Kong Chinese children, whether the Diab story was understood by them, and whether it had potential to influence them both during the game and afterward. SUBJECTS AND METHODS: Thirty-four students (21 males, 13 females) 9-12 years of age were included. Upon completion of all the Diab episodes, children completed an immersion scale with 18 items, as well as an individual interview with 10 open-ended questions. RESULTS: Children achieved average immersion after playing Diab with the mean score at 39.1 (standard deviation = 9.0), higher than the median (36) of possible scores (range, 18-54). Four themes using framework analysis emerged from the interviews, including intuitive feelings about the interface, playing experience, perception of the effect of Diab on behavior change, and the applicability of Diab to Hong Kong children. The story and game developed for American children were found acceptable and applicable to Hong Kong Chinese children. CONCLUSIONS: The combination of quantitative and qualitative methods confirmed the acceptability and applicability of Diab to Hong Kong Chinese children. PMID- 26382016 TI - Addressing the overdose epidemic requires timely access to data to guide interventions. AB - Fatal opioid overdose, the leading cause of injury death in the USA, is regularly described as an epidemic. The response to the overdose crisis, however, has largely failed to utilise many of the public health tools that have proven effective in combating epidemics. Chief among these is the systematic and timely use of data by public health officials to track outbreaks and effectively target interventions. This failure is particularly acute regarding data from prescription monitoring programmes, which are routinely used by clinicians and law enforcement agents, but often unavailable to health officials. We argue for a shift in emphasis and resources towards an evidence-based public health approach to data use for overdose prevention. [Davis CS, Green TC, Zaller ND. Addressing the overdose epidemic requires timely access to data to guide interventions. Drug Alcohol Rev 2016;35:383-386]. PMID- 26382017 TI - Within-season yield prediction with different nitrogen inputs under rain-fed condition using CERES-Wheat model in the northwest of China. AB - BACKGROUND: Yield prediction within season is of great use to improve agricultural risk management and decision making. The objectives of this study were to access the yield forecast performance with increasing nitrogen inputs and to determine when the acceptable predicted yield can be achieved using the CERES Wheat model. RESULTS: the calibrated model simulated wheat yield very well under various water and nitrogen conditions. Long-term simulation demonstrated that nitrogen input enlarged the annual variability of wheat yield generally. Within season yield prediction showed that, regardless of nitrogen inputs, yield forecasts in the later growing season improved the accuracy and reduced the uncertainty of yield prediction. In a low-yielding year (2011-2012) and a high yielding year (1991-1992), the date of acceptable predicted yield was achieved 62 and 65 days prior to wheat maturity, respectively. In a normal-yielding year (1983-1984), inadequate precipitation after the jointing stage in most historical years led to the underestimation of wheat yield and the date of accurate yield prediction was delayed to 235-250 days after simulation (7-22 days prior to maturity) for different N inputs. CONCLUSION: Yield prediction was highly influenced by the distribution of meteorological elements during the growing season and may show great improvement if future weather can be reliably forecast early. (c) 2015 Society of Chemical Industry. PMID- 26382018 TI - Drug Shortages and Tipping Points. PMID- 26382019 TI - Photoelectrochemical aptasensor for the sensitive and selective detection of kanamycin based on Au nanoparticle functionalized self-doped TiO2 nanotube arrays. AB - In this communication, a new photoelectrochemical aptasensor with Au nanoparticle functionalized self-doped TiO2 nanotube arrays (Au/SD-TiO2 NTs) as the core sensing unit and aptamers as the recognition unit was set up to accomplish the sensitive and selective detection of kanamycin with the lowest detection limit of 0.1 nM. PMID- 26382020 TI - Miniscrew implant fracture and effects of such retained tip on dentin-pulp complex: a histological report. AB - Miniscrew implants provide an excellent orthodontic anchorage. Besides the clinical benefits, miniscrew implants cause minor discomforts and in certain instances poses problematic complications. Damage to the adjacent tooth structure is the most feared complication of miniscrew implant placement, while fracture of miniscrew implants is the rarest. Miniscrew fracture could occur either during its placement or during its removal. An unusual case report is presented of a miniscrew implant tip fracture following root contact while attempting to remove it. This report highlights the effect of such miniscrew implant fracture on the dentin-pulp complex. The present case is probably the first to give direct histological evidence in humans that a miniscrew fracture or a retained miniscrew implant tip along the dentin/cementum without obvious miniscrew implant penetration could elicit pulp changes. Therefore this case report emphasizes the fact that prior to placing miniscrew implant, clinicians should have acquired proper training and adequate skills in terms of MSI placement and management of fractured MSI. PMID- 26382021 TI - Editorial. PMID- 26382022 TI - Transport, Distribution and Elimination of Mammalian Sperm Following Natural Mating and Insemination. AB - The integrity of transport, distribution and elimination of sperm in the female genital tract plays a pivotal role for successful reproduction in mammals. At coitus, millions or billions of sperm are deposited either into the anterior vagina (human, primates), the cervix (most mammalian species) or the uterus (pig). In most species, the first anatomical barrier is the cervix, where spermatozoa with poor morphology and motility are filtered out by sticking to the cervical mucus. The second anatomical barrier is the uterotubal junction (UTJ) with its tortuous and narrow lumen. Finally, only a few thousand sperm enter the oviduct and less than 100 sperm reach the site of fertilization. As soon as the sperm enter the oviduct, they form a sperm reservoir enabling them to stay vital and maintain fertilizing capacity for 3-4 days (cow, horse) up to several months (bats). After ovulation, mammalian sperm show hyperactivation which allows them to detach from the tubal epithelium and migrate to the site of fertilization. This review will focus on recent insights of sperm transport, sperm storage and sperm-oviduct interaction in mammals which have been gained by live cell imaging in cows and mice under near in vivo conditions. Detailed knowledge of the biology of spermatozoa within the female genital tract creates the basis for new therapeutic concepts for male subfertility and infertility - an essential prerequisite to increase success rates in assisted reproduction. PMID- 26382023 TI - The Role of Conceptus-maternal Signalling in the Acquisition of Uterine Receptivity to Implantation in Mammals. AB - Implantation is a pivotal step in the establishment of mammalian pregnancy. Although implantation strategies vary between species, many aspects of conceptus maternal signalling necessary to induce uterine receptivity to implantation are conserved. The temporal 'window' for the initiation of implantation is short and precisely controlled by endocrine, paracrine and autocrine factors. An invariable prerequisite for the development of uterine receptivity to implantation is continuous exposure of the endometrium to progesterone which, after a species specific interval, downregulates progesterone receptor (PGR) expression in the epithelium and stimulates the production of progestamedins. Uterine receptivity involves temporal changes in the expression of genes, leading to modifications in surface, extracellular matrix and secretory characteristics that support growth, proliferation, migration and attachment of the conceptus. Moreover, a complex interplay between endometrial progestamedins and estramedins and conceptus derived oestrogens, cytokines and interferons (INFs), prostaglandins (PGs) and cortisol is crucial to the preparation for implantation. Understanding the individual roles and combined actions of conceptus and endometrial autocrine and paracrine factors in the development of uterine receptivity to implantation is essential for translational research into strategies to reduce pregnancy loss in man and animals. PMID- 26382024 TI - Endocrine Disruptors in Domestic Animal Reproduction: A Clinical Issue? AB - The objective of this review was to discuss whether endocrine disruption is a clinical concern in domestic animal reproduction. To that end, we firstly summarize the phenomenon of endocrine disruption, giving examples of the agents of concern and their effects on the mammalian reproductive system. Then there is a brief overview of the literature on endocrine disruptors and domestic animal reproduction. Finally, the clinical implications of endocrine disruptors on the reproductive system of farm animals as well as in dogs and cats are discussed. It is concluded that the evidence for clinical cases of endocrine disruption by chemical pollutants is weak, whereas for phytooestrogens, it is well established. However, there is concern that particular dogs and cats may be exposed to man made endocrine disruptors. PMID- 26382025 TI - Sperm Membrane Behaviour during Cooling and Cryopreservation. AB - Native sperm is only marginally stable after collection. Cryopreservation of semen facilitates transport and storage for later use in artificial reproduction technologies, but cryopreservation processing may result in cellular damage compromising sperm function. Membranes are thought to be the primary site of cryopreservation injury. Therefore, insights into the effects of cooling, ice formation and protective agents on sperm membranes may help to rationally design cryopreservation protocols. In this review, we describe membrane phase behaviour of sperm at supra- and subzero temperatures. In addition, factors affecting membrane phase transitions and stability, sperm osmotic tolerance limits and mode of action of cryoprotective agents are discussed. It is shown how cooling only results in minor thermotropic non-cooperative phase transitions, whereas freezing causes sharp lyotropic fluid-to-gel phase transitions. Membrane cholesterol content affects suprazero membrane phase behaviour and osmotic tolerance. The rate and extent of cellular dehydration coinciding with freezing-induced membrane phase transitions are affected by the cooling rate and ice nucleation temperature and can be modulated by cryoprotective agents. Permeating agents such as glycerol can move across cellular membranes, whereas non-permeating agents such as sucrose cannot. Both, permeating and non-permeating protectants preserve biomolecular and cellular structures by forming a protective glassy state during freezing. PMID- 26382027 TI - Simultaneous determination of tanshinones and polyphenolics in rat plasma by UPLC MS/MS and its application to the pharmacokinetic interaction between them. AB - The aim of this study was to investigate the pharmacokinetic interaction between tanshinones and polyphenolics which act as the main bioactive compounds in Saliva miltiorrhiza Bunge (SMB). Thus, a rapid and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine the concentrations of Tanshinone IIA (TSIIA), Tanshinone I (TI), Cryptotanshinone (CT), Salvianolic acid B (Sal B), Protocatechuic aldehyde (PAL), Rosmarinic acid (RA), and Danshensu (DSS) in rat plasma. The Sprague-Dawley rats were allocated to three groups which orally administered tanshinones (DST), polyphenolics (DFS), and a mixture of tanshinones and polyphenolics (DTF). These samples were processed by a simple liquid-liquid extraction (LLE) method with ethyl acetate. Chromatographic separation was achieved on an Acquity BEH C18 column (100 mm * 2. 1 mm, 1.7 um) with the mobile phase consisting of 0.1% (v/v) formic acid and acetonitrile by gradient elution at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer TQ-MS/MS equipped with negative and positive electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) mode. The statistical analysis was performed by the Student's t-test with P <= 0.05 as the level of significance. The method showed good precision, accuracy, recovery, sensitivity, linearity, and stability. The pharmacokinetic profiles and parameters of these polyphenolics changed when co-administrated with tanshinones. The tanshinones improved the bioavailability of DSS, accelerated the eliminating rate of RA and Sal B and promoted their distribution in vivo. They also contributed to promoting the biotransformation of Sal B to DSS. The polyphenolics could affect the pharmacokinetic of tanshinones, especially CT and TSIIA. Furthermore, the biotransformation of CT to TSIIA and the bioavailability of TSIIA were both improved. This study may provide useful information to avoid unexpected increase of the plasma drug concentration in the clinical practice. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26382029 TI - Characterization and changes in neurotrophin receptor p75-expressing motor neurons in SOD1(G93A) G1H mice. PMID- 26382028 TI - Regulation of Certified Nurse-Midwife Scope of Practice: Change in the Professional Practice Index, 2000 to 2015. AB - INTRODUCTION: Certified nurse-midwives (CNMs) across the United States are educated in the same core competencies, yet scope of practice varies with state regulation. The Health Resources and Services Administration (HRSA) funded studies published in 1994 and 2004 on the professional practice environment of CNMs, nurse practitioners, and physician assistants, and developed the Certified Nurse-Midwife Professional Practice Index (CNMPPI), a 100-point scoring system of state regulation focusing on 3 domains: legal status, reimbursement, and prescriptive authority. The purpose of this study was to examine changes to CNM regulation between 2000 and 2015 by updating scores to the CNMPPI. METHODS: Individual state CNMPPI scores from 2000 were updated for every year through 2015 by reviewing data published in the American College of Nurse-Midwives (ACNM) quarterly publication Quickening, the annual advanced practice registered nurse legislative updates in the journal Nurse Practitioner, and the ACNM State Legislative and Regulatory Guidance. RESULTS: Mean state scores increased 18%, from 69.7 in 2000 to 79.8 in 2015, and variation between state scores fell. Increases were seen in all 3 domains, with the greatest increase in the domain of prescriptive authority and the smallest in the legal domain. Individual state CNMPPI scores tend to be correlated with scores of adjacent states. DISCUSSION: The CNMPPI can be used to document changes in practice authority of CNMs. The increase in state CNMPPI scores and decrease in variance across states can be interpreted as indicating growth of professional authority and increasing consensus regarding the CNM role. The scoring system needs to be updated to reflect the current health systems environment and to include certified midwives and other midwives meeting the International Confederation of Midwives definition of a midwife. Applications of the CNMPPI to future research are discussed. PMID- 26382032 TI - Erratum to: Effectiveness of intra-articular injections of sodium bicarbonate and calcium gluconate in the treatment of osteoarthritis of the knee: a randomized double-blind clinical trial. PMID- 26382031 TI - Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells. AB - BACKGROUND: Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-kappaB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. METHODS: Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-kappaB (p65 and phospho-IKK alpha/beta) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14-28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-alpha (10 ng/ml), the effects of dexamethasone (10(-8)-10(-6) M) and IKK2 (NF kappaB) inhibition (AS602868, 0-3 MUM (0-3*10(-6) M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-kappaB activation was measured by TransAm assay. RESULTS: Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-alpha-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-kappaB activation and in IL-6 and CXCL8 release from PASMC. CONCLUSIONS: Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-kappaB. Future PAH therapies may involve targeting these important inflammatory pathways. PMID- 26382033 TI - Fstl1 is involved in the regulation of radial glial scaffold development. AB - BACKGROUND: Radial glial cells (RGCs), the instructive scaffolds for neuronal migration, are well characterized by their unique morphology and polarization; these cells extend elongated basal processes to the pial basement membrane (BM) and parallel to one another. However, little is known about the mechanisms that underlie the developmental regulation and maintenance of this unique morphology. RESULTS: Here, by crossing Fstl1 (fl/fl) mice with an EIIa-Cre line, we identified a new role for the secreted glycoprotein Follistatin like-1 (FSTL1). The ablation of Fstl1 in both of its cortical expression domains, the ventricular zone (VZ) and the pia mater, resulted in RGC morphologic disruption; basal processes were not parallel to each other, and endfeet exhibited greater density and branching. However, Fstl1 deletion in only the VZ in the Emx1 (IREScre); Fstl1 (fl/fl) line did not affect RGC morphology, indicating that FSTL1 derived from the pia mater might be more important for RGC morphology. In addition, upper layer projection neurons, not deeper-layer projection neurons, failed to reach their appropriate positions. We also found that BMP, AKT/PKB, Cdc42, GSK3beta, integrin and reelin signals, which have previously been reported to regulate RGC development, were unchanged, indicating that Fstl1 may function through a unique mechanism. CONCLUSIONS: In the present study, we identified a new role for FSTL1 in the development of radial glial scaffolds and the neuronal migration of upper layer projection neurons. Our findings will improve understanding of the regulation of RGC development and neuronal migration. PMID- 26382034 TI - Congenital atresia of the left main coronary artery in an adult: A rare anomaly with an unfavorable prognosis. Review of the literature. AB - Congenital atresia of the left main coronary artery (LMCA) is one of the rarest congenital anomalies, which may have an unfavorable prognosis leading to myocardial ischemia, ventricle dysfunction or even sudden cardiac death. There are 34 cases of LMCA in adults reported in the literature, most of them successfully treated with coronary revascularization. We report the case of an adult with LMCA who presented with terminal heart failure that required biventricular assistance and heart transplant. PMID- 26382035 TI - Larval and adult environmental temperatures influence the adult reproductive traits of Anopheles gambiae s.s. AB - BACKGROUND: Anopheles mosquito life-history parameters and population dynamics strongly influence malaria transmission, and environmental factors, particularly temperature, strongly affect these parameters. There are currently some studies on how temperature affects Anopheles gambiae s.s. survival but very few exist examining other life-history traits. We investigate here the effect of temperature on population dynamics parameters. METHODS: Anopheles gambiae s.s. immatures were reared individually at 23 +/- 1 degrees C, 27 +/- 1 degrees C, 31 +/- 1 degrees C, and 35 +/- 1 degrees C, and adults were held at their larval temperature or at one of the other temperatures. Larvae were checked every 24 h for development to the next stage and measured for size; wing length was measured as a proxy for adult size. Females were blood fed three times, and the number of females feeding and laying eggs was counted. The numbers of eggs and percentage of eggs hatched were recorded. RESULTS: Increasing temperatures during the larval stages resulted in significantly smaller larvae (p = 0.005) and smaller adults (p < 0.001). Adult temperature had no effect on the time to egg laying, and the larval temperature of adults only affected the incubation period of the first egg batch. Temperature influenced the time to hatching of eggs, as well as the time to development at every stage. The number of eggs laid was highest when adults were kept at 27 degrees C, and lowest at 31 degrees C, and higher adult temperatures decreased the proportion of eggs hatching after the second and third blood meal. Higher adult temperatures significantly decreased the probability of blood feeding, but the larval temperature of adults had no influence on the probability of taking a blood meal. Differences were observed between the first, second, and third blood meal in the times to egg laying and hatching, number of eggs laid, and probabilities of feeding and laying eggs. CONCLUSIONS: Our study shows that environmental temperature during the larval stages as well as during the adult stages affects Anopheles life-history parameters. Data on how temperature and other climatic factors affect vector life history parameters are necessary to parameterise more reliably models predicting how global warming may influence malaria transmission. PMID- 26382036 TI - Azospirillum soli sp. nov., a nitrogen-fixing species isolated from agricultural soil. AB - An aerobic, Gram-stain-negative, rod or spiral-shaped diazotrophic bacterium (designated strain CC-LY788T), was isolated from agricultural soil in Taiwan. Strain CC-LY788T was able to grow at 25-40 degrees C, pH 6.0-8.0 and tolerated NaCl to 2.0% (w/v). Positive for nitrogen fixation with the activity recorded as 6.5 nmol ethylene h(-1). Strain CC-LY788T showed highest 16S rRNA gene sequence similarity to Azospirillum picis DSM 19922T (97.2%) and Azospirillum rugosum DSM 19657T (97.1%) and lower sequence similarities (<96.6%) to all other species of the genus Azospirillum. According to the DNA-DNA hybridization, the relatedness values of strain CC-LY788T with A. picis DSM 19922T and A. rugosum DSM 19657T were 51.1+/-5.5% and 46.8+/-2.1%, respectively. Strain CC-LY788T was positive for the rapid identification of the genus-specific primer set. The respiratory quinone system was ubiquinone (Q-10) and the DNAG+C content was 69.8 mol%. The major fatty acids found in strain CC-LY788T were C16 : 0, C18 : 1 2-OH, C14 : 0 3 OH/C16 : 1 iso I (summed feature 2), C16 : 1omega7c/C16 : 1omega6c (summed feature 3), C18 : 0 ante/C18 : 2omega6,9c (summed feature 5) and C18 : 1omega7c/C18 : 1omega6c (summed feature 8). Based on the phylogenetic, phenotypic and chemotaxonomic features, strain CC-LY788T represents a novel species of the genus Azospirillum, for which the name Azospirillum soli sp. nov. is proposed. The type strain is CC-LY788T (=BCRC 80569T=JCM 18820T). PMID- 26382037 TI - Deficiency of macrophage migration inhibitory factor attenuates tau hyperphosphorylation in mouse models of Alzheimer's disease. AB - BACKGROUND: Pathological features of Alzheimer's disease (AD) include aggregation of amyloid beta (Abeta) and tau protein. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, has been implicated in the toxicity of aggregated Abeta. It remains unclear whether MIF affects hyperphosphorylation and aggregation of tau. METHODS: The effects of MIF deficiency in tau hyperphosphorylation were examined in Mif (-/-) mice receiving intracerebroventricular (ICV) injection of streptozotocin (STZ) and in APP/PS1 transgenic mice mated with Mif (-/-) mice. MIF expression and astrocyte activation were evaluated in ICV-STZ mice using immunofluorescence staining. Cultured primary astrocytes were treated with high glucose to mimic STZ function in vitro, and the condition medium (CM) was collected. The level of tau hyperphosphorylation in neurons treated with the astrocyte CM was determined using Western blotting. RESULTS: MIF deficiency attenuated tau hyperphosphorylation in mice. ICV injection of STZ increased astrocyte activation and MIF expression in the hippocampus. MIF deficiency attenuated astrocyte activation in ICV-STZ mice. CM from high glucose-treated WT astrocytes increased tau hyperphosphorylation in cultured primary neurons, an effect absent from Mif ( /-) astrocytes and WT astrocytes treated with the MIF inhibitor ISO-1. ISO-1 had no direct effect on tau phosphorylation in cultured primary neurons. CONCLUSIONS: These results suggest that MIF deficiency is associated with reduced astrocyte activation and tau hyperphosphorylation in the mouse AD models tested. Inhibition of MIF and MIF-induced astrocyte activation may be useful in AD prevention and therapy. PMID- 26382038 TI - Menorrhagia. AB - INTRODUCTION: Menorrhagia (also known as heavy menstrual bleeding) limits normal activities, affects quality of life, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of surgical treatments for menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). RESULTS: At this update, searching of electronic databases retrieved 205 studies. After deduplication and removal of conference abstracts, 102 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 56 studies and the further review of 46 full publications. Of the 46 full articles evaluated, three systematic reviews and five RCTs were added at this update. We performed a GRADE evaluation for 30 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for three surgical interventions based on information about the effectiveness and safety of dilatation and curettage, endometrial destruction (resection or ablation), and hysterectomy. PMID- 26382039 TI - Two cases of annular erythema without bullous lesions by autoimmune blistering diseases. AB - Although annular erythema is usually observed as one of the cutaneous manifestations of Sjogren's syndrome or subacute cutaneous lupus erythematosus, autoimmune blistering diseases also present with annular erythema. However, bullous lesions are not always found, and there is a rare type without bullous lesions. We present two cases of autoimmune blistering diseases showing annular erythema without bullous lesions. It is important to perform direct or indirect immunofluorescence examination when we encounter multiple annular erythema. PMID- 26382040 TI - miRNA Expression Analyses in Prostate Cancer Clinical Tissues. AB - A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA). PMID- 26382041 TI - A PCR-RFLP Assay targeting RPS8 gene for the discrimination between bovine Babesia and Theileria species in China. AB - BACKGROUND: Bovine babesiosis and theileriosis is an important hemoprotozoal disease in cattles and yaks in tropical and subtropical regions leading to significant economic losses. In the field, the risk of co-infection between the bovine Babesia and Theileria species is very high. Thus, it is necessary to develop a simple, accurate, rapid and cost-effective method for large-scale epidemic investigation, in particular for the detection of co-infection in field. METHODS: In this study, DNA sequences of a ribosomal protein S8 (RPS8) gene from eight species of cattle piroplasms in China were used to develop a species specific PCR-RFLP diagnostic tool. The eight Theileria and Babesia species could be differentiated by digesting the RPS8 PCR product with Mbo I. RESULTS: The sensitivity of the PCR assays was 0.1 pg DNA for Babesia species but 1 pg DNA for Theileria species. The clearly different size of the PCR-RFLP products allowed for a direct discrimination between eight bovine Theileria and Babesia species (T. annulata, T. sinensis, T. sergenti, B. ovata, B. bovis, B. bigemina, B. major and Babesia species Kashi isolate). CONCLUSION: Our results indicated that the established method based on the RPS8 gene was a reliable molecular diagnostic tool for the simultaneous detection and identification of bovine Babesia and Theileria species in China, which could be applicable for the survey of parasite dynamics, epidemiological studies as well as prevention and control of the disease. PMID- 26382042 TI - The road to the first, fully active and more stable human insulin variant with an additional disulfide bond. AB - Insulin, a small peptide hormone, is crucial in maintaining blood glucose homeostasis. The stability and activity of the protein is directed by an intricate system involving disulfide bonds to stabilize the active monomeric species and by their non-covalent oligomerization. All known insulin variants in vertebrates consist of two peptide chains and have six cysteine residues, which form three disulfide bonds, two of them link the two chains and a third is an intra-chain bond in the A-chain. This classical insulin fold appears to have been conserved over half a billion years of evolution. We addressed the question whether a human insulin variant with four disulfide bonds could exist and be fully functional. In this review, we give an overview of the road to engineering four-disulfide bonded insulin analogs. During our journey, we discovered several active four disulfide bonded insulin analogs with markedly improved stability and gained insights into the instability of analogs with seven cysteine residues, importance of dimerization for stability, insulin fibril formation process, and the conformation of insulin binding to its receptor. Our results also open the way for new strategies in the development of insulin biopharmaceuticals. PMID- 26382044 TI - Comparative efficacy of CO2 and ozone gases against Ephestia cautella (Lepidoptera: Pyralidae) larvae under different temperature regimes. AB - Comparative efficacy of three different modified atmospheres: 100% CO2, 75% CO2 + 25% N2, and 22 ppm ozone were examined against larval mortality of the almond moth, Ephestia cautella (Walker) (Lepidoptera: Pyralidae) at temperature regimes of 25 degrees C and 35 +/- 2 degrees C and 60 +/- 5% relative humidity, and 9:15 dark and light. Wandering young larval instars, which are fast growing, large enough in size and considered as more tolerant to modified atmosphere, were collected directly from the rearing culture, placed inside pitted date fruits of vars.: "Khudri," "Ruziz," and "Saqie," were treated with aforementioned gases for 24, 48, and 72 h. The immediate and delayed larval mortality was recorded after each exposure timing. Ozone possessed the strongest fumigant toxicity causing 100% mortality with all varieties, at 25 and 35 degrees C after 24 h exposure and was more effective than 75% CO2 that caused 83 and 100% immediate mortality with variety ruziz at 25 and 35 degrees C, respectively. Extending the treatments exposure time to 72 h, 100% mortality was recorded by exposing larvae to any of the studied gases at 25 and 35 degrees C. These results suggest that gases and temperature used in this study can be effectively used to control E. cautella in dates and stored grains. PMID- 26382043 TI - Modeling the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus excretors and the potential benefits of antiviral drugs. AB - BACKGROUND: A small number of individuals with B-cell-related primary immunodeficiency diseases (PIDs) may exhibit long-term (prolonged or chronic) excretion of immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) following infection with oral poliovirus vaccine (OPV). These individuals pose a risk of live poliovirus reintroduction into the population after global wild poliovirus eradication and subsequent OPV cessation. Treatment with polio antiviral drugs may potentially stop excretion in some of these individuals and thus may reduce the future population risk. METHODS: We developed a discrete event simulation model to characterize the global prevalence of long-term iVDPV excretors based on the best available evidence. We explored the impact of different assumptions about the effectiveness of polio antiviral drugs and the fraction of long-term excretors identified and treated. RESULTS: Due to the rarity of long-term iVDPV excretion and limited data on the survival of PID patients in developing countries, uncertainty remains about the current and future prevalence of long-term iVDPV excretors. While the model suggests only approximately 30 current excretors globally and a rapid decrease after OPV cessation, most of these excrete asymptomatically and remain undetected. The possibility that one or more PID patients may continue to excrete iVDPVs for several years after OPV cessation represents a risk for reintroduction of live polioviruses after OPV cessation, particularly for middle-income countries. With the effectiveness of a single polio antiviral drug possibly as low as 40% and no system in place to identify and treat asymptomatic excretors, the impact of passive use of a single polio antiviral drug to treat identified excretors appears limited. Higher drug effectiveness and active efforts to identify long term excretors will dramatically increase the benefits of polio antiviral drugs. CONCLUSIONS: Efforts to develop a second polio antiviral compound to increase polio antiviral effectiveness and/or to maximize the identification and treatment of affected individuals represent important risk management opportunities for the polio endgame. Better data on the survival of PID patients in developing countries and more longitudinal data on their exposure to and recovery from OPV infections would improve our understanding of the risks associated with iVDPV excretors and the benefits of further investments in polio antiviral drugs. PMID- 26382045 TI - Signet Ring-Like Cells: A New Reflectance Confocal Microscopy Clue of Interface Dermatitis Correlated to Basal Cell Vacuolization in Histopathology. PMID- 26382046 TI - Ginkgolide B Reduces the Degradation of Membrane Phospholipids to Prevent Ischemia/Reperfusion Myocardial Injury in Rats. AB - Platelet-activating factor (PAF), a bioactive phospholipid, plays an important role in the integrity of the cellular membrane structure, and is involved in the pathogenesis of myocardial ischemia/reperfusion (IR) injuries. In this study, we tested the hypothesis that blockage of PAF receptor by BN 52021 (Ginkgolide B) can prevent IR-induced degradation of the myocardial membrane phospholipid, and deterioration of the cardiac function. Rat hearts in situ were subjected to 5 min ischemia and followed by 10 min reperfusion. Cardiac performances during periods of ischemia and reperfusion were monitored, and the amount of membrane phospholipids was analyzed. Myocardial total phospholipids, phosphatidylcholine, and phosphatidylethanolamine were decreased significantly in ischemia-reperfusion rat hearts compared with those of sham-operated rat hearts. Degradation of the membrane phospholipid was accompanied by the deterioration of cardiac functions and increase in serum lactate dehydrogenase (LDH) activity. BN 52021 (15 mg/kg), given by intravenous infusion 10 min prior to the left anterior descending coronary artery occlusion, reduced IR-related degradation of the myocardial phospholipids, the activity of serum LDH, and was concomitant with improvement of cardiac function. Furthermore, we demonstrated that the production of PAF was increased and BN 52021 decreased cellular damage in cultured anoxic cardiomyocytes. These results indicated that PAF antagonist BN 52021 has a protective effect against IR-induced myocardial dysfunction and degradation of the membrane phospholipids. PMID- 26382047 TI - Identification of Bacteria Synthesizing Ribosomal RNA in Response to Uranium Addition During Biostimulation at the Rifle, CO Integrated Field Research Site. AB - Understanding which organisms are capable of reducing uranium at historically contaminated sites provides crucial information needed to evaluate treatment options and outcomes. One approach is determination of the bacteria which directly respond to uranium addition. In this study, uranium amendments were made to groundwater samples from a site of ongoing biostimulation with acetate. The active microbes in the planktonic phase were deduced by monitoring ribosomes production via RT-PCR. The results indicated several microorganisms were synthesizing ribosomes in proportion with uranium amendment up to 2 MUM. Concentrations of U (VI) >2 MUM were generally found to inhibit ribosome synthesis. Two active bacteria responding to uranium addition in the field were close relatives of Desulfobacter postgateii and Geobacter bemidjiensis. Since RNA content often increases with growth rate, our findings suggest it is possible to rapidly elucidate active bacteria responding to the addition of uranium in field samples and provides a more targeted approach to stimulate specific populations to enhance radionuclide reduction in contaminated sites. PMID- 26382048 TI - Genetic Variations in the TP53 Pathway in Native Americans Strongly Suggest Adaptation to the High Altitudes of the Andes. AB - The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway (TP53, rs1042522; MDM2, rs2279744; MDM4, rs1563828; USP7, rs1529916; and LIF, rs929271) were studied in a total of 282 individuals belonging to Quechua, Aymara, Chivay, Cabanaconde, Yanke, Taquile, Amantani, Anapia, Uros, Guarani Nandeva, and Guarani Kaiowa populations, characterized as Native American or as having a high level (> 90%) of Native American ancestry. In addition, published data pertaining to 100 persons from five other Native American populations (Surui, Karitiana, Maya, Pima, and Piapoco) were analyzed. The populations were classified as living in high altitude (>= 2,500 m) or in lowlands (< 2,500 m). Our analyses revealed that alleles USP7-G, LIF-T, and MDM2 T showed significant evidence that they were selected for in relation to harsh environmental variables related to high altitudes. Our results show for the first time that alleles of classical TP53 network genes have been evolutionary co-opted for the successful human colonization of the Andes. PMID- 26382050 TI - Gastric residual volume after split-dose compared with evening-before polyethylene glycol bowel preparation. AB - BACKGROUND AND AIMS: Split-dose bowel preparation for colonoscopy results in superior preparation quality. However, some endoscopy units remain hesitant to prescribe split-dose preparation given theoretical concerns about possible aspiration caused by gastric residual fluid when a second dose is given close to the time of endoscopy. Our aim was to compare gastric residual volume (GRV) in patients taking split-dose bowel preparation and those taking preparation the evening before colonoscopy. METHODS: We performed a prospective observational comparison of GRV among random inpatients undergoing same-day EGD and colonoscopy either after a split-dose bowel preparation or after a bowel preparation the prior evening. RESULTS: GRV was measured in 150 patients undergoing EGD and colonoscopy: 75 who completed a split-dose bowel preparation 2 to 3 hours before endoscopy and 75 who completed the bowel preparation regimen the prior evening. The mean GRV 2 to 3 hours after the last ingestion of bowel preparation among split-dose group patients was 21 +/- 24 mL (+/- standard deviation; range, 0 to 125 mL), which was not different from the mean GRV of 24 +/- 22 mL (range, 0 to 135 mL) in patients who ingested the preparation the prior evening (P = .08). GRV had no association with the presence of diabetes, gastroparesis, or opioid use. CONCLUSIONS: GRV is the same after a split preparation and fasting for 2 to 3 hours or after preparation with overnight fasting. The data suggest that the risk of aspiration is identical after either preparation technique and thus that sedation for colonoscopy can be performed safely 2 hours after bowel preparation ingestion. PMID- 26382049 TI - Correlated spectroscopic imaging of calf muscle in three spatial dimensions using group sparse reconstruction of undersampled single and multichannel data. AB - PURPOSE: To implement a 5D (three spatial + two spectral) correlated spectroscopic imaging sequence for application to human calf. THEORY AND METHODS: Nonuniform sampling was applied across the two phase encoded dimensions and the indirect spectral dimension of an echo planar-correlated spectroscopic imaging sequence. Reconstruction was applied that minimized the group sparse mixed l2,1 norm of the data. Multichannel data were compressed using a sensitivity map-based approach with a spatially dependent transform matrix and utilized the self sparsity of the individual coil images to simplify the reconstruction. RESULTS: Single channel data with 8* and 16* undersampling are shown in the calf of a diabetic patient. A 15-channel scan with 12* undersampling of a healthy volunteer was reconstructed using 5 virtual channels and compared to a fully sampled single slice scan. Group sparse reconstruction faithfully reconstructs the lipid cross peaks much better than l1 minimization. CONCLUSION: COSY spectra can be acquired over a 3D spatial volume with scan time under 15 min using echo planar readout with highly undersampled data and group sparse reconstruction. PMID- 26382051 TI - Needle-based confocal endomicroscopy for pancreatic cysts: the current agreement in interpretation. AB - BACKGROUND AND AIMS: Diagnosis of pancreatic cystic lesions (PCLs) remains challenging. EUS with FNA is limited by sampling error and nondiagnostic cytology. Needle-based confocal laser endomicroscopy (nCLE) performed during EUS can be used to improve diagnostic yield via FNA by providing in vivo histology of PCLs. However, the interobserver agreement (IOA) of nCLE of PCLs has yet to be studied. METHODS: Fifteen deidentified nCLE video clips of PCLs were sent to 6 interventional endoscopists at 5 institutions. Six variables were assessed for IOA: presence or absence of (1) vessels, (2) villi, (3) dark clumps, (4) reticular pattern, (5) acinar cells pattern, and (6) debris. PCL interpretation was categorized as mucinous, serous, pseudocyst, malignant, or indeterminate and final diagnosis as benign, malignant, or indeterminate. RESULTS: IOA ranged from "poor" to "fair." The K statistics were -.04 (SE = .05) for vessels, .16 (SE = .07) for villi, .22 (SE = .06) for dark clumps, .13 (SE = .06) for reticular pattern, .14 (SE = .06) for acinar cells pattern, .06 (SE = .06) for debris, .15 (SE = .03) for interpretation, .13 (SE = .05) for final diagnosis, and .19 (SE = .05) for image quality. The final diagnosis was malignant (10), benign (13), and indeterminate (2). The mean accuracy of the observers was 46%, with the lowest being 20% and highest being 67%. CONCLUSIONS: The IOA and accuracy for PCL diagnosis were low. The results of this study support the need to identify and validate imaging criteria to determine whether nCLE has diagnostic value for pancreatic pathology. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02166086.). PMID- 26382052 TI - Use of a novel polyp "ruler snare" improves estimation of colon polyp size. AB - BACKGROUND AND AIMS: Prior studies have demonstrated that endoscopists' estimates of polyp size are imprecise. The aim of this study was to determine whether a modified polypectomy "ruler snare" improves the accuracy of assessment of polyp size in real time without the use of additional devices. METHODS: Ten artificial polyps of predetermined sizes (4 to 25 mm) were affixed to the inside of a colon model. A standard polypectomy snare was modified by adding 5-mm graduated markings to the distal end of the plastic sheath. Study participants estimated the sizes of the artificial polyps during simulated colonoscopies, first using a standard snare and then with the modified ruler snare. RESULTS: Thirty-four private practice and academic gastroenterologists participated in the study. Endoscopists' ability to accurately classify polyps by size (diminutive, small, or large) improved from 48.5% to 60.3% with the ruler snare (P = .002). The greatest improvement in precision was seen among the large polyps, where accuracy increased from 35.9% to 58.2% with use of the ruler snare (P < .0001). Participants underestimated polyp size by a mean of 3.6 mm (interquartile range, 5 to -2 mm) with the standard snare and 1.8 mm (interquartile range, -3 to 0 mm) with the ruler snare, which corresponded to a 44.2% improvement in accuracy with the ruler snare (P < .05). CONCLUSIONS: The modified ruler snare improved polyp size assessment compared with a standard snare, particularly with large polyps. Overall, although size estimation continues to be imprecise, the addition of calibrated markings to a polypectomy snare is a simple and likely low-cost means to improve neoplasia surveillance recommendations. PMID- 26382053 TI - Evolution of the DEAD box helicase family in chicken: chickens have no DHX9 ortholog. AB - Viral RNA represents a pattern molecule that can be recognized by RNA sensors in innate immunity. Humans and mice possess cytoplasmic DNA/RNA sensors for detecting viral replication. There are a number of DEAD (Asp-Glu-Ala-Asp; DExD/H) box-type helicases in mammals, among which retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA50) are indispensable for RNA sensing; however, they are functionally supported by a number of sensors that directly bind viral RNA or replicative RNA intermediates to convey signals to RIG I and MDA5. Some DEAD box helicase members recognize DNA irrespective of the origin. These sensors transmit IFN-inducing signals through adaptors, including mitochondrial antiviral signaling. Viral double-stranded RNAs are reportedly sensed by the helicases DDX1, DDX21, DHX36, DHX9, DDX3, DDX41, LGP2 and DDX60, in addition to RIG-I and MDA5, and induce type I IFNs, thereby blocking viral replication. Humans and mice have all nucleic acid sensors listed here. In the RNA sensing system in chicken, it was found in the present study that most DEAD box helicases are conserved; however, DHX9 is genetically deficient in addition to reported RIG-I. Based on the current genome databases, similar DHX9 deficiency was observed in ducks and several other bird species. Because chicken, but not duck, was found to be deficient in RIG-I, the RNA-sensing system of chicken lacks RIG-I and DHX9 and is thus more fragile than that of duck or mammal. DHX9 may generally compensate for the function of RIG-I and deficiency of DHX9 possibly participates in exacerbations of viral infection such as influenza in chickens. PMID- 26382054 TI - Treatment of Frey's syndrome with topical ammonium alum: first report with twenty two cases. PMID- 26382055 TI - Eccentric Left Ventricular Hypertrophy and Sudden Death in Patients with End Stage Kidney Disease. AB - BACKGROUND/AIMS: Both all-cause and cardiovascular mortality risks are extremely high in patients with end-stage kidney disease (ESKD). Sudden death accounts for approximately one-quarter of all fatal events. Left ventricular hypertrophy (LVH) is a known risk factor for mortality and can be divided in 2 types: concentric and eccentric. This study evaluated possible differences in all-cause mortality, cardiovascular mortality and sudden death between prevalent ESKD patients with concentric and eccentric LVH. METHODS: Participants of the CONvective TRAnsport STudy (CONTRAST) who underwent transthoracic echocardiography (TTE) at baseline were analyzed. In patients with LVH, a relative wall thickness of <=0.42 was considered eccentric and >0.42 was considered concentric hypertrophy. Cox proportional hazards models, adjusted for potential confounders, were used to calculate hazard ratios (HRs) of patients with eccentric LVH versus patients with concentric LVH for all-cause mortality, cardiovascular mortality and sudden death. RESULTS: TTE was performed in 328 CONTRAST participants. LVH was present in 233 participants (71%), of which 87 (37%) had concentric LVH and 146 (63%) eccentric LVH. The HR for all-cause mortality of eccentric versus concentric LVH was 1.14 (p = 0.52), 1.79 (p = 0.12) for cardiovascular mortality and 4.23 (p = 0.02) for sudden death in crude analyses. Propensity score-corrected HR for sudden death in patients with eccentric LVH versus those with concentric LVH was 5.22 (p = 0.03). CONCLUSIONS: (1) The hazard for all-cause mortality, cardiovascular mortality and sudden death is markedly increased in patients with LVH. (2) The sudden death risk is significantly higher in ESKD patients with eccentric LVH compared to subjects with concentric LVH. PMID- 26382056 TI - Mannose-binding lectin (MBL) insufficiency protects against the development of systemic inflammatory response after pediatric cardiac surgery. AB - We investigated MBL2 and MASP2 genotypes, serum MBL (mannose-binding lectin) levels and activities of its complexes with associated serine proteases (MASP-1, MASP -2), in relation to complications following cardiac surgery in 195 children. The incidence of SIRS was lower in patients carrying MBL2 A/O and O/O genotypes (p=0.024). Children with MBL levels <500ng/ml had a lower risk of SIRS (p=0.014) and fever (p=0.044). Median MBL concentration was higher in patients who developed SIRS (p=0.048) but lower in those with post-operative infections (p=0.046). MBL-MASP-2 activities <100mU/ml protected from SIRS (p=0.007), low cardiac output syndrome (p=0.03) and multiorgan failure (p=0.012). In contrast, MBL2 YA/YA genotypes were associated with SIRS (p=0.018), low cardiac output syndrome (p=0.018), fever (p=0.018) and high inotropic score (VIS>30) (p=0.021). Thus, low MBL concentrations and associated genotypes may protect patients from systemic inflammation while high MBL serum levels and corresponding genotypes are risk factors of postoperative complications. PMID- 26382057 TI - Reduced expression of membrane-bound (m)RAGE is a biomarker of multiple sclerosis disease progression. AB - OBJECTIVES: This study is one in series measuring RAGE axis (receptor for advanced glycation end products, its isoforms, and ligands) as a biomarker in multiple sclerosis (MS). We identified and quantified membrane-bound RAGE (mRAGE) expression levels on freshly isolated PBMCs and its subpopulation (monocytes and T cells), and determined the relationship between mRAGE expression levels and MS disease severity. MATERIALS AND METHODS: mRAGE expression was determined for 28 MS patients and 16HCs, by flow cytometry, using fluorochrome unconjugated primary RAGE monoclonal antibody and a polyclonal secondary antibody conjugated to R Phycoerythrin (PE). RESULTS: After adjusting for multiple comparisons and correcting for group differences in age and gender, MS patients showed higher percentages of mRAGE-positive on PBMCs (12.4+/-2.1 vs. 4.08+/-0.8, P=0.02), monocytes (37.4+/-5.8 vs. 20.1+/-5.0, P=0.08) and T cells (4.1+/-1.2 vs. 2.1+/ 0.3, P=0.05). SPMS patients' showed lower percentages of RAGE-positive monocytes (13.7+/-5.5 vs. 49.5+/-6.6, P=0.0006) and RAGE-positive T cells (4.1+/-1.8 vs. 6.6+/-1.5, P=0.04) than RRMS patients. We observed a negative relationship between the percentages of mRAGE-positive PBMCs and MS severity scale (MSSS) (r= 0.39, P=0.04), monocytes and EDSS (r=-0.48, P=0.01), monocytes and MSSS (r=-0.58, P=0.001), and T cells and MSSS (r=-0.40, P=0.04). Monocytes expression of mRAGE showed 0.811 area under the curve (95% CI: 0.64-0.98) sensitivity/specificity for MSSS. CONCLUSION: The reduced mRAGE expression on PBMCs in general, and on monocytes in particular, can be used as biomarker of MS disease severity and progression. PMID- 26382058 TI - Immune gene expression profiling of PBMC isolated from horses vaccinated with attenuated African horsesickness virus serotype 4. AB - Development of African horsesickness (AHS) subunit vaccines will have to include a rational approach that uses knowledge of how the virus interacts with the host immune system. The global in vivo immune response induced by attenuated AHSV serotype 4 in horses was characterised using transcriptome sequencing. PBMC were collected with 24h intervals for four days after inoculation and four days after a second boost, 21 days later. Transcriptome data were normalised to the day 0 naive transcriptome and up- or down-regulated immune genes identified using the CLC workbench. Peak expression was observed 24h after each inoculation. Innate immunity was up-regulated after both inoculations and was characterised by type-1 interferon activation via the RIG-1/MDA5 pathway and the up-regulation of complement cascade components. After the second boost an adaptive immune response could be identified that included the production of cytokines indicative of T helper (Th)1, Th2 and Th17 responses. PMID- 26382059 TI - Neutron Activated Samarium-153 Microparticles for Transarterial Radioembolization of Liver Tumour with Post-Procedure Imaging Capabilities. AB - INTRODUCTION: Samarium-153 (153Sm) styrene divinylbenzene microparticles were developed as a surrogate for Yttrium-90 (90Y) microspheres in liver radioembolization therapy. Unlike the pure beta emitter 90Y, 153Sm possess both therapeutic beta and diagnostic gamma radiations, making it possible for post procedure imaging following therapy. METHODS: The microparticles were prepared using commercially available cation exchange resin, Amberlite IR-120 H+ (620-830 MUm), which were reduced to 20-40 MUm via ball mill grinding and sieve separation. The microparticles were labelled with 152Sm via ion exchange process with 152SmCl3, prior to neutron activation to produce radioactive 153Sm through 152Sm(n,gamma)153Sm reaction. Therapeutic activity of 3 GBq was referred based on the recommended activity used in 90Y-microspheres therapy. The samples were irradiated in 1.494 x 10(12) n.cm(-2).s(-1) neutron flux for 6 h to achieve the nominal activity of 3.1 GBq.g(-1). Physicochemical characterisation of the microparticles, gamma spectrometry, and in vitro radiolabelling studies were carried out to study the performance and stability of the microparticles. RESULTS: Fourier Transform Infrared (FTIR) spectroscopy of the Amberlite IR-120 resins showed unaffected functional groups, following size reduction of the beads. However, as shown by the electron microscope, the microparticles were irregular in shape. The radioactivity achieved after 6 h neutron activation was 3.104 +/- 0.029 GBq. The specific activity per microparticle was 53.855 +/- 0.503 Bq. Gamma spectrometry and elemental analysis showed no radioactive impurities in the samples. Radiolabelling efficiencies of 153Sm-Amberlite in distilled water and blood plasma over 48 h were excellent and higher than 95%. CONCLUSION: The laboratory work revealed that the 153Sm-Amberlite microparticles demonstrated superior characteristics for potential use in hepatic radioembolization. PMID- 26382060 TI - E. adenophorum Induces Cell Cycle and Apoptosis of Renal Cells through Mitochondrial Pathway and Caspase Activation in Saanen Goat. AB - The cytotoxicity effects of E. adenophorum on cell cycle and apoptosis of renal cells in Saanen goat was evaluated by TUNEL, DAPI, AO/EB staining, DNA fragmentation assay, Caspase activity, Western-blot, qRT-PCR and flow cytometry analysis. 16 saanen goats randomly divided into four groups were fed on 0%, 40%, 60% and 80% E. adenophorum diets. The Results showed that E. adenophorum induced typical apoptotic features of renal cells. E. adenophorum significantly suppressed renal cells viability, caused cell cycle activity arrest and induced typical apoptotic features in a dose-dependent manner. However, the protein levels of Fas/FasL, Bid and caspase-8 did not appear significant changes in the process of E. adenophorum-induced apoptosis. Moreover, E. adenophorum administration slightly decreased Bcl-2 expression, promoted Bax translocation to mitochondria, triggered the release of Cyt c from mitochondria into cytosol and activated caspase-9, -3, and cleaved PARP. The mitochondrial p53 translocation was significantly activated, accompanied by a significant increase in the loss of DeltaPsim, Cyt c release and caspase-9 activation. Above all, these data suggest that E. adenophorum induces renal cells apoptosis via the activation of mitochondria-mediated apoptosis pathway in renal cells. These findings may provide new insights to understand the mechanisms involved in E. adenophorum caused cytotoxicity of renal cells. PMID- 26382061 TI - Dental composite components induce DNA-damage and altered nuclear morphology in gingiva fibroblasts. AB - OBJECTIVE: Released dental composite components can damage human gingival fibroblasts (HGFs) and their DNA. The cytotoxicity, chromatin condensation and the induction of DNA double strand breaks (DSBs) by different compounds of dental composites was investigated using an improved gamma-H2AX focus assay. METHODS: HGFs were incubated with the monomers: bisphenol-A-ethoxylate-dimethacrylate (Bis DMA), bisphenol-A-glycerolate-dimethacrylate (BisGMA), ethyltriethylen glycol methacrylate (ETEGMA), glycidyl methacrylate (GMA), 1,6-hexandiol-dimethycrylate (HDDMA), trimethylolpropane ethoxylate triacrylate (TMPTA), and acrylamide (ACR). DSBs were determined by enumerating gamma-H2AX and 53BP1 foci colocalized at DSBs. RESULTS: A concentration-dependent induction of DSBs was found in the order: GMA>BisGMA>ACR>Bis-DMA>HDDMA>TMPTA>ETEGMA. HGFs exposure to GMA (0.3mM) and to BisGMA (0.09mM) induced the highest rate of DSB foci, i.e. 12-fold and 8 fold, respectively, relative to control (0.33 DSB foci/cell). At the highest concentrations (EC50) prominent changes in the chromatin morphology of HGF cell nuclei, i.e. compaction of nuclear chromatin and reduction of the area covered by the ovoid fibroblast nuclei, were observed. Nuclear condensation was significantly induced by GMA (1.7-fold at 0.3mM) and BisGMA (1.6-fold at 0.09mM), which correlated with the highest numbers of induced DSB foci (GMA, BisGMA, 3.9 and 2.6 foci/cell, respectively). SIGNIFICANCE: The improved gamma-H2AX/53BP1 focus assay revealed a concentration-dependent increase in DSBs for all tested substances. Furthermore, concentration-dependent changes in HGF cell nucleus morphology was noted, demonstrating genotoxic effects of the substances tested. PMID- 26382062 TI - Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers. AB - Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers. PMID- 26382063 TI - Ghrelin directly affects GnRH neurons: Comment on the review article "Peptides: Basic determinants of reproductive functions". PMID- 26382064 TI - Chemical analysis and biological properties of two different formulations of white portland cements. AB - White Portland cement (WPC) has generated research interests in the field of endodontics. This study compared between the properties of two formulations of white Portland cement (WPC) of different origin (Malaysia [MA] and Egypt [EG]). WPCs with and without calcium chloride dihydrate were prepared. Scanning electron microscope (SEM), energy dispersive X-ray micro-analysis, and X-ray diffraction were used for surface morphology evaluation, elemental, and phase analysis, respectively. After the preparation of optimized serial dilutions, the cytotoxicity was evaluated on human periodontal ligament fibroblasts (HPLFs) and dental pulp stem cells (DPSCs) using methyl-thiazol-diphenyltetrazolium assay after 24 and 72 h. Cell attachment properties were examined under SEM after 24 and 72 h. Results showed that the surface morphology and chemical composition of both formulations demonstrated detectable variations. The cytotoxicity evaluation showed different cellular responses of HPLFs compared to DSPCs. Both formulations favored the viability of HPLFs. However, the fast set formulations demonstrated severe cytotoxicity on DPSCs. Significant differences between EGWPC and MAWPC were identified (p < 0.05). The cell attachment properties were favorable; however, HPLFs attached and spread over the samples better than DPSCs. In conclusion, WPC of different origin may show differences in chemical and biological properties. The addition of CaCl2 .2H2 O to WPC can affect its properties. Human cell types may react differently towards different formulations of WPCs. SCANNING 38:303-316, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26382065 TI - Red Light Combined with Blue Light Irradiation Regulates Proliferation and Apoptosis in Skin Keratinocytes in Combination with Low Concentrations of Curcumin. AB - Curcumin is a widely known natural phytochemical from plant Curcuma longa. In recent years, curcumin has received increasing attention because of its capability to induce apoptosis and inhibit cell proliferation as well as its anti inflammatory properties in different cancer cells. However, the therapeutic benefits of curcumin are severely hampered due to its particularly low absorption via trans-dermal or oral bioavailability. Phototherapy with visible light is gaining more and more support in dermatological therapy. Red light is part of the visible light spectrum, which is able to deeply penetrate the skin to about 6 mm, and directly affect the fibroblast of the skin dermis. Blue light is UV-free irradiation which is fit for treating chronic inflammation diseases. In this study, we show that curcumin at low concentrations (1.25-3.12 MUM) has a strong anti-proliferative effect on TNF-alpha-induced psoriasis-like inflammation when applied in combination with light-emitting-diode devices. The treatment was especially effective when LED blue light at 405 nm was combined with red light at 630 or 660 nm, which markedly amplified the anti-proliferative and apoptosis inducing effects of curcumin. The experimental results demonstrated that this treatment reduced the viability of human skin keratinocytes, decreased cell proliferation, induced apoptosis, inhibited NF-kappaB activity and activated caspase-8 and caspase-9 while preserving the cell membrane integrity. Moreover, the combined treatment also down-regulated the phosphorylation level of Akt and ERK. Taken together, our results indicated that the combination of curcumin with LED blue light united red light irradiation can attain a higher efficiency of regulating proliferation and apoptosis in skin keratinocytes. PMID- 26382067 TI - Developmental robustness in the Caenorhabditis elegans embryo. AB - Developmental robustness is the ability of an embryo to develop normally despite many sources of variation, from differences in the environment to stochastic cell to-cell differences in gene expression. The nematode Caenorhabditis elegans exhibits an additional level of robustness: Unlike most other animals, the embryonic pattern of cell divisions is nearly identical from animal to animal. The endoderm (gut) lineage is an ideal model for studying such robustness as the juvenile gut has a simple anatomy, consisting of 20 cells that are derived from a single cell, E, and the gene regulatory network that controls E specification shares features with developmental regulatory networks in many other systems, including genetic redundancy, parallel pathways, and feed-forward loops. Early studies were initially concerned with identifying the genes in the network, whereas recent work has focused on understanding how the endoderm produces a robust developmental output in the face of many sources of variation. Genetic control exists at three levels of endoderm development: Progenitor specification, cell divisions within the developing gut, and maintenance of gut differentiation. Recent findings show that specification genes regulate all three of these aspects of gut development, and that mutant embryos can experience a "partial" specification state in which some, but not all, E descendants adopt a gut fate. Ongoing studies using newer quantitative and genome-wide methods promise further insights into how developmental gene-regulatory networks buffer variation. PMID- 26382066 TI - Mycobacterium tuberculosis Is Resistant to Isoniazid at a Slow Growth Rate by Single Nucleotide Polymorphisms in katG Codon Ser315. AB - An important aim for improving TB treatment is to shorten the period of antibiotic therapy without increasing relapse rates or encouraging the development of antibiotic-resistant strains. In any M. tuberculosis population there is a proportion of bacteria that are drug-tolerant; this might be because of pre-existing populations of slow growing/non replicating bacteria that are protected from antibiotic action due to the expression of a phenotype that limits drug activity. We addressed this question by observing populations of either slow growing (constant 69.3h mean generation time) or fast growing bacilli (constant 23.1h mean generation time) in their response to the effects of isoniazid exposure, using controlled and defined growth in chemostats. Phenotypic differences were detected between the populations at the two growth rates including expression of efflux mechanisms and the involvement of antisense RNA/small RNA in the regulation of a drug-tolerant phenotype, which has not been explored previously for M. tuberculosis. Genotypic analyses showed that slow growing bacilli develop resistance to isoniazid through mutations specifically in katG codon Ser315 which are present in approximately 50-90% of all isoniazid resistant clinical isolates. The fast growing bacilli persisted as a mixed population with katG mutations distributed throughout the gene. Mutations in katG codon Ser315 appear to have a fitness cost in vitro and particularly in fast growing cultures. Our results suggest a requirement for functional katG-encoded catalase-peroxide in the slow growers but not the fast-growing bacteria, which may explain why katG codon Ser315 mutations are favoured in the slow growing cultures. PMID- 26382069 TI - Long-Term (>5 Years) Clinical and Histological Follow-up of Pediatric Liver Transplant Recipients After Successful Radiological Percutaneous Treatment of Biliary Strictures. PMID- 26382068 TI - Low to Moderate Average Alcohol Consumption and Binge Drinking in Early Pregnancy: Effects on Choice Reaction Time and Information Processing Time in Five-Year-Old Children. AB - BACKGROUND: Deficits in information processing may be a core deficit after fetal alcohol exposure. This study was designed to investigate the possible effects of weekly low to moderate maternal alcohol consumption and binge drinking episodes in early pregnancy on choice reaction time (CRT) and information processing time (IPT) in young children. METHOD: Participants were sampled based on maternal alcohol consumption during pregnancy. At the age of 60-64 months, 1,333 children were administered a modified version of the Sternberg paradigm to assess CRT and IPT. In addition, a test of general intelligence (WPPSI-R) was administered. RESULTS: Adjusted for a wide range of potential confounders, this study showed no significant effects of average weekly maternal alcohol consumption during pregnancy on CRT or IPT. There was, however, an indication of slower CRT associated with binge drinking episodes in gestational weeks 1-4. CONCLUSION: This study observed no significant effects of average weekly maternal alcohol consumption during pregnancy on CRT or IPT as assessed by the Sternberg paradigm. However, there were some indications of CRT being associated with binge drinking during very early pregnancy. Further large-scale studies are needed to investigate effects of different patterns of maternal alcohol consumption on basic cognitive processes in offspring. PMID- 26382070 TI - When dogs look back: inhibition of independent problem-solving behaviour in domestic dogs (Canis lupus familiaris) compared with wolves (Canis lupus). AB - Domestic dogs have been recognized for their social sensitivity and aptitude in human-guided tasks. For example, prior studies have demonstrated that dogs look to humans when confronted with an unsolvable task; an action often interpreted as soliciting necessary help. Conversely, wolves persist on such tasks. While dogs' 'looking back' behaviour has been used as an example of socio-cognitive advancement, an alternative explanation is that pet dogs show less persistence on independent tasks more generally. In this study, pet dogs, shelter dogs and wolves were given up to three opportunities to open a solvable puzzle box: when subjects were with a neutral human caretaker, alone and when encouraged by the human. Wolves were more persistent and more successful on this task than dogs, with 80% average success rate for wolves versus a 5% average success rate for dogs in both the human-in and alone conditions. Dogs showed increased contact with the puzzle box during the encouragement condition, but only a moderate increase in problem-solving success. Social sensitivity appears to play an important role in pet and shelter dogs' willingness to engage in problem-solving behaviour, which could suggest generalized dependence on, or deference to, human action. PMID- 26382071 TI - Consumption of dietary sugar by gut bacteria determines Drosophila lipid content. AB - Gut microorganisms are essential for the nutritional health of many animals, but the underlying mechanisms are poorly understood. This study investigated how lipid accumulation by adult Drosophila melanogaster is reduced in flies associated with the bacterium Acetobacter tropicalis which displays oral-faecal cycling between the gut and food. We demonstrate that the lower lipid content of A. tropicalis-colonized flies relative to bacteria-free flies is linked with a parallel bacterial-mediated reduction in food glucose content; and can be accounted for quantitatively by the amount of glucose acquired by the flies, as determined from the feeding rate and assimilation efficiency of bacteria-free and A. tropicalis-colonized flies. We recommend that nutritional studies on Drosophila include empirical quantification of food nutrient content, to account for likely microbial-mediated effects on diet composition. More broadly, this study demonstrates that selective consumption of dietary constituents by microorganisms can alter the nutritional balance of food and, thereby, influence the nutritional status of the animal host. PMID- 26382072 TI - The metabolic cost of changing walking speeds is significant, implies lower optimal speeds for shorter distances, and increases daily energy estimates. AB - Humans do not generally walk at constant speed, except perhaps on a treadmill. Normal walking involves starting, stopping and changing speeds, in addition to roughly steady locomotion. Here, we measure the metabolic energy cost of walking when changing speed. Subjects (healthy adults) walked with oscillating speeds on a constant-speed treadmill, alternating between walking slower and faster than the treadmill belt, moving back and forth in the laboratory frame. The metabolic rate for oscillating-speed walking was significantly higher than that for constant-speed walking (6-20% cost increase for +/-0.13-0.27 m s(-1) speed fluctuations). The metabolic rate increase was correlated with two models: a model based on kinetic energy fluctuations and an inverted pendulum walking model, optimized for oscillating-speed constraints. The cost of changing speeds may have behavioural implications: we predicted that the energy-optimal walking speed is lower for shorter distances. We measured preferred human walking speeds for different walking distances and found people preferred lower walking speeds for shorter distances as predicted. Further, analysing published daily walking bout distributions, we estimate that the cost of changing speeds is 4-8% of daily walking energy budget. PMID- 26382073 TI - Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo. AB - There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2 in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26 fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. PMID- 26382074 TI - Traffic noise exposure affects telomere length in nestling house sparrows. AB - In a consistently urbanizing world, anthropogenic noise has become almost omnipresent, and there are increasing evidence that high noise levels can have major impacts on wildlife. While the effects of anthropogenic noise exposure on adult animals have been widely studied, surprisingly, there has been little consideration of the effects of noise pollution on developing organisms. Yet, environmental conditions experienced in early life can have dramatic lifelong consequences for fitness. Here, we experimentally manipulated the acoustic environment of free-living house sparrows (Passer domesticus) breeding in nest boxes. We focused on the impact of such disturbance on nestlings' telomere length and fledging success, as telomeres (the protective ends of chromosomes) appear to be a promising predictor of longevity. We showed that despite the absence of any obvious immediate consequences (growth and fledging success), nestlings reared under traffic noise exposure exhibited reduced telomere lengths compared with their unexposed neighbours. Although the mechanisms responsible for this effect remain to be determined, our results provide the first experimental evidence that noise alone can affect a wild vertebrate's early-life telomere length. This suggests that noise exposure may entail important costs for developing organisms. PMID- 26382075 TI - Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus). AB - Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44-48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication. PMID- 26382076 TI - Satyrization without evidence of successful insemination from interspecific mating between invasive mosquitoes. AB - Previous research has documented low frequencies of interspecific mating in nature between the invasive vectors Aedes aegypti and Aedes albopictus. It is also known that heterospecific male accessory gland substances transferred during mating sterilize A. aegypti but not A. albopictus females, leading to satyrization, a form of reproductive interference. This paper demonstrates that satyrization of A. aegypti by A. albopictus may occur without evidence of successful insemination. Our results show that A. aegypti females, previously exposed to A. albopictus males, are rendered refractory to subsequent conspecific mating even though their spermathecae contain no heterospecific sperm. Additional experiments demonstrating transfer of labelled semen from A. albopictus males to A. aegypti females and low production of viable eggs of females housed with conspecific males, following exposure to A. albopictus males, confirm higher incidences of satyrization than expected, based on heterospecific insemination rates. We conclude that frequencies of satyrization based on detection of interspecific sperm in spermathecae may underestimate the impact of this form of reproductive interference. PMID- 26382077 TI - Polarized skylight does not calibrate the compass system of a migratory bat. AB - In a recent study, Greif et al. (Greif et al. Nat Commun 5, 4488. (doi:10.1038/ncomms5488)) demonstrated a functional role of polarized light for a bat species confronted with a homing task. These non-migratory bats appeared to calibrate their magnetic compass by using polarized skylight at dusk, yet it is unknown if migratory bats also use these cues for calibration. During autumn migration, we equipped Nathusius' bats, Pipistrellus nathusii, with radio transmitters and tested if experimental animals exposed during dusk to a 90 degrees rotated band of polarized light would head in a different direction compared with control animals. After release, bats of both groups continued their journey in the same direction. This observation argues against the use of a polarization-calibrated magnetic compass by this migratory bat and questions that the ability of using polarized light for navigation is a consistent feature in bats. This finding matches with observations in some passerine birds that used polarized light for calibration of their magnetic compass before but not during migration. PMID- 26382078 TI - Phylogenetic network analysis as a parsimony optimization problem. AB - BACKGROUND: Many problems in comparative biology are, or are thought to be, best expressed as phylogenetic "networks" as opposed to trees. In trees, vertices may have only a single parent (ancestor), while networks allow for multiple parent vertices. There are two main interpretive types of networks, "softwired" and "hardwired." The parsimony cost of hardwired networks is based on all changes over all edges, hence must be greater than or equal to the best tree cost contained ("displayed") by the network. This is in contrast to softwired, where each character follows the lowest parsimony cost tree displayed by the network, resulting in costs which are less than or equal to the best display tree. Neither situation is ideal since hard-wired networks are not generally biologically attractive (since individual heritable characters can have more than one parent) and softwired networks can be trivially optimized (containing the best tree for each character). Furthermore, given the alternate cost scenarios of trees and these two flavors of networks, hypothesis testing among these explanatory scenarios is impossible. RESULTS: A network cost adjustment (penalty) is proposed to allow phylogenetic trees and soft-wired phylogenetic networks to compete equally on a parsimony optimality basis. This cost is demonstrated for several real and simulated datasets. In each case, the favored graph representation (tree or network) matched expectation or simulation scenario. CONCLUSIONS: The softwired network cost regime proposed here presents a quantitative criterion for an optimality-based search procedure where trees and networks can participate in hypothesis testing simultaneously. PMID- 26382079 TI - Polymerase Synthesis and Restriction Enzyme Cleavage of DNA Containing 7 Substituted 7-Deazaguanine Nucleobases. AB - Previous studies of polymerase synthesis of base-modified DNAs and their cleavage by restriction enzymes have mostly related only to 5-substituted pyrimidine and 7 substituted 7-deazaadenine nucleotides. Here we report the synthesis of a series of 7-substituted 7-deazaguanine 2'-deoxyribonucleoside 5'-O-triphosphates (dG(R) TPs), their use as substrates for polymerase synthesis of modified DNA and the influence of the modification on their cleavage by type II restriction endonucleases (REs). The dG(R) TPs were generally good substrates for polymerases but the PCR products could not be visualised on agarose gels by intercalator staining, due to fluorescence quenching. The presence of 7-substituted 7 deazaguanine residues in recognition sequences of REs in most cases completely blocked the cleavage. PMID- 26382080 TI - (13)C-NMR glycosylation effects in (1->3)-linked furanosyl-pyranosides. AB - Synthesis, theoretical conformational analysis (molecular mechanics and DFT calculations) and NMR spectral data including the (13)C-NMR glycosylation effects for six pairs of isomeric furanosyl-(1->3)-pyranosides with different anomeric and absolute configurations of furanosyl units as well as configurations of C2 and C4 in the pyranoside units are described. The determined (13)C-NMR glycosylation effects were shown to correlate with the pattern of intramolecular interactions around the inter-unit bonds. PMID- 26382081 TI - Structure elucidation and biosynthesis gene cluster organization of the O-antigen of Escherichia coli O170. AB - Enterotoxigenic Escherichia coli are causative agents of diarrhea in humans as well as animals, and E.coli O170 belongs to this virotype. Upon mild acid degradation of the lipopolysaccharide of E.coli O170, the branched O polysaccharide chain was partially cleaved at beta-d-glactofuranosidic linkages to give multiple products, including a linear tetrasaccharide and oligomers thereof. Studies of the acid degradation products and O-deacylated lipopolysaccharide by 1D and 2D (1)H and (13)C NMR spectroscopy enabled elucidation of the following O-polysaccharide structure: Functions of genes in the O-antigen biosynthesis gene cluster were tentatively assigned and found to be in agreement with the O-polysaccharide structure. PMID- 26382082 TI - High-resolution electrospray mass spectra of hexaethylene glycol connected biotinylated HNK-1 antigenic trisaccharide molecular probe and its non-sulfated analogue. AB - High-resolution electrospray mass spectra in positive and negative ion modes (MS and MS/MS) were measured and described for biotinylated hexaethylene glycol (HEG) connected molecular probes bearing HNK-1 (abbreviation of human natural killer cell-1 epitope) antigenic trisaccharide (1) and its non-sulfated analogue (2). For molecular probe 2, in its CID MS/MS of [M+2Na](2+), unexpected peak at m/z 530.2475 [C22H41N3O8SNa](+) was observed and attributed to the fragmentation of the aglycone at the end of the HEG chain distant from the biotin fragment. No homologous ions having the difference C2H4O smaller than that one were observed. The same cleavage was revealed in negative ion spectra. A similar fragmentation was found for other non-sulfated, biotinylated HEG-spacered molecular probes thus demonstrates this type of fragmentation characteristic for such glycosides. PMID- 26382083 TI - The proposed new classification of coronary microcirculation as the predictor of the heart failure progression in idiopathic dilated cardiomyopathy. AB - BACKGROUND: The appropriate condition of the coronary microcirculation is essential for proper cardiac muscle activity. The understanding of the pathological microcirculation changes in different stages of idiopathic dilated cardiomyopathy (IDCM) could provide a reliable background for proper therapeutic decisions and prognosis. METHODS AND RESULTS: The study population consisted of 116 patients (86.2% males, mean age 50.4+/-13.2 years) with IDCM and heart failure. In samples from left ventricular endomyocardial biopsy, the coronary microcirculation was evaluated by staining with hematoxylin and eosin, Masson's trichrome, and anti-CD34 antibody. The microvessel density (MVD) was calculated. Also, the electron microscopic evaluation of the extracellular matrix capillaries was performed. Samples were assigned to one of four types according to the microcirculation condition: 1, normal microvessels (MVs) (18 patients); 2, mostly normal, some MVs with slightly decreased lumen diameter and thickened wall, absent/mild intravascular fibrosis, and MVD decrease (37 patients); 3, MVs with moderately decreased lumen diameter and thickened wall, moderate intravascular fibrosis, and MVD decrease (45 patients); and 4, MVs with significantly decreased lumen diameter and thickened wall, significant intravascular fibrosis, and MVD decrease (16 patients). Taking all types of the proposed classification into consideration, in type 4, clinical (incidence of New York Heart Association 3 and 4, dyspnea on exertion, pulmonary congestion) and echocardiographic (left atrial and right ventricular diameter, left ventricular mass and ejection fraction, tricuspid annular plane systolic excursion, early diastolic mitral annular velocity measured at the interventricular-septal annulus [E'med], ratio of early diastolic mitral inflow velocity to E'med) parameters were worst. Only atrial fibrillation, diabetes, tricuspid annular plane systolic excursion, and the type of the microcirculation significantly correlated with the incidence of cardiovascular hospitalizations in the linear regression models. CONCLUSION: The condition of the coronary microcirculation corresponds with the heart failure progression in patients with IDCM. PMID- 26382084 TI - Prostate Cancer Screening Biomarkers: An Emerging Embarrassment of 'Riches'? PMID- 26382085 TI - Prediction of Pulmonary Metastasis in Renal Cell Carcinoma Patients with Indeterminate Pulmonary Nodules. AB - BACKGROUND: Indeterminate pulmonary nodules (IPN) are of uncertain significance in patients with renal cell carcinoma. OBJECTIVE: We sought to determine predictors of IPN progression to pulmonary metastasis and develop a tool for individualized risk stratification of patients who present with IPN on preoperative chest imaging in the setting of localized or locally advanced renal cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: We reviewed all patients who had radical nephrectomy with no evidence of distant metastases at a single institution from 2005-2009 who had >=1 IPN on chest computed tomography that measured <2 cm. All chest computed tomographies were rereviewed by a radiologist who was blinded to outcomes, to independently determine number, size, and location of nodules. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary objective of the study was to develop a prognostic model to predict pulmonary metastases among radical nephrectomy patients who present with IPN based on readily available preoperative imaging and postoperative pathological criteria. Univariable and multivariable Cox regression models were used to assess the predictive factors for development of pulmonary metastasis. We developed a nomogram that predicted the 3-yr and 5-yr lung metastasis-free survival (LMFS), with assessment of discrimination and internal validation. RESULTS AND LIMITATIONS: Among 251 patients with IPN who underwent nephrectomy, 72 (29%) developed pulmonary metastases. Median follow-up for the cohort was 36.6 mo. Three-yr and 5-yr probability of LMFS for the overall cohort was 71% (95% confidence interval 65-77%) and 65% (95% confidence interval 57-72%), respectively. The nomogram developed included number and size of IPN along with postoperative pathological variables, and showed calibration with a concordance index (c-index) of 0.81 and a bootstrap corrected c-index of 0.78. Limitations include retrospective study with no external validation. CONCLUSIONS: We developed a nomogram to predict the individualized risk LMFS for patients who underwent nephrectomy for localized or locally advanced renal cell carcinoma. PATIENT SUMMARY: We reviewed outcomes among kidney cancer patients who presented with small lung nodules and developed a clinical tool to predict risk of developing lung metastases. PMID- 26382086 TI - Positron Emission Tomography-computed Tomography with Prostate-specific Membrane Antigen Ligands as a Promising Tool for Imaging of Prostate Cancer. PMID- 26382087 TI - Greenlight Photovaporisation of the Prostate: Now Ready for Prime Time. PMID- 26382088 TI - Autologous Mesenchymal Stem Cells Show More Benefit on Systolic Function Compared to Bone Marrow Mononuclear Cells in a Porcine Model of Chronic Myocardial Infarction. AB - Cardiac cell therapy is a strategy to treat patients with chronic myocardial infarction (MI). No consensus exists regarding the optimal cell type. First, a comparison between autologous bone marrow-derived mononuclear cells (BMMNC) and mesenchymal stem cells (MSC) on therapeutic efficacy after MI was performed. Next, the effect of repetitive, NOGA-guided transendocardial injection was determined via a crossover design. Nineteen pigs were allocated in three groups: (1) placebo (at 4 and 8 weeks), (2) MSC (followed by placebo at 8 weeks), or (3) BMMNC (followed by MSC at 8 weeks) delivery including a priming strategy to enhance MSC effect. At 4 weeks, ejection fraction (EF) was significantly improved after MSC injection and not by BMMNC injection. After 8 weeks, no difference was observed in EF between cell-treated groups demonstrating the positive systolic effect of MSC. This study showed that MSC rather than BMMNC injection improves systolic function in chronic MI. PMID- 26382089 TI - The social practice of rescue: the safety implications of acute illness trajectories and patient categorisation in medical and maternity settings. AB - The normative position in acute hospital care when a patient is seriously ill is to resuscitate and rescue. However, a number of UK and international reports have highlighted problems with the lack of timely recognition, treatment and referral of patients whose condition is deteriorating while being cared for on hospital wards. This article explores the social practice of rescue, and the structural and cultural influences that guide the categorisation and ordering of acutely ill patients in different hospital settings. We draw on Strauss et al.'s notion of the patient trajectory and link this with the impact of categorisation practices, thus extending insights beyond those gained from emergency department triage to care management processes further downstream on the hospital ward. Using ethnographic data collected from medical wards and maternity care settings in two UK inner city hospitals, we explore how differences in population, cultural norms, categorisation work and trajectories of clinical deterioration interlink and influence patient safety. An analysis of the variation in findings between care settings and patient groups enables us to consider socio-political influences and the specifics of how staff manage trade-offs linked to the enactment of core values such as safety and equity in practice. PMID- 26382090 TI - Perineal body anatomy seen by three-dimensional endovaginal ultrasound of asymptomatic nulliparae. AB - AIM: The perineal body (PB) plays an important role in supporting the pelvic floor and the posterior vaginal wall, but its attachments and relationships are still debated. This study aimed to assess the normal anatomy of the PB using high resolution three-dimensional endovaginal ultrasound (3D-EVUS) in asymptomatic nulliparae. METHOD: To validate the identification of perineal structures, 3D EVUS was initially performed on nulliparous cadavers. Fresh frozen pelves were prepared and echogenic structures thought to be the PB, the external anal sphincter, the superficial and deep transverse perineii, pubovaginalis, puboperinealis, puboanalis, puborectalis and iliococcygeus muscles were tagged with biopsy needles, and marked with indigo carmine dye for localization during dissection. In the second part of the study, consecutive asymptomatic nulliparae were prospectively imaged with the same ultrasound modality. Interrater reproducibility was assessed off-line from stored 3D US volumes using a standardized technique. RESULTS: Five fresh frozen pelves and 44 asymptomatic nulliparae were assessed with 3D-EVUS. The PB was seen as an ovoid structure of mixed echogenicity between the rectum and vagina. It appeared to be divided into a superficial level, in contact with the external anal sphincter, the bulbospongiousus and the superficial transverse perineii muscle and a deep level, in contact with puboperinealis and puboanalis muscles. Interobserver repeatability was excellent for the measurements of PB height [intraclass correlation coefficient (ICC) 0.927], PB depth (ICC 0.969) and PB width (ICC 0.932). CONCLUSION: The PB is divided into two levels with different anatomical relationships with the pelvic floor muscles. 3D-EVUS yields reproducible assessment of this complex structure. PMID- 26382091 TI - Systemic Mastocytosis: Clinical Update and Future Directions. AB - Systemic mastocytosis (SM) is defined as the accumulation of abnormal mast cells (MC) in 1 or more extracutaneous tissues. Symptoms are due to either MC activation or organ infiltration and vary depending on disease subtype. More benign forms of SM, such as indolent SM, result in a life expectancy similar to the general population, while more aggressive subtypes, such as MC leukemia (MCL), have a median survival measured on the order of months. Treatment of indolent SM is directed at controlling the symptoms associated with MC activation. In advanced forms, such as aggressive SM and MCL, agents targeting MC proliferation such as KIT tyrosine kinase inhibitors, cladribine, and thalidomide may be provided. Newer agents based on preclinical rationale are also being actively investigated. However, the only potentially curative therapy for aggressive SM/MCL remains hematopoietic stem cell transplantation. Given that SM is a relatively rare disease, clinicians are often underprepared to evaluate, diagnose, and effectively treat this clinically heterogeneous condition. Here we seek to familiarize clinicians with this orphan disease and review current and future treatment approaches. PMID- 26382093 TI - Flashback: 50 Years Ago ... . PMID- 26382095 TI - Multidimensional Electronic Spectroscopy of Photochemical Reactions. AB - Coherent multidimensional electronic spectroscopy can be employed to unravel various channels in molecular chemical reactions. This approach is thus not limited to analysis of energy transfer or charge transfer (i.e. processes from photophysics), but can also be employed in situations where the investigated system undergoes permanent structural changes (i.e. in photochemistry). Photochemical model reactions are discussed by using the example of merocyanine/spiropyran-based molecular switches, which show a rich variety of reaction channels, in particular ring opening and ring closing, cis-trans isomerization, coherent vibrational wave-packet motion, radical ion formation, and population relaxation. Using pump-probe, pump-repump-probe, coherent two dimensional and three-dimensional, triggered-exchange 2D, and quantum-control spectroscopy, we gain intuitive pictures on which product emerges from which reactant and which reactive molecular modes are associated. PMID- 26382099 TI - Evaluation of vector competence for West Nile virus in Italian Stegomyia albopicta (=Aedes albopictus) mosquitoes. AB - West Nile virus (WNV) is a zoonotic arboviral pathogen transmitted by mosquitoes in a cycle that involves wild birds as reservoir hosts. The virus is responsible for outbreaks of viral encephalitis in humans and horses. In Europe, Culex pipiens (Diptera: Culicidae) is considered to be the main vector of WNV, but other species such as Stegomyia albopicta (=Aedes albopictus) (Diptera: Culicidae) may also act as competent vectors of this virus. Since 2008 human cases of WNV disease have been reported in northeast Italy. In 2011, new areas of southern Italy became involved and a first outbreak of WNV lineage 1 occurred on the island of Sardinia. On the assumption that a potential involvement of St. albopicta in WNV transmission cannot be excluded, and in order to evaluate the competence of this species for the virus, an experimental infection of an St. albopicta laboratory colony, established from mosquitoes collected in Sardinia, was carried out. The results were compared with those obtained in a colony of the main vector Cx. pipiens. The study showed St. albopicta collected on Sardinia to be susceptible to WNV infection, which suggests this Italian mosquito species is able to act as a possible secondary vector, particularly in urban areas where the species reaches high levels of seasonal abundance. PMID- 26382100 TI - What caused the changes in the usage of Atractylodis Macrocephalae Rhizoma from ancient to current times? AB - Ancient Chinese medicine treatises on Atractylodis Macrocephalae Rhizoma (AMR), the rhizome of Atractylodes macrocephala Koidz, indicated that it possessed an expectorant effect. However, in modern times, it is commonly used as a tocolytic agent. In this study, the components of AMR that are responsible for its expectorant and tocolytic effects were evaluated in order to clarify the differences in its application between ancient and modern times. A decoction of AMR was separated into five fractions, namely, volatile oil (VO), petroleum ether (PE), alcohol eluate from macroporous resin (AE), water eluate from macroporous resin (WE), and polysaccharides (PS), using various separation methods. The expectorant experiment indicated that the VO fraction, which mainly contains atractylone, produced an obvious expectorant effect. The experiment that assessed the irritability of uterine smooth muscle (USM) showed that the PE, which is mainly composed of atractylenolides, and the PS, which is mainly composed of inulin-type polysaccharides, were the active fractions for tocolysis, but the VO fraction had the opposite action. These data suggested that volatile oils are the key components responsible for the usage change of AMR in both ancient and current usage. PMID- 26382101 TI - Oncological results of oncoplastic breast-conserving surgery: Long term follow-up of a large series at a single institution: A matched-cohort analysis. AB - PURPOSE: Oncoplastic surgery is a well-established discipline that combines conserving treatment for breast cancer with immediate plastic reconstruction. Although widely practiced, the oncologic outcomes of this combined approach are reported only in small series. The aim of the present paper is to assess the safety of oncoplastic surgery for invasive primary breast cancer. METHODS: We compared 454 consecutive patients who underwent an oncoplastic approach between 2000 and 2008 for primary invasive breast tumors (study group) with twice the number of patients who received conservation alone in the same interval time (control group). Disease free survival and overall survival were estimated using the Kaplan-Meier method. The log-rank test was used to assess differences between groups. RESULTS: The median follow-up was 7.2 years. The overall survival is similar within the two groups, being 91.4% and 91.3% at 10-yr in the study group and in the control group respectively. The disease free survival is slightly lower in the oncoplastic group (69 vs.73.1% at 10-yr). The difference is not statistically significant. DISCUSSION: We have compared a large series of primary breast cancer patients that have undergone oncoplastic surgery (454) with a control group (908) and they were followed for a prolonged period of time. It provides the best available evidence to suggest that oncoplastic surgery is a safe and reliable treatment option for the managing of invasive breast cancer. PMID- 26382102 TI - The role of regional chemotherapy in the management of extremity soft tissue malignancies. AB - BACKGROUND: Regional chemotherapy involves the targeted delivery of high dose chemotherapy to an affected area. In the limbs, the two main methods employed are isolated limb perfusion (ILP) and isolated limb infusion (ILI), with advantages and disadvantages to each technique. The aim of this review was to clarify the roles of each technique in the management of locally advanced soft tissue malignancies of the extremities. METHODS: Relevant articles were identified from a comprehensive literature search using the PubMed database. Keywords included isolated limb perfusion, isolated limb infusion, in-transit melanoma and sarcoma. No restrictions on publication date were used. RESULTS: Regional chemotherapy may be used to secure local control in a range of soft tissue malignancies not amenable to standard excision and is increasingly used as an induction treatment in soft tissue sarcoma. Though both ILI and ILP are well established in the management of in-transit melanoma, ILP should be preferentially used in soft tissue sarcoma. CONCLUSION: Regional chemotherapy is an effective treatment for locally advanced extremity malignancies and the technique used should be tailored to patient and tumour factors. PMID- 26382103 TI - Impact of taurine depletion on glucose control and insulin secretion in mice. AB - Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism. PMID- 26382104 TI - Elevated permeability of the blood-brain barrier in mice intratracheally administered porcine pancreatic elastase. AB - Chronic obstructive pulmonary disease (COPD) shows progressive, irreversible airflow limitation induced by emphysema and lung inflammation. The aim of the present study was to determine if COPD conditions induce blood-brain barrier (BBB) dysfunction. We found that the intratracheal administration of porcine pancreatic elastase (PPE; 3 U) induced alveolar enlargement, increased neutrophil number in bronchoalveolar lavage fluid, and decreased blood oxygen saturation in mice at 21 days after inhalation. In parallel with these lung damages, BBB permeability to sodium fluorescein and Evans blue albumin was markedly increased. Our findings demonstrate that COPD conditions are associated with risk for BBB impairment. PMID- 26382105 TI - Structural brain network analysis in families multiply affected with bipolar I disorder. AB - Disrupted structural connectivity is associated with psychiatric illnesses including bipolar disorder (BP). Here we use structural brain network analysis to investigate connectivity abnormalities in multiply affected BP type I families, to assess the utility of dysconnectivity as a biomarker and its endophenotypic potential. Magnetic resonance diffusion images for 19 BP type I patients in remission, 21 of their first degree unaffected relatives, and 18 unrelated healthy controls underwent tractography. With the automated anatomical labelling atlas being used to define nodes, a connectivity matrix was generated for each subject. Network metrics were extracted with the Brain Connectivity Toolbox and then analysed for group differences, accounting for potential confounding effects of age, gender and familial association. Whole brain analysis revealed no differences between groups. Analysis of specific mainly frontal regions, previously implicated as potentially endophenotypic by functional magnetic resonance imaging analysis of the same cohort, revealed a significant effect of group in the right medial superior frontal gyrus and left middle frontal gyrus driven by reduced organisation in patients compared with controls. The organisation of whole brain networks of those affected with BP I does not differ from their unaffected relatives or healthy controls. In discreet frontal regions, however, anatomical connectivity is disrupted in patients but not in their unaffected relatives. PMID- 26382106 TI - Increased prefrontal and parietal cortical thickness does not correlate with anhedonia in patients with untreated first-episode major depressive disorders. AB - Cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment and course of illness in chronic medicated patients. The present study examined cortical thickness in patients with untreated first-episode MDD to elucidate the early pathophysiology of this illness. Here, we examined cortical thickness in patients with first-episode MDD (N=27) and healthy controls (N=27) using an automated surface-based method (in FreeSurfer). By assessing the correlation between caudate volume and cortical thickness at each vertex on the cortical surface, a caudate-cortical network was obtained for each group. Subsequent analysis was performed to assess the effect of anhedonia by the Temporal Experience of Pleasure Scale. We observed increased cortical thickness at the right orbital frontal cortex and the left inferior parietal gyrus in MDD patients compared with healthy controls. Furthermore, morphometric correlational analysis using cortical thickness measurement revealed increased caudate-cortical connectivity in the bilateral superior parietal gyrus in MDD patients. All changes were not related to anhedonia. These preliminary findings may reflect disorder manifestation close to illness onset and may provide insight into the early neurobiology of MDD. PMID- 26382107 TI - Self-reported social functioning and prefrontal hemodynamic responses during a cognitive task in schizophrenia. AB - Impaired social functioning is a characteristic of schizophrenia that affects patients' quality of life. The aim of the study was to assess prefrontal hemodynamic responses during a cognitive task and establish its influence on psychiatric symptoms, cognitive function, global functioning, and self-reported social functioning in patients with schizophrenia. Thirty-three patients with schizophrenia and 30 age-and sex-matched healthy controls participated in the study. We measured hemodynamic responses in the prefrontal and superior temporal cortical surface areas with 52-channel near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Self-reported social functioning was assessed using the Social Functioning Scale (SFS). Regional hemodynamic responses were significantly smaller in the prefrontal and temporal regions in subjects with schizophrenia than in the controls, and prefrontal hemodynamic responses during the VFT showed a strong correlation with SFS total scores. These results suggest an association between self-reported social functioning and prefrontal activation in subjects with schizophrenia. The present study provides evidence that NIRS imaging could be helpful in understanding the neural basis of social functioning. PMID- 26382108 TI - Anatomical alignment, but not goniometry, predicts femorotibial cartilage loss as well as mechanical alignment: data from the Osteoarthritis Initiative. AB - OBJECTIVE: To determine how frontal plane lower limb alignment obtained using a new femorotibial angle (FTA) measurement and non-radiographic handheld goniometry, predict femorotibial cartilage thickness loss in varus and valgus knees, compared with the gold standard mechanical axis (hip-knee-ankle [HKA]). METHODS: 934 Osteoarthritis (OA) Initiative knees with radiographic OA had the above alignment measures and 3T knee MRIs acquired. The new FTA measure was compared to the gold standard, with and without adjusting FTA for the sex specific varus shift. Changes in medial (MFTC) and lateral femorotibial (LFTC) cartilage thickness were quantified over 1-year and 2-years. Adjusted odds ratios (adjORs) were used to compare how the different alignment measures predict medial and lateral cartilage loss in varus and valgus knees. RESULTS: Pearson correlation coefficients between 2-year MFTC/LFTC cartilage loss and alignment measures were small to moderate, and were similar for FTA (r = 0.28/-0.30) and for HKA (r = 0.28/-0.29). Using the adjusted FTA measure, varus and valgus predicted MFTC progression (adjOR = 3.73) and LFTC progression (adjOR = 2.55) as well as HKA (adjOR = 3.16 and 2.31) over 1-year, and this relationship was also observed over 2-years. Goniometry was a weak predictor for MFTC and LFTC progression (adjOR1-year = 1.65 and 1.71; adjOR2-year = 0.68 and 1.24). CONCLUSIONS: After adjustment, the new FTA measure obtained from short (fixed flexion) knee films was as good as the gold standard in predicting medial and lateral cartilage loss over 1- or 2-years, without need for obtaining long-limb radiographs for determining the mechanical axis. Goniometry and non-adjusted FTA measures, in contrast, were poor predictors of cartilage loss. PMID- 26382109 TI - Does pre-surgical central modulation of pain influence outcome after total knee replacement? A systematic review. AB - The aim of this study is to systematically review whether the presence of altered central pain modulation pre-surgical influences outcome after total knee replacement (TKR) in patients with knee osteoarthritis (OA), and if so which indices of central pain modulation predict poor outcome after TKR. To identify relevant articles, PubMed and Web of Science were searched. The search strategy was a combination of key words related to "Knee Osteoarthritis and Total Knee Replacement", "Central Pain Modulation" and "Post-Surgical Outcome Measures". Articles fulfilling the inclusion criteria were screened for methodological quality and results were analyzed and summarized. Sixteen prospective cohort studies were included. Strong evidence is available that presence of catastrophic thinking and poor coping strategies predict more pain after TKR and that there is no association between fear of movement and post-surgical pain or function. Evidence on other psychosocial influences is limited or conflicting. Literature on the influence of other signs of altered central pain modulation on post surgical outcome is scarce. It is plausible that pre-surgical signs of altered central pain modulation, such as joint pain at rest or widespread pain sensitization, predict more post-surgical pain. Surgeons should be attentive for patients with signs of altered central pain modulation before surgery as they might be at risk for unfavorable outcome. A broader therapeutic approach aiming to desensitize the central nervous system can be adapted in these patients. Further research is however needed to identify the influence of central pain modulation pre-surgical in predicting outcome after TKR. PMID- 26382111 TI - Changing the Action of Iron from Stoichiometric to Electrocatalytic in the Hydrogenation of Ketones in Aqueous Acidic Media. AB - Cyclohexanone, a model compound chosen to conveniently represent small oxygenates present in the aqueous phase of biomass hydrothermal upgrading streams, was hydrogenated in the presence of electrodeposited iron(0) using aqueous formic or sulfuric acid as a hydrogen donor. Under these conditions, zero-valent iron is consumed stoichiometrically and serves as both a formic acid decomposition site and a hydrogen transfer agent. However, the resulting iron(II) can be used to continuously regenerate iron(0) when a potential is applied to the glassy carbon working electrode. Controlled potential electrolysis experiments show a 17% conversion of cyclohexanone (over 1000 seconds) to cyclohexanol with >80% efficiency of iron deposition from an iron(II) sulfate solution containing formic or sulfuric acid. In the absence of electrodeposited iron, formation of cyclohexanol could not be detected. PMID- 26382110 TI - UTE bi-component analysis of T2* relaxation in articular cartilage. AB - OBJECTIVES: To determine T2* relaxation in articular cartilage using ultrashort echo time (UTE) imaging and bi-component analysis, with an emphasis on the deep radial and calcified cartilage. METHODS: Ten patellar samples were imaged using two-dimensional (2D) UTE and Car-Purcell-Meiboom-Gill (CPMG) sequences. UTE images were fitted with a bi-component model to calculate T2* and relative fractions. CPMG images were fitted with a single-component model to calculate T2. The high signal line above the subchondral bone was regarded as the deep radial and calcified cartilage. Depth and orientation dependence of T2*, fraction and T2 were analyzed with histopathology and polarized light microscopy (PLM), confirming normal regions of articular cartilage. An interleaved multi-echo UTE acquisition scheme was proposed for in vivo applications (n = 5). RESULTS: The short T2* values remained relatively constant across the cartilage depth while the long T2* values and long T2* fractions tended to increase from subchondral bone to the superficial cartilage. Long T2*s and T2s showed significant magic angle effect for all layers of cartilage from the medial to lateral facets, while the short T2* values and T2* fractions are insensitive to the magic angle effect. The deep radial and calcified cartilage showed a mean short T2* of 0.80 +/- 0.05 ms and short T2* fraction of 39.93 +/- 3.05% in vitro, and a mean short T2* of 0.93 +/- 0.58 ms and short T2* fraction of 35.03 +/- 4.09% in vivo. CONCLUSION: UTE bi-component analysis can characterize the short and long T2* values and fractions across the cartilage depth, including the deep radial and calcified cartilage. The short T2* values and T2* fractions are magic angle insensitive. PMID- 26382112 TI - Phi-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays. AB - Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Phi-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Phi score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Phi-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Phi-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection. PMID- 26382115 TI - Family Medicine for America's Health: A Special Issue of Family Medicine. PMID- 26382113 TI - Molecular helices as electron acceptors in high-performance bulk heterojunction solar cells. AB - Despite numerous organic semiconducting materials synthesized for organic photovoltaics in the past decade, fullerenes are widely used as electron acceptors in highly efficient bulk-heterojunction solar cells. None of the non fullerene bulk heterojunction solar cells have achieved efficiencies as high as fullerene-based solar cells. Design principles for fullerene-free acceptors remain unclear in the field. Here we report examples of helical molecular semiconductors as electron acceptors that are on par with fullerene derivatives in efficient solar cells. We achieved an 8.3% power conversion efficiency in a solar cell, which is a record high for non-fullerene bulk heterojunctions. Femtosecond transient absorption spectroscopy revealed both electron and hole transfer processes at the donor-acceptor interfaces. Atomic force microscopy reveals a mesh-like network of acceptors with pores that are tens of nanometres in diameter for efficient exciton separation and charge transport. This study describes a new motif for designing highly efficient acceptors for organic solar cells. PMID- 26382114 TI - High-resolution adaptive imaging with a single photodiode. AB - During the past few years, the emergence of spatial light modulators operating at the tens of kHz has enabled new imaging modalities based on single-pixel photodetectors. The nature of single-pixel imaging enforces a reciprocal relationship between frame rate and image size. Compressive imaging methods allow images to be reconstructed from a number of projections that is only a fraction of the number of pixels. In microscopy, single-pixel imaging is capable of producing images with a moderate size of 128 * 128 pixels at frame rates under one Hz. Recently, there has been considerable interest in the development of advanced techniques for high-resolution real-time operation in applications such as biological microscopy. Here, we introduce an adaptive compressive technique based on wavelet trees within this framework. In our adaptive approach, the resolution of the projecting patterns remains deliberately small, which is crucial to avoid the demanding memory requirements of compressive sensing algorithms. At pattern projection rates of 22.7 kHz, our technique would enable to obtain 128 * 128 pixel images at frame rates around 3 Hz. In our experiments, we have demonstrated a cost-effective solution employing a commercial projection display. PMID- 26382116 TI - Family Medicine's Agenda to Make Health Primary. PMID- 26382117 TI - Envisioning a New Health Care System for America. AB - BACKGROUND AND OBJECTIVES: Between August 2013 and April 2014, eight family medicine organizations convened to develop a strategic plan and communication strategy for how our discipline might partner with patients and communities to build a new foundation for American health care. An outline of this initiative, Family Medicine for America's Health (FMAHealth), was formally announced to the public in October 2014. The purpose of this paper and the five papers to follow is to describe the guiding principles of FMAHealth in greater detail. FMAHealth is taking place at a pivotal point in the history of American health care, when the deficiencies of our overly expensive, underperforming health care delivery system are becoming more apparent than ever. By forming strategic partnerships to implement this initiative, family medicine seeks to define a new approach to health system leadership, care delivery, education, and research. This will require substantial reorientation of existing priorities and reimbursement systems, which are focused on delivering services, instead of on improving health. Family medicine is committed to engaging and empowering patients, their families and communities, and other health care professionals to establish a more equitable, effective, and efficient delivery system--a system in which health is the primary design element and the "Triple Aim" is the guiding principle. PMID- 26382118 TI - Partnering With Patients, Families, and Communities. AB - BACKGROUND AND OBJECTIVES: Collaborating with patients, families, and communities is a core principle of family medicine. However, the health care system in the United States has grown increasingly complex, fragmented, and difficult to navigate. This system, focused on disease-specific care delivered by specialists, often treats patients as the objects of care rather than as partners in care. Family Medicine for America's Health (FMAHealth) offers an opportunity to challenge the status quo in collaborative care through enhanced patient outreach and community engagement. With a central focus on improving health and achieving the Triple Aim, the FMAHealth initiative recognizes that successful transformation of the US health care system requires collaborative partnerships between clinicians, patients, families, and communities. Patient and population level outcomes can be improved through shared decision making; application of new technology; and authentic partnerships with patient, families, and communities. Broader collaboration in practice transformation, research, and policymaking can lead to identification of common goals and mutually embraced transformation. The discipline of family medicine aspires to encourage patients, families, and communities to demand change as consumers, as citizens, and as voters. PMID- 26382119 TI - A New Foundation for the Delivery and Financing of American Health Care. AB - BACKGROUND AND OBJECTIVES: For the past decade, primary care practices across America have worked to implement a practice model called the Patient-Centered Medical Home (PCMH) to revitalize practice, better support clinicians and patients, improve efficiency, and facilitate growth in primary care capacity. In spite of substantial progress, this work has not been matched by sufficient change in the payment system to allow these goals to be accomplished. Nevertheless, improving the quality and availability of primary care remains essential to achieving the goals of the Triple Aim (better health care, better population health, and containment of health care costs). For this to occur, the PCMH model of care must be further refined, and the payment system for primary care must be completely restructured. The need for these changes is urgent. In October 2014, the discipline of family medicine announced a comprehensive strategic plan called Family Medicine for America's Health (FMAHealth). FMAHealth proposes to expand the PCMH care model by fully integrating our nation's behavioral/mental health, public health, and primary care systems to create a new foundation for American health care. Accomplishing these ambitious goals will require a broad coalition of private and public interests across the health care disciplines as well as patients, communities, government, and businesses. These changes require additional infrastructure that existing financing systems do not adequately support, so comprehensive payment reform is essential for large-scale dissemination and sustainability of this model. The new payment model must reward value rather than volume of service and must provide a secure financial foundation for practices designed to care for patients and communities at affordable costs. PMID- 26382120 TI - Transforming Training to Build the Family Physician Workforce Our Country Needs. AB - BACKGROUND AND OBJECTIVES: The Affordable Care Act has spurred significant change in the US health care system, including expansion of Medicaid and private insurance coverage to millions of Americans. As a result, the need for the medical education continuum to produce a family physician workforce that is sizable enough and highly skilled is significant. These two interdependent goals have emerged as top priorities for Family Medicine for America's Health, a new, 5 year, $21 million collaborative strategic effort of the eight US family medicine organizations to lead continued change in the US health care system. To achieve these important goals, reforms are needed across the entire educational continuum, including how we recruit, train, and help practicing family physicians refresh their skills. Such reforms must provide opportunities to acquire skills needed in new practice and payment environments, to incorporate new educational standards that reflect the public's expectations of family physicians, to collaborate with our primary care colleagues to develop effective interprofessional training, and to design educational programs that are socially accountable to the patients, families, and communities we serve. Through Family Medicine for America's Health, the discipline is well positioned to emerge as a leader in primary care workforce development and educational quality. PMID- 26382122 TI - A Plan for Useful and Timely Family Medicine and Primary Care Research. AB - BACKGROUND AND OBJECTIVES: Our nation's health care system is changing. Nowhere is this more evident than in primary care, where fundamental improvements are necessary if we are to achieve the Triple Aim. Such improvements are possible if we can put useful and timely information into the hands of stakeholders to enable practical decision-making. To do this, family medicine and primary care researchers need to (1) build on our substantial current research foundation, (2) increase the relevance and pace of our research, (3) reconceive the research workforce to engage new partners, (4) disseminate findings more rapidly into the hands of those who can take action, and (5) build a "question-ready" research infrastructure to make this possible. Family medicine researchers face exciting opportunities: technical capacity to generate and manage large amounts of data; clinic- and system-level networks for testing innovations; digital health technologies for real-time and asynchronous monitoring and management of risk factors and chronic diseases; the know-how to make fast, local improvements in our systems of care; partnerships beyond those traditionally engaged in research that can multiply our capacity to generate new knowledge; and new methods for creating generalizable knowledge from the study of local efforts. This is a historic time for family medicine research. Now is the time to build on our past work, accelerate the pace, and capitalize on emerging opportunities that open an incredibly bright future. PMID- 26382121 TI - A Family Medicine Health Technology Strategy for Achieving the Triple Aim for US Health Care. AB - BACKGROUND AND OBJECTIVES: Health information technology (health IT) and health technology, more broadly, offer tremendous promise for connecting, synthesizing, and sharing information critical to improving health care delivery, reducing health system costs, and achieving personal and community health. While efforts to spur adoption of electronic health records (EHRs) among US practices and hospitals have been highly successful, aspirations for effective data exchanges and translation of data into measureable improvements in health outcomes remain largely unrealized. There are shining examples of health enhancement through new technologies, and the discipline of family medicine is well poised to take advantage of these innovations to improve patient and population health. The Future of Family Medicine led to important family medicine health IT initiatives over the past decade. For example, the American Academy of Family Physicians (AAFP) Center for Health Information Technology and the Robert Graham Center provided important leadership for informing health IT policy and standard setting, such as the Centers for Medicare and Medicaid Services EHR incentives programs (often referred to as "meaningful use."). As we move forward, there is a need for a new and more comprehensive family medicine strategy for technology. To inform the Family Medicine for America's Health (FMAHealth) initiative, this paper explores strategies and tactics that family medicine could pursue to improve the utility of technology for primary care and to help primary care become a leader in rapid development, testing, and implementation of new technologies. These strategies were also designed with a broader stakeholder audience in mind, intending to reach beyond the work being done by FMAHealth. Specific suggestions include: a shared primary care health IT center, meaningful primary care quality measures and capacity to assess/report them, increased primary care technology research, a national family medicine registry, enhancement of family physicians' technology leadership, and championing patient centered technology functionality. PMID- 26382123 TI - Family Medicine for America's Health and Escape Velocity. PMID- 26382124 TI - The Future of Family Medicine's Role in American Medicine. PMID- 26382125 TI - Student and Resident Perspective: Family Medicine Is a Major Landmark on the Health Care Landscape. PMID- 26382126 TI - FMAHealth and Academic Family Medicine: On the Frontlines or on the Sidelines? PMID- 26382127 TI - Owning the FMAHealth Vision. PMID- 26382128 TI - Cardiovascular Responses to Unilateral, Bilateral, and Alternating Limb Resistance Exercise Performed Using Different Body Segments. AB - Moreira, OC, Faraci, LL, de Matos, DG, Mazini Filho, ML, da Silva, SF, Aidar, FJ, Hickner, RC, and de Oliveira, CEP. Cardiovascular responses to unilateral, bilateral and alternating limb resistance exercise performed using different body segments. J Strength Cond Res 31(3): 644-652, 2017-The aim of this study was to verify and compare the cardiovascular responses to unilateral, bilateral, and alternating limb resistance exercise (RE) performed using different body segments. Fifteen men experienced in RE were studied during biceps curls, barbell rows, and knee extension exercises when performed bilaterally, unilaterally, and using alternating limbs. The protocol consisted of 3 sets of 10 repetitions at 80% of 10 repetition maximum with 2-minute rest between sets. Heart rate (HR) and blood pressure (BP) were measured after the last repetition. There was a statistically significant increase in HR, systolic blood pressure (SBP), and rate pressure product (RPP), from rest to postexercise. The RPP was higher in the third set of all exercises and in all 3 forms of execution, when compared with the first set. Bilateral biceps curls caused a greater increase in RPP (first and second sets) and HR, compared with the same exercise performed unilaterally. Furthermore, the performance of bilateral biceps curls induced greater HR and RPP, in all sets, compared with bilateral knee extension and barbell rows. There was also a significantly higher SBP for the alternating second and third sets and also for the bilateral third set of the knee extensions as compared with the barbell rows. It was concluded from the data of this study that the cardiovascular response was increased from rest to postexercise in all forms of exercise, especially immediately after the third set of RE. For exercises performed bilaterally with the upper body (biceps curls), there was a greater cardiovascular response when compared with the same exercise performed unilaterally or with lower-body exercise performed bilaterally. PMID- 26382129 TI - Physiological Responses of Young Tennis Players to Training Drills and Simulated Match Play. AB - The aim of this study was to investigate the responses of young tennis players during 5 different training drills and to compare the responses between drills. Ten (17.0 +/- 1.2 years) male tennis players participated in this study. Each athlete completed 5 total training drills. Drills 1-4 consisted of each player returning balls from a ball-serving machine and were stroke/time-controlled over 6 points. The fifth drill was a simulated match (SM) play, between 2 opposing players, and also lasted 6 points. The 4 stroke/time-controlled drills had the following strokes/time for each point: drill 1: 2 strokes/~4 seconds, drill 2: 4 strokes/~8 seconds, drill 3: 7 strokes/~14 seconds, drill 4: 10 strokes/~20 seconds. Peak heart rate (HR), blood lactate concentration (LA), and rating of perceived exertion (RPE) were measured after the first, third, and sixth point of each drill. Drills were performed in a randomized crossover design; a 2-way repeated-measures analysis of variance was used with significance set at p <= 0.05. All dependent variables (HR, LA, and RPE) significantly increased (p <= 0.05) as strokes, and time per rally increased in each drill. Furthermore, all variables were elevated to a greater magnitude (p <= 0.05) during the 7 and 10 stroke drills after the first, third, and sixth points when compared with the SM and the 2 and 4 stroke drills at the corresponding time points. These results suggest that the physiological responses to tennis training drills were stroke/time-dependent. Therefore, because of the intense intermittent nature of tennis, stroke/time-controlled drills, which require significant physiological demands, should be incorporated along with technically focused shorter drills to fully mimic the conditions of competitive match play. PMID- 26382130 TI - Modifying the Functional Movement Screen Deep Squat Test: The Effect of Foot and Arm Positional Variations. AB - The functional movement screen (FMS) was developed as an evaluation tool for assessing the fundamental movement patterns believed to be prerequisites for functional activity. However, some of the FMS component movements, such as the deep overhead squat test (DST), likely represent novel motor challenges on which poor performance might reflect inexperience with the task rather than a movement impairment. The purpose of this study was to examine the effects of positional variations on DST scores in a population of young, healthy adults. We hypothesized that self-selecting foot positioning, removal of an overhead component, or changing both aspects of the DST would result in improvement in FMS scores. Twenty healthy subjects completed 4 squatting conditions in a counterbalanced sequence to eliminate carry over effects: DST, modified squat with hands at chest level and feet in the DST position (DSTO), modified squat with arms in the DST position and self-selected foot placement (DSTF), and modified squat with hands at chest level and self-selected foot placement (DSTB). A Friedman's analysis of variance and Wilcoxon signed-ranks' post hoc analysis revealed a significant difference between all squat conditions (p = 0.036), between DSTB-DST groups (p < 0.001), DSTO-DST groups (p = 0.004), and DSTO-DSTB groups (p = 0.046). Each modified squat condition had an average score higher than the DST. These findings suggest that the FMS DST might underestimate an individual's ability to squat during functional tasks that involve self-selected foot and arm placement. PMID- 26382131 TI - Estimations of One Repetition Maximum and Isometric Peak Torque in Knee Extension Based on the Relationship Between Force and Velocity. AB - We aimed to investigate whether a linear regression formula based on the relationship between joint torque and angular velocity measured using a high speed video camera and image measurement software is effective for estimating 1 repetition maximum (1RM) and isometric peak torque in knee extension. Subjects comprised 20 healthy men (mean +/- SD; age, 27.4 +/- 4.9 years; height, 170.3 +/- 4.4 cm; and body weight, 66.1 +/- 10.9 kg). The exercise load ranged from 40% to 150% 1RM. Peak angular velocity (PAV) and peak torque were used to estimate 1RM and isometric peak torque. To elucidate the relationship between force and velocity in knee extension, the relationship between the relative proportion of 1RM (% 1RM) and PAV was examined using simple regression analysis. The concordance rate between the estimated value and actual measurement of 1RM and isometric peak torque was examined using intraclass correlation coefficients (ICCs). Reliability of the regression line of PAV and % 1RM was 0.95. The concordance rate between the actual measurement and estimated value of 1RM resulted in an ICC(2,1) of 0.93 and that of isometric peak torque had an ICC(2,1) of 0.87 and 0.86 for 6 and 3 levels of load, respectively. Our method for estimating 1RM was effective for decreasing the measurement time and reducing patients' burden. Additionally, isometric peak torque can be estimated using 3 levels of load, as we obtained the same results as those reported previously. We plan to expand the range of subjects and examine the generalizability of our results. PMID- 26382132 TI - Tuck Jump Assessment: An Exploratory Factor Analysis in a College Age Population. AB - Lininger, MR, Smith, CA, Chimera, NJ, Hoog, P, and Warren, M. Tuck Jump Assessment: An exploratory factor analysis in a college age population. J Strength Cond Res 31(3): 653-659, 2017-Due to the high rate of noncontact lower extremity injuries that occur in the collegiate setting, medical personnel are implementing screening mechanisms to identify those athletes that may be at risk for certain injuries before starting a sports season. The tuck jump assessment (TJA) was created as a "clinician friendly" tool to identify lower extremity landing technique flaws during a plyometric activity. There are 10 technique flaws that are assessed as either having the apparent deficit or not during the TJA. Technique flaws are then summed up for an overall score. Through expert consensus, these 10 technique flaws have been grouped into 5 modifiable risk factors: ligament dominance, quadriceps dominance, leg dominance or residual injury deficits, trunk dominance ("core" dysfunction), and technique perfection. Research has not investigated the psychometric properties of the TJA technique flaws or the modifiable risk factors. The present study is a psychometric analysis of the TJA technique flaws to measure the internal structure using an exploratory factor analysis (EFA) using data from collegiate athletes (n = 90) and a general college cohort (n = 99). The EFA suggested a 3 factor model accounting for 46% of the variance. The 3 factors were defined as fatigue, distal landing pattern, and proximal control. The results differ from the 5 modifiable risk categories as previously suggested. These results may question the use of a single score, a unidimensional construct, of the TJA for injury screening. PMID- 26382133 TI - (-)-Epicatechin Attenuates Degradation of Mouse Oxidative Muscle Following Hindlimb Suspension. AB - The purpose of this study was to conduct a 14-day hindlimb suspension (HS) with and without (-)-epicatechin supplementation to determine whether (-)-epicatechin treatment can attenuate the loss in muscle degradation, angiogenesis, and mitochondrial signaling in oxidative skeletal muscle. Adult mice were randomized into 3 groups: (a) control (C); (b) HS with vehicle (HS-V); and (c) HS with (-) epicatechin (HS-(-)-Epi). Animals in the HS-(-)-Epi group received (-) epicatechin (1.0 mg . kg(-1) of body mass) twice daily through oral gavage. For markers related to muscle degradation, the HS-V group had significantly higher protein expression compared with the control and HS-(-)-Epi groups. Moreover, protein expression for myosin heavy chain type I was significantly reduced by approximately 45% in the HS-V group compared with the control and HS-(-)-Epi groups. In addition, capillarity contact and capillary-to-fiber ratio were significantly higher in the HS-(-)-Epi group compared with the HS-V group. Furthermore, protein expression for thrombospondin-1 was significantly higher in HS-V group compared with the control and HS-(-)-Epi groups. Hindlimb suspension also significantly reduced protein expression for mitochondrial signaling compared with the control and HS-(-)-Epi groups. These findings suggest that (-) epicatechin supplementation attenuates degradation in oxidative muscles after HS. PMID- 26382134 TI - Quantification of Competitive Game Demands of NCAA Division I College Football Players Using Global Positioning Systems. AB - The aim of the present study was to examine the competitive physiological movement demands of National Collegiate Athletic Association (NCAA) Division I college football players using portable global positioning system (GPS) technology during games and to examine positional groups within offensive and defensive teams, to determine if a player's physiological requirements during games are influenced by playing position. Thirty-three NCAA Division I Football Bowl Subdivision football players were monitored using GPS receivers with integrated accelerometers (GPSports) during 12 regular season games throughout the 2014 season. Individual data sets (n = 295) from players were divided into offensive and defensive teams and subsequent position groups. Movement profile characteristics, including total, low-intensity, moderate-intensity, high intensity, and sprint running distances (m), sprint counts, and acceleration and deceleration efforts, were assessed during games. A one-way ANOVA and post-hoc Bonferroni statistical analysis were used to determine differences in movement profiles between each position group within offensive and defensive teams. For both offensive and defensive teams, significant (p <= 0.05) differences exist between positional groups for game physical performance requirements. The results of the present study identified that wide receivers and defensive backs completed significantly (p <= 0.05) greater total distance, high-intensity running, sprint distance, and high-intensity acceleration and deceleration efforts than their respective offensive and defensive positional groups. Data from the present study provide novel quantification of position-specific physical demands of college football games and support the use of position-specific training in the preparation of NCAA Division I college football players for competition. PMID- 26382135 TI - Using a Verification Test for Determination of V[Combining Dot Above]O2max in Sedentary Adults With Obesity. AB - A constant-load exercise bout to exhaustion after a graded exercise test to verify maximal oxygen uptake (V[Combining Dot Above]O2max) during cycle ergometry has not been evaluated in sedentary adults with obesity. Nineteen sedentary men (n = 10) and women (n = 9) with obesity (age = 35.8 +/- 8.6 years; body mass index [BMI] = 35.9 +/- 5.1 kg.m; body fat percentage = 44.9 +/- 7.2) performed a ramp-style maximal exercise test (ramp), followed by 5-10 minutes of active recovery, and then performed a constant-load exercise bout to exhaustion (verification test) on a cycle ergometer for determination of V[Combining Dot Above]O2max and maximal heart rate (HRmax). V[Combining Dot Above]O2max did not differ between tests (ramp: 2.29 +/- 0.71 L.min, verification: 2.34 +/- 0.67 L.min; p = 0.38). Maximal heart rate was higher on the verification test (177 +/- 13 b.min vs. 174 +/- 16 b.min; p = 0.03). Thirteen subjects achieved a V[Combining Dot Above]O2max during the verification test that was >=2% (range: 2.0-21.0%; 0.04-0.47 L.min) higher than during the ramp test, and 8 subjects achieved a HRmax during the verification test that was 4-14 b.min higher than during the ramp test. Duration of verification or ramp tests did not affect V[Combining Dot Above]O2max results, but the difference in HRmax between the tests was inversely correlated with ramp test duration (r = -0.57, p = 0.01). For both V[Combining Dot Above]O2max and HRmax, differences between ramp and verification tests were not correlated with BMI or body fat percentage. A verification test may be useful for identifying the highest V[Combining Dot Above]O2max and HRmax during cycle ergometry in sedentary adults with obesity. PMID- 26382136 TI - Quasi-two-dimensional superconductivity in FeSe0.3Te0.7 thin films and electric field modulation of superconducting transition. AB - We report the structural and superconducting properties of FeSe0.3Te0.7 (FST) thin films with different thicknesses grown on ferroelectric Pb(Mg1/3Nb2/3)0.7Ti0.3O3 substrates. It was shown that the FST films undergo biaxial tensile strains which are fully relaxed for films with thicknesses above 200 nm. Electrical transport measurements reveal that the ultrathin films exhibit an insulating behavior and superconductivity appears for thicker films with Tc saturated above 200 nm. The current-voltage curves around the superconducting transition follow the Berezinskii-Kosterlitz-Thouless (BKT) transition behavior and the resistance-temperature curves can be described by the Halperin-Nelson relation, revealing quasi-two-dimensional phase fluctuation in FST thin films. The Ginzburg number decreases with increasing film thickness indicating the decrease of the strength of thermal fluctuations. Upon applying electric field to the heterostructure, Tc of FST thin film increases due to the reduction of the tensile strain in FST. This work sheds light on the superconductivity, strain effect as well as electric-field modulation of superconductivity in FST films. PMID- 26382137 TI - Atomic-like spin noise in solid-state demonstrated with manganese in cadmium telluride. AB - Spin noise spectroscopy is an optical technique which can probe spin resonances non-perturbatively. First applied to atomic vapours, it revealed detailed information about nuclear magnetism and the hyperfine interaction. In solids, this approach has been limited to carriers in semiconductor heterostructures. Here we show that atomic-like spin fluctuations of Mn ions diluted in CdTe (bulk and quantum wells) can be detected through the Kerr rotation associated to excitonic transitions. Zeeman transitions within and between hyperfine multiplets are clearly observed in zero and small magnetic fields and reveal the local symmetry because of crystal field and strain. The linewidths of these resonances are close to the dipolar limit. The sensitivity is high enough to open the way towards the detection of a few spins in systems where the decoherence due to nuclear spins can be suppressed by isotopic enrichment, and towards spin resonance microscopy with important applications in biology and materials science. PMID- 26382147 TI - DFT+U studies of Cu doping and p-type compensation in crystalline and amorphous ZnS. AB - Zinc sulfide is an excellent candidate for the development of a p-type transparent conducting material that has great demands in solar energy and optoelectronic applications. Doping with Cu is one potential way to make ZnS p type while preserving its optical transparency for the solar spectrum; however, this is limited by the extremely low solubility of Cu in ZnS and charge compensation mechanisms that eliminate the p-type characteristics. These mechanisms are different in crystalline (c-ZnS) and amorphous structures (a-ZnS), leading to different tendencies of doping Cu in these two ZnS phases, as well as the feasibility to form the p-type material. In this work, we have carried out fundamental studies of Cu doping in both c-ZnS and a-ZnS, using the continuous random network model and density functional theory with Hubbard's energy correction (DFT+U). The formation of a complex that contains two CuZn and one S vacancy is highly favorable in both phases. The local environment of this charge compensated Cu complex obtained by DFT calculations agrees well with the previous EXAFS measurements. The incorporation of Cu into a-ZnS, on the one hand, is more tolerable compared to its crystal counterparts (zincblende), indicating possible higher Cu concentration. On the other hand, there is also another intrinsic mechanism to compensate the p-type characteristics in a-ZnS: the formation of the covalent S-S "dumbbell" units. This reconstruction of the local structure to form a S-S bond could occur spontaneously, thus making the p-type doping for ZnS challenging even in the amorphous phase. PMID- 26382146 TI - Protein-based photothermal theranostics for imaging-guided cancer therapy. AB - The development of imageable photothermal theranostics has attracted considerable attention for imaging guided photothermal therapy (PTT) with high tumor ablation accuracy. In this study, we strategically constructed a near-infrared (NIR) cyanine dye by introducing a rigid cyclohexenyl ring to the heptamethine chain to obtain a heptamethine dye CySCOOH with high fluorescence intensity and good stability. By covalent conjugation of CySCOOH onto human serum albumin (HSA), the as-prepared HSA@CySCOOH nanoplatform is highly efficient for NIR fluorescence/photoacoustic/thermal multimodality imaging and photothermal tumor ablation. The theranostic capability of HSA@CySCOOH was systematically evaluated both in vitro and in vivo. Most intriguingly, complete tumor elimination was achieved by intravenous injection of HSA@CySCOOH (CySCOOH, 1 mg kg(-1); 808 nm, 1.0 W cm(-2) for 5 min) into 4T1 tumor-bearing mice, with no weight loss, noticeable toxicity, or tumor recurrence being observed. This as-prepared protein based nanotheranostics exhibits high water dispersibility, no off target cytotoxicity, and good biodegradability and biocompatibility, thus facilitating its clinical translation to cancer photothermal theranostics. PMID- 26382148 TI - Determination of Fatty Acid Oxidation and Lipogenesis in Mouse Primary Hepatocytes. AB - Lipid metabolism in liver is complex. In addition to importing and exporting lipid via lipoproteins, hepatocytes can oxidize lipid via fatty acid oxidation, or alternatively, synthesize new lipid via de novo lipogenesis. The net sum of these pathways is dictated by a number of factors, which in certain disease states leads to fatty liver disease. Excess hepatic lipid accumulation is associated with whole body insulin resistance and coronary heart disease. Tools to study lipid metabolism in hepatocytes are useful to understand the role of hepatic lipid metabolism in certain metabolic disorders. In the liver, hepatocytes regulate the breakdown and synthesis of fatty acids via beta-fatty oxidation and de novo lipogenesis, respectively. Quantifying metabolism in these pathways provides insight into hepatic lipid handling. Unlike in vitro quantification, using primary hepatocytes, making measurements in vivo is technically challenging and resource intensive. Hence, quantifying beta-fatty acid oxidation and de novo lipogenesis in cultured mouse hepatocytes provides a straight forward method to assess hepatocyte lipid handling. Here we describe a method for the isolation of primary mouse hepatocytes, and we demonstrate quantification of beta-fatty acid oxidation and de novo lipogenesis, using radiolabeled substrates. PMID- 26382149 TI - Catalytic Enantioselective 1,4-Iodofunctionalizations of Conjugated Dienes. AB - The first catalytic enantioselective 1,4-iodofunctionalizations of conjugated dienes have been developed. Starting from beta,gamma,delta,epsilon-unsaturated oximes and 4-Ns hydrazones, these N-iodosuccinimide-mediated reactions are catalyzed by newly modified tertiary aminothiourea derivatives and furnish Delta(2)-isoxazoline and Delta(2)-pyrazoline derivatives, respectively, containing an (E)-allyl iodide group at the quaternary stereogenic center generally in high yield and with excellent enantioselectivity (up to 98.5:1.5 er). PMID- 26382145 TI - MYC, Metabolism, and Cancer. AB - The MYC oncogene encodes a transcription factor, MYC, whose broad effects make its precise oncogenic role enigmatically elusive. The evidence to date suggests that MYC triggers selective gene expression amplification to promote cell growth and proliferation. Through its targets, MYC coordinates nutrient acquisition to produce ATP and key cellular building blocks that increase cell mass and trigger DNA replication and cell division. In cancer, genetic and epigenetic derangements silence checkpoints and unleash MYC's cell growth- and proliferation-promoting metabolic activities. Unbridled growth in response to deregulated MYC expression creates dependence on MYC-driven metabolic pathways, such that reliance on specific metabolic enzymes provides novel targets for cancer therapy. SIGNIFICANCE: MYC's expression and activity are tightly regulated in normal cells by multiple mechanisms, including a dependence upon growth factor stimulation and replete nutrient status. In cancer, genetic deregulation of MYC expression and loss of checkpoint components, such as TP53, permit MYC to drive malignant transformation. However, because of the reliance of MYC-driven cancers on specific metabolic pathways, synthetic lethal interactions between MYC overexpression and specific enzyme inhibitors provide novel cancer therapeutic opportunities. PMID- 26382150 TI - A Double Activation Method for the Conversion of Vinyl Epoxides into vic-Amino Alcohols and Chiral Benzoxazine/Quinoxaline Derivatives. AB - A new method for the synthesis of 1,2-syn-vic amino alcohols (with double inversion of configuration) from vinyl epoxides, by the amination of a pi-allyl palladium-borate complex generated by using Pd(0) and phenyl-o-phenylene borate (a double activation technique), is reported. Further, this new method with broad functional group compatibility was extended to a one-pot/two-step synthesis of chiral benzoxazine and quinoxaline derivatives. PMID- 26382151 TI - Pyradinodithiazole: An Electron-Accepting Monomer Unit for Hole-Transporting and Electron-Transporting Conjugated Copolymers. AB - Pyradinodithiazole (PDTz) was designed as a new electron-accepting unit. The physical property measurements indicated that the PDTz unit has stronger electron accepting characteristics than thiazolothiazole and benzodithiazole. A donor acceptor copolymer containing PDTz as an acceptor unit was synthesized for hole transporting semiconductors in organic photovoltaics (OPV). Furthermore, an acceptor-acceptor copolymer containing PDTz has also been developed for electron transporting OPV materials. These copolymer-based blend films showed expected photovoltaic characteristics in individual OPV devices. PMID- 26382152 TI - Triarylphosphines as Aryl Donors for Pd(II)-Catalyzed Aromatic Coupling of Oxabenzonorbornadienes. AB - A new approach was developed for Pd(II)-catalyzed aromatic coupling of oxabenzonorbornadienes with triarylphosphines as both ligands and aryl donors. Diverse functional groups including halo- (F-, Cl-, and Br-), CF3(-), and furyl groups are well tolerated. For unsymmetrical triarylphosphines, the migration ability of aryls is consistent with the electronic property of substituents and maintains the order EDG-Ar > H-Ar > EWD-Ar (EDG means electron-donating group, EWG means electron-withdrawing group). A preliminary mechanistic study was also disclosed. PMID- 26382153 TI - Bacterial transport of colloids in liquid crystalline environments. AB - We describe the controlled transport and delivery of non-motile eukaryotic cells and polymer microparticles by swimming bacteria suspended in nematic liquid crystals. The bacteria push reversibly attached cargo in a stable, unidirectional path (or along a complex patterned director field) over exceptionally long distances. Numerical simulations and analytical predictions for swimming speeds provide a mechanistic insight into the hydrodynamics of the system. This study lays the foundation for using cargo-carrying bacteria in engineering applications and for understanding interspecies interactions in polymicrobial communities. PMID- 26382154 TI - Treatment of patients with severe and enduring eating disorders. AB - PURPOSE OF REVIEW: Severe and enduring eating disorder is a new concept to the field that has potential to aid assessment and inform treatment. The aim of this review is to report recent developments in the conceptualization and treatment of people with severe and enduring eating disorder. RECENT FINDINGS: A systematic search identified 28 included papers. These addressed conceptualization of recovery and staging models (4 studies), clinical care, presentations and treatment experiences (7 studies), four new randomized controlled trials of treatment (9 studies), two open trials of novel approaches (2 studies) and problems of treatment resistance and involuntary care (6 studies). SUMMARY: The staging model appears to have validity and clinical utility in anorexia nervosa, but this is less clear in other eating disorders. Most literature on treatment, including new randomised controlled trials, is on underweight individuals, and there is a small literature on emerging psychological therapies that may improve outcomes. There is an expectation that with better treatment engagement, there may also be a reduced need for involuntary interventions. PMID- 26382155 TI - Treating eating disorders using the internet. AB - PURPOSE OF REVIEW: This article evaluates the empirical standing of online treatment (eTherapy) for people with an established eating disorder. RECENT FINDINGS: There have been four randomized controlled trials of eTherapy for people with an eating disorder. All four focused on eating disorders characterized by binge eating and recruited adult participants direct from the community. The interventions were cognitive behavioural in nature, lasted between 3 and 7 months, and were accompanied by external support. In common with eTherapy for other mental health problems, there were problems engaging and retaining the users, and maximizing their implementation of the intervention. A minority (10 37%, intent-to-treat figures) improved substantially. SUMMARY: This is a new field. The findings of the four randomized controlled trials are consistent with the earlier reports indicating that guided eTherapy interventions of a cognitive behavioural nature are acceptable to (female) adults with a binge eating problem and that a subgroup improves substantially. More effective interventions are required and their use in different healthcare settings needs to be investigated. Direct-to-sufferer eTherapy interventions have the potential to increase access to effective forms of treatment and, in younger cases, they might serve as a form of secondary prevention. PMID- 26382156 TI - Cognitive remediation therapy for eating disorders. AB - PURPOSE OF REVIEW: This review compares the literature on cognitive remediation therapy (CRT) for eating disorders with findings in the field of schizophrenia, and discusses future directions for CRT for eating disorders. RECENT FINDINGS: First studies using a randomized controlled trial design show the added value of CRT for eating disorders. Patients reported lessened symptoms and further improvements in quality of life and cognitive flexibility. Furthermore, the acceptability of the intervention was good and attrition rates for CRT itself were low. Research into the use of cognitive remediation for schizophrenia is extensive and the results on global cognition appeared to be robust at post treatment and durable at follow-up, with small to medium effect sizes. Recent articles within the field of schizophrenia emphasize the necessity of intrinsic motivation to translate cognitive gains into actual changes in everyday life. SUMMARY: A next step is to examine the impact of CRT for eating disorders on motivation. It is also important to focus on the transdiagnostic use of CRT, considering the overlap in cognitive inefficiencies between eating disorders. Another important step may be to develop effective personalized methods of CRT by taking into account individual differences in cognitive processes most relevant to improvement in outcome. PMID- 26382157 TI - Picky eating: the current state of research. AB - PURPOSE OF REVIEW: In this review, an overview of literature on picky eating is given, with the focus on recently published studies. RECENT FINDINGS: Papers on picky eating published over the past 2 years broadly covered three themes: characterization of picky eating; factors contributing to the development of picky eating in children; and management of picky eating. Findings suggest that picky eating is a reasonably robust concept, comprising food neophobia, eating a limited variety of food, and other specific features related to food and eating (e.g. low enjoyment of food, slowness in eating, and higher satiety responsiveness). Picky eating has a higher prevalence in preschool children and seems to decrease thereafter. Studies investigating factors influencing the development of picky eating in childhood have examined a range of child factors, parent factors, and parent-child interactions. Only very limited guidance has emerged regarding the management of picky eating. SUMMARY: Picky eating is a descriptive term with greater emerging clarity about its core characteristics and associations. Research remains limited with ongoing difficulties related to lack of standardized assessment measures, and poor ability to differentiate between normal and clinically significant picky eating. PMID- 26382158 TI - Family therapy for adolescent anorexia nervosa. AB - PURPOSE OF REVIEW: Research into the efficacy and practice of family therapy for the treatment of adolescent anorexia nervosa has been ongoing for the past 4 decades. Research results continue to highlight the effective role of family therapy for the treatment of anorexia in adolescents. This review aims to present findings and opinions from relevant articles published over the past 12 months, related to the treatment of adolescent anorexia, utilizing family therapy and multi-family therapy. RECENT FINDINGS: A number of recent articles continue to explore family therapy for adolescent anorexia, with particular emphasis being placed on attempting to pinpoint those elements of the approaches that may hold significance in relation to recovery from this dangerous illness and the development of new interventions that draw on the evidence to date for a family approach to the treatment of anorexia. SUMMARY: Ongoing research is needed to identify the active ingredients of family therapy for anorexia. PMID- 26382159 TI - Sex drive and sexual desire. AB - PURPOSE OF REVIEW: Loss of sexual desire is increasingly recognized as a consequence of many disease processes, and one that can have a significant negative impact on quality of life. This review explores the biological and psychological aspects of desire, as well as the aetiology and therapeutic options for loss of desire. RECENT FINDINGS: Discoveries have been made in terms of the physiology of desire in men, in that it is affected by estradiol as well as testosterone. It has also been shown that desire is less gender specific in androphilic women than in androphilic men and gynaephilic men and women. Fatigue has been described as the most common self-reported cause of loss of desire, with communication as the most common method for addressing this. In men, a clear distinction has been shown between disorders of arousal and disorders of desire, suggesting that they should remain as separate conditions in the Diagnostic and Statistical Manual of Mental Disorders criteria. Loss of desire has been proven to be a significant consequence of diabetes, multiple sclerosis and polycystic ovary syndrome and can occur as a side-effect of statins and 5alpha-reductase inhibitors. Testosterone therapy may be an effective treatment for loss of desire in both men and women, and is safe in the treatment of men who have been treated for prostate cancer. It also has a significant impact on desire when used in the treatment of individuals with gender dysphoria. Nonhormonal treatments including flibanserin and new methods of therapy may also be effective. SUMMARY: Loss of desire is underrecognized as a symptom of disease or as a complaint in its own right. As further developments in treatment options, both therapies based and pharmacological, are made, it is increasingly important that clinicians enquire about sexual dysfunction, including loss of desire, at every consultation. PMID- 26382160 TI - Sleep and postpartum depression. AB - PURPOSE OF REVIEW: The perinatal period introduces a myriad of changes. One important but often overlooked change is the increased risk for sleep disturbance. Although casually regarded as a consequence of pregnancy or postpartum, there is emerging evidence to suggest that women with significant sleep disturbance, characterized by insomnia symptoms and/or poor sleep quality, are more likely to report an increase in depressive symptomatology or develop postpartum depression (PPD). Significant consequences may arise as a result including issues with maternal-infant bonding, effective care for the infant and behavioral or emotional difficulties in the infant. This review discusses the relevant literature as to how disturbed sleep during pregnancy as well as in the postpartum may increase the risk for PPD. RECENT FINDINGS: Symptoms of insomnia and poor sleep quality are independently associated with greater depressive symptoms across pregnancy and throughout postpartum. Likewise, both can negatively impact the ability to mother effectively. SUMMARY: The presence of insomnia or sleep disturbance during the perinatal period is a risk factor for depressive symptoms. Women with depression are at an increased risk of developing sleep disturbance thereby increasing depressive symptomatology. This bidirectional and additive relationship needs more clinical attention as both sleep disturbance and depression are noted risk factors for adverse pregnancy outcomes. PMID- 26382161 TI - Gender dysphoria in children and adolescents: a review of recent research. AB - PURPOSE OF REVIEW: With the advent of medical treatments such as puberty suppression and cross-sex hormones in gender dysphoric minors, there has been a debate around questions of gender identity and brain development. This review aimed to identify recent empirical studies that addressed this controversial topic. RECENT FINDINGS: Epidemiological data from several countries indicate that gender dysphoria in children and adolescents is far more common than initially anticipated. This is in line with the currently observed steady increase in referrals to gender clinics. Minors with gender dysphoria are a vulnerable population as they may face a high psychopathological burden. Recently published data on the long-term outcome of puberty suppression and subsequent hormonal and surgical treatment indicate that young people with gender dysphoria may benefit substantially with regard to psychosocial outcomes. Brain development studied by neuroimaging methods seems not to be disturbed by puberty suppression. SUMMARY: The first reports about long-term outcome in adolescents having undergone puberty suppression have shown promising results. However, in a substantial part of gender dysphoric minors, puberty suppression is not indicated so far because of psychiatric comorbidity and long-term follow-up data from these patients are still scarce. PMID- 26382162 TI - Sexual pain disorders. AB - PURPOSE OF REVIEW: The purpose of this review was to assess recent research (the last 18 months) and its impact on understanding sexual pain disorders relevant to daily clinical practice. RECENT FINDINGS: It has been highlighted that sexual pain is related to the number of tender points, pressure pain threshold, more deliberate fear and less global positive affective associations with sexual stimuli, episiotomy, attachment styles, drug abuse and the influence of ambivalence over emotional expression in couples.The efficacy of a multidisciplinary vulvodynia programme of treatment, another type of therapy based on the fear-avoidance and pain self-efficacy model and a novel cognitive behavioral couple therapy has been stated. SUMMARY: There is a gradual advance in the knowledge of sexual pain disorder etiology. At the same time different therapeutics strategies have been increasing, but it is necessary to introduce guidelines on the basis of the evidence to approach with efficacy this severe disorder. VIDEO ABSTRACT: http://links.lww.com/YCO/A31. PMID- 26382164 TI - Eating disorders and the media. AB - PURPOSE OF REVIEW: In June 2015, the newspapers in England once again pointed at the media industry as responsible for the spread of eating disorders. RECENT FINDINGS: This article reviews this argument and previous research on the role of the media industry in the perpetration of images that may foster eating disorders. SUMMARY: It has been recently argued, coherently with previous research, that the media may be responsible for the spread of eating disorders. This article reviews this literature, and evaluates what the real role of the media in the spread of eating disorders is. The article argues that considering the portrait of thin models in the media industry as responsible for eating disorders is a misanalysis of the problem and evaluates some of the more profound reasons that may lead to the adoption of the disordered eating symptomatology. PMID- 26382163 TI - Sleep and anxiety in late childhood and early adolescence. AB - PURPOSE OF REVIEW: Adolescence is a period of dynamic change in both sleep and emotional systems, with related increases in problems controlling emotion and behavior. Youth with anxiety enter adolescence with pre-existing vulnerabilities in systems of sleep and emotion that may place them at heightened risk. This review summarizes recent research on sleep and anxiety during the transition to adolescence, and highlights emerging themes. RECENT FINDINGS: Prospective studies support that sleep predicts anxiety symptoms in early adolescence. Notably, robust evidence for subjective sleep problems in anxious youth is not well corroborated by objective assessments. Longitudinal designs and methodology that carefully examine dimensions of anxiety and sleep may clarify inconsistencies. Preliminary evidence suggests that late childhood to early adolescence may be a sensitive period for escalating problems with sleep and anxiety. Recent advances in the neuroscience of sleep can further refine integrative mechanistic models of developmental psychopathology - the role of sleep in emotional learning and memory is provided as an example. SUMMARY: Sleep problems are common and prospectively predict escalating anxiety symptoms. Precision is needed regarding the nature of sleep disruption, and how and when sleep affects various aspects of developmental trajectories. This precision, along with advances in the neuroscience of sleep, may lead to developmentally informed translational interventions. PMID- 26382165 TI - Paraphilias. AB - PURPOSE OF REVIEW: The concept of paraphilia still carries an 'unwanted burden' of sexual norms because the pathologization of some sexual practices as paraphilic disorders is still based on the assumption that normal sexuality should be genitally organized with the aim of reproduction. The aim of this review is to give an impression of the ongoing discussion about the changes introduced with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the results of recent research in this area. RECENT FINDINGS: The release of DSM-5 in the spring of 2013 introduced a distinction between paraphilias and paraphilic disorders, implying a destigmatization of consenting adults engaging in unusual sexual behaviour. According to DSM-5 diagnostic criteria, paedophilic disorder is the only paraphilic disorder without an 'in remission' and an 'in a controlled environment' specifier. Today, antiandrogen treatment is offered to sex offenders in many countries as an additional treatment strategy alongside psychotherapy. SUMMARY: The introduction of DSM-5 offers the possibility to distinguish between paraphilia and paraphilic disorders. The aetiology of paraphilias is still unknown. Paraphilias are much more common in men than in women, but the reasons for this difference remain unknown. So far there is no clear consent on the best therapeutic approach for a paraphilic disorder. PMID- 26382166 TI - Sexual disorders in DSM-5 and ICD-11: a conceptual framework. AB - PURPOSE OF REVIEW: The nature and classification of sexual disorders has been a focus during work on the development of DSM-5 and ICD-11. This article proposes different conceptual approaches to the sexual disorders, including classical, critical and integrative positions. Disorders associated with sexual orientation, gender dysphoria/incongruence and paraphilias/paraphilic disorders are discussed from each of these positions. RECENT FINDINGS: A range of conventional and nonconventional consensual sexual behaviours are prevalent but not necessarily indicative of a mental disorder; there is little diagnostic validity or clinical utility for including these in the nosology. When such behaviours are clinically excessive and associated with distress or impairment, however, a disorder may be present. Debate surrounds the medicalization of some sexual behaviours that are criminal in nature. SUMMARY: The classification of sexual behaviour as disordered is necessarily theory-dependent and value-laden. Nevertheless, reasoned debate about the relevant data and values is possible, and will hopefully further improve the diagnostic validity and clinical utility of psychiatric nosology. PMID- 26382167 TI - New developments in the treatment of eating disorders. PMID- 26382168 TI - Sexual side-effects of antidepressant and antipsychotic drugs. AB - PURPOSE OF REVIEW: Psychotropic-related sexual dysfunction is a quite frequent issue in clinical practice, mainly in chronic treatments affecting both quality of life and compliance. RECENT FINDINGS: In the last decade fortunately antidepressants and antipsychotic compounds have been deeply screened in order to identify sexual adverse events that were commonly underdiagnosed and previously underestimated by clinicians and perhaps by pharmaceutical companies as well. Some differences in the mechanism of action are the nucleus of this poorly tolerated adverse event. All antidepressants with serotonergic activity can cause mild to severe sexual dysfunction such as decreased libido and delayed orgasm frequently (>60%) or anorgasmia and arousal difficulties sometimes (30%). In contrast, noradrenergic, dopaminergic, or melatonergic antidepressants do not cause sexual dysfunction but perhaps the clinical profile of patients receiving these compounds could be different. Antipsychotics that highly increase prolactin levels and strongly block dopamine receptors could be related to sexual dysfunction as well. Unfortunately, these dysfunctions are present during the long term after the antipsychotic onset to provide continued symptom control and enable recovery. Young patients suffering psychosis and concomitant sexual dysfunction (erectile and/or orgasmic difficulties) tend to show poor compliance in chronic treatments affecting the outcomes. SUMMARY: The implications of psychotropic-related sexual dysfunction in clinical practice are relevant mainly in patients under long-term treatment with previous satisfactory sexual life. Implications for future research about sexual dysfunction in all new treatments should be strongly taken into account. PMID- 26382169 TI - Editorial: sexual disorders. PMID- 26382170 TI - Objective and subjective evaluations of the Nurotron Venus cochlear implant system via animal experiments and clinical trials. AB - CONCLUSION: This study described objective and subjective evaluations of the Nurotron(r) VenusTM Cochlear Implant System and indicated that this system produced a satisfactory performance. OBJECTIVE: To observe the performance of the Nurotron(r) VenusTM cochlear implant (CI) system via electrophysiological and psychophysical evaluations. METHODS: A 26-electrode CI system was specially designed. The performance of MRI in animal and cadaveric head experiments, EABR in cats experiment, the correlation between ESRT and C level, and psychophysics evaluations in clinical trials were observed. RESULTS: In the animal and cadaveric head experiments, magnet dislocation could not be prevented in the 1.5 T MRI without removal of the internal magnet. The EABR was clearly elicited in cat experiment. In the clinical trial, the ESRT was strongly correlated with C level (p < 0.001). The human clinical trial involving 57 post-lingually deafened native Mandarin-speaking patients was performed. Residual hearing protection in the implanted ear at each audiometric frequency was observed in 27.5-46.3% patients post-operatively. A pitch ranking test revealed that place pitches were generally ordered from apical to basal electrodes. The recognitions of the perceptions of 301 disyllabic words, environment sounds, disyllabic words, and numerals were significantly better than the pre-operative performance and reached plateaus. PMID- 26382171 TI - Protective role of polyphenols from Bauhinia hookeri against carbon tetrachloride induced hepato- and nephrotoxicity in mice. AB - The hepatoprotective and nephroprotective activity of a polyphenol-rich fraction (BHPF) obtained from Bauhinia hookeri was investigated against CCl4-induced acute hepatorenal toxicity in mice. BHPF was administered (100, 200 and 400 mg/kg/day) for 5 days, then CCl4 was administered. BHPF pretreatment significantly (p < 0.001) inhibited the CCl4-induced increase in ALT, AST, ALP, LDH, total bilirubin, cholesterol, creatinine, uric acid, urea and malondialdehyde in a dose dependent manner. In contrast, BHPF pretreatment markedly increased the contents of glutathione and superoxide dismutase in the liver and kidney tissues, indicating the strong in vivo antioxidant activity of BHPF. Pretreatment with BHPF preserved the hepatic architecture and conferred marked protection against necrosis and ballooning degeneration. Pretreatment with BHPF reduced the inflammatory cell aggregation and degenerative changes in the lining epithelium of the kidney tubules. It can be concluded that BHPF has a remarkable hepato- and nephroprotective activity by enhancing the antioxidant defense status, reducing lipid peroxidation and protecting against the histopathological changes induced by CCl4 in the liver and kidney tissues. PMID- 26382172 TI - Ultrasound and Clinical Predictors of Recurrent Ischemia in Symptomatic Internal Carotid Artery Occlusion. AB - BACKGROUND AND PURPOSE: Occlusion of the internal carotid artery puts patients at risk of recurrent ischemic events because of hemodynamic compromise. Our goal was to characterize clinical and duplex parameters indicating patients at risk of recurrent ischemia. METHODS: We retrospectively identified patients with symptomatic internal carotid artery occlusion. Clinical characteristics and ultrasound parameters, including collateral networks, were analyzed. Predictors for recurrent ipsilateral ischemia were investigated by Cox regression analysis. RESULTS: Of 68 patients, at least 1 recurrent ischemic event within the same vascular territory was observed in 14 patients (20.6%) within 2 to 92 days (median, 29.5 days). The median follow-up period was 6 months. Diabetes mellitus and previous transient ischemic attack were associated with recurrence, as was activation of the maximum number of collateral pathways on transcranial ultrasound (28.6% versus 5.6%; P=0.03). Furthermore, flow in the posterior cerebral arteries was higher in patients with recurrence in ipsilateral and contralateral posterior cerebral artery P2 segments (76 IQR 37.5 versus 59, IQR 22.5 cm/s and 68, IQR 35.6 versus 52, IQR 21 cm/s; P<0.01 and 0.02). CONCLUSIONS: Flow increases in both posterior cerebral artery P2 segments suggest intensified compensatory efforts when other collaterals are insufficient. Together with the presence of diabetes mellitus and a history of transient ischemic attack, this duplex parameter indicates that patients with internal carotid artery are at particular risk of recurrent ischemia. PMID- 26382173 TI - Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis? AB - BACKGROUND AND PURPOSE: Although the Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial showed that medical therapy alone was superior to stenting plus medical therapy for preventing recurrent strokes in patients with symptomatic intracranial stenosis, we determined whether SAMMPRIS supported the use of stenting in any subpopulations of patients with symptomatic intracranial arterial stenosis. METHODS: The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared in those with and without baseline factors in the 2 treatment arms, percutaneous transluminal angioplasty and stenting (PTAS) plus aggressive medical therapy versus aggressive medical therapy alone. Baseline factors included sex, age, race, diabetes mellitus, hypertension, lipid disorder, smoking status, type of qualifying event, qualifying event hypoperfusion symptoms, use of antithrombotic or proton pump inhibitor at baseline, days to enrollment, old infarcts in the same territory, percent stenosis, other artery stenosis, and location of the symptomatic artery. RESULTS: A total of 451 patients were enrolled, 227 randomized to aggressive medical therapy and 224 to PTAS. Of all variables evaluated, the observed 2-year event rates were higher with PTAS than with aggressive medical therapy in the vast majority and the interaction with treatment was not statistically significant for any of the factors. CONCLUSIONS: The SAMMPRIS results do not provide evidence to support the use of PTAS using the Wingspan stent system compared with medical treatment in any examined subpopulation of patients with symptomatic intracranial stenosis, including those with qualifying event hypoperfusion symptoms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576693. PMID- 26382174 TI - Influence of Amyloid-beta on Cognitive Decline After Stroke/Transient Ischemic Attack: Three-Year Longitudinal Study. AB - BACKGROUND AND PURPOSE: We hypothesized that comorbid amyloid-beta (Abeta) deposition played a key role in long-term cognitive decline in subjects with stroke/transient ischemic attack. METHODS: We recruited 72 subjects with cognitive impairment after stroke/transient ischemic attack to receive Carbon-11 labeled Pittsburgh compound B positron emission tomography. We excluded subjects with known clinical Alzheimer's disease. Those with and without Alzheimer's disease-like Abeta deposition were classified as mixed vascular cognitive impairment (mVCI, n=14) and pure VCI (pVCI, n=58), respectively. We performed Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment to evaluate global cognition and cognitive domains (memory, visuospatial function, language, attention, and executive function) at 3 to 6 months (baseline) and annually for 3 years after the index event. We compared cognitive changes between mVCI and pVCI using linear mixed models and analysis of covariance adjusted for age and education. RESULTS: Over 3 years, there were significant differences between mVCI and pVCI on change of MMSE score over time (group*time interaction, P=0.007). We observed a significant decline on MMSE score (P=0.020) in the mVCI group but not in the pVCI group (P=0.208). The annual rates of decline on MMSE (P=0.023) and Montreal Cognitive Assessment score (P=0.003) were greater in the mVCI group than in the pVCI group. Memory, visuospatial, and executive function domain scores on the Montreal Cognitive Assessment were related to Abeta deposition. CONCLUSIONS: Compared with subjects without Alzheimer's disease-like Abeta deposition, those with Abeta deposition experienced a more severe and rapid cognitive decline over 3 years after stroke/transient ischemic attack. Abeta was associated with changes in multiple cognitive domains. PMID- 26382175 TI - Cerebellar Cortical Infarct Cavities: Correlation With Risk Factors and MRI Markers of Cerebrovascular Disease. AB - BACKGROUND AND PURPOSE: Small cerebellar infarct cavities have been recently found on magnetic resonance imaging (MRI) to preferentially involve the cerebellar cortex, but epidemiological studies are lacking. We aimed to determine the prevalence and risk factor profiles of cerebellar cortical infarct cavities (<=1.5 cm) as well as their association with MRI markers of cerebrovascular disease and functioning. METHODS: We analyzed the 1.5 Tesla MRI of 636 patients (mean age, 62+/-9 years; 81% men) from the Second Manifestations of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study. Logistic regression analyses were performed to estimate the associations of age, sex, vascular risk factors, MRI markers of cerebrovascular disease, and functioning with cerebellar cortical cavities, adjusted for age and sex. RESULTS: Cerebellar cortical infarct cavities occurred on MRI in 10% of patients and were significantly associated with age, intima-media thickness (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.7), high levels of homocysteinemia (OR, 1.8; 95% CI, 1.0-3.3), cortical infarcts (OR, 2.9; 95% CI, 1.6-5.4), gray matter lacunes of presumed vascular origin (OR, 3.0; 95% CI, 1.6-5.8), brain stem infarcts (OR, 5.1; 95% CI, 1.9-13.6), and decreased brain parenchymal fraction (OR, 0.84; 95% CI, 0.74 0.94), but not with white matter hyperintensities (OR, 1.2; 95% CI, 0.8-1.8) or white matter lacunes of presumed vascular origin (OR, 1.1; 95% CI, 0.5-2.5). They were also associated with worse physical functioning (OR, 0.96; 95% CI, 0.94 to 0.99) [corrected] but not with mental functioning. CONCLUSIONS: Cerebellar cortical infarct cavities are far more common than previously assumed based on symptomatic case series and are associated with markers of atherothromboembolic cerebrovascular disease. PMID- 26382177 TI - Association of Non-High-Density Lipoprotein Cholesterol with Psychosocial Dysfunction in Children and Adolescents with Obesity. AB - BACKGROUND: Children with obesity have worse psychosocial functioning compared to their non-overweight peers. Adult studies suggest that several metabolic factors may participate in the etiology of depression in obesity. METHODS: We evaluated the association of several metabolic parameters with psychosocial dysfunction in children with obesity, through a retrospective review of electronic medical records in patients ages 6-17. All parents were asked to complete the Pediatric Symptom Checklist (PSC) questionnaire, a validated measurement of psychosocial dysfunction in children. RESULTS: PSC scores were available in 618 patients. Overall, 11.2% of patients had a PSC score >=28, suggestive of psychosocial dysfunction. Non-high-density lipoprotein (HDL) cholesterol was associated with a higher PSC score (p = 0.02), after adjusting for age, sex, race, socioeconomic status, and BMI z-score. CONCLUSIONS: Consistent with adult studies, in children and adolescents with obesity, non-HDL cholesterol may play a role in the etiology of psychosocial dysfunction. Further studies are warranted. PMID- 26382176 TI - Trail Making Test Elucidates Neural Substrates of Specific Poststroke Executive Dysfunctions. AB - BACKGROUND AND PURPOSE: Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates. METHODS: One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute-subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented. RESULTS: Multiple linear regression analyses were completed. Although larger infarcts (beta=0.37, P<0.0001) were associated with slower processing speed, cholinergic hyperintensities projections scale severity (beta=0.39, P<0.0001) was associated with all metrics of set shifting. Left superior longitudinal fasciculus damage, however, was only associated with the difference score (beta=0.17, P=0.03). These findings were replicated in both cohorts. Patients with >=2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity. CONCLUSIONS: In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting. PMID- 26382178 TI - Reference values for the fetal lateral ventricle atrium measurement in the second and third trimesters of pregnancy in a Brazilian population. AB - OBJECTIVE: To establish reference values for the fetal atrium lateral ventricle measurements in the second and third trimesters of pregnancy in a Brazilian population. METHODS: A retrospective cross-sectional study was performed with low risk pregnant women who underwent ultrasound examination at 16-41 weeks of gestation. The atrium of lateral ventricle measurement was performed in the transventricular plane at the end of choroid plexus. We assessed reference curves (percentiles 5th, 50th and 95th) for the atrium of lateral ventricle measurement with gestational age (GA), using the best-fit polynomial equation, and determination coefficient (R(2)) and modeling the variability. RESULTS: The fetal atrium of lateral ventricle measurements was assessed in 519 singleton pregnancies. However, seven fetuses were excluded because of central nervous system malformations, and therefore data from 512 pregnancies were included in the analysis. The mean +/- standard deviation (range) of the fetal atrium lateral ventricle measurement (mm) was 5.1 +/- 1.4 (1.6-9.7). A best-fit curve was a first-degree polynomial regression: atrium lateral ventricle = 6.455 - 0.049 * GA (R(2) = 0.05). CONCLUSION: Reference values for the fetal atrium lateral ventricle measurements in the second and third trimesters of pregnancy in a Brazilian population were established. PMID- 26382179 TI - Brown fat activity deepens depression: True or false? AB - Circadian clocks have evolved a slowing-down mechanism. Temperature may be the original and universal time-giver to the organism. Brown adipose tissue generates heat and guides the circadian rhythm of core body temperature. The cryptochrome proteins regulate the temperature entrainability, and their dysfunction may let the activation of brown adipose tissue affect the brain more easily. Therefore, the activity of brown adipose tissue may compromise the slowing-down mechanism and thereby contribute to the emergence of mood disorders and the increase in suicide mortality around the time of puberty. PMID- 26382180 TI - Complications associated with bacitracin powder in surgical wounds. AB - OBJECT: There has been renewed interest in the application of concentrated antibiotic powder to surgical wounds as a method to decrease infection rates. While there is substantial medical literature describing the effectiveness and complications associated with vancomycin and gentamycin powders, very little has been reported regarding the safety and effectiveness of bacitracin powder in surgical wounds. In this paper the authors report their detailed analysis of potential bacitracin powder-related complications in a population of pediatric patients who underwent shunt surgery. METHODS: A detailed retrospective analysis was completed of all CSF shunt surgeries performed by the corresponding author at a large children's hospital between 2001 and 2013. This cohort consisted of many patients who were the subject of a previous report that showed the use of bacitracin powder in shunt wounds potentially decreased infection rates. Data were collected regarding the most common known complications of bacitracin, i.e., anaphylaxis, wound healing difficulties, and renal dysfunction. Data were stratified by typical demographic, medical, and surgical variables, including whether bacitracin powder was applied to wounds prior to closure. RESULTS: A total of 597 patients were reviewed in the analysis: 389 underwent surgery without bacitracin powder and 208 had concentrated bacitracin powder applied to the wounds prior to closure. The application of bacitracin powder was not associated with anaphylaxis (n = 0 both groups) or with an increase in wound breakdown (n = 5 in the control group, n = 0 in the bacitracin powder group) or renal dysfunction (creatinine/estimated glomerular filtration rate) using both comparative and multivariate analyses between the 2 groups. The sample size evaluating renal function was significantly lower (range 6-320) than that of anaphylaxis and wound breakdown analysis because only clinical values acquired during the routine care of these patients were available for analysis. The only significant difference in demographics was the more frequent use of intrathecal vancomycin and gentamycin in patients who received bacitracin powder (n = 1 for controls, n = 21 for bacitracin powder). In the multivariate analysis, only 1 factor, surgery performed on a premature infant within the first 3 months of life, was independently associated with a change in creatinine at 3 months (creatinine decreased by 0.18) compared with the level before surgery (p < 0.0001). Bacitracin powder was not a significant factor. CONCLUSIONS: To the authors' knowledge, this is the first study to systematically analyze the potential complications of concentrated bacitracin powder applied to surgical wounds. The use of topical bacitracin powder in CSF shunt wounds was not associated with anaphylaxis, wound breakdown, or renal dysfunction. Further study using standardized protocols is necessary before widespread use can be recommended. PMID- 26382181 TI - Transsutural distraction osteogenesis for 285 children with craniosynostosis: a single-institution experience. AB - OBJECT Although distraction osteogenesis (DO) requires a secondary procedure in the surgical correction of craniosynostosis, it is relatively simple, requires less transfusion, results in a shorter intensive care unit stay, and is quite safe. Because of these positive factors, various DO techniques have been developed. However, there is disagreement regarding the superiority of DO. The authors reported on a new DO technique, transsutural DO (TSDO), 6 years ago that was performed in 23 patients over a period of 6 months, and it continues to be used at the present time. In this paper the authors report the results of TSDO performed in 285 patients with craniosynostosis over a period of 6 years at a single institution. METHODS TSDO consists of a simple suturectomy of the pathological suture followed by direct distraction of the suturectomy site only. Types of TSDO conducted included sagittal TSDO in 95 patients, bicoronal in 14, unilateral coronal in 57, lambdoid in 26, metopic in 13, multiple in 19, syndromic in 33, and secondary in 28. The mean age (+/- SD) of the patients was 19.4 +/- 23.0 months, and mean follow-up was 39.5 +/- 21.0 months. RESULTS The mean operating time was 115 +/- 43 minutes, and mean anesthesia time was 218 +/- 56 minutes. The mean transfusion volume of red blood cell components was 48 +/- 58 ml, and mean transfusion volume of fresh-frozen plasma was 19 +/- 35 ml. Total transfusion volume was significantly less in infants younger than 12 months of age and in children with lower lumbar puncture pressures (p < 0.05). Complications included 1 (0.4%) death from postoperative acute pneumonia after a distractor removal operation and 23 (8%) surgical morbidities comprising 10 revisions (3.5%) and 13 early removals of distracters (4.6%). CONCLUSIONS TSDO is a simple, effective, and safe method to use for treating all types of craniosynostosis. Some morbidity was experienced in this study, but it may be attributed to the learning curve of the technique. PMID- 26382182 TI - Durotomy and foramen magnum decompression. PMID- 26382183 TI - Fecal incontinence as a predominant symptom in a case of multiply recurrent tethered cord: diagnosis and operative strategies. AB - Recurrent manifestations of tethered spinal cord after an initial operative intervention for a simple fatty filum terminale is fairly uncommon. The authors present the case of an unusual clinical course in which there were 3 distinct episodes of recurrence, each time presenting predominantly as fecal incontinence and resolving with operative intervention. Typical signs of tethering were absent on radiological evaluation, and operative intervention was based on clinical grounds. Intraoperatively, sacral nerve roots to the anal sphincter were found tethered to the filar stump with electrophysiological evidence of regained activity on disentanglement. To the best of the authors' knowledge, a similar clinical course or operative findings have not been reported. PMID- 26382184 TI - Incidence of hemorrhage in the pediatric population with placement and removal of external ventricular drains. AB - OBJECT: External ventricular drains (EVDs) are regularly used in pediatric neurosurgery for diagnostic and therapeutic purposes. Hemorrhage caused by placing an EVD is a common complication noted in the adult literature. In the pediatric literature, on the other hand, only a few articles have assessed the risk of hemorrhage with placement, and none have reported the occurrence of hemorrhage with removal of an EVD. The authors investigated the incidence of hemorrhage with both placement and removal of the EVD in a pediatric population. METHODS: After obtaining institutional review board approval, a comprehensive database was created to include all pediatric patients who required EVD placement between March 2008 and June 2014 at the authors' institution. A retrospective chart review was completed, and all imaging was reviewed for evidence of hemorrhage with placement and removal of the EVD. RESULTS: During the designated time period, 73 EVDs were placed in 63 patients (ages 2 weeks-17 years). Indications for EVD placement were as follows: shunt infection/malfunction (21), tumor (12), hydrocephalus (18), hemorrhage (12), edema (4), trauma (1), and other (5). Hemorrhage with placement was noted in 5 of the 50 patients who underwent imaging, with a volume ranging from 0.48 cm3 to 7.7 cm3. Thirty-two patients had imaging after EVD removal, and 7 of these patients were noted to have hemorrhage (volume range 0.012 cm3 to 81.5 cm3). CONCLUSIONS: The authors found the incidence of hemorrhage at EVD placement to be 10%, and the incidence of hemorrhage on EVD removal to be 21.9% in those patients who underwent imaging after each event. Although none of the hemorrhages were of obvious clinical significance, these data can be useful in decision making, and in discussing the risks of EVDs with the patient's family. PMID- 26382185 TI - Reduction in CSF shunt infection over a 10-year period associated with the application of concentrated topical antibiotic powder directly to surgical wounds prior to closure. AB - OBJECT: The application of concentrated topical antibiotic powder directly to surgical wounds has been associated with a reduction in wound infection in cardiac, spinal, and deep brain stimulator surgery. As a result of these findings, the corresponding author began systematically applying concentrated bacitracin powder directly to wounds during shunt surgery more than 5 years ago. The object of this study was to evaluate the effectiveness of concentrated bacitracin powder applied directly to wounds prior to closure during cranial shunt surgery and to evaluate the association between shunt infection and other risk factors. A single surgeon's cranial shunt surgery experience, equally divided between periods during which antibiotic powder was and was not applied, was studied to assess the effect of concentrated bacitracin powder application on shunt infection rates. METHODS: This retrospective cohort study included all patients who underwent a cranial shunting procedure at All Children's Hospital performed by a single surgeon (G.F.T.) from 2001 to 2013. The surgeon applied bacitracin powder to all shunt wounds prior to closure between 2008 and 2013, whereas no antibiotic powder was applied to wounds prior to 2008. Both initial and revision shunting procedures were included, and all procedures were performed at a large children's hospital (All Children's Hospital). The primary outcome measure was shunt infection, which was defined using clinical criteria previously used by the Hydrocephalus Clinical Research Network. The association between bacitracin powder use and shunt infection was estimated using hazard ratios (HRs) and 95% CIs from Cox proportional hazard regression models. RESULTS: A total of 47 infections out of 539 shunt operations occurred during the study period, resulting in an overall infection rate of 8.7%. Procedures performed before the use of concentrated bacitracin powder was instituted resulted in a 13% infection rate, whereas procedures performed after systematic use of bacitracin powder had been adopted experienced a 1% infection rate. Bacitracin powder use was associated with a reduced risk of shunt infection in univariate analysis (HR 0.11, 95% CI 0.03-0.34, p = 0.0002) and also in multivariate analysis (HR 0.12, 95% CI 0.04-0.41, p = 0.0006) when controlling for covariates that were associated with infection from the univariate analysis. The presence of a tracheostomy or a gastrostomy tube was also found to be independently associated with shunt infection in multivariate analysis (HR 3.15, 95% CI 1.05-9.50, p = 0.04, and HR 2.82, 95% CI 1.33-5.96, p = 0.007, respectively). CONCLUSIONS: This study suggests, for the first time, that the systematic application of concentrated bacitracin powder to surgical wounds prior to closure during shunt surgery may be associated with a reduction in cranial shunt infection. This initial finding requires validation in a large prospective study before widespread application can be advocated. PMID- 26382186 TI - Analysis of metabolic pools in broilers chicks. AB - This paper shows the possibility of obtaining new parameters for the mathematical modelling of data on stable isotopes in biological systems and its application in obtaining data on metabolic pools of blood plasma, blood serum, liver and muscle of broilers. This theory states that the modelling of turnover used for studies of isotopic incorporation when the metabolism has a single metabolic pool is feasible by the technique of setting an exponential. However, when the metabolism has more than one metabolic pool, it is necessary to apply the linearization technique, linear regression adjustment and evaluation of the assumptions of regression to obtain the kinetic parameters such as half-life (T1/2) and isotope exchange rate (k). The application of this technique on carbon-13 data from 100 one-day-old chicks, with the change of diet composed of grains of the photosynthetic cycle of plants from C4 to C3, in broilers has enabled the discovery that the liver, blood plasma and blood serum have a single metabolic pool; however, the pectoral muscle has two metabolic pools. For the liver, blood plasma and blood serum, the half-life values were found by the exponential fit being T1/2 = 1.4 days with the rate of exchange of k = 0.502, T1/2 = 2.4 days with k = 0.293 and T1/2 = 2.0 days with k = 0.348, respectively. For the pectoral muscle, after linearization, the half-life values were found for T1/2(1) = 1.7 and T1/2(2) = 3 days, with exchange rates of k1 = 0.405 and k2 = 0.235, representing approximately 66 and 34%, respectively. PMID- 26382188 TI - Those harmed by others' drinking in the US population are more depressed and distressed. AB - INTRODUCTION AND AIMS: Harms from second-hand smoke were instrumental in enacting tobacco controls. Documenting negative impacts of harms from others' drinking (also called second-hand effects of drinking) is vital to increase political will for optimal alcohol policies. We assessed associations between harms from others' drinking and depression in a national sample of US adults. DESIGN AND METHODS: Using the landline sample from the 2010 National Alcohol Survey (n = 5388), weighted logistic regression models adjusting for alcohol problems in family of origin, respondent drinking pattern (volume and heaviest drinking), poverty and other demographics were used to analyse associations between experiencing harms from others' drinking in the last 12 months with mild to moderate depression (8 item Center for Epidemiologic Studies Depression scale; alpha = 0.92; using cut point >=8) and current distress. RESULTS: Past 12 month family/marital harms, financial troubles, assaults, and vandalised property attributed to others' drinking were each associated with higher depression scores (all P < 0.001). In a combined model, all harms other than assaults remained highly significant. Similar patterns were found for current distress, but with some specific differences because of measurement and analytic approaches chosen also evident. DISCUSSION: Findings suggest recently experiencing particular harms from others' drinking significantly affects mental health (both depression and distress). This confirms in a US population results recently reported in Australasian samples. CONCLUSIONS: Studies that quantify the extent to which heavy drinkers victimise others are important for alcohol policy. [Greenfield TK, Karriker-Jaffe KJ, Kerr WC, Ye Y, Kaplan LM. Those harmed by others' drinking in the US population are more depressed and distressed. Drug Alcohol Rev 2015;??:??-??]. PMID- 26382189 TI - Meiotic recombination heats up. PMID- 26382190 TI - Genomic science provides new insights into the biology of forest trees. PMID- 26382191 TI - Corrigendum. PMID- 26382192 TI - Component-wise gradient boosting and false discovery control in survival analysis with high-dimensional covariates. AB - MOTIVATION: Technological advances that allow routine identification of high dimensional risk factors have led to high demand for statistical techniques that enable full utilization of these rich sources of information for genetics studies. Variable selection for censored outcome data as well as control of false discoveries (i.e. inclusion of irrelevant variables) in the presence of high dimensional predictors present serious challenges. This article develops a computationally feasible method based on boosting and stability selection. Specifically, we modified the component-wise gradient boosting to improve the computational feasibility and introduced random permutation in stability selection for controlling false discoveries. RESULTS: We have proposed a high dimensional variable selection method by incorporating stability selection to control false discovery. Comparisons between the proposed method and the commonly used univariate and Lasso approaches for variable selection reveal that the proposed method yields fewer false discoveries. The proposed method is applied to study the associations of 2339 common single-nucleotide polymorphisms (SNPs) with overall survival among cutaneous melanoma (CM) patients. The results have confirmed that BRCA2 pathway SNPs are likely to be associated with overall survival, as reported by previous literature. Moreover, we have identified several new Fanconi anemia (FA) pathway SNPs that are likely to modulate survival of CM patients. AVAILABILITY AND IMPLEMENTATION: The related source code and documents are freely available at https://sites.google.com/site/bestumich/issues. CONTACT: yili@umich.edu. PMID- 26382193 TI - ICT: isotope correction toolbox. AB - SUMMARY: Isotope tracer experiments are an invaluable technique to analyze and study the metabolism of biological systems. However, isotope labeling experiments are often affected by naturally abundant isotopes especially in cases where mass spectrometric methods make use of derivatization. The correction of these additive interferences--in particular for complex isotopic systems--is numerically challenging and still an emerging field of research. When positional information is generated via collision-induced dissociation, even more complex calculations for isotopic interference correction are necessary. So far, no freely available tools can handle tandem mass spectrometry data. We present isotope correction toolbox, a program that corrects tandem mass isotopomer data from tandem mass spectrometry experiments. Isotope correction toolbox is written in the multi-platform programming language Perl and, therefore, can be used on all commonly available computer platforms. AVAILABILITY AND IMPLEMENTATION: Source code and documentation can be freely obtained under the Artistic License or the GNU General Public License from: https://github.com/jungreuc/isotope_correction_toolbox/ CONTACT: {christian.jungreuthmayer@boku.ac.at,juergen.zanghellini@boku.ac.at} SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26382194 TI - ScaffoldScaffolder: solving contig orientation via bidirected to directed graph reduction. AB - MOTIVATION: The contig orientation problem, which we formally define as the MAX DIR problem, has at times been addressed cursorily and at times using various heuristics. In setting forth a linear-time reduction from the MAX-CUT problem to the MAX-DIR problem, we prove the latter is NP-complete. We compare the relative performance of a novel greedy approach with several other heuristic solutions. RESULTS: Our results suggest that our greedy heuristic algorithm not only works well but also outperforms the other algorithms due to the nature of scaffold graphs. Our results also demonstrate a novel method for identifying inverted repeats and inversion variants, both of which contradict the basic single orientation assumption. Such inversions have previously been noted as being difficult to detect and are directly involved in the genetic mechanisms of several diseases. AVAILABILITY AND IMPLEMENTATION: http://bioresearch.byu.edu/scaffoldscaffolder. CONTACT: paulmbodily@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26382195 TI - P-SAMS: a web site for plant artificial microRNA and synthetic trans-acting small interfering RNA design. AB - SUMMARY: The Plant Small RNA Maker Site (P-SAMS) is a web tool for the simple and automated design of artificial miRNAs (amiRNAs) and synthetic trans-acting small interfering RNAs (syn-tasiRNAs) for efficient and specific targeted gene silencing in plants. P-SAMS includes two applications, P-SAMS amiRNA Designer and P-SAMS syn-tasiRNA Designer. The navigation through both applications is wizard assisted, and the job runtime is relatively short. Both applications output the sequence of designed small RNA(s), and the sequence of the two oligonucleotides required for cloning into 'B/c' compatible vectors. AVAILABILITY AND IMPLEMENTATION: The P-SAMS website is available at http://p sams.carringtonlab.org. CONTACT: acarbonell@ibmcp.upv.es or nfahlgren@danforthcenter.org. PMID- 26382196 TI - CLAMMS: a scalable algorithm for calling common and rare copy number variants from exome sequencing data. AB - MOTIVATION: Several algorithms exist for detecting copy number variants (CNVs) from human exome sequencing read depth, but previous tools have not been well suited for large population studies on the order of tens or hundreds of thousands of exomes. Their limitations include being difficult to integrate into automated variant-calling pipelines and being ill-suited for detecting common variants. To address these issues, we developed a new algorithm--Copy number estimation using Lattice-Aligned Mixture Models (CLAMMS)--which is highly scalable and suitable for detecting CNVs across the whole allele frequency spectrum. RESULTS: In this note, we summarize the methods and intended use-case of CLAMMS, compare it to previous algorithms and briefly describe results of validation experiments. We evaluate the adherence of CNV calls from CLAMMS and four other algorithms to Mendelian inheritance patterns on a pedigree; we compare calls from CLAMMS and other algorithms to calls from SNP genotyping arrays for a set of 3164 samples; and we use TaqMan quantitative polymerase chain reaction to validate CNVs predicted by CLAMMS at 39 loci (95% of rare variants validate; across 19 common variant loci, the mean precision and recall are 99% and 94%, respectively). In the Supplementary Materials (available at the CLAMMS Github repository), we present our methods and validation results in greater detail. AVAILABILITY AND IMPLEMENTATION: https://github.com/rgcgithub/clamms (implemented in C). CONTACT: jeffrey.reid@regeneron.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26382197 TI - NanoOK: multi-reference alignment analysis of nanopore sequencing data, quality and error profiles. AB - MOTIVATION: The Oxford Nanopore MinION sequencer, currently in pre-release testing through the MinION Access Programme (MAP), promises long reads in real time from an inexpensive, compact, USB device. Tools have been released to extract FASTA/Q from the MinION base calling output and to provide basic yield statistics. However, no single tool yet exists to provide comprehensive alignment based quality control and error profile analysis--something that is extremely important given the speed with which the platform is evolving. RESULTS: NanoOK generates detailed tabular and graphical output plus an in-depth multi-page PDF report including error profile, quality and yield data. NanoOK is multi reference, enabling detailed analysis of metagenomic or multiplexed samples. Four popular Nanopore aligners are supported and it is easily extensible to include others. AVAILABILITY AND IMPLEMENTATION: NanoOK is an open-source software, implemented in Java with supporting R scripts. It has been tested on Linux and Mac OS X and can be downloaded from https://github.com/TGAC/NanoOK. A VirtualBox VM containing all dependencies and the DH10B read set used in this article is available from http://opendata.tgac.ac.uk/nanook/. A Docker image is also available from Docker Hub--see program documentation https://documentation.tgac.ac.uk/display/NANOOK. CONTACT: richard.leggett@tgac.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26382198 TI - Practitioner and Practice Characteristics of Certified Professional Midwives in the United States: Results of the 2011 North American Registry of Midwives Survey. AB - INTRODUCTION: No data describing certified professional midwives (CPMs) currently exist in the literature, although CPMs attend the majority of home births in the United States. This study addresses this gap by assessing the demographics, education levels, routes to certification, and practice characteristics of currently practicing CPMs. METHODS: Data were collected from a survey of CPMs conducted by the North American Registry of Midwives (NARM) between July and October 2011. In order to assess generalization to the entire population of practicing CPMs, we also completed a nonresponse bias analysis. We examined midwives' demographic, education, certification, and practice characteristics using descriptive and nonparametric, bivariable statistics. RESULTS: More than 90% of the 568 respondents attended at least some college, and 47.1% hold a bachelor's degree or greater. CPMs spent a median of 3 years (interquartile range, 2-5 years) in training before attending births as a primary midwife. However, 38.9% of currently practicing CPMs had less than 3 years of training. Regarding pathways to certification, 48.5% utilized the portfolio evaluation process (PEP); 36.9% graduated from a Midwifery Education and Accreditation Council (MEAC)-accredited school; 14.5% were already licensed by a state as a direct-entry midwife; and 0.7% were already a certified nurse-midwife or certified midwife, although many CPMs reported a blended education pathway. One fifth (21%) of respondents identified as midwives of color. Whereas nearly one third (31.8%) of CPM respondents reported that 95% or more of their clients were white, 5.2% serve populations that are 90% or more nonwhite. CPMs of color are significantly more likely to serve clients of color (P < .001). DISCUSSION: Training and nonmidwifery education levels of most CPMs practicing in the United States align with the Global Standards for Midwifery Education established by the International Confederation of Midwives, although there are still clear areas for improvement. PMID- 26382199 TI - MALDI MSI and LC-MS/MS: Towards preclinical determination of the neurotoxic potential of fluoroquinolones. AB - Fluoroquinolones are broad-spectrum antibiotics with efficacy against a wide range of pathogenic microbes associated with respiratory and meningeal infections. The potential toxicity of this class of chemical agents is a source of major concern and is becoming a global issue. The aim of this study was to develop a method for the brain distribution and the pharmacokinetic profile of gatifloxacin in healthy Sprague-Dawley rats, via Multicenter matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). We developed a sensitive LC-MS/MS method to quantify gatifloxacin in plasma, lung, and brain homogenates. A pharmacokinetic profile was observed where there is a double peak pattern; a sharp initial increase in the concentration soon after dosing followed by a steady decline until another increase in concentration after a longer period post dosing in all three biological samples was observed. The imaging results showed the drug gradually entering the brain via the blood brain barrier and into the cortical regions from 15 to 240 min post dose. As time elapses, the drug leaves the brain following the same path as it followed on its entry and finally concentrates at the cortex. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26382200 TI - Fast Photoresponse and Long Lifetime UV Photodetectors and Field Emitters Based on ZnO/Ultrananocrystalline Diamond Films. AB - We have designed photodetectors and UV field emitters based on a combination of ZnO nanowires/nanorods (ZNRs) and bilayer diamond films in a metal-semiconductor metal (MSM) structure. The ZNRs were fabricated on different diamond films and systematic investigations showed an ultra-high photoconductive response from ZNRs prepared on ultrananocrystalline diamond (UNCD) operating at a lower voltage of 2 V. We found that the ZNRs/UNCD photodetector (PD) has improved field emission properties and a reduced turn-on field of 2.9 V MUm(-1) with the highest electron field emission (EFE) by simply illuminating the sample with ultraviolet (UV) light. The photoresponse (Iphoto /Idark ) behavior of the ZNRs/UNCD PD exhibits a much higher photoresponse (912) than bare ZNRs (229), ZNRs/nanocrystalline diamond (NCD; 518), and ZNRs/microcrystalline diamond (MCD; 325) under illumination at lambda=365 nm. A photodetector with UNCD films offers superior stability and a longer lifetime compared with carbon materials and bare ZNRs. The lifetime stability of the ZNRs/UNCD-based device is about 410 min, which is markedly superior to devices that use bare ZNRs (92 min). The ZNRs/UNCD PD possesses excellent photoresponse properties with improved lifetime and stability; in addition, ZNRs/UNCD-based UV emitters have great potential for applications such as cathodes in flat-panel displays and microplasma display devices. PMID- 26382201 TI - The AJT Report. PMID- 26382203 TI - The Best-Laid Schemes of Mice and Men Often Go Awry; How Should We Repair Them? PMID- 26382204 TI - Prevention and Control of Influenza With Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 Influenza Season. PMID- 26382205 TI - Graft Tenderness 9 Years After Kidney Transplant. PMID- 26382206 TI - Erratum. PMID- 26382207 TI - Retraction: 'Rapamycin Attenuates Liver Graft Injury in Cirrhotic Recipient-The Significance of Down-Regulation of Rho-ROCK-VEGF Pathway' by K. Man, M. Su, K.T. Ng, C.M. Lo, Y. Zhao, J.W. Ho, C.K. Sun, T.K. Lee, and S.T. Fan. PMID- 26382208 TI - Retraction: 'Fat-Derived Hormone Adiponectin Combined with FTY720 Significantly Improves Small-for-Size Fatty Liver Graft Survival' by K. Man, Y. Zhao, A. Xu, C.M. Lo, K.S.L. Lam, K.T. Ng, J.W.Y. Ho, C.K. Sun, T.K. Lee, X.L. Li, and S.T. Fan. PMID- 26382210 TI - B1 is involved in autophagy inhibition caused by SNCA/a-synuclein overexpression: a process modulated by the natural autophagy inducer corynoxine B. PMID- 26382211 TI - Are Right to Left Shunts Underdiagnosed in the Etiology of Migraine Headache? --A Response. PMID- 26382212 TI - Separation of Ofloxacin and Its Six Related Substances Enantiomers by Chiral Ligand-Exchange Chromatography. AB - A chiral ligand-exchange high-performance liquid chromatography method was developed for the enantioseparation of ofloxacin and its six related substances termed impurities A, B, C, D, E, and F. The separation was performed on a conventional C18 column. Different organic modifiers, copper salts, amino acids, the ratio of Cu(2+) to amino acid, pH of aqueous phase, and column temperature were optimized. The optimal mobile phase conditions were methanol-water systems consisting of 5 mmol/L copper sulfate and 10 mmol/L L-isoleucine (L-Ile). Under such conditions, good enantioseparation of ofloxacin and impurities A, C, E, and F could be observed with resolutions (RS ) of 3.54, 1.97, 3.21, 3.50, and 2.12, respectively. On the relationship between the thermodynamic parameters and structures of analytes, the mechanism of chiral recognition was investigated. It was concluded that ofloxacin and impurities A, C, E, and F were all enthalpically driven enantioseparation and that low column temperature was beneficial to enantioseparation. Furthermore, the structure-separation relationship of these analytes is also discussed. PMID- 26382213 TI - Liquor ammonia mediated V(V) insertion in thin Co3O4 sheets for improved pseudocapacitors with high energy density and high specific capacitance value. AB - Ultrathin 2D Co3O4 and Co3V2O8 nanosheets have been produced from our modified hydrothermal technique (MHT). Both the materials have been proved to be extraordinary electrode materials for pseudocapacitors. The neat nanosheets of Co3O4 and Co3V2O8 exhibit a record specific capacitance value of 1256 F g(-1) and 4194 F g(-1) at 1 A g(-1) current density, respectively. PMID- 26382214 TI - Blowfly Larval Tissues as a Secondary Detector for Determining Paraquat-Related Death in Rabbit Carcass. AB - Paraquat poisoning is commonly associated with suicide or homicide in Malaysia. In a case involving advanced body decomposition, pathological analysis regarding the cause of death may become difficult or almost impossible. Insects serve as common alternative matrix for poison detection in forensic analysis. Paraquat detection via secondary bioaccumulation in fly larvae tissue has never been reported. In this study, tissues from blowfly larvae collected from a rabbit carcass with paraquat poisoning were analyzed for secondary bioaccumulation. Larvae samples were collected and analyzed using liquid-liquid extraction. The detection was performed via reduction of quaternary ammonium presence in paraquat and analyzed using gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring mode (SIM mode). GC-MS showed the elution of reduced paraquat was at retention time 12.8 min. Blowfly larvae tissue has proven useful as a secondary detector in paraquat-related deaths. PMID- 26382215 TI - Altered myocardial response in patients with diabetic retinopathy: an exercise echocardiography study. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) complicated by retinopathy is associated with altered left ventricular (LV) structure and resting myocardial dysfunction unlike T2DM without retinopathy. The myocardial response to stress has not been compared in patients with and without diabetic retinopathy. The aim of this retrospective study was to determine the relationship between retinopathy and myocardial function in patients with T2DM at rest and during exercise echocardiography. METHODS: 134 patients with T2DM and no evidence of underlying coronary artery disease were recruited. All patients underwent retinal photography to screen for diabetic retinopathy, and resting and exercise echocardiography. Resting echocardiography was analyzed by conventional echocardiographic parameters and speckle tracking derived global longitudinal strain (GLS). Exercise echocardiography parameters included diastolic function reserve index (DFRI) and stress GLS. RESULTS: The mean age of participants was 60 years and 49% were male. Diabetic retinopathy was identified in 43 patients (32%). Resting echocardiography revealed that those with diabetic retinopathy had a higher prevalence of impaired diastolic function, higher E/E' ratio (LV filling pressures) and impaired resting GLS compared with those without. Exercise echocardiography revealed that those with diabetic retinopathy also had more impaired DFRI and stress GLS. Multivariable analysis showed that the presence of diabetic retinopathy was independently associated with high resting E/E', diastolic dysfunction grade, impaired resting GLS, low DFRI and impaired stress GLS. CONCLUSIONS: In conclusion, the presence of diabetic retinopathy was independently associated with impaired resting myocardial function (diastolic and systolic function) and myocardial function during stress (evaluated by DFRI and stress GLS). PMID- 26382216 TI - Does turning trauma patients with an unstable spinal injury from the supine to a lateral position increase the risk of neurological deterioration?--A systematic review. AB - BACKGROUND: Airway protection and spinal precautions are competing concerns in the treatment of unconscious trauma patients. The placement of such patients in a lateral position may facilitate the acquisition of an adequate airway. However, trauma dogma dictates that patients should be transported in the supine position to minimize spinal movement. In this systematic review, we sought to answer the following question: Given an existing spinal injury, will changing a patient's position from supine to lateral increase the risk of neurological deterioration? METHODS: The review protocol was published in the PROSPERO database (Reg. no. CRD42012001190). We performed literature searches in PubMed, Medline, EMBASE, the Cochrane Library, CINAHL and the British Nursing Index and included studies of traumatic spinal injury, lateral positioning and neurological deterioration. The search was updated prior to submission. Two researchers independently completed each step in the review process. RESULTS: We identified 1,164 publications. However, none of these publications reported mortality or neurological deterioration with lateral positioning as an outcome measure. Twelve studies used movement of the injured spine with lateral positioning as an outcome measure; eleven of these investigations were cadaver studies. All of these cadaver studies reported spinal movement during lateral positioning. The only identified human study included eighteen patients with thoracic or lumbar spinal fractures; according to the study authors, the logrolling technique did not result in any neurological deterioration among these patients. CONCLUSIONS: We identified no clinical studies demonstrating that rotating trauma patients from the supine position to a lateral position affects mortality or causes neurological deterioration. However, in various cadaver models, this type of rotation did produce statistically significant displacements of the injured spine. The clinical significance of these cadaver-based observations remains unclear. The present evidence for harm in rotating trauma patients from the supine position to a lateral position, including the logroll maneuver, is inconclusive. PMID- 26382217 TI - Biologic predictors of clinical improvement in rituximab-treated refractory myositis. AB - BACKGROUND: To examine the longitudinal utility of a biomarker signature in conjunction with myositis autoantibodies (autoAbs) as predictors of disease improvement in refractory myositis patients treated with rituximab. METHODS: In the RIM Trial, all subjects received rituximab on 2 consecutive weeks. Using start of treatment as baseline, serum samples (n = 177) were analyzed at baseline and after rituximab with multiplexed sandwich immunoassays to quantify type-1 IFN regulated and other pro-inflammatory chemokines and cytokines. Biomarker scores were generated for the following pathways: type-1 IFN-inducible (IFNCK), innate, Th1, Th2, Th17 and regulatory cytokines. Myositis autoAbs (anti-synthetase n = 28, TIF-gamma n = 19, Mi-2 n = 25, SRP n = 21, MJ n = 18, non-MAA n = 24, unidentified autoantibody n = 9, and no autoantibodies n = 33) determined by immunoprecipitation at baseline, were correlated with outcome measures. Kruskal Wallis rank sum tests were used for comparisons. RESULTS: The mean (SD) values for muscle disease and physician global disease activity VAS scores (0-100 mm) were 46 (22) and 49 (19). IFNCK scores (median values) were higher at baseline in subjects with anti-synthetase (43), TIF1-gamma (31) and Mi-2 (30) compared with other autoAb groups (p < 0.001). At 16 weeks after rituximab, anti-synthetase and Mi-2 autoAb positive subjects and non-MAA had a greater improvement in IFNCK scores (- 6.7, - 6.1 and -7.2, p < .001). Both IFNCK high scores (>30) and autoAb group (Mi-2, non-MAA, and undefined autoantibody) demonstrated the greatest clinical improvement based on muscle VAS (muscle-interaction p = 0.075). CONCLUSION: Biomarker signatures in conjunction with autoAbs help predict response to rituximab in refractory myositis. Biomarker and clinical responses are greatest at 16 weeks after rituximab. PMID- 26382218 TI - High degree of mitochondrial gene heterogeneity in the bat tick species Ixodes vespertilionis, I. ariadnae and I. simplex from Eurasia. AB - BACKGROUND: Phylogeographical studies allow precise genetic comparison of specimens, which were collected over large geographical ranges and belong to the same or closely related animal species. These methods have also been used to compare ticks of veterinary-medical importance. However, relevant data are missing in the case of ixodid ticks of bats, despite (1) the vast geographical range of both Ixodes vespertilionis and Ixodes simplex, and (2) the considerable uncertainty in their taxonomy, which is currently unresolvable by morphological clues. METHODS: In the present study 21 ticks were selected from collections or were freshly removed from bats or cave walls in six European and four Asian countries. The DNA was extracted and PCRs were performed to amplify part of the cytochrome oxidase I (COI), 16S and 12S rDNA genes, followed by sequencing for identification and molecular-phylogenetic comparison. RESULTS: No morphological differences were observed between Ixodes vespertilionis specimens from Spain and from other parts of Europe, but corresponding genotypes had only 94.6 % COI sequence identity. An I. vespertilionis specimen collected in Vietnam was different both morphologically and genetically (i.e. with only 84.1 % COI sequence identity in comparison with I. vespertilionis from Europe). Two ticks (collected in Vietnam and in Japan) formed a monophyletic clade and shared morphological features with I. ariadnae, recently described and hitherto only reported in Europe. In addition, two Asiatic specimens of I. simplex were shown to differ markedly from European genotypes of the same species. Phylogenetic relationships of ticks showed similar clustering patterns with those of their associated bat host species. CONCLUSIONS: Although all three ixodid bat tick species evaluated in the present study appear to be widespread in Eurasia, they exhibit pronounced genetic differences. Data of this study also reflect that I. vespertilionis may represent a species complex. PMID- 26382219 TI - Idiomarina aquatica sp. nov., a moderately halophilic bacterium isolated from salterns. AB - Four bacterial strains, SN-14T, SN-4, M6-46 and M6-58B, were isolated from water of ponds of two salterns located in Huelva (Spain). They were Gram-stain negative, aerobic and slightly curved rods. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the four strains belong to the genus Idiomarina, being related most closely to Idiomarina fontislapidosi F23T (98.4 98.0% sequence similarity), Idiomarina seosinensis CL-SP19T (98.3-98.0%), Idiomarina piscisalsi TPS4-2T (97.9-97.4%), Idiomarina baltica OS145T (97.5 97.4%) and Idiomarina zobellii KMM 231T (97.6-97.0%). The level of similarity with the type species of the genus, Idiomarina abyssalis KMM 227T, was 97.2 96.7%. The novel strains exhibited optimal growth at 5-10% (w/v) total salts, pH 7 and 37 degrees C. The major fatty acids of strain SN-14T were iso-C15 : 0, iso C17 : 0, C18 : 1omega7c/C18 : 1omega6c, C16 : 0 and iso-C17 : 1omega9c/C16 : 0 10 methyl. The DNA G+C content range was 47.6-50.8 mol%. The level of DNA-DNA relatedness between strain SN-14T and I. fontislapidosi F23T was 13%, while those between strain SN-14T and the other three new isolates were between 77 and 99%. These data demonstrated that the four isolates constitute a novel species of the genus Idiomarina. Based on the phylogenetic, genotypic, phenotypic and chemotaxonomic data, the four strains represent a novel species of the genus Idiomarina, for which the name Idiomarina aquatica sp. nov. is proposed. The type strain is SN-14T ( = CCM 8471T = CECT 8360T = LMG 27613T). PMID- 26382220 TI - Potential Effect of Antiplatelet and Anticoagulant Therapy on the Timing of the Diagnosis of Bladder Cancer. AB - BACKGROUND: The most common presenting symptom of bladder cancer (BCa) is hematuria. The present study was designed to define whether patients taking antiplatelet and/or anticoagulant drugs might experience hematuria at an earlier stage or grade of BCa. PATIENTS AND METHODS: The data from 1532 consecutive patients who presented to the emergency unit of our institute from 2004 to 2012 because of gross hematuria as a single symptom were evaluated. Patients (n = 227) with a further diagnosis of BCa were included in our study. For the purpose of the present study, patients were divided into 2 groups: patients receiving antiplatelet or anticoagulant therapy (AAT) (group 1) and patients not receiving AAT (group 2) at the moment of the macroscopic hematuria episode. The effect of AAT on the pathologic stage and grade of BCa was statistically assessed using univariate and multivariate logistic regression analysis. RESULTS: A total of 59 (26%) and 168 (74%) patients were included in groups 1 and 2, respectively. On multivariate logistic regression analysis, ATT conferred a protective effect against both pathologic stage >= T2 (odds ratio [OR], 0.37; 95% confidential interval [CI], 0.12-0.66; P = .01) and higher grade (OR, 0.56; 95% CI, 0.26-0.85; P = .02) at tumor presentation. CONCLUSION: According to the results of the present retrospective investigation, patients who received AAT seem to experience gross hematuria significantly earlier than do untreated patients, resulting in the chance of an earlier diagnosis and treatment of bladder cancer. PMID- 26382221 TI - Absence of Significant Correlation of Adverse Events Between First- and Second Line Tyrosine Kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma. AB - Several adverse events (AEs) are known to be commonly observed during treatment with different tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) patients. However, no significant correlation appears present in the profiles of such AEs between first- and second-line TKI therapies. Therefore, a second-line targeted agent for patients with mRCC could be selected irrespective of the AE profile during first-line TKI therapy. BACKGROUND: Several adverse events (AEs) commonly observed during treatment with different tyrosine kinase inhibitors (TKIs). The objective of the present study was to investigate whether the appearance of such AEs during treatment with first-line TKIs significantly affects the occurrence of AEs during second-line TKI therapy for patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: The present study included 154 consecutive patients with mRCC treated with second line TKIs after the discontinuation of first-line TKIs. The association of AEs, including diarrhea, fatigue, hand-foot syndrome, hypertension, and hypothyroidism, between first- and second-line therapies was analyzed in these 154 patients. RESULTS: For all 5 AEs assessed in the present study, the proportion of patients experiencing AEs or those grade >= 3 during second-line TKI therapy was not significantly different among the following 3 groups: patients without AEs, those with grade <= 2 AEs, and those with grade >= 3 AEs during first-line TKI therapy. Furthermore, no significant difference was seen in progression-free or overall survival after the introduction of second-line TKIs between patients with and without grade >= 3 AEs during treatment with first-line TKIs. CONCLUSION: The incidence of AEs or grade >= 3 AEs during second-line TKI therapy are not dependent on the profiles of AEs during first-line TKI therapy in patients with mRCC. Therefore, AEs that occur during first-line TKI therapy should not affect the selection of second-line targeted agents for patients with mRCC. PMID- 26382222 TI - Safety and Clinical Outcomes of Abiraterone Acetate After Docetaxel in Octogenarians With Metastatic Castration-Resistant Prostate Cancer: Results of the Italian Compassionate Use Named Patient Programme. AB - Metastatic castration-resistant prostate cancer mainly affects older men, opening issues about the efficacy and safety of therapies in this population. We have demonstrated that abiraterone, a selective androgen biosynthesis inhibitor, is a safe and active therapeutic option in a subgroup of 47 very elderly adults (aged > 80 years) enrolled in the Italian named patient program, with a tolerability profile and clinical outcomes comparable to those of younger population. BACKGROUND: Prostate cancer mainly affects elderly men, who are often frail and whose reduced physiological reserves and multiple comorbidities increase the risk of side effects. The availability of new drugs has improved the overall survival (OS) of patients with castration-resistant prostate cancer (CRPC) but has increased the number of very elderly CRPC patients receiving anticancer drugs, raising questions about their efficacy and safety in this population. PATIENTS AND METHODS: We assessed the tolerability of abiraterone (AA) in a cohort of very elderly adults with metastatic CRPC (mCRPC) enrolled in the Italian AA named patient program and analyzed their clinical outcomes. We retrospectively reviewed the clinical records of 47 mCRPC patients aged > 80 years who had received AA after docetaxel. The Kaplan-Meier method was used to calculate OS and progression free survival (PFS). Safety and clinical outcomes were also analyzed by age group (< 80 and > 80 years). Cox regression analysis was used to calculate the differences in PFS and OS between the groups according to the stratification variables. RESULTS: In very elderly men, the prostate-specific antigen response rate was 48.9%, and the median PFS and OS were 8 and 18 months, respectively. The differences in toxicities between the older and younger age groups were not major. The limitation of the present study was mainly its retrospective nature. CONCLUSION: Our data show that AA is active and safe in very elderly patients and leads to outcomes similar to those observed in younger patients, thus confirming that AA is a manageable therapeutic option for this patient population. PMID- 26382223 TI - Resource Use in the Last Year of Life Among Patients Who Died With Versus of Prostate Cancer. AB - We conducted a retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data of men with prostate cancer. Among 34,727 patients, those who died of their prostate cancer had more hospice and outpatient use, less inpatient and intensive care unit use, and lower overall costs. Efforts to shift care toward the outpatient setting might provide more efficient and judicious care for patients during the end of life. BACKGROUND: Prostate cancer poses a significant financial burden in the United States. However, most men with prostate cancer will die from noncancer causes. Concerns about increased resource utilization at the end of life have not been appropriately examined in this context. MATERIALS AND METHODS: We conducted a retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data of men who were diagnosed with and died of, as opposed to with, prostate cancer between 2000 and 2007. Within these 2 populations, we compared changes in the use of medical interventions, hospice, and overall health care costs to Medicare in the last year of life. RESULTS: Among 34,727 patients, those who died of prostate cancer had lower costs ($43,572 vs. $45,830; P < .001), largely because of lower mean inpatient costs ($20,769 vs. $29,851) and fewer hospitalizations (1.8 vs. 2.1), inpatient days (12.2 vs. 15.7), intensive care unit (ICU) days (1.4 vs. 3.4), and skilled nursing facility days (11.7 vs. 14.7; P < .001 for all). Outpatient and hospice costs were significantly greater among patients who died of prostate cancer, as was use of chemotherapy and androgen deprivation therapy. Patients who died of prostate cancer had approximately 12% lower costs than patients who died from other causes in adjusted analyses (fold-change, 0.88; 95% confidence interval [CI], 0.85-0.92). The single strongest predictor of increased costs at the end of life was receipt of multiple invasive procedures (fold increase in costs, 2.39; 95% CI, 2.22-2.58). CONCLUSION: Patients who died of prostate cancer rather than from other causes had more hospice and outpatient use, less inpatient and ICU use, and lower overall costs. Efforts to shift care toward outpatient settings might provide more efficient and judicious care for patients during the end of life. PMID- 26382224 TI - Delayed diagnosis of ankylosing spondylitis in a Japanese population. AB - OBJECTIVES: This study was conducted to evaluate the period from symptom onset to diagnosis of ankylosing spondylitis (AS) in Japanese patients and to examine possible reasons for delayed diagnosis. METHODS: Seventy-two consecutive patients with AS were studied. Diagnostic delay was defined as the gap between the first spondyloarthropathic symptom and diagnosis of AS according to the modified New York criteria. RESULTS: The mean patient ages at disease onset and diagnosis were 25.6 +/- 11.3 and 33.3 +/- 13.2 years old, respectively, resulting in diagnostic delay of 6.7 years. The number of medical institutions to which patients were referred before diagnosis was 2.4, and orthopedic surgeons were most commonly visited (62%). Non-specific low back pain or lumbar spondylitis (33%) and degenerative arthritis (28%) were the primary diagnoses preceding that of AS. Absence of articular symptoms significantly correlated with diagnostic delay. The patients with disease onset on year 2000 or later had significantly shorter periods until diagnosis than those before 2000 (3.6 vs. 7.5 years). CONCLUSIONS: The present study showed a marked diagnostic delay among Japanese patients with AS. Although it has been improved, continuing medical education focusing on inflammatory back pain in adolescent is required for early diagnosis of AS. PMID- 26382225 TI - Deciphering and Imaging Pathogenesis and Cording of Mycobacterium abscessus in Zebrafish Embryos. AB - Zebrafish (Danio rerio) embryos are increasingly used as an infection model to study the function of the vertebrate innate immune system in host-pathogen interactions. The ease of obtaining large numbers of embryos, their accessibility due to external development, their optical transparency as well as the availability of a wide panoply of genetic/immunological tools and transgenic reporter line collections, contribute to the versatility of this model. In this respect, the present manuscript describes the use of zebrafish as an in vivo model system to investigate the chronology of Mycobacterium abscessus infection. This human pathogen can exist either as smooth (S) or rough (R) variants, depending on cell wall composition, and their respective virulence can be imaged and compared in zebrafish embryos and larvae. Micro-injection of either S or R fluorescent variants directly in the blood circulation via the caudal vein, leads to chronic or acute/lethal infections, respectively. This biological system allows high resolution visualization and analysis of the role of mycobacterial cording in promoting abscess formation. In addition, the use of fluorescent bacteria along with transgenic zebrafish lines harbouring fluorescent macrophages produces a unique opportunity for multi-color imaging of the host-pathogen interactions. This article describes detailed protocols for the preparation of homogenous M. abscessus inoculum and for intravenous injection of zebrafish embryos for subsequent fluorescence imaging of the interaction with macrophages. These techniques open the avenue to future investigations involving mutants defective in cord formation and are dedicated to understand how this impacts on M. abscessus pathogenicity in a whole vertebrate. PMID- 26382226 TI - Comparative analysis of the Cancer Council of Victoria and the online Commonwealth Scientific and Industrial Research Organisation FFQ. AB - FFQ are commonly used to examine the association between diet and disease. They are the most practical method for usual dietary data collection as they are relatively inexpensive and easy to administer. In Australia, the Cancer Council of Victoria FFQ (CCVFFQ) version 2 and the online Commonwealth Scientific and Industrial Research Organisation FFQ (CSIROFFQ) are used. The aim of our study was to establish the level of agreement between nutrient intakes captured using the online CSIROFFQ and the paper-based CCVFFQ. The CCVFFQ and the online CSIROFFQ were completed by 136 healthy participants. FFQ responses were analysed to give g per d intake of a range of nutrients. Agreement between twenty-six nutrient intakes common to both FFQ was measured by a variety of methods. Nutrient intake levels that were significantly correlated between the two FFQ were carbohydrates, total fat, Na and MUFA. When assessing ranking of nutrients into quintiles, on average, 56 % of the participants (for all nutrients) were classified into the same or adjacent quintiles in both FFQ, with the highest percentage agreement for sugar. On average, 21 % of participants were grossly misclassified by three or four quintiles, with the highest percentage misclassification for fibre and Fe. Quintile agreement was similar to that reported by other studies, and we concluded that both FFQ are suitable tools for dividing participants' nutrient intake levels into high- and low-consumption groups. Use of either FFQ was not appropriate for obtaining accurate estimates of absolute nutrient intakes. PMID- 26382227 TI - NEUROBIOLOGICAL PREDICTORS OF RESPONSE TO DORSOLATERAL PREFRONTAL CORTEX REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION IN DEPRESSION: A SYSTEMATIC REVIEW. AB - BACKGROUND: A significant proportion of patients with depression fail to respond to psychotherapy and standard pharmacotherapy, leading to treatment-resistant depression (TRD). Due to the significant prevalence of TRD, alternative therapies for depression have emerged as viable treatments in the armamentarium for this disorder. Repetitive transcranial magnetic stimulation (rTMS) is now being offered in clinical practice in broader numbers. Many studies have investigated various different neurobiological predictors of response of rTMS. However, a synthesis of this literature and an understanding of what biological targets predict response is lacking. This review aims to systematically synthesize the literature on the neurobiological predictors of rTMS in patients with depression. METHODS: Medline (1996-2014), Embase (1980-2014), and PsycINFO (1806-2014) were searched under set terms. Two authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. RESULTS: The search identified 1,673 articles, 41 of which met both inclusion and exclusion criteria. Various biological factors at baseline appear to predict response to rTMS, including levels of certain molecular factors, blood flow in brain regions implicated in depression, electrophysiological findings, and specific genetic polymorphisms. CONCLUSIONS: Significant methodological variability in rTMS treatment protocols limits the ability to generalize conclusions. However, response to treatment may be predicted by baseline frontal lobe blood flow, and presence of polymorphisms of the 5-hydroxytryptamine (5-HT) -1a gene, the LL genotype of the serotonin transporter linked polymorphic region (5-HTTLPR) gene, and Val/Val homozygotes of the brain-derived neurotrophic factor (BDNF) gene. PMID- 26382228 TI - Assessment of quality of antenatal care services in Nigeria: evidence from a population-based survey. AB - BACKGROUND: The aim of the newly introduced "focused Antenatal Care (ANC)" is not only to achieve a minimum number of 4 visits, but also the timeliness of the commencement of the visits as well as the quality and relevance of services offered during the visits. This study is therefore designed to assess the quality of ANC services in Nigeria. METHODS: We used information supplied by the 13410 respondents who claimed to have used the ANC facilities at least once within five year preceding the 2013 Nigeria Demographic and Household Survey (NDHS). Ten components of ANC including: offer of HIV test, Tetanus Toxoid injection, receiving iron supplementation, intermittent preventive treatment (IPT), intestinal preventive drug (IPD), timely ANC enrollment and number of visits were assessed. Receipts of all the ten components were classified as desirable (good) quality of ANC services while receipt of eight critical components among the ten were assumed to be the minimum acceptable quality. Data was weighted and analyzed using descriptive statistics and logistic regression models at 5 % significance level. RESULTS: Measurement of blood pressure and receiving iron supplementation were the most commonly offered ANC component in Nigeria with 91.0 % each while IPD and IPT were given to only 20.7 % and 37.6 % respectively. Less than two thirds were taught on PMTCT while 41.7 % had HIV test and obtained results. Only 4.6 % (95 % CI: 4.2-5.1) of women received good quality of ANC while nearly 1.0 % did not receive any of the components. About 11.3 % (95 % CI: 10.6-11.9 %) of the attendees had minimum acceptable quality of ANC. Receipt of good quality ANC services was higher among users who initiated ANC early, had at least 4 ANC visits, attended to by skilled health workers, attended government and private hospitals and clinics. Higher odds of receiving good quality of ANC were found among users who lives in urban areas, having higher educational attainment, belonging to households in upper wealth quintiles and attended to by skilled ANC provider. CONCLUSIONS: The levels of desirable and minimum acceptable quality of ANC services were poor in Nigeria thereby jeopardizing efforts to achieve the MDGs. There is need for intensified commitment by national and state governments in Nigeria as well as other stakeholders to ensure that main components of ANC are received by the users. PMID- 26382229 TI - Reversible Regional Myocardial Ischemia in a Six-Month-Old Infant Post Arterial Switch Operation Demonstrated by Speckle Tracking Echocardiography. PMID- 26382230 TI - A study of autorotating plant seeds. AB - A leading edge vortex exists on the upper surface of an autorotating plant seed. The vortex enhances the vertical aerodynamic force acting on the seed and decreases the rate of descent. We analyzed the flight data of rotary seeds and revealed that the lift-drag ratio affects the descent factor more strongly than the vertical force coefficient. This has also been confirmed by falling tests of model rotors, which have various aspect ratios, airfoil shapes and total masses. PMID- 26382231 TI - Maximal dinucleotide and trinucleotide circular codes. AB - We determine here the number and the list of maximal dinucleotide and trinucleotide circular codes. We prove that there is no maximal dinucleotide circular code having strictly less than 6 elements (maximum size of dinucleotide circular codes). On the other hand, a computer calculus shows that there are maximal trinucleotide circular codes with less than 20 elements (maximum size of trinucleotide circular codes). More precisely, there are maximal trinucleotide circular codes with 14, 15, 16, 17, 18 and 19 elements and no maximal trinucleotide circular code having less than 14 elements. We give the same information for the maximal self-complementary dinucleotide and trinucleotide circular codes. The amino acid distribution of maximal trinucleotide circular codes is also determined. PMID- 26382232 TI - Ubiquitous bacteria Borrelia crocidurae in Western African ticks Ornithodoros sonrai. AB - BACKGROUND: In West Africa, tick-borne relapsing fever is a neglected arthropod borne infection caused by Borrelia crocidurae transmitted by the argasid tick Ornithodoros sonrai. From an epidemiological point of view, it is of interest to know whether some genotypes of the vector are specialized in carrying certain genotypes of the pathogen. FINDINGS: Thirty-five O. sonrai ticks collected in Mali, Senegal, Mauritania and Morocco confirmed to be B. crocidurae-infected, were genotyped by 16S rRNA gene sequencing. B. crocidurae was genotyped by Multispacer Sequence Typing. The 35 O. sonrai ticks grouped into 12 genotypes with strong geographical structuration. MST resolved the 35 B. crocidurae isolates into 29 genotypes with pairwise divergence of 0.09 - 1.56 % without strict geographical structuration as genotype ST22 was found in Mali, Senegal and Mauritania. There was no evidence of tick-borrelia specialization as one O. sonrai genotype carried several B. crocidurae genotypes and one B. crocidurae genotype was found in different O. sonrai genotypes. CONCLUSIONS: This report illustrates a non-specialized circulation of B. crocidurae borreliae within O. sonrai ticks in West Africa. PMID- 26382233 TI - Whole genome analysis of Vietnamese G2P[4] rotavirus strains possessing the NSP2 gene sharing an ancestral sequence with Chinese sheep and goat rotavirus strains. AB - Because imminent introduction into Vietnam of a vaccine against Rotavirus A is anticipated, baseline information on the whole genome of representative strains is needed to understand changes in circulating strains that may occur after vaccine introduction. In this study, the whole genomes of two G2P[4] strains detected in Nha Trang, Vietnam in 2008 were sequenced, this being the last period during which virtually no rotavirus vaccine was used in this country. The two strains were found to be >99.9% identical in sequence and had a typical DS-1 like G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation. Analysis of the Vietnamese strains with >184 G2P[4] strains retrieved from GenBank/EMBL/DDBJ DNA databases placed the Vietnamese strains in one of the lineages commonly found among contemporary strains, with the exception of the NSP2 and NSP4 genes. The NSP2 genes were found to belong to a previously undescribed lineage that diverged from Chinese sheep and goat rotavirus strains, including a Chinese rotavirus vaccine strain LLR with 95% nucleotide identity; the time of their most recent common ancestor was 1975. The NSP4 genes were found to belong, together with Thai and USA strains, to an emergent lineage (VIII), adding further diversity to ever diversifying NSP4 lineages. Thus, there is a need to enhance surveillance of locally-circulating strains from both children and animals at the whole genome level to address the effect of rotavirus vaccines on changing strain distribution. PMID- 26382235 TI - Minimally invasive treatment of patients with Pott's puffy tumour with or without endocranial extension - a case series of six patients: Our Experience. PMID- 26382234 TI - The differential impact of oral poliovirus vaccine formulation choices on serotype-specific population immunity to poliovirus transmission. AB - BACKGROUND: Prior analyses demonstrated the need for some countries and the Global Polio Eradication Initiative (GPEI) to conduct additional supplemental immunization activities (SIAs) with trivalent oral poliovirus vaccine (tOPV) prior to globally-coordinated cessation of all serotype 2-containing OPV (OPV2 cessation) to prevent the creation of serotype 2 circulating vaccine-derived poliovirus (cVDPV2) outbreaks after OPV2 cessation. The GPEI continues to focus on achieving and ensuring interruption of wild poliovirus serotype 1 (WPV1) and making vaccine choices that prioritize bivalent OPV (bOPV) for SIAs, nominally to increase population immunity to serotype 1, despite an aggressive timeline for OPV2 cessation. METHODS: We use an existing dynamic poliovirus transmission model of northwest Nigeria and an integrated global model for long-term poliovirus risk management to explore the impact of tOPV vs. bOPV vaccine choices on population immunity and cVDPV2 risks. RESULTS: Using tOPV instead of bOPV for SIAs leads to a minimal decrease in population immunity to transmission of serotypes 1 and 3 polioviruses, but a significantly higher population immunity to transmission of serotype 2 polioviruses. Failure to use tOPV in enough SIAs results in cVDPV2 emergence after OPV2 cessation in both the northwest Nigeria model and the global model. Despite perceptions to the contrary, prioritizing the use of bOPV over tOPV prior to OPV2 cessation does not significantly improve serotype 1 population immunity to transmission. CONCLUSIONS: Immunization leaders need to focus on all three poliovirus serotypes to appropriately manage the risks of OPV cessation in the polio endgame. Focusing on population immunity to transmission to interrupt WPV1 transmission and manage pre-OPV cessation risks of cVDPVs, all countries performing poliovirus SIAs should use tOPV up until the time of OPV2 cessation, after which time they should continue to use the OPV vaccine formulation with all remaining serotypes until coordinated global cessation of those serotypes. PMID- 26382236 TI - Tobacco Smoke and Chloracne: An Old Story Comes to Light. PMID- 26382237 TI - Alternative to LRRK2-IN-1 for Pharmacological Studies of Parkinson's Disease. AB - BACKGROUND/AIMS: LRRK2 (leucine-rich repeat protein kinase 2) is one of the most commonly accepted genes associated with Parkinson's disease (PD). The overexpression of disease-associated mutations in LRRK2 is toxic to the cells, while reduction or elimination of LRRK2 expression promotes cell health and growth. Thus, the identification of an LRRK2 inhibitor with good physiochemical and pharmacokinetic properties is of great interest for the treatment of PD. METHODS: In this study, we have investigated LRRK2 compounds, LRRK2-IN-1 and Compound 1, in vitro and in vivo to determine how suitable they are as a selective LRRK2 tool compound. RESULTS: We report that Compound 1, patented by GSK, is a potent and selective LRRK2 inhibitor with good blood-brain barrier permeability as reflected by its high brain to plasma ratio in rats. In addition, Compound 1 can significantly promote neurite outgrowth in a primary cortical culture, indicating an optimistic cellular function of this compound in a biological system. In contrast, LRRK2-IN-1 is a less selective LRRK2 inhibitor and has low brain penetration. Furthermore, LRRK2-IN-1 is cyto- and genotoxic, while Compound 1 does not exhibit any toxicity. CONCLUSIONS: These results suggest that Compound 1 may be a superior tool compound than LRRK2-IN-1 to advance future pharmacological research on LRRK2. PMID- 26382238 TI - Long Term Hippocampal and Cortical Changes Induced by Maternal Deprivation and Neonatal Leptin Treatment in Male and Female Rats. AB - Maternal deprivation (MD) during neonatal life has diverse long-term behavioral effects and alters the development of the hippocampus and frontal cortex, with several of these effects being sexually dimorphic. MD animals show a marked reduction in their circulating leptin levels, not only during the MD period, but also several days later (PND 13). A neonatal leptin surge occurs in rodents (beginning around PND 5 and peaking between PND 9 and 10) that has an important neurotrophic role. We hypothesized that the deficient neonatal leptin signaling of MD rats could be involved in the altered development of their hippocampus and frontal cortex. Accordingly, a neonatal leptin treatment in MD rats would at least in part counteract their neurobehavioural alterations. MD was carried out in Wistar rats for 24 h on PND 9. Male and female MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg/day sc) or vehicle. In adulthood, the animals were submitted to the open field, novel object memory test and the elevated plus maze test of anxiety. Neuronal and glial population markers, components of the glutamatergic and cannabinoid systems and diverse synaptic plasticity markers were evaluated by PCR and/or western blotting. Main results include: 1) In some of the parameters analyzed, neonatal leptin treatment reversed the effects of MD (eg., mRNA expression of hippocampal IGF1 and protein expression of GFAP and vimentin) partially confirming our hypothesis; 2) The neonatal leptin treatment, per se, exerted a number of behavioral (increased anxiety) and neural effects (eg., expression of the following proteins: NG2, NeuN, PSD95, NCAM, synaptophysin). Most of these effects were sex dependent. An adequate neonatal leptin level (avoiding excess and deficiency) appears to be necessary for its correct neuro-programing effect. PMID- 26382239 TI - Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial. AB - BACKGROUND: Major protease mutations are rarely observed following failure with protease inhibitors (PI), and other viral determinants of failure to PI are poorly understood. We therefore characterized Gag-Protease phenotypic susceptibility in subtype A and D viruses circulating in East Africa following viral rebound on PIs. METHODS: Samples from baseline and treatment failure in patients enrolled in the second line LPV/r trial SARA underwent phenotypic susceptibility testing. Data were expressed as fold-change in susceptibility relative to a LPV-susceptible reference strain. RESULTS: We cloned 48 Gag Protease containing sequences from seven individuals and performed drug resistance phenotyping from pre-PI and treatment failure timepoints in seven patients. For the six patients where major protease inhibitor resistance mutations did not emerge, mean fold-change EC50 to LPV was 4.07 fold (95% CI, 2.08-6.07) at the pre-PI timepoint. Following viral failure the mean fold-change in EC50 to LPV was 4.25 fold (95% CI, 1.39-7.11, p = 0.91). All viruses remained susceptible to DRV. In our assay system, the major PI resistance mutation I84V, which emerged in one individual, conferred a 10.5-fold reduction in LPV susceptibility. One of the six patients exhibited a significant reduction in susceptibility between pre-PI and failure timepoints (from 4.7 fold to 9.6 fold) in the absence of known major mutations in protease, but associated with changes in Gag: V7I, G49D, R69Q, A120D, Q127K, N375S and I462S. Phylogenetic analysis provided evidence of the emergence of genetically distinct viruses at the time of treatment failure, indicating ongoing viral evolution in Gag-protease under PI pressure. CONCLUSIONS: Here we observe in one patient the development of significantly reduced susceptibility conferred by changes in Gag which may have contributed to treatment failure on a protease inhibitor containing regimen. Further phenotype-genotype studies are required to elucidate genetic determinants of protease inhibitor failure in those who fail without traditional resistance mutations whilst PI use is being scaled up globally. PMID- 26382240 TI - Angiotensin Converting Enzyme Inhibitor Dialyzability and Outcomes in Older Patients Receiving Hemodialysis. AB - BACKGROUND/AIMS: Some angiotensin converting enzyme (ACE) inhibitors are efficiently removed from circulation by hemodialysis ('high dialyzability'), whereas others are not ('low dialyzability'). In patients receiving hemodialysis, this may influence the effectiveness of ACE inhibitors. METHODS: Using linked healthcare databases we identified older patients receiving chronic hemodialysis who filled new ACE inhibitor prescriptions. The low dialyzability group (n = 3,369) included fosinopril and ramipril. The high dialyzability group (n = 5,974) included enalapril, lisinopril, and perindopril. The primary outcome was all cause mortality within 180 days of first ACE inhibitor prescription. RESULTS: There were 361 deaths among 5,974 patients (6.0%) prescribed with low dialyzability ACE inhibitors and 179 deaths among 3,369 patients (5.3%) prescribed with high dialyzability ACE inhibitors (relative risk 1.1, 95% CI 0.9 1.3, p = 0.6). CONCLUSION: In this study of older patients receiving hemodialysis, the dialyzability of ACE inhibitors was not associated with mortality or cardiovascular outcomes. PMID- 26382242 TI - Will Public Health England lead research? PMID- 26382241 TI - Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. AB - BACKGROUND: In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. METHODS: We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. FINDINGS: Between 1990 and 2013, life expectancy from birth in England increased by 5.4 years (95% uncertainty interval 5.0-5.8) from 75.9 years (75.9-76.0) to 81.3 years (80.9-81.7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41.1% (38.3-43.6), whereas DALYs were reduced by 23.8% (20.9-27.1), and YLDs by 1.4% (0.1-2.8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8.2 years for men and decreased from 7.2 years in 1990 to 6.9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39.6% (37.7-41.7) of DALYs; leading behavioural risk factors were suboptimal diet (10.8% [9.1-12.7]) and tobacco (10.7% [9.4-12.0]). INTERPRETATION: Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. FUNDING: Bill & Melinda Gates Foundation and Public Health England. PMID- 26382243 TI - Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients: A Randomized Crossover Pilot Trial. AB - BACKGROUND: The optimal pacing rate during cardiac resynchronization therapy (CRT) is unknown. Therefore, we investigated the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL). METHODS: Twelve CRT patients with non ischemic heart failure (NYHA class II-III) were enrolled in a randomized, double blind, crossover trial, in which the basal pacing rate was set at DDD-60 and DDD 80 for 3 months (DDD-R for 2 patients). At baseline, 3 months and 6 months, we assessed sympathetic nerve activity by microneurography (MSNA), peak oxygen consumption (pVO2), N-terminal pro-brain natriuretic peptide (p-NT-proBNP), echocardiography and QoL. RESULTS: DDD-80 pacing for 3 months increased the mean heart rate from 77.3 to 86.1 (p = 0.001) and reduced sympathetic activity compared to DDD-60 (51+/-14 bursts/100 cardiac cycles vs. 64+/-14 bursts/100 cardiac cycles, p<0.05). The mean pVO2 increased non-significantly from 15.6+/-6 mL/min/kg during DDD-60 to 16.7+/-6 mL/min/kg during DDD-80, and p-NT-proBNP remained unchanged. The QoL score indicated that DDD-60 was better tolerated. CONCLUSION: In CRT patients with non-ischemic heart failure, 3 months of DDD-80 pacing decreased sympathetic outflow (burst incidence only) compared to DDD-60 pacing. However, Qol scores were better during the lower pacing rate. Further and larger scale investigations are indicated. TRIAL REGISTRATION: ClinicalTrials.gov NCT02258061. PMID- 26382244 TI - Utility of Real-Time Shear Wave Elastography in the Assessment of Testicular Torsion. AB - Real-time shear-wave elastography (SWE) is a newly developed method which can obtain the stiffness of tissues and organs based on tracking of shear wave propagation through a structure. Several studies have demonstrated its potential in the differentiation between diseased and normal tissue in clinical practices, however the applicability to testicular disease has not been well elucidated. We investigated the feasibility and reproducibility of SWE in the detection of testicular torsion. This prospective study comprised 15 patients with complete testicular torsion. Results obtained from SWE along with conventional gray-scale and color Doppler sonography and post-operative pathology were compared. The results revealed that (i) the size of injured testis was increased and the twisted testis parenchyma was heterogeneous. The blood flow signals in injured testis were barely visible or absent; (ii) The Young's modulus, including Emean, Emax, Emin and SD values in the border area of torsional testis were higher than those of normal testis (Emean, 78.07+/-9.01 kPa vs 22.0+/-5.10 kPa; Emax, 94.07+/ 6.53 kPa vs 27.87+/-5.78 kPa; Emin, 60.73+/-7.84 kPa vs 18.90+/-4.39 kPa; SD, 7.67+/-0.60 kPa vs 2.30+/-0.36 kPa, [P<0.05]); The Emax and SD values in the central area of the torsional testis were higher than the corresponding area of the normal testis (Emax, 8.23+/-0.30 kPa vs 3.97+/-0.95 kPa; SD, 1.5+/-0.26 kPa vs 0.67+/-0.35 kPa,[P<0.05]) and Emin values was lower than those of normal testicles (0.93+/-0.51 kPa vs 1.6+/-0.36 kPa; [P<0.05]); (iii) The Young's modulus measurement between two physicians showed good agreement. The pathological findings were accordance with SWE measurement. SWE is a non invasive, convenient and high reproducible method and may serve as an important alternative tool in the diagnosis and monitoring the progression of the acute scrotums, in additional to conventional Doppler sonography. PMID- 26382245 TI - Combined Non-Target Effects of Insecticide and High Temperature on the Parasitoid Bracon nigricans. AB - We studied the acute toxicity and the sublethal effects, on reproduction and host killing activity, of four widely used insecticides on the generalist parasitoid Bracon nigricans (Hymenoptera: Braconidae), a natural enemy of the invasive tomato pest, Tuta absoluta (Lepidoptera: Gelechiidae). Laboratory bioassays were conducted applying maximum insecticide label rates at three constant temperatures, 25, 35 and 40 degrees C, considered as regular, high and very high, respectively. Data on female survival and offspring production were used to calculate population growth indexes as a measure of population recovery after pesticide exposure. Spinetoram caused 80% mortality at 25 degrees C and 100% at higher temperatures, while spinosad caused 100% mortality under all temperature regimes. Cyantraniliprole was slightly toxic to B. nigricans adults in terms of acute toxicity at the three temperatures, while it did not cause any sublethal effects in egg-laying and host-killing activities. The interaction between the two tested factors (insecticide and temperature) significantly influenced the number of eggs laid by the parasitoid, which was the lowest in the case of females exposed to chlorantraniliprole at 35 degrees C. Furthermore, significantly lower B. nigricans demographic growth indexes were estimated for all the insecticides under all temperature conditions, with the exception of chlorantraniliprole at 25 degrees C. Our findings highlight an interaction between high temperatures and insecticide exposure, which suggests a need for including natural stressors, such as temperature, in pesticide risk assessments procedures. PMID- 26382247 TI - HLA-E regulates NKG2C+ natural killer cell function through presentation of a restricted peptide repertoire. AB - NK cells interact with the HLA-E molecule via the inhibitory receptor NKG2A and the activating receptor NKG2C. Hence, HLA-E can have a dual role in the immune response. In the present study, we aim to investigate the functional consequences of HLA-E for NKG2A and NKG2C expressing NK cell subsets by using a panel of HLA-E binding peptides derived from CMV, Hsp60 and HLA class I. PBMC derived from healthy subjects were used as targets for isolated NK cells and NK cell activation was examined by analysis of the expression of the degranulation marker CD107a. Peptide induced HLA-E expression inhibited degranulation of NKG2A+ NK cell subsets with almost all peptides, whereas NKG2A- NKG2C+ NK cell responses were enhanced only after incubation with four peptides; 1.3-fold with CMV(I), A80 and B13 and 3.2-fold with HLA-G derived peptide. In addition, the HLA-E:G peptide complex triggered NKG2C receptor internalization, as evidenced by reduction in the percentage of NKG2C+ NK cells when incubated with the peptide, which could be restored by addition of Bafilomycin. IN CONCLUSION: in contrast to NKG2A, NKG2C is regulated by HLA-E only when HLA-E is in complex with a restricted peptide repertoire, especially in combination with the HLA-G leader peptide. PMID- 26382246 TI - Donor-specific antibody to trans-encoded donor HLA-DQ heterodimer. AB - The majority of de novo donor specific HLA antibodies (DSAs) in transplant patients are directed to HLA-DQ antigens, which consist of a heterodimer of alpha and beta chains. Although a heterodimer can theoretically be cis- or trans encoded, the sensitizing forms generally appear to be forms. DSA to DQ trans heterodimer has never been reported. We reviewed 360 post-kidney transplant recipients (transplant: 2002-2013; follow-up: 5.6+/-3.3years). DQ DSA was detected in 46 of 57 patients who developed DSA. DSA specificity was consistent with donor mismatched DQ trans-heterodimers in three patients: DQ2.5 (DQB1*02, DQA1*05), DQ2.3 (DQB1*02, DQA1*03), and DQ4.3 (DQB1*04, DQA1*03). Two of them eventually lost grafts (2 and 5years later) with allograft nephropathy. In conclusion, post-transplant patients may develop DSA to donor DQ trans heterodimers. Further studies are warranted to determine the clinical significance of such DSAs. PMID- 26382248 TI - The decoy Fcgamma receptor encoded by the cytomegalovirus UL119-UL118 gene has differential affinity to IgG proteins expressing different GM allotypes. AB - Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been implicated in many diseases. However, there is significant divergence between HCMV seroprevalence and the prevalence of HCMV-associated diseases, implying the presence of host genetic factors that might modulate immunity to this virus. HCMV deploys many sophisticated strategies to evade host immunosurveillance. One strategy involves encoding for proteins that have functional properties of the Fcgamma receptor (FcgammaR). The aim of the present investigation was to determine whether the UL119-UL118-encoded recombinant FcgammaR ectodomain binds differentially to genetically disparate IgG1 proteins. Results show that mean absorbance values for binding of HCMV UL119-UL118-encoded Fcgamma receptor to the immunoglobulin GM (gamma marker) 1,17-expressing IgG1 were significantly higher than to the IgG1 expressing the allelic GM 3 allotype (0.225 vs. 0.151; p=0.039). These findings suggest possible mechanisms underlying the maintenance of immunoglobulin GM gene polymorphism and its putative role in the etiology of HCMV associated diseases. PMID- 26382249 TI - T-cell receptor repertoire of human peripheral CD161hiTRAV1-2+ MAIT cells revealed by next generation sequencing and single cell analysis. AB - Mucosal-associated invariant T (MAIT) cells are a T-cell subset that expresses a conserved TRAV1-2 (Valpha7.2) T-cell receptor (TCR) chain and the surface marker CD161. They are involved in the defence against microbes as they recognise small organic molecules of microbial origin that are presented by the non-classical MHC molecule 1 (MR1). MAIT cells express a semi-restricted TCR alpha chain with TRAV1 2 preferentially linked to TRAJ33, TRAJ12, or TRAJ20 which pairs with a limited set of beta chains. To investigate the TCR repertoire of human CD161(hi)TRAV1 2(+) T cells in depth we analysed the alpha and beta chains of this T-cell subset by next generation sequencing. Concomitantly we analysed 132 paired alpha and beta chains from single cells to assess the alphabeta pairing preferences. We found that the CD161(hi)TRAV1-2(+) TCR repertoire in addition to the typical MAIT TCRs further contains polyclonal elements reminiscent of classical alphabeta T cells. PMID- 26382250 TI - Caudal Mandibular Bone Height and Buccal Cortical Bone Thickness Measured by Computed Tomography in Healthy Dogs. AB - OBJECTIVE: To characterize bone height and buccal cortical bone thickness of the caudal mandible of healthy dogs. STUDY DESIGN: Prospective original study. SAMPLE POPULATION: Client-owned dogs (n = 36). METHODS: Dogs were distributed by weight into 3 groups (<10, 10-20, >20 kg). Thirteen transverse plane computed tomography images were selected for each dog based on anatomic landmarks from the 4th premolar (PM4) through the 2nd molar. On each image, bone thickness was measured along the buccal surface of both mandibles from the alveolar margin to the ventral border in 3 mm increments. The number of 3 mm increments were recorded as an estimation of mandibular height. RESULTS: Buccal bone was generally thicker ventrally in the area studied with decreasing bone thickness over both roots of PM4 and the mesial root of the 1st molar (M1). Cortical bone thickness of <2.0 mm was measured across all groups at most locations 3 mm ventral from the alveolar margin. Mandibular bone height demonstrated significantly fewer (P < .05) 3 mm increments over the distal root of M1 in dogs >10 kg compared with the number of observations at the immediately mesial and distal locations. CONCLUSION: Thin cortical bone overlying the mesial and distal roots of PM4 and the mesial root of M1 limits use of these areas for application of monocortical anchorage devices. Decreased mandibular bone height at mandibular M1 may create a stress riser at this location, which along with thin cortical bone may explain why this is a common area for mandibular fracture. PMID- 26382251 TI - Detection of Tuberculosis Infection Hotspots Using Activity Spaces Based Spatial Approach in an Urban Tokyo, from 2003 to 2011. AB - BACKGROUND: Identifying ongoing tuberculosis infection sites is crucial for breaking chains of transmission in tuberculosis-prevalent urban areas. Previous studies have pointed out that detection of local accumulation of tuberculosis patients based on their residential addresses may be limited by a lack of matching between residences and tuberculosis infection sites. This study aimed to identify possible tuberculosis hotspots using TB genotype clustering statuses and a concept of "activity space", a place where patients spend most of their waking hours. We further compared the spatial distribution by different residential statuses and describe urban environmental features of the detected hotspots. METHODS: Culture-positive tuberculosis patients notified to Shinjuku city from 2003 to 2011 were enrolled in this case-based cross-sectional study, and their demographic and clinical information, TB genotype clustering statuses, and activity space were collected. Spatial statistics (Global Moran's I and Getis-Ord Gi* statistics) identified significant hotspots in 152 census tracts, and urban environmental features and tuberculosis patients' characteristics in these hotspots were assessed. RESULTS: Of the enrolled 643 culture-positive tuberculosis patients, 416 (64.2%) were general inhabitants, 42 (6.5%) were foreign-born people, and 184 were homeless people (28.6%). The percentage of overall genotype clustering was 43.7%. Genotype-clustered general inhabitants and homeless people formed significant hotspots around a major railway station, whereas the non-clustered general inhabitants formed no hotspots. This suggested the detected hotspots of activity spaces may reflect ongoing tuberculosis transmission sites and were characterized by smaller residential floor size and a higher proportion of non-working households. CONCLUSIONS: Activity space-based spatial analysis suggested possible TB transmission sites around the major railway station and it can assist in further comprehension of TB transmission dynamics in an urban setting in Japan. PMID- 26382252 TI - Understanding the impact of a clinical care pathway for major head and neck cancer resection on postdischarge healthcare utilization. AB - BACKGROUND: The purposes of this study were to explore the association of a postoperative clinical care pathway for patients undergoing major head and neck surgery with microvascular reconstruction on postdischarge health care utilization and cost and to compares a nonpathway group (n = 60) to a prospective, pathway-managed group (n = 54). Our primary purpose was to understand whether pathway-managed patients used postdischarge health care resources differently than patients managed without a care pathway. METHODS: Health care utilization data (counts and costs) were collected for the 3 months after discharge. Differences in utilization were compared using Poisson regression. The null hypothesis was that there were no differences in utilization between the pathway and nonpathway groups. RESULTS: Pathway patients had fewer postdischarge encounters in 2 of 4 sectors. Readmission costs were significantly less in the pathway group only. CONCLUSION: A postoperative inpatient clinical care pathway in patients with head and neck cancer is associated with decreased health care utilization and inpatient costs in the 3 months after discharge. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1216-E1220, 2016. PMID- 26382253 TI - "I Owe Her So Much; Without Her I Would Be Dead": Developing a Model of Mother Infant Bonding Following a Maternal Antenatal HIV Diagnosis. AB - Women can face a period of psychological vulnerability following antenatal HIV diagnosis, affecting feelings about both the pregnancy and motherhood. Our study explored the impact of being diagnosed with HIV during pregnancy on mother-infant bonding. Grounded Theory was used to assess perceived challenges and facilitating factors for mother-infant bonding for 10 mothers given an HIV diagnosis during pregnancy. Data analysis led to a model of mother-infant bonding composed of four theoretical codes: (a) facing barriers to bonding, (b) feeling disconnected from the baby, (c) developing a special bond, and (d) strengthening and moving on. Challenges with bonding emerged primarily during early stages after diagnosis and birth, with maternal resilience and positivity about the future developing as the infant HIV testing process progressed. Study recommendations include more timely information regarding vertical transmission and more targeted psychological support along with greater promotion of services to support women diagnosed with HIV antenatally. PMID- 26382254 TI - Acceleration of the Rate-Limiting Step of Thioredoxin Folding by Replacement of its Conserved cis-Proline with (4 S)-Fluoroproline. AB - The incorporation of the non-natural amino acids (4R)- and (4S)-fluoroproline (Flp) has been successfully used to improve protein stability, but little is known about their effect on protein folding kinetics. Here we analyzed the influence of (4R)- and (4S)-Flp on the rate-limiting trans-to-cis isomerization of the Ile75-Pro76 peptide bond in the folding of Escherichia coli thioredoxin (Trx). While (4R)-Flp at position 76 had essentially no effect on the isomerization rate in the context of the intact tertiary structure, (4S)-Flp accelerated the folding reaction ninefold. Similarly, tenfold faster trans-to-cis isomerization of Ile75-(4S)-Flp76 relative to Ile75-Pro76 was observed in the unfolded state of Trx. Our results show that the replacement of cis prolines by non-natural proline analogues can be used for modulating the folding rates of proteins with cis prolyl-peptide bonds in the native state. PMID- 26382255 TI - Seminars in Pediatric Surgery. The Management of Conjoined Twins: The Great Ormond Street Experience. Preface. PMID- 26382256 TI - Prenatal diagnosis and obstetric management. AB - Conjoined twins are rare, representing 1 in 50,000 to 1 in 200,000 live births, and the prognosis is generally poor. Accurate prenatal diagnosis by an experienced multidisciplinary team using a combination of imaging modalities allows parents to make fully informed choices. This may include termination of pregnancy, which is easier and safer at the earlier gestations at which diagnosis is now being made; continuing with the pregnancy but accepting that only palliative care is appropriate after birth; or planned intensive care and separation of the twins after birth. Delivery will invariably be by cesarean section in order to minimize the risk of peripartum harm to both mother and babies. PMID- 26382257 TI - Classification and clinical evaluation. AB - Conjoined twins represent a great challenge for most pediatric specialists including pediatric surgeons, anesthetists, neonatologists, urologists, neurosurgeons, and orthopedic surgeons. This anomaly can be classified according to the type of twins' fusion. Various organs can be fused making the separation difficult. Conjoined twins are usually diagnosed antenatally by ultrasound. Detailed fetal echocardiography is necessary to counsel the parents during pregnancy. Postnatally, the majority of the conjoined twins can be thoroughly investigated using various imaging techniques. This allows careful planning of the operation. However, in approximately one-third of the patients an urgent operation is required at birth without a complete assessment of the joining. This is associated with a poorer outcome. PMID- 26382258 TI - Conjoined twins: Radiological experience. AB - Imaging plays a key role in the management of conjoined twins. Pre-operative multi-modality studies are vital to assess operability and to aid surgical planning. Technical advances in imaging such as high-resolution isovolumetric magnetic resonance imaging (MRI) techniques and three-dimensional modeling now result in extremely accurate anatomical information. Varied information from a comprehensive radiological work-up enables the surgeons to plan the safest possible operative procedure, helps the anesthetic team before and during surgery, and guides the intensive care team in the post-operative phase. This article will review the radiological techniques used in our institution, highlighting potential pitfalls with the various imaging modalities. PMID- 26382259 TI - The management of conjoined twins: Cardiology assessment. AB - Structural cardiac defects occur in at least 1 twin in about 75% of conjoined twins with thoracic level fusion. Outcomes after surgical separation of thoracic level conjoined twins have been favorable when the hearts have been separate. However, even in this situation, the outlook is poor for an individual twin with an important cardiac defect. Arterial anastomosis between twin circulations is an important additional consideration, with poor outcomes for perfusion recipient twins. Surgical separation is contraindicated when ventricular level cardiac fusion exists. Cardiac assessment is a key component of prenatal counseling. PMID- 26382260 TI - Planning the operation. AB - The management of conjoined twins falls into three distinct groups-non-operative, emergency separation and elective separation. Planning meetings involving all the personnel who will be required during the operation are held. The radiological findings are presented and the anaesthetic, nursing and intensive care requirements are highlighted. PMID- 26382261 TI - The anaesthetic management of conjoined twins. AB - The management of anaesthesia for conjoined twins poses unique anatomical, physiological and logistic challenges. Although many possible configurations of union exist and each is unique, we describe the principles of anaesthesia for conjoined twins drawing on our institutional experience of managing 26 sets for a variety of procedures including separation. PMID- 26382262 TI - Theatre setup. AB - The theatre staff would have been made aware of the special requirements for the operation at the planning meetings. Two sets of scrubs nurses will be required but only one set will be needed for the actual separation. The second set of scrub nurses will be needed only when both twins have survived the separation and the second twin is moved to another operating room for closure of the wound. PMID- 26382263 TI - The separation procedure. AB - The various stages of the separation are carefully planned but despite this, variations which will change the schedule of the procedure may exist. In general the operation commences on the opposite side from the main procedure and then the twins are turned for the remainder of the operation. Each type of conjoined twin is different but basically thoracopagus involves the hearts, omphalopagus involves the liver and small intestine and ischiopagus involves the large intestine and genito-urinary system. Our results are presented together with interesting cases from which lessons have been learned. PMID- 26382264 TI - Urological management. AB - The pediatric urologists role is confined to ischio-, para-, and pygopagus conjoined twins. The aim is to preserve renal function, to address problems with urinary continence, and to optimize genital issues with particular reference to sexual and reproductive function. Full urological imaging is essential prior to separation for planning and for the operation itself. PMID- 26382265 TI - Staged separation of craniopagus twins. AB - Craniopagus twins are rare and account for up to 6% of all conjoined twins. No hospital will encounter many such twins and the opportunity to develop expertise is limited. We have dealt with 2 such sets and illustrate our approach by reference to our most recent set. We believe that detailed imaging allows precise delineation of the anatomy and facilitates detailed planning of the surgery. When venous drainage from the 2 brains is connected, we believe that staged separation is preferable as gradual alteration of hemodynamics may be safer than a single stage procedure. PMID- 26382266 TI - Orthopedic aspects of separation. AB - In the management of conjoined twins the orthopedic surgeon may be involved directly, as part of the surgical team at operation or indirectly, in dealing with associated anomalies or the sequelae of surgery. The overwhelming indication for orthopedic involvement is ischiopagus, either tripus or tetrapus. The main role of the orthopedic surgeon is to facilitate midline closure through the use of pelvic osteotomies, which allow the symphysis pubis to be approximated. PMID- 26382267 TI - Cardiothoracic surgery. AB - Conjoined twins often have complex cardiac anomalies associated with other congenital defects. The correct cardiac diagnosis delineates the degree of cardiac fusion and the feasibility of separation. The outcome in twins with fused hearts remains poor. PMID- 26382268 TI - Peri-operative intensive care. AB - All good intensive care requires attention to detail of the routine elements of care. These include staffing and monitoring, drug prescription and administration, feeding and fluid balance, analgesia and sedation, organ support and reducing the risk of healthcare-associated infection. Doing this well requires an understanding of the relevant physiology and an awareness of the limited evidence base. Detailed protocols and implementation checklist are valuable in ensuring that these minimum standards are met. However, peri operative care is not all predictable and amenable to protocolization. This is especially true following separation of conjoined twins. Despite the sophisticated imaging and multi-disciplinary planning that precede elective separation, the acute physiological changes in each twin cannot always be predicted reliably. In this article, we review briefly each element of peri operative care and how this might vary in conjoined twins. PMID- 26382269 TI - A parents perspective. PMID- 26382270 TI - Ethics in the management of conjoined twins. AB - In dealing with conjoined twins, we have adopted a pragmatic approach in balancing what is possible, parental wishes and the likely outcome for the children. We believe that separation where feasible should be undertaken but appreciate that a few parents may wish their children to remain joined. The advice that we give balances the very real risks of surgery against the type of life the twins will experience if they remain joined. In some types of union such as end to end ischiopagus, the twins will never stand and will be bedridden. With other types of union, independent walking is not possible. Such limitations on living seem intolerable to us, but we have left the final decision to parents. PMID- 26382271 TI - Regulation of the Flt3 Gene in Haematopoietic Stem and Early Progenitor Cells. AB - The MYB transcription factor plays critical roles in normal and malignant haematopoiesis. We previously showed that MYB was a direct activator of FLT3 expression within the context of acute myeloid leukaemia. During normal haematopoiesis, increasing levels of FLT3 expression determine a strict hierarchy within the haematopoietic stem and early progenitor compartment, which associates with lymphoid and myeloid commitment potential. We use the conditional deletion of the Myb gene to investigate the influence of MYB in Flt3 transcriptional regulation within the haematopoietic stem cell (HSC) hierarchy. In accordance with previous report, in vivo deletion of Myb resulted in rapid biased differentiation of HSC with concomitant loss of proliferation capacity. We find that loss of MYB activity also coincided with decreased FLT3 expression. At the chromatin level, the Flt3 promoter is primed in immature HSC, but occupancy of further intronic elements determines expression. Binding to these locations, MYB and C/EBPalpha need functional cooperation to activate transcription of the locus. This cooperation is cell context dependent and indicates that MYB and C/EBPalpha activities are inter-dependent in controlling Flt3 expression to influence lineage commitment of multipotential progenitors. PMID- 26382272 TI - Magnetic Nanocomposite Scaffold-Induced Stimulation of Migration and Odontogenesis of Human Dental Pulp Cells through Integrin Signaling Pathways. AB - Magnetism is an intriguing physical cue that can alter the behaviors of a broad range of cells. Nanocomposite scaffolds that exhibit magnetic properties are thus considered useful 3D matrix for culture of cells and their fate control in repair and regeneration processes. Here we produced magnetic nanocomposite scaffolds made of magnetite nanoparticles (MNPs) and polycaprolactone (PCL), and the effects of the scaffolds on the adhesion, growth, migration and odontogenic differentiation of human dental pulp cells (HDPCs) were investigated. Furthermore, the associated signaling pathways were examined in order to elucidate the molecular mechanisms in the cellular events. The magnetic scaffolds incorporated with MNPs at varying concentrations (up to 10%wt) supported cellular adhesion and multiplication over 2 weeks, showing good viability. The cellular constructs in the nanocomposite scaffolds played significant roles in the stimulation of adhesion, migration and odontogenesis of HDPCs. Cells were shown to adhere to substantially higher number when affected by the magnetic scaffolds. Cell migration tested by in vitro wound closure model was significantly enhanced by the magnetic scaffolds. Furthermore, odontogenic differentiation of HDPCs, as assessed by the alkaline phosphatase activity, mRNA expressions of odontogenic markers (DMP-1, DSPP,osteocalcin, and ostepontin), and alizarin red staining, was significantly stimulated by the magnetic scaffolds. Signal transduction was analyzed by RT-PCR, Western blotting, and confocal microscopy. The magnetic scaffolds upregulated the integrin subunits (alpha1, alpha2, beta1 and beta3) and activated downstream pathways, such as FAK, paxillin, p38, ERK MAPK, and NF kappaB. The current study reports for the first time the significant impact of magnetic scaffolds in stimulating HDPC behaviors, including cell migration and odontogenesis, implying the potential usefulness of the magnetic scaffolds for dentin-pulp tissue engineering. PMID- 26382273 TI - A case of MYH9 disorders caused by a novel mutation (p.K74E). PMID- 26382274 TI - D-CAG (decitabine followed by cytarabine, aclarubicin, and G-CSF) for relapsed acute myeloid leukemia after hematopoietic cell transplantation. PMID- 26382275 TI - CD34+ highly enriched allogeneic stem cell transplantation in a patient with mixed phenotype acute leukemia and Fusarium solani sepsis. PMID- 26382276 TI - Lymphomatoid granulomatosis mimicking vasculitis. PMID- 26382277 TI - Screening for viral hepatitis prior to rituximab chemotherapy. AB - In 2008, the CDC published guidelines recommending screening of all persons undergoing treatment with rituximab to identify persons at risk of hepatitis B virus (HBV) reactivation. We evaluated implementation of this recommendation in veterans, who are at increased risk of HBV, and determined characteristics of those screened. We also evaluated a control setting, rates of hepatitis C virus (HCV) screening among the same rituximab-treated patients. There are no guidelines that recommend HCV screening prior to initiation of rituximab. Medical records of patients receiving rituximab between January 2006 and December 2012 were reviewed according to two time periods: 2006-2008 (period 1, pre-guidelines) and 2009-2012 (period 2, post-guidelines). Patient demographics, concomitant chemotherapy regimen (protocol, dose, duration), treatment indication, risk factors for hepatitis infection (substance abuse, homelessness, human immunodeficiency virus (HIV)), and HBV/HCV screening status were documented. During the study period, 102 patients were treated with rituximab (49 in period 1 and 53 in period 2). During periods 1 and 2, 22 and 32 % of rituximab-treated patients were screened for HBV, respectively (p = 0.375). Treatment during 2009 was the only significant predictor of HBV screening in the adjusted model (p = 0.01). For HCV during periods 1 and 2, 22 and 21 % of patients were screened, respectively (p = 1.00). There were no significant predictors of HCV screening. Rates of screening for HBV among rituximab-treated patients were low, both before and after dissemination of guidelines recommending universal HBV screening of rituximab-treated patients. PMID- 26382279 TI - The effect of peginterferon alpha-2a vs. interferon alpha-2a on intrahepatic covalently closed circular DNA in HBeAg-positive chronic hepatitis B patients. AB - BACKGROUND AND OBJECTIVE: The covalently closed circular DNA (cccDNA), as the template of HBV transcription, plays a key role in the virus infection. The present study aimed to compare the effect of pegylated interferon (IFN)-alpha-2a with that of conventional IFN-alpha-2a on intrahepatic covalently closed circular (ccc)DNA in patients with chronic hepatitis B. METHODS: Seventy-six HBeAg positive chronic hepatitis B patients were randomly divided into two groups (n=38): group A was treated with interferon alpha-2a (IFN-alpha-2a) and group B was treated with peginterferon alpha-2a (peg IFN-alpha-2a). The intrahepatic level of cccDNA and its detection rate, levels of hepatitis B virus (HBV) DNA in liver and serum, histologic inflammation and some biochemistry parameters (alanine aminotransferase, aspartate aminotransferase and total bilirubin levels) were measured. RESULTS: The outcome of 48 weeks therapy showed that the mean level of intrahepatic HBV cccDNA level and its detection rate, the levels of HBV DNA and the histology and biochemistry parameters were significantly decreased following therapy in two groups (P<0.05). While, the reductions in the group treated with peg IFN-alpha-2a were greater (P<0.05). CONCLUSIONS: It may be concluded that the ability of the peg IFN-alpha-2a to clear and suppress cccDNA and HBV DNA was superior compared with that of conventional IFN-alpha-2a. Furthermore, the effects of peg IFN-alpha-2a on histology and biochemistry parameters were also more obvious than conventional IFN-alpha-2a. PMID- 26382278 TI - DNA-hydrolysing activity of IgG antibodies from the sera of patients with schizophrenia. AB - It is believed that damage to the membranes of brain cells of schizophrenia (SCZ) patients induces the formation of autoantigens and autoantibodies. Nevertheless, the importance of immunological changes leading to the loss of tolerance to self antigens in the genesis of SCZ has not been established. The MALDI mass spectra of the IgG light chains of 20 healthy donors were relatively homogeneous and characterized by one peak with only one maximum. In contrast to the healthy donors, the MALDI mass spectra of IgG light chains corresponding to 20 SCZ patients demonstrated, similarly to 20 autoimmune systemic lupus erythematosus (SLE) patients, two maxima of a comparable intensity. In addition, the MALDI spectra of the IgG light chains of five SLE and four SCZ patients contained a small additional brightly pronounced peak with remarkably lower molecular mass compared with the main one. DNase autoantibodies (abzymes) can be found in the blood of patients with several autoimmune diseases, while the blood of healthy donors or patients with diseases without a significant disturbance of the immune status does not contain DNase abzymes. Here, we present the first analysis of anti-DNA antibodies and DNase abzymes in the sera of SCZ patients. Several strict criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of SCZ patients. The sera of approximately 30% of SCZ patients displayed a higher content of antibodies (compared with 37% of SLE) interacting with single- and double-stranded DNA compared with healthy donors. Antibodies with DNase activity were revealed in 80% of the patients. These data indicate that some SCZ patients may show signs of typical autoimmune processes to a certain extent. PMID- 26382280 TI - Menetrier's disease: Long-term remission with lanreotide. AB - Menetrier's disease is a rare hypertrophic gastropathy, causing protein leak. An overexpression of transforming growth factor alpha is involved. In inhibiting the epidermal growth factor receptor, cetuximab and somatostatin analogues are the two most promising treatments, allowing to avoid radical gastrectomy. We report the case of a patient with a sustained clinical remission after treatment with lanreotide, but without complete endoscopic healing. We discuss the available therapeutic options and present a literature review of somatostatin analogues for the treatment of Menetrier's disease. PMID- 26382281 TI - Clinical outcomes and risk factors of hepatocellular carcinoma treated by liver transplantation: A multi-centre comparison of living donor and deceased donor transplantation. AB - BACKGROUND: The different outcomes of deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) are currently being debated. We aimed to retrospectively compare the outcomes following LDLT and DDLT and to analyse the factors influencing this. METHODS: We compared the overall survival (OS) and disease-free survival (DFS) rates of HCC patients after LDLT (n=389) and DDLT (n=6471) from 81 centres over a 10-year period. OS and DFS rates were calculated with the Kaplan-Meier method. And univariate and multivariate Cox proportional hazards regressions were performed on the entire cohort to identify predictors. RESULTS: Of 6860 patients, the 1-, 3 , and 5-year OS rates were 86.79%, 70.16%, and 66.31% after LDLT, respectively, and 74.2%, 54.21%, and 46.97% after DDLT, respectively (P<0.001). The 1-, 3-, and 5-year DFS rates were 78.46%, 63.68%, and 61.63% after LDLT, respectively, and 65.65%, 48.61%, and 41.87% after DDLT, respectively (P<0.001). The multivariate Cox regression model determined that the DFS and OS of HCC patients post-liver transplantation (LT) were strongly associated with tumour morphology and biology, but not graft type. CONCLUSIONS: With regards to OS and DFS, there were no disadvantages to LDLT as compared with DDLT; tumour morphology and biology may affect the prognosis of LT. PMID- 26382282 TI - ShRNA-mediated silencing of the Ndc80 gene suppress cell proliferation and affected hepatitis B virus-related hepatocellular carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies in the world, and hepatitis B virus (HBV) has been well established to cause HCC. Ndc80 complex is a conserved mitotic regulator dedicated to ensuring faithful chromosome segregation and plays an important role in inducing tumor formation. However, its role in HCC caused by HBV infection remains unclear. METHODS: Immunohistochemistry (IHC), Western blot (WB), and real-time qRT-PCR were used to measure the expression of Ndc80 in HBV-related HCC tissues. Ndc80-specific short hairpin RNA (shRNA) was used to knock-down Ndc80 expression in the hepatoma cell line HeG2 and HepG2.2.15, which is stable transcribed with HBV genome. Furthermore, the effect of Ndc80 on cellular proliferation and growth were examined, respectively. RESULTS: The expression level of Ndc80 was remarkably up-regulated in HBV-related HCC tissues. Down-regulation of Ndc80 expression suppressed HBV replication. With cell counting and the MTS assay, cellular proliferation and growth of Ndc80 knocking-down cell line was shown to be effectively restrained. CONCLUSION: This study suggests that Ndc80 may play an important role in the process of HBV-related HCC, and that it may be a potential biological treatment target in the future. PMID- 26382283 TI - Definitive seton management for transsphincteric fistula-in-ano: harm or charm? AB - AIM: The treatment of transsphincteric anal fistula requires a balance between eradication of the disease and preservation of faecal control. A cutting seton is an old tool that is now out of vogue for many surgeons. We hypothesized that the concept remains reliable and safe with results that exceed those reported for many of the more recently described methods. METHOD: A retrospective review was conducted of real-time electronic health records (single institution, single surgeon) of patients presenting during the 14 years between 2001 and 2014 with a transsphincteric anal fistula who were treated with a cutting seton. Excluded were patients with Crohn's disease, fistulae related to malignancy or a previous anastomosis and patients whose fistula was treated by another method including a loose draining seton. Data collection included demographics, duration of the disease, duration of the treatment, outcome and continence. RESULTS: In all, 121 patients (80 men) of mean age 40.2 +/- 12.2 years (range 18-76) with a mean follow-up of 5.1 +/- 3.3 (1-24) months were included in the analysis. The median duration of symptoms was 6 (1-84) months; 36% had failed other fistula surgery, 12% had a complex fistula with more than one track and 35% had some form of comorbidity. The median time to healing was 3 (1-18) months; 7.4% required further surgery, but eventually 98% had complete fistula healing. The incontinence rate decreased postoperatively to 11.6% from 19% before treatment with 17/121 with pre-existing incontinence resolved and 8/107 new cases developing. CONCLUSION: Despite its retrospective non-comparative design, the study has demonstrated that a cutting seton is a safe, well tolerated and highly successful treatment for transsphincteric anal fistula and is followed overall by improved continence. The results compare very favourably with other techniques. PMID- 26382284 TI - Cloacal malformation patients report similar quality of life as female patients with less complex anorectal malformations. AB - PURPOSE: Cloacal malformations are the most complex type of anorectal malformation in females. This study aimed to report quality of life (QoL) of patients with a cloacal malformation for the first time in literature. MATERIALS AND METHODS: Female patients with an anorectal malformation participating in a follow-up program for congenital malformation survivors aged 5 or older were eligible for this study. QoL was assessed with the PedsQLTM 4.0 inventory. Scores of patients with a cloacal malformation (CM) were compared with those of female patients with rectoperineal or rectovestibular fistulas (RP/RV) and with reference data. RESULTS: A total of 59 patients (67% response rate; 13 patients with cloacal malformation) were included, QoL was assessed by patient self-report at median age of 12years (8-13), and by parent proxy-report at median age of 8years (5-12). There were no differences between groups regarding the presence of associated anomalies, with also no differences regarding anomalies in the urinary tract (CM vs. RP/RV=31% vs. 15%, p=0.237). Scores of the cloacal malformations group were similar to those of the comparison group, except the proxy-reported scores on school functioning (60.0 vs. 80.0, p=0.003). Proxy-reported scores of cloacal malformation patients were significantly lower than reference values on total QoL-score, psychosocial health, and emotional and school performance. Patients (irrespective of type of ARM) who suffered from fecal soiling reported significantly lower scores with regard to psychosocial health (71.7 vs. 81.7, p=0.034) and its subscale school performance (65.0 vs. 80.0, p<0.001). QoL-scores reported by cloacal malformation patients did not differ significantly from the reference values of the healthy population. Parents of cloacal malformation patients reported significantly lower total QoL, emotional and school performances, as well as a lower general psychosocial health for their children relative to reference data of healthy children. CONCLUSION: Patients with cloacal malformations and females with less complex anorectal malformations report similar QoL. Parents of cloacal malformation patients report more problems on several psychosocial domains relative to the healthy reference group. To monitor these matters, long-term follow-up protocols should contain multidisciplinary treatment including periodical assessment of psychosocial well-being. PMID- 26382285 TI - Long-term functional outcomes of PPPD in children--Nutritional status, pancreatic function, GI function and QOL. AB - PURPOSE: The purpose of this study was to analyze the long-term outcomes, such as nutritional status, pancreatic function, gastrointestinal (GI) function, and quality of life (QOL), in children who underwent pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: Between 1992 and 2013, there were 15 children who underwent PPPD at Seoul National University Children's Hospital, and 10 of them participated in this study. A retrospective review of the patients' medical records and follow-up was done. Their nutritional statuses were estimated by height, body weight, weight for age Z-score, body mass index (BMI), and serum protein, albumin levels. The endocrine and exocrine functions of the pancreas were estimated by diabetes mellitus (DM), steatorrhea, and Bristol stool chart. The GI function and QOL were evaluated via questionnaires. The follow-up period ranged from 3 to 18years. RESULTS: There were no severe growth disturbances, 6 patients experienced mild steatorrhea and 3 showed above the category 6 in Bristol stool chart. All the patients experienced mild GI symptoms. As for the QOL, there were no significant negative answers, except for one patient with DM. CONCLUSIONS: Almost all the study subjects, who underwent PPPD in their childhood, did not present significant problems except for one patient with DM. PMID- 26382286 TI - Different techniques for biliary diversion in progressive familial intrahepatic cholestasis. AB - BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a cholestatic liver disease of childhood. Pruritus resulting from increased bile salts in serum might not respond to medical treatment, and internal or external biliary drainage methods have been described. In this study, we aimed to evaluate different internal drainage techniques in patients with PFIC. PATIENTS AND METHODS: Between 2009 and 2014, seven children (4 male, 3 female, 3months-5years old), (median 2years of age) with PFIC were evaluated. The patients were reviewed according to age, gender, complaints, surgical technique, laboratory findings and outcome. In each two patients, cholecystoileocolonic anastomosis, cholecystojejunocolonic anastomosis and cholecystocolostomy were performed. Cholecysto-appendico-colonic anastomosis was the technique used in one patient. RESULTS: Jaundice and excessive pruritus were the main complaints. One of the patients with cholecystoileocolonic anastomosis died of comorbid pathologies (cirrhosis, adhesive obstruction and severe sepsis). Temporary rectal bleeding was observed in all the patients postoperatively. Regardless of the surgical technique, pruritus was dramatically decreased in all the patients in the postoperative period. CONCLUSION: Regardless of the technique, internal biliary diversion methods are beneficial for the relief of pruritus in PFIC patients. Selection of the surgical method might vary depending on the surgeon's preference and the surgical anatomy of the gastrointestinal system of the patient. PMID- 26382287 TI - 'Less may be best'-Pediatric parapneumonic effusion and empyema management: Lessons from a UK center. AB - BACKGROUND: Children with empyema are managed at our center using a protocol driven clinical care pathway. Chemical fibrinolysis is deployed as first-line management for significant pleural disease. We therefore examined clinical outcome(s) to benchmark standards of care while analyzing disease severity with introduction of the pneumococcal conjugate vaccine. METHODS: Medical case-records of children managed at a UK pediatric center were surveyed from Jan 2006 to Dec 2012. Binary logistic regression was utilized to study failure of fibrinolytic therapy. The effects of age, comorbidity, number of days of intravenous antibiotics prior to drainage and whether initial imaging showed evidence of necrotizing disease were also studied. RESULTS: A total of 239 children were treated [age range 4months-19years; median 4years]. A decreasing number of patients presenting year-on-year since 2006 with complicated pleural infections was observed. The majority of children were successfully managed without surgery using antibiotics alone (27%) or a fine-bore chest-drain and urokinase (71%). Only 2% of cases required primary thoracotomy. 14.7% cases failed fibrinolysis and required a second intervention. The only factor predictive of failure and need for surgery was suspicion of necrotizing disease on initial imaging (P=0.002, OR 8.69). CONCLUSION: Pediatric patients with pleural empyema have good outcomes when clinical care is led by a multidisciplinary team and protocol driven care pathway. Using a 'less is best' approach few children require surgery. PMID- 26382289 TI - Disulfonimide-Catalyzed Asymmetric Reduction of N-Alkyl Imines. AB - A chiral disulfonimide (DSI)-catalyzed asymmetric reduction of N-alkyl imines with Hantzsch esters as a hydrogen source in the presence of Boc2 O has been developed. The reaction delivers Boc-protected N-alkyl amines with excellent yields and enantioselectivity. The method tolerates a large variety of alkyl amines, thus illustrating potential for a general reductive cross-coupling of ketones with diverse amines, and it was applied in the synthesis of the pharmaceuticals (S)-Rivastigmine, NPS R-568 Hydrochloride, and (R)-Fendiline. PMID- 26382288 TI - Antiretroviral therapy and changing patterns of HIV stigmatisation in Entebbe, Uganda. AB - Antiretroviral therapy (ART) has the potential to change processes of HIV stigmatisation. In this article, changing processes of stigmatisation among a group of people living with HIV (PLWH) on ART in Wakiso District, Uganda, are analysed using qualitative data from a study of PLWH's self-management of HIV on ART. There were 38 respondents (20 women, 18 men) who had been taking ART for at least 1 year. They were purposefully selected from government and non-government ART providers. Two in-depth interviews were held with each participant. Processes of reduced self-stigmatisation were clearly evident, caused by the recovery of their physical appearance and support from health workers. However most participants continued to conceal their status because they anticipated stigma; for example, they feared gossip, rejection and their status being used against them. Anticipated stigma was gendered: women expressed greater fear of enacted forms of stigma such as rejection by their partner; in contrast men's fears focused on gossip, loss of dignity and self-stigmatisation. The evidence indicates that ART has not reduced underlying structural drivers of stigmatisation, notably gender identities and inequalities, and that interventions are still required to mitigate and tackle stigmatisation, such as counselling, peer-led education and support groups that can help PLWH reconstruct alternative and more positive identities. A video abstract of this article can be found at: https://youtu.be/WtIaZJQ3Y_8. PMID- 26382290 TI - Growth and survival of blowfly Lucilia sericata larvae under simulated wound conditions: implications for maggot debridement therapy. AB - Maggot debridement therapy has become a well-established method of wound debridement. Despite its success, little information is available about the optimum duration of the treatment cycle and larval growth in wounds. This study examines the development of Lucilia sericata (Diptera: Calliphoridae) larvae under two containment conditions (bagged and free range) under simulated wound conditions and assesses the impact of transport and further storage of larvae on their survival and growth. There was no significant difference in size between bagged and free-range larvae over the 72-h experimental period. Larvae grew fastest 8-24 h after inoculation and completed their growth at 40-48 h. Mortality rates were similar (0.12-0.23% per hour) in both containment conditions and did not differ significantly (P = 0.3212). Survival of free-range larvae was on average 16% lower than survival of bagged larvae. Refrigeration of larvae upon simulated delivery for > 1 day reduced their survival to < 50% and caused a reduction in growth of up to 30% at 12 h, but not at 48 h, of incubation. Therefore, it is recommended that free-range larvae are left in the wound for a maximum of 40-48 h, and bagged larvae for 48-72 h. Larvae should be used within 24 h of delivery to avoid high mortality caused by prolonged refrigeration. PMID- 26382291 TI - Disruptions in a cluster of computationally identified enhancers near FOXC1 and GMDS may influence brain development. AB - Regulatory elements are more evolutionarily conserved and provide a larger mutational target than coding regions of the human genome, suggesting that mutations in non-coding regions contribute significantly to development and disease. Using a computational approach to predict gene regulatory enhancers, we found that many known and predicted embryonic enhancers cluster in genomic loci harboring development-associated genes. One of the densest clusters of predicted enhancers in the human genome is near the genes GMDS and FOXC1. GMDS encodes a short-chain mannose dehydrogenase enzyme involved in the regulation of hindbrain neural migration, and FOXC1 encodes a developmental transcription factor required for brain, heart, and eye development. We experimentally validate four novel enhancers in this locus and demonstrate that these enhancers show consistent activity during embryonic development in domains that overlap with the expression of FOXC1 and GMDS. These four enhancers contain binding motifs for several transcription factors, including the ZIC family of transcription factors. Removal of the ZIC binding sites significantly alters enhancer activity in three of these enhancers, reducing expression in the eye, hindbrain, and limb, suggesting a mechanism whereby ZIC family members may transcriptionally regulate FOXC1 and/or GMDS expression. Our findings uncover novel enhancer regions that may control transcription in a topological domain important for embryonic development. PMID- 26382292 TI - Regadenoson-induced coronary vasospasm resulting in severe reversible perfusion defects and transient ischemic dilation on SPECT stress myocardial perfusion imaging. PMID- 26382293 TI - The feminine mystique of AUC. PMID- 26382294 TI - Meeting the Challenges of Immunizing Adults. AB - The overall burden of illness from diseases for which vaccines are available disproportionately falls on adults. Adults are recommended to receive vaccinations based on their age, underlying medical conditions, lifestyle, prior vaccinations, and other considerations. Updated vaccine recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Vaccine use among U.S. adults is low. Although receipt of a provider (physician or other vaccinating healthcare provider) recommendation is a key predictor of vaccination, more often consumers report not receiving vaccine recommendations at healthcare provider visits. Although providers support the benefits of vaccination, they also report several barriers to vaccinating adults, including the cost of providing vaccination services, inadequate or inconsistent payment for vaccines and vaccine administration, and acute medical care taking precedence over preventive services. Despite these challenges, a number of strategies have been demonstrated to substantially improve adult vaccine coverage, including patient and provider reminders and standing orders for vaccination. Providers are encouraged to incorporate routine assessment of their adult patients' vaccination needs during all clinical encounters to ensure patients receive recommendations for needed vaccines and are either offered needed vaccines or referred for vaccination. PMID- 26382295 TI - Anti-inflammatory effects of miR-21 in the macrophage response to peritonitis. AB - We investigated the role of microRNA-21 in the macrophage response to peritonitis; microRNA-21 expression increases in peritoneal macrophages after lipopolysaccharide stimulation but is delayed until 48 hours after cecal ligation and puncture. MicroRNA-21-null mice and bone marrow-derived cell lines were exposed to cecal ligation and puncture or lipopolysaccharide, and survival, microRNA-21 levels, target messenger RNAs and proteins, and cytokines were assayed. Macrophages were also transfected with microRNA-21 mimics and antagomirs, and similar endpoints were measured. Survival in microRNA-21-null mice was significantly decreased after lipopolysaccharide-induced peritonitis but unchanged after cecal ligation and puncture compared with similarly treated wild type mice. MicroRNA-21 expression, tumor necrosis factor-alpha, interleukin 6, and programmed cell death protein 4 levels were increased after lipopolysaccharide addition in peritoneal cells. Pelino1 and sprouty (SPRY) messenger RNAs were similarly increased early, whereas programmed cell death protein 4 messenger RNA was decreased after lipopolysaccharide, and all microR-21 target messenger RNAs were subsequently decreased by 24 hours after lipopolysaccharide. Transfection with mimics and antagomirs led to appropriate responses in microRNA-21 and tumor necrosis factor-alpha. Knockdown of microRNA 21 in bone marrow-derived cells showed increased tumor necrosis factor-alpha and decreased interleukin 10 in response to lipopolysaccharide. Target proteins were unaffected by knockdown as was extracellular signal-regulated kinase; however, the nuclear factor kappaB p65 subunit was increased after lipopolysaccharide in the microRNA-21 knockout cells. In contrast, there was little change in these parameters after cecal ligation and puncture induction between null and wild-type mice. MicroRNA-21 is beneficial to survival in mice following lipopolysaccharide peritonitis. Overexpression of microRNA-21 decreased tumor necrosis factor-alpha secretion, whereas suppression of microRNA-21 expression increased tumor necrosis factor-alpha and interleukin 6, and decreased interleukin 10 levels after lipopolysaccharide. Protein targets of microRNA-21 were not different following suppression of microRNA-21. Nuclear factor kappaB was increased by suppression of microRNA-21. These findings demonstrate microRNA-21 is beneficial in modulating the macrophage response to lipopolysaccharide peritonitis and an improved understanding of the anti-inflammatory effects of microRNA-21 may result in novel, targeted therapy against peritonitis and sepsis. PMID- 26382296 TI - Endogenously produced TNF-alpha contributes to the expression of CXCL10/IP-10 in IFN-lambda3-activated plasmacytoid dendritic cells. AB - The interplay between IFN-lambdas and dendritic cells is becoming increasingly relevant, particularly in light of their key role in inducing the antiviral state, including in hepatitis C virus infection. In this work, we have analyzed extensively how human plasmacytoid dendritic cells respond to IFN-lambda3. We report that plasmacytoid dendritic cells incubated with IFN-lambda3 prolong their survival; alter their expression pattern of surface HLA-DRalpha, CD123, CD86, and CD303; and time dependently produce IFN-alpha, CXCL10/IFN-gamma-induced protein 10, and even modest quantities of TNF-alpha. Nevertheless, endogenously produced TNF-alpha, but not IFN-alpha, was found to be essential for driving the expression of CXCL10/IFN-gamma-induced protein 10 in IFN-lambda3-treated plasmacytoid dendritic cells, as revealed by neutralizing experiments by use of adalimumab, etanercept, and infliximab. We also observed that based on the kinetics and levels of IFN-alpha and CXCL10/IFN-gamma-induced protein 10 produced by their IFN-lambda3-treated plasmacytoid dendritic cells, healthy donors could be categorized into 2 and 3 groups, respectively. In particular, we identified a group of donors whose plasmacytoid dendritic cells produced modest quantities of CXCL10/IFN-gamma-induced protein 10; another one whose plasmacytoid dendritic cells produced elevated CXCL10/IFN-gamma-induced protein 10 levels, already after 18 h, declining thereafter; and a 3rd group characterized by plasmacytoid dendritic cells releasing very high CXCL10/IFN-gamma-induced protein 10 levels after 42 h only. Finally, we report that in plasmacytoid dendritic cells, equivalent concentrations of IFN-lambda3 and IFN-lambda1 promote survival, antigen modulation, and cytokine production in a comparable manner and without acting additively/synergistically. Altogether, data not only extend the knowledge on the biologic effects that IFN-lambdas exert on plasmacytoid dendritic cells but also add novel light to the networking between IFN-lambdas and plasmacytoid dendritic cells in fighting viral diseases. PMID- 26382299 TI - Ultrasonic approach for surface nanostructuring. AB - The review is about solid surface modifications by cavitation induced in strong ultrasonic fields. The topic is worth to be discussed in a special issue of surface cleaning by cavitation induced processes since it is important question if we always find surface cleaning when surface modifications occur, or vice versa. While these aspects are extremely interesting it is important for applications to follow possible pathways during ultrasonic treatment of the surface: (i) solely cleaning; (ii) cleaning with following surface nanostructuring; and (iii) topic of this particular review, surface modification with controllably changing its characteristics for advanced applications. It is important to know what can happen and which parameters should be taking into account in the case of surface modification when actually the aim is solely cleaning or aim is surface nanostructuring. Nanostructuring should be taking into account since is often accidentally applied in cleaning. Surface hydrophilicity, stability to Red/Ox reactions, adhesion of surface layers to substrate, stiffness and melting temperature are important to predict the ultrasonic influence on a surface and discussed from these points for various materials and intermetallics, silicon, hybrid materials. Important solid surface characteristics which determine resistivity and kinetics of surface response to ultrasonic treatment are discussed. It is also discussed treatment in different solvents and presents in solution of metal ions. PMID- 26382297 TI - Analysis of IgM antibody production and repertoire in a mouse model of Sjogren's syndrome. AB - This study tested the hypothesis that B cells from salivary tissue are distinct in terms of proliferative capacity, immunoglobulin M secretion, repertoire, and autoantibody enrichment in Sjogren's syndrome. We sorted purified B cells from the spleen, cervical lymph nodes, and submandibular glands of a primary Sjogren's syndrome mouse model (Id3(-/-)). Enzyme-linked immunospot and proliferation assays were performed with stimulated B cells. We single-cell sorted B cells from the spleen, cervical lymph nodes, and submandibular gland tissue from Sjogren's syndrome mice and sequenced immunoglobulin M heavy-chain variable regions. Finally, autoantigen arrays were performed using immunoglobulin M derived from sera, cervical lymph nodes, spleens, and submandibular gland tissue of Id3(-/-) animals. Results suggest B cells from salivary tissue of Sjogren's syndrome mice are similar to those from secondary immune sites in terms of proliferative and secretory capacity. However, differences in repertoire usage, heavy chain complementarity-determining region 3 length, mutational frequency, and N region addition were observed among B cells derived from submandibular gland, cervical lymph node, and spleen tissue. Moreover, autoantigen array data show immunoglobulin M from salivary B cells have enriched specificity for Ro (Sjogren's syndrome A) and La (Sjogren's syndrome B). All together, these data suggest salivary B cells have unique repertoire characteristics that likely influence autoantigen binding and contribute to Sjogren's syndrome disease in a tissue-specific manner. PMID- 26382298 TI - Purinergic signaling during macrophage differentiation results in M2 alternative activated macrophages. AB - Macrophages represent a highly heterogenic cell population of the innate immune system, with important roles in the initiation and resolution of the inflammatory response. Purinergic signaling regulates both M1 and M2 macrophage function at different levels by controlling the secretion of cytokines, phagocytosis, and the production of reactive oxygen species. We found that extracellular nucleotides arrest macrophage differentiation from bone marrow precursors via adenosine and P2 receptors. This results in a mature macrophage with increased expression of M2, but not M1, genes. Similar to adenosine and ATP, macrophage growth arrested with LPS treatment resulted in an increase of the M2-related marker Ym1. Recombinant Ym1 was able to affect macrophage proliferation and could, potentially, be involved in the arrest of macrophage growth during hematopoiesis. PMID- 26382300 TI - Adding a lens Improves spinning speed characterization. AB - Highly stable sample rotation is important in many solid-state NMR experiments. Whether the necessary stability is achieved is not always clear. Typically only an average frequency over some time interval (often relatively long and unknown) is available from the spinning speed controller readout, which is not representative of the short-term variations of instantaneous rotation frequency. The necessity of the relatively slow measurement of spinning speed is a consequence of phase noise in the tachometer, which prevents speed measurement to be both rapid and precise at the same time. We show that adding a lens to the tachometer, without any other changes in the probe, reduces phase noise by nearly an order of magnitude and allows improved measurement of the spinning speed. PMID- 26382301 TI - Magnetic microbes: Bacterial magnetite biomineralization. AB - Magnetotactic bacteria are a diverse group of prokaryotes with the ability to orient and migrate along the magnetic field lines in search for a preferred oxygen concentration in chemically stratified water columns and sediments. These microorganisms produce magnetosomes, the intracellular nanometer-sized magnetic crystals surrounded by a phospholipid bilayer membrane, typically organized in chains. Magnetosomes have nearly perfect crystal structures with narrow size distribution and species-specific morphologies, leading to well-defined magnetic properties. As a result, the magnetite biomineralization in these organisms is of fundamental interest to diverse disciplines, from biotechnology to astrobiology. This article highlights recent advances in the understanding of the bacterial magnetite biomineralization. PMID- 26382302 TI - Mass-transport Control on the Discharge Mechanism in Li-O2 Batteries Using Carbon Cathodes with Varied Porosity. AB - By comparing carbon electrodes with varying porosity in Li-O2 cells, we show that the effect of electrolyte stirring at a given current density can result in a change from 2D to 3D growth of discharged deposits. The change of morphology is evident using electron microscopy and by analyzing electrode pore size distribution with respect to discharge capacity. As a consequence, carbon electrodes with different textural properties exhibit different capacity enhancements in stirred-electrolyte cells. We demonstrate that mass transport can directly control the discharge mechanism, similar to the electrolyte composition and current density, which have already been recognized as determining factors. PMID- 26382303 TI - Modeling a healthy and a person with heart failure conditions using the object oriented modeling environment Dymola. AB - Several mathematical models of different physiological systems are spread through literature. They serve as tools which improve the understanding of (patho-) physiological processes, may help to meet clinical decisions and can even enhance medical therapies. These models are typically implemented in a signal-flow oriented simulation environment and focus on the behavior of one specific subsystem. Neglecting other physiological subsystems and using a technical description of the physiology hinders the exchange with and acceptance of clinicians. By contrast, this paper presents a new model implemented in a physical, object-oriented modeling environment which includes the cardiovascular, respiratory and thermoregulatory system. Simulation results for a healthy subject at rest and at the onset of exercise are given, showing the validity of the model. Finally, simulation results showing the interaction of the cardiovascular system with a ventricular assist device in case of heart failure are presented showing the flexibility and mightiness of the model and the simulation environment. Thus, we present a new model including three important physiological systems and one medical device implemented in an innovative simulation environment. PMID- 26382304 TI - Structural basis for the inhibition of voltage-dependent K+ channel by gating modifier toxin. AB - Voltage-dependent K(+) (Kv) channels play crucial roles in nerve and muscle action potentials. Voltage-sensing domains (VSDs) of Kv channels sense changes in the transmembrane potential, regulating the K(+)-permeability across the membrane. Gating modifier toxins, which have been used for the functional analyses of Kv channels, inhibit Kv channels by binding to VSD. However, the structural basis for the inhibition remains elusive. Here, fluorescence and NMR analyses of the interaction between VSD derived from KvAP channel and its gating modifier toxin, VSTx1, indicate that VSTx1 recognizes VSD under depolarized condition. We identified the VSD-binding residues of VSTx1 and their proximal residues of VSD by the cross-saturation (CS) and amino acid selective CS experiments, which enabled to build a docking model of the complex. These results provide structural basis for the specific binding and inhibition of Kv channels by gating modifier toxins. PMID- 26382305 TI - Intrinsic homogeneous linewidth and broadening mechanisms of excitons in monolayer transition metal dichalcogenides. AB - The band-edge optical response of transition metal dichalcogenides, an emerging class of atomically thin semiconductors, is dominated by tightly bound excitons localized at the corners of the Brillouin zone (valley excitons). A fundamental yet unknown property of valley excitons in these materials is the intrinsic homogeneous linewidth, which reflects irreversible quantum dissipation arising from system (exciton) and bath (vacuum and other quasiparticles) interactions and determines the timescale during which excitons can be coherently manipulated. Here we use optical two-dimensional Fourier transform spectroscopy to measure the exciton homogeneous linewidth in monolayer tungsten diselenide (WSe2). The homogeneous linewidth is found to be nearly two orders of magnitude narrower than the inhomogeneous width at low temperatures. We evaluate quantitatively the role of exciton-exciton and exciton-phonon interactions and population relaxation as linewidth broadening mechanisms. The key insights reported here-strong many-body effects and intrinsically rapid radiative recombination-are expected to be ubiquitous in atomically thin semiconductors. PMID- 26382306 TI - Do's and don'ts in evaluation of endoscopic screening for gastrointestinal cancers. AB - Endoscopic screening for cancers of the esophagus, stomach, and colon has been introduced in many countries of the world. Endoscopic screening has the potential to reduce incidence and mortality of the target diseases, but may also be harmful and have unwanted side effects. Precise estimates of the magnitude of benefits and harms of endoscopic screening for cancer are a prerequisite for informed decision making for or against participation in screening for individuals in the target population. This paper outlines the most common pitfalls in the evaluation of screening and offers some recommendations for future studies. PMID- 26382307 TI - Comparison of the clinical impact of endoscopic ultrasound-guided choledochoduodenostomy and hepaticogastrostomy for bile duct obstruction with duodenal obstruction. AB - BACKGROUND AND STUDY AIM: To date, only a few reports with small numbers of patients have described double stenting (biliary and duodenal), in particular endoscopic ultrasound (EUS)-guided biliary drainage, for patients with obstructive jaundice. In addition, no reports have sought to determine which EUS guided biliary drainage route has better outcomes. The aim of the current study was to investigate adverse events and stent patency in patients who underwent EUS guided biliary drainage and duodenal stenting. PATIENTS AND METHODS: Patients who were admitted to the Osaka Medical College with obstructive jaundice caused by lower biliary obstruction and duodenal obstruction due to malignant tumor between June 2012 and April 2014 were retrospectively enrolled in the study. RESULTS: A total of 39 patients were enrolled in the study; 13 underwent EUS-guided choledochoduodenostomy (EUS-CDS), and 26 underwent EUS-guided hepaticogastrostomy (EUS-HGS). Adjusted analyses for covariates using propensity scores showed that the EUS-HGS group had significantly longer stent patency than the EUS-CDS group (duodenal stent patency: median 113 vs. 34 days; hazard ratio [HR] 0.415, 95 % confidence interval [CI] 0.175 - 0.984; P = 0.046; biliary stent patency: median 133 vs. 37 days; HR 0.391, 95 %CI 0.156 - 0.981; P = 0.045). On logistic regression analysis, only EUS-CDS was associated with adverse events, in particular reflux cholangitis (OR 10.285, 95 %CI 1.686 - 62.733; P = 0.012). CONCLUSION: In cases of obstructive jaundice with duodenal obstruction, EUS-HGS may be better than EUS-CDS, with longer stent patency and fewer adverse events. PMID- 26382309 TI - Comparative efficacy and safety of estradiol transdermal preparations for the treatment of vasomotor symptoms in postmenopausal women: an indirect comparison meta-analysis. AB - OBJECTIVE: Divigel and Estrogel are estradiol gels for the treatment of postmenopausal women with moderate to severe vasomotor symptoms. They differ with respect to several factors including estradiol concentration and surface application, and cannot be compared solely on the basis of their estradiol dose. No randomized clinical trials have compared them head to head, but both have been compared with placebo. Therefore, the objective of this study was to conduct a systematic review and network meta-analysis of the two estradiol gels. METHODS: We performed a comprehensive systematic literature review. One publication reporting on one Divigel trial, three publications reporting on two Estrogel trials, and five publications reporting on other estradiol transdermal preparations were identified. Efficacy outcomes were change from baseline in daily hot flush frequency and change from baseline in daily hot flush severity. Safety outcomes were frequency of treatment-related adverse events (AEs) and frequency of treatment-emergent AEs leading to discontinuation. Bayesian indirect treatment comparison meta-analysis of trial-level data was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research, Academy of Managed Care Pharmacy, National Pharmaceutical Council (ISPOR-AMCP-NPC) Good Practice Questionnaire. All outcomes were compared with respect to doses of the considered preparations. RESULTS: For hot flush frequency, Divigel 0.25 mg was similar to Divigel 0.5 mg and to Estrogel 0.75 mg, and was statistically significantly superior to Estrogel 1.5 mg. The largest effect was observed with Divigel 1.0 mg (mean difference of 3.91 hot flushes/wk vs placebo), and was statistically significantly superior to all other interventions. The 1.5 mg Estrogel dose was associated with the smallest estimate of efficacy. For hot flush severity, Divigel 0.25 mg was similar to the efficacy of Divigel 0.5 mg, and for 0.25 mg and 0.5 mg of other estradiol gels, but was statistically inferior to Divigel 1.0 mg, Estrogel 0.75 mg, Estrogel 1.5 mg, and the 1.0 and 1.5 mg doses of all other estradiol gels. The estimated efficacy of Divigel 0.5 mg was similar to that of Estrogel 0.75 mg, Estrogel 1.5 mg, and the 0.25 and 0.5 mg doses of other transdermal estradiol preparations. Risks of treatment-related AEs for Divigel 0.25 mg, Divigel 0.5 mg, Estrogel 0.75 mg, and Estrogel 1.5 mg were similar and all were of a slightly higher risk than placebo. Among these, Divigel 1.0 mg, Estrogel 1.5 mg, and other gels 0.5 mg were statistically significantly less safe than placebo. However, for treatment emergent AEs leading to discontinuation, none of the gels were associated with statistically significantly higher relative risks compared with placebo. In this study, statistically significant refers to the 95% credible intervals used in the Bayesian Network Analysis. CONCLUSIONS: Using network meta-analysis for indirect treatment comparison, we have shown that the efficacy of Divigel 0.25 mg, as measured by reduced hot flush frequency and severity, was similar to that of Divigel 0.5 mg and of Estrogel 0.75 and 1.5 mg. Overall, our analysis showed that Divigel 1.0 mg provided the best efficacy profile, but that this treatment was also associated with a higher risk of AEs. The network meta-analysis also showed that treatment with Estrogel 1.5 mg was associated with the smallest estimate of reduction in frequency of hot flushes. PMID- 26382308 TI - Preoperative biliary drainage in perihilar cholangiocarcinoma: identifying patients who require percutaneous drainage after failed endoscopic drainage. AB - BACKGROUND AND STUDY AIMS: Preoperative biliary drainage is often initiated with endoscopic retrograde cholangiopancreatography (ERCP) in patients with potentially resectable perihilar cholangiocarcinoma (PHC), but additional percutaneous transhepatic catheter (PTC) drainage is frequently required. This study aimed to develop and validate a prediction model to identify patients with a high risk of inadequate ERCP drainage. PATIENTS AND METHODS: Patients with potentially resectable PHC and (attempted) preoperative ERCP drainage were included from two specialty center cohorts between 2001 and 2013. Indications for additional PTC drainage were failure to place an endoscopic stent, failure to relieve jaundice, cholangitis, or insufficient drainage of the future liver remnant. A prediction model was derived from the European cohort and externally validated in the USA cohort. RESULTS: Of the 288 patients, 108 (38%) required additional preoperative PTC drainage after inadequate ERCP drainage. Independent risk factors for additional PTC drainage were proximal biliary obstruction on preoperative imaging (Bismuth 3 or 4) and predrainage total bilirubin level. The prediction model identified three subgroups: patients with low risk (7%), moderate risk (40%), and high risk (62%). The high-risk group consisted of patients with a total bilirubin level above 150 umol/L and Bismuth 3a or 4 tumors, who typically require preoperative drainage of the angulated left bile ducts. The prediction model had good discrimination (area under the curve 0.74) and adequate calibration in the external validation cohort. CONCLUSIONS: Selected patients with potentially resectable PHC have a high risk (62%) of inadequate preoperative ERCP drainage requiring additional PTC drainage. These patients might do better with initial PTC drainage instead of ERCP. PMID- 26382310 TI - Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society. AB - OBJECTIVE: To update and expand The North American Menopause Society's evidence based position on nonhormonal management of menopause-associated vasomotor symptoms (VMS), previously a portion of the position statement on the management of VMS. METHODS: NAMS enlisted clinical and research experts in the field and a reference librarian to identify and review available evidence. Five different electronic search engines were used to cull relevant literature. Using the literature, experts created a document for final approval by the NAMS Board of Trustees. RESULTS: Nonhormonal management of VMS is an important consideration when hormone therapy is not an option, either because of medical contraindications or a woman's personal choice. Nonhormonal therapies include lifestyle changes, mind-body techniques, dietary management and supplements, prescription therapies, and others. The costs, time, and effort involved as well as adverse effects, lack of long-term studies, and potential interactions with medications all need to be carefully weighed against potential effectiveness during decision making. CONCLUSIONS: Clinicians need to be well informed about the level of evidence available for the wide array of nonhormonal management options currently available to midlife women to help prevent underuse of effective therapies or use of inappropriate or ineffective therapies. Recommended: Cognitive-behavioral therapy and, to a lesser extent, clinical hypnosis have been shown to be effective in reducing VMS. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS, although other selective serotonin reuptake/norepinephrine reuptake inhibitors, gabapentinoids, and clonidine show evidence of efficacy. Recommend with caution: Some therapies that may be beneficial for alleviating VMS are weight loss, mindfulness-based stress reduction, the S-equol derivatives of soy isoflavones, and stellate ganglion block, but additional studies of these therapies are warranted. Do not recommend at this time: There are negative, insufficient, or inconclusive data suggesting the following should not be recommended as proven therapies for managing VMS: cooling techniques, avoidance of triggers, exercise, yoga, paced respiration, relaxation, over-the-counter supplements and herbal therapies, acupuncture, calibration of neural oscillations, and chiropractic interventions. Incorporating the available evidence into clinical practice will help ensure that women receive evidence based recommendations along with appropriate cautions for appropriate and timely management of VMS. PMID- 26382311 TI - Menopause and exercise. AB - OBJECTIVE: Accumulating data suggest that regular physical exercise reduces mortality and extends the functional life span of men and women. This review seeks to describe the current state of the medical literature on this topic. METHODS: A narrative review of the current medical literature including randomized clinical trials and clinical guidelines that address the benefits of physical fitness and regular exercise on the health of midlife and postmenopausal women. RESULTS: Reduction and avoidance of obesity and its related comorbidities (hypertension, glucose intolerance, dyslipidemia, and heart disease) are one major benefit of exercise. However, long-term physical exercise is also associated with reduced rates of cancer, dementia and cognitive decline, adverse mood and anxiety symptoms, and reduction of osteoporosis, osteopenia, falls, and fractures. Beneficial physical activity includes exercise that will promote cardiovascular fitness (aerobic), muscle strength (resistance), flexibility (stretching), and balance (many of the preceding, and additional activities such as yoga). CONCLUSIONS: Given that it is unambiguously beneficial, inexpensive, and minimal risk, maintaining a healthy exercise regimen should be a goal for every participant to enhance lifelong wellness. Clinicians should use a number of behavioral strategies to support the physical fitness goals of their participants. PMID- 26382312 TI - Obesity and sexual function. PMID- 26382313 TI - Differential effects of selective estrogen receptor modulators on the vagina and its supportive tissues. AB - OBJECTIVE: Some selective estrogen receptor modulators (SERMs) have been associated with increased incidence of urinary incontinence and pelvic organ prolapse. This study explored the effects of five SERMs on the function and matrix components of the vagina and its supportive tissues. METHODS: Fifty-six rats were administered SERMs by oral gavage for 8 weeks (n = 8 for each SERM): raloxifene, tamoxifen, idoxifene, bazedoxifene at three different doses, and bazedoxifene with conjugated estrogens. Thirty-two rats were used as controls (n = 8 per group): sham operation (no ovariectomy), ovariectomy only, ovariectomy with vehicle gavage, and 17beta-estradiol (subcutaneous). Vaginal supportive tissue complex was tested by uniaxial tensile testing. Total collagen content (hydroxyproline) and glycosaminoglycan content (Blyscan) were measured. RESULTS: Ovariectomy significantly decreased the mechanical integrity of the vagina and its supportive tissue complex, with a decrease in ultimate load and stiffness (all P < 0.05). Although 17beta-estradiol supplementation maintained these properties similarly to sham operation, none of the SERMs was as effective- particularly idoxifene, bazedoxifene at higher doses, and bazedoxifene with conjugated estrogens (all P < 0.05). In addition, idoxifene and bazedoxifene induced increased total collagen content compared with sham or 17beta-estradiol treatment (all P < 0.05). Glycosaminoglycan content did not change significantly. CONCLUSIONS: Unlike 17beta-estradiol, SERM supplementation does not fully prevent ovariectomy-induced deterioration in the biomechanical properties of the vagina and its supportive tissues, with the effects of idoxifene and bazedoxifene being the least. The paradoxically increased collagen content in these two groups may be related to increased formation of nonfunctional collagen. PMID- 26382314 TI - Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey. AB - OBJECTIVE: A national survey was conducted to determine the extent of use of compounded hormone therapy (C-HT) and to characterize the differences between C HT users and users of hormone therapy approved by the US Food and Drug Administration (FDA-HT users). METHODS: This Internet survey enrolled 3,725 women aged 40 to 84 years who were postmenopausal or experiencing the menopause transition. The sample was weighted slightly by age, region, education, and race to reflect population attributes based on US Census data. RESULTS: Overall, 9% of women were current users of HT, and 28% of all respondents were ever-users of HT. C-HT users represented 31% of ever-users of HT, 35% of current users of HT, and 41% of ever-users aged 40 to 49 years. Approximately 13% of ever-users indicated current or past use of testosterone. The most cited reason for using HT was vasomotor symptoms (~70%). Nonapproved indications for using HT were selected more often by C-HT users. There were four reports of endometrial cancer among the 326 C-HT users compared with none reported among the 738 FDA-HT users. Significance was not determined because of small numbers. CONCLUSIONS: This survey indicates substantial use of C-HT across the country and the possibility of higher rates of endometrial side effects with such products. There is a need for standardized data collection on the extent of use of compounded hormones and their potential risks. PMID- 26382315 TI - Bone structure and turnover in postmenopausal women with type 2 diabetes mellitus. AB - OBJECTIVE: Considering the high prevalence of diabetes and osteoporosis in Iranians, the current research was conducted to study the correlation between these two diseases in a group of postmenopausal women. METHODS: The present study was conducted on postmenopausal women recruited in the third phase of the Iranian Multi-centric Osteoporosis Study. They were divided into two groups (diabetic and nondiabetic) based on their diabetes history and laboratory results. The serum levels of bone markers and bone mineral density values were compared between the two groups. RESULTS: A total of 110 postmenopausal women were included. Although bone mineral density values were nonsignificantly higher in diabetic postmenopausal women, there was no considerable difference between the prevalence of osteoporosis or serum levels of bone markers in the two groups. CONCLUSIONS: There is no difference in bone mass values or bone turnover process between Iranian postmenopausal women with or without diabetes. PMID- 26382316 TI - Potential adverse effects of prophylactic bilateral salpingo-oophorectomy on skin aging in premenopausal women undergoing hysterectomy for benign conditions. AB - OBJECTIVE: This study aimed to assess the effects of hysterectomy and bilateral salpingo-oophorectomy (BSO)--compared with the effects of hysterectomy alone--on skin aging in premenopausal women undergoing hysterectomy for benign conditions. METHODS: One hundred thirty-five premenopausal women who underwent hysterectomy with BSO were compared with a control group of women who underwent hysterectomy alone based on skin parameters (including wrinkling, laxity/sagging, and texture/dryness) and Skindex-29 questionnaire scores. The inclusion criteria were as follows: aged between 40 and 50 years, follicle-stimulating hormone level lower than 40 mIU/mL, undergoing hysterectomy with or without BSO for benign conditions, and not receiving estrogen or progesterone treatment. The exclusion criteria were as follows: adrenocortical hyperplasia or Cushing's syndrome; use of corticosteroids for autoimmune diseases; malignancy, connective tissue diseases (eg, Ehlers-Danlos syndrome), or dermatological diseases (eg, lichen sclerosus); or regular use of medications known to interfere with the condition of the skin. RESULTS: All skin parameters in the hysterectomy group and the hysterectomy with BSO group worsened on weeks 24 and 48. Laxity/sagging and texture/dryness scores on weeks 24 and 48 were significantly worse in the BSO group; laxity/sagging and texture/dryness scores continued to worsen between 24 and 48 weeks. Scores for the Skindex-29 questionnaire emotion and symptom subscales were significantly higher in the BSO group compared with the non-BSO group. CONCLUSIONS: Prophylactic BSO during hysterectomy is a significant independent risk factor for worsening skin laxity/sagging and texture/dryness in premenopausal women undergoing hysterectomy for benign conditions. Prophylactic BSO in the presence of dermatological conditions is also associated with reduced quality of life. PMID- 26382317 TI - Health-related quality of life in midlife women in Qatar: relation to arthritis and symptoms of joint pain. AB - OBJECTIVE: The prevalence of osteoarthritis (OA) and rheumatoid arthritis (RA) has been poorly documented in the Middle East and North African region, including the State of Qatar. Given that musculoskeletal pain is commonly reported among midlife women, we evaluated the association between self-report of either OA or RA and health-related quality of life (HRQoL) among midlife women in Qatar. In addition, HRQoL among women in Qatar was compared with that of women in the Study of Women's Health Across the Nation (SWAN). METHODS: A cross-sectional study was conducted among 841 women 40 to 60 years recruited from primary care centers in Qatar. Face-to-face interviews were conducted and included measures of self reported OA and RA, health-related symptom experience, and HRQoL using the SF-36 health survey. RESULTS: Most women were obese (75.5%) and reported being bothered by aches and stiffness in joints (71.6%). Prevalence of self-reported OA and RA was 4.8% and 4.3%, respectively. OA was significantly associated with reduced physical function (adjusted odds ratio [OR], 2.97; P=0.003). RA was also significantly related to reduced physical function (adjusted OR, 2.94; P = 0.01) and role physical (adjusted OR, 2.67; P = 0.01). When compared with women from the SWAN, women from the current study had significantly lower mean scores for bodily pain (53.0 vs. 68.9, P = 0.0001) and for vitality (49.9 vs. 54.8, P = 0.0001). CONCLUSIONS: Self-report of OA or RA was associated with significant disability in our sample. Because symptoms of aches and stiff joints were so frequently reported, arthritis may be under-diagnosed, especially given the high rates of obesity observed. PMID- 26382318 TI - Shape memory polymers with high and low temperature resistant properties. AB - High temperature shape memory polymers that can withstand the harsh temperatures for durable applications are synthesized, and the aromatic polyimide chains with flexible linkages within the backbone act as reversible phase. High molecular weight (Mn) is demanded to form physical crosslinks as fixed phase of thermoplastic shape memory polyimide, and the relationship between Mn and glass transition temperature (Tg) is explored. Thermoset shape memory polyimide shows higher Tg and storage modulus, better shape fixity than thermoplastic counterpart due to the low-density covalent crosslinking, and the influence of crosslinking on physical properties are studied. The mechanism of high temperature shape memory effects based on chain flexibility, molecular weight and crosslink density is proposed. Exposure to thermal cycling from +150 degrees C to -150 degrees C for 200 h produces negligible effect on the properties of the shape memory polyimide, and the possible mechanism of high and low temperature resistant property is discussed. PMID- 26382319 TI - The seasonal sea-ice zone in the glacial Southern Ocean as a carbon sink. AB - Reduced surface-deep ocean exchange and enhanced nutrient consumption by phytoplankton in the Southern Ocean have been linked to lower glacial atmospheric CO2. However, identification of the biological and physical conditions involved and the related processes remains incomplete. Here we specify Southern Ocean surface-subsurface contrasts using a new tool, the combined oxygen and silicon isotope measurement of diatom and radiolarian opal, in combination with numerical simulations. Our data do not indicate a permanent glacial halocline related to melt water from icebergs. Corroborated by numerical simulations, we find that glacial surface stratification was variable and linked to seasonal sea-ice changes. During glacial spring-summer, the mixed layer was relatively shallow, while deeper mixing occurred during fall-winter, allowing for surface-ocean refueling with nutrients from the deep reservoir, which was potentially richer in nutrients than today. This generated specific carbon and opal export regimes turning the glacial seasonal sea-ice zone into a carbon sink. PMID- 26382320 TI - Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation. AB - Despite many prior studies demonstrating offline behavioral gains in motor skills after sleep, the underlying neural mechanisms remain poorly understood. To investigate the neurophysiological basis for offline gains, we performed single unit recordings in motor cortex as rats learned a skilled upper-limb task. We found that sleep improved movement speed with preservation of accuracy. These offline improvements were linked to both replay of task-related ensembles during non-rapid eye movement (NREM) sleep and temporal shifts that more tightly bound motor cortical ensembles to movements; such offline gains and temporal shifts were not evident with sleep restriction. Interestingly, replay was linked to the coincidence of slow-wave events and bursts of spindle activity. Neurons that experienced the most consistent replay also underwent the most significant temporal shift and binding to the motor task. Significantly, replay and the associated performance gains after sleep only occurred when animals first learned the skill; continued practice during later stages of learning (i.e., after motor kinematics had stabilized) did not show evidence of replay. Our results highlight how replay of synchronous neural activity during sleep mediates large-scale neural plasticity and stabilizes kinematics during early motor learning. PMID- 26382321 TI - The formation mechanism of bimetallic PtRu alloy nanoparticles in solvothermal synthesis. AB - An understanding of the nucleation and growth mechanism of bimetallic nanoparticles in solvothermal synthesis is important for further development of nanoparticles with tailored nanostructures and properties. Here the formation of PtRu alloy nanoparticles in a solvothermal synthesis using metal acetylacetonate salts as precursors and ethanol as both the solvent and reducing agent has been studied by in situ synchrotron radiation powder X-ray diffraction (SR-PXRD). Unlike the classical mechanism for the synthesis of monodisperse sols, the nucleation and growth processes of bimetallic PtRu nanoparticles occur simultaneously under solvothermal conditions. In the literature co-reduction of Pt and Ru is often assumed to be required to form PtRu bimetallic nanocrystals, but it is shown that monometallic Pt nanocrystals nucleate first and rapidly grow to an average size of 5 nm. Subsequently, the PtRu bimetallic alloy is formed in the second nucleation stage through a surface nucleation mechanism related to the reduction of Ru. The calculated average crystallite size of the resulting PtRu nanocrystals is smaller than that of the primary Pt nanocrystals due to the large disorder in the PtRu alloyed structure. PMID- 26382322 TI - The role of N7 protonation of guanine in determining the structure, stability and function of RNA base pairs. AB - The roles of protonated nucleobases in stabilizing different structural motifs and in facilitating catalytic functions of RNA are well known. Among different polar sites of all the nucleobases, N7 of guanine has the highest protonation propensity at physiological pH. However, unlike other easily protonable sites such as N1 and N3 of adenine or N3 of cytosine, N7 protonation of guanine does not lead to the stabilization of base pairs involving its protonated Hoogsteen edge. It also does not facilitate its participation in any acid-base catalysis process. To explore the possible roles of N7 protonated guanine, we have studied its base pairing potentials involving WatsonCrick and sugar edges, which undergo major charge redistribution upon N7 protonation. We have carried out quantum chemical geometry optimization at the M05-2X/6-311G+(2d,2p) level, followed by interaction energy calculation at the MP2/aug-cc-pVDZ level, along with the analysis of the context of occurrence for selected base pairs involving the sugar edge or the WatsonCrick edge of guanine within a non-redundant set of 167 RNA crystal structures. Our results suggest that, four base pairs - G:C W:W trans, G:rC W:S cis, G:G W:H cis and G:G S:H trans may involve N7 protonated guanine. These base pairs deviate significantly from their respective experimental geometries upon QM optimization, but they retain their experimental geometries if guanine N7 protonation is considered during optimization. Our study also reveals the role of guanine N7 protonation (i) in stabilizing important RNA structural motifs, (ii) in providing a framework for designing pH driven molecular motors and (iii) in providing an alternative strategy to mimic the effect of post transcriptional changes. PMID- 26382323 TI - Failure Analysis of Batteries Using Synchrotron-based Hard X-ray Microtomography. AB - Imaging morphological changes that occur during the lifetime of rechargeable batteries is necessary to understand how these devices fail. Since the advent of lithium-ion batteries, researchers have known that the lithium metal anode has the highest theoretical energy density of any anode material. However, rechargeable batteries containing a lithium metal anode are not widely used in consumer products because the growth of lithium dendrites from the anode upon charging of the battery causes premature cell failure by short circuit. Lithium dendrites can also form in commercial lithium-ion batteries with graphite anodes if they are improperly charged. We demonstrate that lithium dendrite growth can be studied using synchrotron-based hard X-ray microtomography. This non destructive imaging technique allows researchers to study the growth of lithium dendrites, in addition to other morphological changes inside batteries, and subsequently develop methods to extend battery life. PMID- 26382324 TI - Synthesis of crosslinked polymeric nanocapsules using catanionic vesicle templates stabilized by compressed CO2. AB - The synthesis of polymeric nanocapsules in the approximate diameter range 40-100 nm (TEM/SEM) using catanionic surfactant vesicle templates stabilized by subcritical CO2 is demonstrated. Near equimolar aqueous solutions of the surfactants sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium bromide (DTAB) experienced immediate vesicle destabilization and precipitation in the absence of CO2. However, pressurization with CO2 (5 MPa) dramatically enhanced the stability of the initial vesicles, and enabled swelling of the bilayers with hydrophobic monomers via diffusion loading (loading of monomers into preformed bilayers). Subsequent radical crosslinking polymerization of the monomers n-butyl methacrylate/tert-butyl methacrylate/ethylene glycol dimethacrylate contained within the bilayers was conducted at room temperature using UV-initiation under CO2 pressure. The hollow structure of the resultant nano-objects was confirmed by successful encapsulation and retention of the dye Nile Blue. It is demonstrated that using this method, polymeric nanocapsules can be successfully prepared using diffusion loading of up to 94 wt% monomer (rel. to surfactant) stabilized by CO2. PMID- 26382325 TI - Temperature inversion in long-range interacting systems. AB - Temperature inversions occur in nature, e.g., in the solar corona and in interstellar molecular clouds: Somewhat counterintuitively, denser parts of the system are colder than dilute ones. We propose a simple and appealing way to spontaneously generate temperature inversions in systems with long-range interactions, by preparing them in inhomogeneous thermal equilibrium states and then applying an impulsive perturbation. In similar situations, short-range systems would typically relax to another thermal equilibrium, with a uniform temperature profile. By contrast, in long-range systems, the interplay between wave-particle interaction and spatial inhomogeneity drives the system to nonequilibrium stationary states that generically exhibit temperature inversion. We demonstrate this mechanism in a simple mean-field model and in a two dimensional self-gravitating system. Our work underlines the crucial role the range of interparticle interaction plays in determining the nature of steady states out of thermal equilibrium. PMID- 26382326 TI - How accurately can the microcanonical ensemble describe small isolated quantum systems? AB - We numerically investigate quantum quenches of a nonintegrable hard-core Bose Hubbard model to test the accuracy of the microcanonical ensemble in small isolated quantum systems. We show that, in a certain range of system size, the accuracy increases with the dimension of the Hilbert space D as 1/D. We ascribe this rapid improvement to the absence of correlations between many-body energy eigenstates. Outside of that range, the accuracy is found to scale either as 1/?D or algebraically with the system size. PMID- 26382327 TI - Gibbs volume entropy is incorrect. AB - We show that the expression for the equilibrium thermodynamic entropy contains an integral over a surface in phase space, and in so doing, we confirm that negative temperature is a valid thermodynamic concept. This demonstration disproves the claims of several recent papers that the Gibbs entropy, which contains an integral over a volume in phase space, is the correct definition and that thermodynamics cannot be extended to include negative temperatures. We further show that the Gibbs entropy fails to satisfy the postulates of thermodynamics and that its predictions for systems with nonmonotonic energy densities of states are incorrect. PMID- 26382328 TI - Particle-density fluctuations and universality in the conserved stochastic sandpile. AB - We examine fluctuations in particle density in the restricted-height, conserved stochastic sandpile (CSS). In this and related models, the global particle density is a temperaturelike control parameter. Thus local fluctuations in this density correspond to disorder; if this disorder is a relevant perturbation of directed percolation (DP), then the CSS should exhibit non-DP critical behavior. We analyze the scaling of the variance Vl of the number of particles in regions of ld sites in extensive simulations of the quasistationary state in one and two dimensions. Our results, combined with a Harris-like argument for the relevance of particle-density fluctuations, strongly suggest that conserved stochastic sandpiles belong to a universality class distinct from that of DP. PMID- 26382329 TI - Mechanical fluctuations suppress the threshold of soft-glassy solids: The secular drift scenario. AB - We propose a dynamical mechanism leading to the fluidization by external mechanical fluctuations of soft-glassy amorphous material driven below the yield stress. The model is based on the combination of memory effect and nonlinearity, leading to an accumulation of tiny effects over a long term. We test this scenario on a granular packing driven mechanically below the Coulomb threshold. We provide evidence for an effective viscous response directly related to small stress modulations in agreement with the theoretical prediction of a generic secular drift. We propose to extend this result more generally to a large class of glassy systems. PMID- 26382330 TI - Percolation in suspensions and de Gennes conjectures. AB - Dense suspensions display complex flow properties, intermediate between solid and liquid. When sheared, a suspension self-organizes and forms particle clusters that are likely to percolate, possibly leading to significant changes in the overall behavior. Some theoretical conjectures on percolation in suspensions were proposed by de Gennes some 35 years ago. Although still used, they have not received any validations so far. In this Rapid Communication, we use three dimensional detailed numerical simulations to understand the formation of percolation clusters and assess de Gennes conjectures. We found that sheared noncolloidal suspensions do show percolation clusters occurring at a critical volume fraction in the range 0.3-0.4 depending on the system size. Percolation clusters are roughly linear, extremely transient, and involve a limited number of particles. We have computed critical exponents and found that clusters can be described reasonably well by standard isotropic percolation theory. The only disagreement with de Gennes concerns the role of percolation clusters on rheology which is found to be weak. Our results eventually validate de Gennes conjectures and demonstrate the relevance of percolation concepts in suspension physics. PMID- 26382331 TI - Local load-sharing fiber bundle model in higher dimensions. AB - We consider the local load-sharing fiber bundle model in one to five dimensions. Depending on the breaking threshold distribution of the fibers, there is a transition where the fracture process becomes localized. In the localized phase, the model behaves as the invasion percolation model. The difference between the local load-sharing fiber bundle model and the equal load-sharing fiber bundle model vanishes with increasing dimensionality with the characteristics of a power law. PMID- 26382332 TI - Reaction-diffusion processes on interconnected scale-free networks. AB - We study the two-particle annihilation reaction A+B->? on interconnected scale free networks, using different interconnecting strategies. We explore how the mixing of particles and the process evolution are influenced by the number of interconnecting links, by their functional properties, and by the interconnectivity strategies in use. We show that the reaction rates on this system are faster than what was observed in other topologies, due to the better particle mixing that suppresses the segregation effect, in line with previous studies performed on single scale-free networks. PMID- 26382333 TI - Finite-size-induced transitions to synchrony in oscillator ensembles with nonlinear global coupling. AB - We report on finite-sized-induced transitions to synchrony in a population of phase oscillators coupled via a nonlinear mean field, which microscopically is equivalent to a hypernetwork organization of interactions. Using a self consistent approach and direct numerical simulations, we argue that a transition to synchrony occurs only for finite-size ensembles and disappears in the thermodynamic limit. For all considered setups, which include purely deterministic oscillators with or without heterogeneity in natural oscillatory frequencies, and an ensemble of noise-driven identical oscillators, we establish scaling relations describing the order parameter as a function of the coupling constant and the system size. PMID- 26382334 TI - Resistive thrust production can be as crucial as added mass mechanisms for inertial undulatory swimmers. AB - In this Rapid Communication, we address a crucial point regarding the description of moderate to high Reynolds numbers aquatic swimmers. For decades, swimming animals have been classified in two different families of propulsive mechanisms based on the Reynolds number: the resistive swimmers, using local friction to produce the necessary thrust force for locomotion at low Reynolds number, and the reactive swimmers, lying in the high Reynolds range, and using added mass acceleration (described by perfect fluid theory). However, inertial swimmers are also systems that dissipate energy, due to their finite size, therefore involving strong resistive contributions, even for high Reynolds numbers. Using a complete model for the hydrodynamic forces, involving both reactive and resistive contributions, we revisit here the physical mechanisms responsible for the thrust production of such swimmers. We show, for instance, that the resistive part of the force balance is as crucial as added mass effects in the modeling of the thrust force, especially for elongated species. The conclusions brought by this work may have significant contributions to the understanding of complex swimming mechanisms, especially for the future design of artificial swimmers. PMID- 26382335 TI - Jet drops from bursting bubbles: How gravity and viscosity couple to inhibit droplet production. AB - When a bubble ruptures at a liquid surface the collapsing cavity produces a central jet that frequently breaks up into a series of droplets. Current experiment and theory predict that the production of jet drops will be limited by either viscous or gravitational effects. However, while there are a number of studies focusing on these two limiting cases, less is understood about the production of jet drops when both gravitational and viscous effects are significant. Here, we uncover the existence of an intermediate region where both gravitational and viscous effects play a critical role in jet-drop formation. We propose that the role of gravity is most important before rupture, and carry out simulations that demonstrate the importance of the equilibrium bubble shape in the production of jet drops. PMID- 26382336 TI - Inverted glass harp. AB - We present an analytical treatment of the acoustics of liquid-filled wine glasses, or "glass harps." The solution is generalized such that under certain assumptions it reduces to previous glass harp models, but also leads to a proposed musical instrument, the "inverted glass harp," in which an empty glass is submerged in a liquid-filled basin. The versatility of the solution demonstrates that all glass harps are governed by a family of solutions to Laplace's equation around a vibrating disk. Tonal analyses of recordings for a sample glass are offered as confirmation of the scaling predictions. PMID- 26382337 TI - Transverse electron-scale instability in relativistic shear flows. AB - Electron-scale surface waves are shown to be unstable in the transverse plane of a sheared flow in an initially unmagnetized collisionless plasma, not captured by (magneto)hydrodynamics. It is found that these unstable modes have a higher growth rate than the closely related electron-scale Kelvin-Helmholtz instability in relativistic shears. Multidimensional particle-in-cell simulations verify the analytic results and further reveal the emergence of mushroomlike electron density structures in the nonlinear phase of the instability, similar to those observed in the Rayleigh Taylor instability despite the great disparity in scales and different underlying physics. This transverse electron-scale instability may play an important role in relativistic and supersonic sheared flow scenarios, which are stable at the (magneto)hydrodynamic level. Macroscopic (?c/omegape) fields are shown to be generated by this microscopic shear instability, which are relevant for particle acceleration, radiation emission, and to seed magnetohydrodynamic processes at long time scales. PMID- 26382338 TI - Chaotic spin-spin entanglement on a recursive lattice. AB - We propose an exactly solvable multisite interaction spin-1/2 Ising-Heisenberg model on a triangulated Husimi lattice for the rigorous studies of chaotic entanglement. By making use of the generalized star-triangle transformation, we map the initial model onto an effective Ising one on a Husimi lattice, which we solve then exactly by applying the recursive method. Expressing the entanglement of the Heisenberg spins, that we quantify by means of the concurrence, in terms of the magnetic quantities of the system, we demonstrate its bifurcation and chaotic behavior. Furthermore, we show that the underlying chaos may slightly enhance the amount of the entanglement and present on the phase diagram the transition lines from the uniform to periodic and from the periodic to chaotic regimes. PMID- 26382339 TI - Critical properties of short-range Ising spin glasses on a Wheatstone-bridge hierarchical lattice. AB - An Ising spin-glass model with nearest-neighbor interactions, following a symmetric probability distribution, is investigated on a hierarchical lattice of the Wheatstone-bridge family characterized by a fractal dimension D~3.58. The interaction distribution considered is a stretched exponential, which has been shown recently to be very close to the fixed-point coupling distribution, and such a model has been considered lately as a good approach for Ising spin glasses on a cubic lattice. An exact recursion procedure is implemented for calculating site magnetizations, mi=T, as well as correlations between pairs of nearest neighbor spins, T (<>T denote thermal averages), for a given set of interaction couplings on this lattice. From these local magnetizations and correlations, one can compute important physical quantities, such as the Edwards Anderson order parameter, the internal energy, and the specific heat. Considering extrapolations to the thermodynamic limit for the order parameter, such as a finite-size scaling approach, it is possible to obtain directly the critical temperature and critical exponents. The transition between the spin-glass and paramagnetic phases is analyzed, and the associated critical exponents beta and nu are estimated as beta=0.82(5) and nu=2.50(4), which are in good agreement with the most recent results from extensive numerical simulations on a cubic lattice. Since these critical exponents were obtained from a fixed-point distribution, they are universal, i.e., valid for any coupling distribution considered. PMID- 26382340 TI - Efficient approach to the free energy of crystals via Monte Carlo simulations. AB - We present a general approach to compute the absolute free energy of a system of particles with constrained center of mass based on the Monte Carlo thermodynamic coupling integral method. The version of the Frenkel-Ladd approach [J. Chem. Phys. 81, 3188 (1984)]JCPSA60021-960610.1063/1.448024, which uses a harmonic coupling potential, is recovered. Also, we propose a different choice, based on one-particle square-well coupling potentials, which is much simpler, more accurate, and free from some of the difficulties of the Frenkel-Ladd method. We apply our approach to hard spheres and compare with the standard harmonic method. PMID- 26382341 TI - Quantum heat baths satisfying the eigenstate thermalization hypothesis. AB - A class of autonomous quantum heat baths satisfying the eigenstate thermalization hypothesis (ETH) criteria is proposed. We show that such systems are expected to cause thermal relaxation of much smaller quantum systems coupled to one of the baths local observables. The process of thermalization is examined through residual fluctuations of local observables of the bath around their thermal values predicted by ETH. It is shown that such fluctuations perturb the small quantum system causing its decoherence to the thermal state. As an example, we investigate theoretically and numerically thermalization of a qubit coupled to a realistic ETH quantum heat bath. PMID- 26382342 TI - Critical fluctuations and the rates of interstate switching near the excitation threshold of a quantum parametric oscillator. AB - We study the dynamics of a nonlinear oscillator near the critical point where period-two vibrations are first excited with the increasing amplitude of parametric driving. Above the threshold, quantum fluctuations induce transitions between the period-two states over the quasienergy barrier. We find the effective quantum activation energies for such transitions and their scaling with the difference of the driving amplitude from its critical value. We also find the scaling of the fluctuation correlation time with the quantum noise parameters in the critical region near the threshold. The results are extended to oscillators with nonlinear friction. PMID- 26382343 TI - Spectral renormalization group for the Gaussian model and psi4 theory on nonspatial networks. AB - We implement the spectral renormalization group on different deterministic nonspatial networks without translational invariance. We calculate the thermodynamic critical exponents for the Gaussian model on the Cayley tree and the diamond lattice and find that they are functions of the spectral dimension, d[over ]. The results are shown to be consistent with those from exact summation and finite-size scaling approaches. At d[over ]=2, the lower critical dimension for the Ising universality class, the Gaussian fixed point is stable with respect to a psi^{4} perturbation up to second order. However, on generalized diamond lattices, non-Gaussian fixed points arise for 21 of the q-state Potts model. Thus, a systematic study of opinion formation in social networks with the effect of interdependence between different social communities, which may be seen as the study of the emerging pattern of the Ising model on MNs, is needed. Here we study a well-known spin model called the Ashkin Teller (AT) model in scale-free networks. The AT model can be regarded as a model for interacting systems between two species of Ising spins placed on respective layers in double-layer networks. Our study shows that, depending on the interlayer coupling strength and a network topology, unconventional PT patterns can also emerge in interaction-based phenomena: continuous, discontinuous, successive, and mixed-order PTs and a continuous PT not satisfying the scaling relation. The origins of such rich PT patterns are elucidated in the framework of Landau-Ginzburg theory. PMID- 26382348 TI - Comparison of eigeninference based on one- and two-point Green's functions. AB - We compare two methods of eigeninference from large sets of data. Our analysis points at the superiority of our eigeninference method based on one-point Green's functions and Pade approximants over a method based on fluctuations and two-point Green's functions. The first method is orders of magnitude faster than the second one; moreover, we found a source of potential instability of the second method and identified it as arising from the spurious zero and negative modes of the estimator for the variance operator of a certain multidimensional Gaussian distribution, inherent for that method. We also present eigeninference based on spectral moments of negative orders, for strictly positive spectra. Finally, we compare the cases of eigeninference of real-valued and complex-valued correlated Wishart distributions, reinforcing our conclusions on the advantage of the one point Green's function method. PMID- 26382349 TI - Effective interactions between fluid membranes. AB - A self-consistent theory is proposed for the general problem of interacting undulating fluid membranes subject to the constraint that they do not interpenetrate. We implement the steric constraint via an exact functional integral representation and, through the use of a saddle-point approximation, transform it into a novel effective steric potential. The steric potential is found to consist of two contributions: one generated by zero-mode fluctuations of the membranes and the other by thermal bending fluctuations. For membranes of cross-sectional area S, we find that the bending fluctuation part scales with the intermembrane separation d as d-2 for d??S but crosses over to d-4 scaling for d??S, whereas the zero-mode part of the steric potential always scales as d-2. For membranes interacting exclusively via the steric potential, we obtain closed form expressions for the effective interaction potential and for the rms undulation amplitude sigma, which becomes small at low temperatures T and/or large bending stiffnesses kappa. Moreover, sigma scales as d for d??S but saturates at ?kBTS/kappa for d??S. In addition, using variational Gaussian theory, we apply our self-consistent treatment to study intermembrane interactions subject to different types of potentials: (i) the Moreira-Netz potential for a pair of strongly charged membranes with an intervening solution of multivalent counterions, (ii) an attractive square well, (iii) the Morse potential, and (iv) a combination of hydration and van der Waals interactions. PMID- 26382350 TI - Fokker-Planck equation of Schramm-Loewner evolution. AB - In this paper we statistically analyze the Fokker-Planck (FP) equation of Schramm Loewner evolution (SLE) and its variant SLE(kappa,rhoc). After exploring the derivation and the properties of the Langevin equation of the tip of the SLE trace, we obtain the long- and short-time behaviors of the chordal SLE traces. We analyze the solutions of the FP and the corresponding Langevin equations and connect it to the conformal field theory (CFT) and present some exact results. We find the perturbative FP equation of the SLE(kappa,rhoc) traces and show that it is related to the higher-order correlation functions. Using the Langevin equation we find the long-time behaviors in this case. The CFT correspondence of this case is established and some exact results are presented. PMID- 26382351 TI - Transition from distributional to ergodic behavior in an inhomogeneous diffusion process: Method revealing an unknown surface diffusivity. AB - Diffusion of molecules in cells plays an important role in providing a biological reaction on the surface by finding a target on the membrane surface. The water retardation (slow diffusion) near the target assists the searching molecules to recognize the target. Here, we consider effects of the surface diffusivity on the effective diffusivity, where diffusion on the surface is slower than that in bulk. We show that the ensemble-averaged mean-square displacements increase linearly with time when the desorption rate from the surface is finite, which is valid even when the diffusion on the surface is anomalous (subdiffusion). Moreover, this slow diffusion on the surface affects the fluctuations of the time averaged mean-square displacements (TAMSDs). We find that fluctuations of the TAMSDs remain large when the measurement time is smaller than a characteristic time, and decays according to an increase of the measurement time for a relatively large measurement time. Therefore, we find a transition from nonergodic (distributional) to ergodic diffusivity in a target search process. Moreover, this fluctuation analysis provides a method to estimate an unknown surface diffusivity. PMID- 26382352 TI - Overlap and activity glass transitions in plaquette spin models with hierarchical dynamics. AB - We consider thermodynamic and dynamic phase transitions in plaquette spin models of glasses. The thermodynamic transitions involve coupled (annealed) replicas of the model. We map these coupled-replica systems to a single replica in a magnetic field, which allows us to analyze the resulting phase transitions in detail. For the triangular plaquette model (TPM), we find for the coupled-replica system a phase transition between high- and low-overlap phases, occurring at a coupling E*(T), which vanishes in the low-temperature limit. Using computational path sampling techniques, we show that a single TPM also displays "space-time" transitions between active and inactive dynamical phases. These first-order dynamical transitions occur at a critical counting field sc(T)?0 that appears to vanish at zero temperature in a manner reminiscent of the thermodynamic overlap transition. In order to extend the ideas to three dimensions, we introduce the square pyramid model, which also displays both overlap and activity transitions. We discuss a possible common origin of these various phase transitions, based on long-lived (metastable) glassy states. PMID- 26382353 TI - Annealed and quenched disorder in sand-pile models with local violation of conservation. AB - In this paper we consider the Bak, Tang, and Wiesenfeld (BTW) sand-pile model with local violation of conservation through annealed and quenched disorder. We have observed that the probability distribution functions of avalanches have two distinct exponents, one of which is associated with the usual BTW model and another one which we propose to belong to a new fixed point; that is, a crossover from the original BTW fixed point to a new fixed point is observed. Through field theoretic calculations, we show that such a perturbation is relevant and takes the system to a new fixed point. PMID- 26382354 TI - Probing local equilibrium in nonequilibrium fluids. AB - We use extensive computer simulations to probe local thermodynamic equilibrium (LTE) in a quintessential model fluid, the two-dimensional hard-disks system. We show that macroscopic LTE is a property much stronger than previously anticipated, even in the presence of important finite-size effects, revealing a remarkable bulk-boundary decoupling phenomenon in fluids out of equilibrium. This allows us to measure the fluid's equation of state in simulations far from equilibrium, with an excellent accuracy comparable to the best equilibrium simulations. Subtle corrections to LTE are found in the fluctuations of the total energy which strongly point to the nonlocality of the nonequilibrium potential governing the fluid's macroscopic behavior out of equilibrium. PMID- 26382355 TI - Optimizing linked-cluster expansions by white graphs. AB - We introduce a white-graph expansion for the method of perturbative continuous unitary transformations when implemented as a linked-cluster expansion. The essential idea behind an expansion in white graphs is to perform an optimized bookkeeping during the calculation by exploiting the model-independent effective Hamiltonian in second quantization and the associated inherent cluster additivity. This approach is shown to be especially well suited for microscopic models with many coupling constants, since the total number of relevant graphs is drastically reduced. The white-graph expansion is exemplified for a two dimensional quantum spin model of coupled two-leg XXZ ladders. PMID- 26382356 TI - Ground states of stealthy hyperuniform potentials: I. Entropically favored configurations. AB - Systems of particles interacting with "stealthy" pair potentials have been shown to possess infinitely degenerate disordered hyperuniform classical ground states with novel physical properties. Previous attempts to sample the infinitely degenerate ground states used energy minimization techniques, introducing algorithmic dependence that is artificial in nature. Recently, an ensemble theory of stealthy hyperuniform ground states was formulated to predict the structure and thermodynamics that was shown to be in excellent agreement with corresponding computer simulation results in the canonical ensemble (in the zero-temperature limit). In this paper, we provide details and justifications of the simulation procedure, which involves performing molecular dynamics simulations at sufficiently low temperatures and minimizing the energy of the snapshots for both the high-density disordered regime, where the theory applies, as well as lower densities. We also use numerical simulations to extend our study to the lower density regime. We report results for the pair correlation functions, structure factors, and Voronoi cell statistics. In the high-density regime, we verify the theoretical ansatz that stealthy disordered ground states behave like "pseudo" disordered equilibrium hard-sphere systems in Fourier space. The pair statistics obey certain exact integral conditions with very high accuracy. These results show that as the density decreases from the high-density limit, the disordered ground states in the canonical ensemble are characterized by an increasing degree of short-range order and eventually the system undergoes a phase transition to crystalline ground states. In the crystalline regime (low densities), there exist aperiodic structures that are part of the ground-state manifold but yet are not entropically favored. We also provide numerical evidence suggesting that different forms of stealthy pair potentials produce the same ground-state ensemble in the zero-temperature limit. Our techniques may be applied to sample the zero-temperature limit of the canonical ensemble of other potentials with highly degenerate ground states. PMID- 26382357 TI - Ground states of stealthy hyperuniform potentials. II. Stacked-slider phases. AB - Stealthy potentials, a family of long-range isotropic pair potentials, produce infinitely degenerate disordered ground states at high densities and crystalline ground states at low densities in d-dimensional Euclidean space R^{d}. In the previous paper in this series, we numerically studied the entropically favored ground states in the canonical ensemble in the zero-temperature limit across the first three Euclidean space dimensions. In this paper, we investigate using both numerical and theoretical techniques metastable stacked-slider phases, which are part of the ground-state manifold of stealthy potentials at densities in which crystal ground states are favored entropically. Our numerical results enable us to devise analytical models of this phase in two, three, and higher dimensions. Utilizing this model, we estimated the size of the feasible region in configuration space of the stacked-slider phase, finding it to be smaller than that of crystal structures in the infinite-system-size limit, which is consistent with our recent previous work. In two dimensions, we also determine exact expressions for the pair correlation function and structure factor of the analytical model of stacked-slider phases and analyze the connectedness of the ground-state manifold of stealthy potentials in this density regime. We demonstrate that stacked-slider phases are distinguishable states of matter; they are nonperiodic, statistically anisotropic structures that possess long-range orientational order but have zero shear modulus. We outline some possible future avenues of research to elucidate our understanding of this unusual phase of matter. PMID- 26382358 TI - Phase coexistence and particle nonconservation in a closed asymmetric exclusion process with inhomogeneities. AB - We construct a one-dimensional totally asymmetric simple exclusion process (TASEP) on a ring with two segments having unequal hopping rates, coupled to particle nonconserving Langmuir kinetics (LK) characterized by equal attachment and detachment rates. In the steady state, in the limit of competing LK and TASEP, the model is always found in states of phase coexistence. We uncover a nonequilibrium phase transition between a three-phase and a two-phase coexistence in the faster segment, controlled by the underlying inhomogeneity configurations and LK. The model is always found to be half-filled on average in the steady state, regardless of the hopping rates and the attachment-detachment rate. PMID- 26382359 TI - Finite-size scaling, dynamic fluctuations, and hyperscaling relation in the Kuramoto model. AB - We revisit the Kuramoto model to explore the finite-size scaling (FSS) of the order parameter and its dynamic fluctuations near the onset of the synchronization transition, paying particular attention to effects induced by the randomness of the intrinsic frequencies of oscillators. For a population of size N, we study two ways of sampling the intrinsic frequencies according to the same given unimodal distribution g(omega). In the "random" case, frequencies are generated independently in accordance with g(omega), which gives rise to oscillator number fluctuation within any given frequency interval. In the "regular" case, the N frequencies are generated in a deterministic manner that minimizes the oscillator number fluctuations, leading to quasiuniformly spaced frequencies in the population. We find that the two samplings yield substantially different finite-size properties with clearly distinct scaling exponents. Moreover, the hyperscaling relation between the order parameter and its fluctuations is valid in the regular case, but it is violated in the random case. In this last case, a self-consistent mean-field theory that completely ignores dynamic fluctuations correctly predicts the FSS exponent of the order parameter but not its critical amplitude. PMID- 26382360 TI - Stationary ensemble approximations of dynamic quantum states: Optimizing the generalized Gibbs ensemble. AB - In this work we investigate the nonequilibrium dynamics of closed quantum systems. In particular we focus on the stationary properties of integrable systems. Here we show how a generalized Gibbs ensemble (GGE) can be constructed as the best approximation to the time-dependent density matrix. Our procedure allows for a systematic construction of the GGE by a constrained minimization of the distance between the latter and the true state. Moreover, we show that the entropy of the GGE is a direct measure for the quality of the approximation. We apply our method to a quenched hard core Bose gas. Whereas a correlated GGE properly describes all stationary nonlocal correlations, a simple harmonic GGE is sufficient to completely describe reduced local states. PMID- 26382361 TI - Dimensionality dependence of aging in kinetics of diffusive phase separation: Behavior of order-parameter autocorrelation. AB - Behavior of two-time autocorrelation during the phase separation in solid binary mixtures is studied via numerical solutions of the Cahn-Hilliard equation as well as Monte Carlo simulations of the Ising model. Results are analyzed via state-of the-art methods, including the finite-size scaling technique. Full forms of the autocorrelation in space dimensions 2 and 3 are obtained empirically. The long time behavior is found to be power law, with exponents unexpectedly higher than the ones for the ferromagnetic ordering. Both Cahn-Hilliard and Ising models provide consistent results. PMID- 26382362 TI - Strength distribution of planar local load-sharing bundles. AB - Monte Carlo simulations and probabilistic modeling are employed to understand the strength distribution of a planar bundle of local load-sharing fibers. The fibers are distributed randomly within a unit square according to a Poisson process, and the fiber strengths are Weibull distributed with exponent rho. Monte Carlo failure simulations of bundles comprised of up to 10(5) fibers suggests that the bundle strength distribution obeys weakest-link scaling for all rho. Also, a probabilistic model of the weakest-link event is proposed. This model introduces a failure event at a size scale between that of the fiber and that of the bundle, whose failure statistics follows that of equal load-sharing bundles. The weakest link event is modelled as the growth of a tight cluster of these equal load sharing bundles. The size of the equal load-sharing bundles increases with decreasing rho. The simulated bundle strength distributions and those predicted by the model are compared, and excellent agreement is obtained. PMID- 26382363 TI - Normalizing the causality between time series. AB - Recently, a rigorous yet concise formula was derived to evaluate information flow, and hence the causality in a quantitative sense, between time series. To assess the importance of a resulting causality, it needs to be normalized. The normalization is achieved through distinguishing a Lyapunov exponent-like, one dimensional phase-space stretching rate and a noise-to-signal ratio from the rate of information flow in the balance of the marginal entropy evolution of the flow recipient. It is verified with autoregressive models and applied to a real financial analysis problem. An unusually strong one-way causality is identified from IBM (International Business Machines Corporation) to GE (General Electric Company) in their early era, revealing to us an old story, which has almost faded into oblivion, about "Seven Dwarfs" competing with a giant for the mainframe computer market. PMID- 26382364 TI - Percolation of the site random-cluster model by Monte Carlo method. AB - We propose a site random-cluster model by introducing an additional cluster weight in the partition function of the traditional site percolation. To simulate the model on a square lattice, we combine the color-assignation and the Swendsen Wang methods to design a highly efficient cluster algorithm with a small critical slowing-down phenomenon. To verify whether or not it is consistent with the bond random-cluster model, we measure several quantities, such as the wrapping probability Re, the percolating cluster density Pinfinity, and the magnetic susceptibility per site chip, as well as two exponents, such as the thermal exponent yt and the fractal dimension yh of the percolating cluster. We find that for different exponents of cluster weight q=1.5, 2, 2.5, 3, 3.5, and 4, the numerical estimation of the exponents yt and yh are consistent with the theoretical values. The universalities of the site random-cluster model and the bond random-cluster model are completely identical. For larger values of q, we find obvious signatures of the first-order percolation transition by the histograms and the hysteresis loops of percolating cluster density and the energy per site. Our results are helpful for the understanding of the percolation of traditional statistical models. PMID- 26382365 TI - Universal dynamic scaling in three-dimensional Ising spin glasses. AB - We use a nonequilibrium Monte Carlo simulation method and dynamical scaling to study the phase transition in three-dimensional Ising spin glasses. The transition point is repeatedly approached at finite velocity v (temperature change versus time) in Monte Carlo simulations starting at a high temperature. This approach has the advantage that the equilibrium limit does not have to be strictly reached for a scaling analysis to yield critical exponents. For the dynamic exponent we obtain z=5.85(9) for bimodal couplings distribution and z=6.00(10) for the Gaussian case. Assuming universal dynamic scaling, we combine the two results and obtain z=5.93+/-0.07 for generic 3D Ising spin glasses. PMID- 26382366 TI - Energy repartition for a harmonic chain with local reservoirs. AB - We exactly analyze the vibrational properties of a chain of harmonic oscillators in contact with local Langevin heat baths. Nonequilibrium steady-state fluctuations are found to be described by a set of mode temperatures, independent of the strengths of both the harmonic interaction and the viscous damping. Energy is equally distributed between the conjugate variables of a given mode but differently among different modes, in a manner which depends exclusively on the bath temperatures and on the boundary conditions. We outline how bath-temperature profiles can be designed to enhance or reduce fluctuations at specific frequencies in the power spectrum of the chain length. PMID- 26382367 TI - Principle of minimal work fluctuations. AB - Understanding and manipulating work fluctuations in microscale and nanoscale systems are of both fundamental and practical interest. For example, in considering the Jarzynski equality =e-betaDeltaF, a change in the fluctuations of e-betaW may impact how rapidly the statistical average of e-betaW converges towards the theoretical value e-betaDeltaF, where W is the work, beta is the inverse temperature, and DeltaF is the free energy difference between two equilibrium states. Motivated by our previous study aiming at the suppression of work fluctuations, here we obtain a principle of minimal work fluctuations. In brief, adiabatic processes as treated in quantum and classical adiabatic theorems yield the minimal fluctuations in e-betaW. In the quantum domain, if a system initially prepared at thermal equilibrium is subjected to a work protocol but isolated from a bath during the time evolution, then a quantum adiabatic process without energy level crossing (or an assisted adiabatic process reaching the same final states as in a conventional adiabatic process) yields the minimal fluctuations in e-betaW, where W is the quantum work defined by two energy measurements at the beginning and at the end of the process. In the classical domain where the classical work protocol is realizable by an adiabatic process, then the classical adiabatic process also yields the minimal fluctuations in e betaW. Numerical experiments based on a Landau-Zener process confirm our theory in the quantum domain, and our theory in the classical domain explains our previous numerical findings regarding the suppression of classical work fluctuations [G. Y. Xiao and J. B. Gong, Phys. Rev. E 90, 052132 (2014)]. PMID- 26382368 TI - Collisional statistics and dynamics of two-dimensional hard-disk systems: From fluid to solid. AB - We perform extensive MD simulations of two-dimensional systems of hard disks, focusing on the collisional statistical properties. We analyze the distribution functions of velocity, free flight time, and free path length for packing fractions ranging from the fluid to the solid phase. The behaviors of the mean free flight time and path length between subsequent collisions are found to drastically change in the coexistence phase. We show that single-particle dynamical properties behave analogously in collisional and continuous-time representations, exhibiting apparent crossovers between the fluid and the solid phases. We find that, both in collisional and continuous-time representation, the mean-squared displacement, velocity autocorrelation functions, intermediate scattering functions, and self-part of the van Hove function (propagator) closely reproduce the same behavior exhibited by the corresponding quantities in granular media, colloids, and supercooled liquids close to the glass or jamming transition. PMID- 26382369 TI - Enhancement of mobility in an interacting colloidal system under feedback control. AB - Feedback control schemes are a promising way to manipulate transport properties of driven colloidal suspensions. In the present article, we suggest a feedback scheme to enhance the collective transport of colloidal particles with repulsive interactions through a one-dimensional tilted washboard potential. The control is modeled by a harmonic confining potential, mimicking an optical "trap," with the center of this trap moving with the (instantaneous) mean particle position. Our theoretical analysis is based on the Smoluchowski equation combined with dynamical density functional theory for systems with hard-core or ultrasoft (Gaussian) interactions. For either type of interaction, we find that the feedback control can lead to an enhancement of the mobility by several orders of magnitude relative to the uncontrolled case. The largest effects occur for intermediate stiffness of the trap and large particle numbers. Moreover, in some regions of the parameter space the feedback control induces oscillations of the mean velocity. Finally, we show that the enhancement of mobility is robust against a small time delay in implementing the feedback control. PMID- 26382370 TI - First-order phase transition and tricritical scaling behavior of the Blume-Capel model: A Wang-Landau sampling approach. AB - We investigate the tricritical scaling behavior of the two-dimensional spin-1 Blume-Capel model by using the Wang-Landau method of measuring the joint density of states for lattice sizes up to 48*48 sites. We find that the specific heat deep in the first-order area of the phase diagram exhibits a double-peak structure of the Schottky-like anomaly appearing with the transition peak. The first-order transition curve is systematically determined by employing the method of field mixing in conjunction with finite-size scaling, showing a significant deviation from the previous data points. At the tricritical point, we characterize the tricritical exponents through finite-size-scaling analysis including the phenomenological finite-size scaling with thermodynamic variables. Our estimation of the tricritical eigenvalue exponents, yt=1.804(5), yg=0.80(1), and yh=1.925(3), provides the first Wang-Landau verification of the conjectured exact values, demonstrating the effectiveness of the density-of-states-based approach in finite-size scaling study of multicritical phenomena. PMID- 26382371 TI - Source-enhanced coalescence of trees in a random forest. AB - The time evolution of a random graph with varying number of edges and vertices is considered. The edges and vertices are assumed to be added at random by one at a time with different rates. A fresh edge connects either two linked components and forms a new component of larger order g (coalescence of graphs) or increases (by one) the number of edges in a given linked component (cycling). Assuming the vertices to have a finite valence (the number of edges connected with a given vertex is limited) the kinetic equation for the distribution of linked components of the graph over their orders and valences is formulated and solved exactly by applying the generating function method for the case of coalescence of trees. The evolution process is shown to reveal a phase transition: the emergence of a giant linked component whose order is comparable to the total order of the graph. The time dependencies of the moments of the distribution of linked components over their orders and valences are found explicitly for the pregelation period and the critical behavior of the spectrum is analyzed. It is found that the linked components are gamma distributed over g with the algebraic prefactor g-5/2. The coalescence process is shown to terminate by the formation of the steady-state gamma spectrum with the same algebraic prefactor. PMID- 26382372 TI - Lower-critical spin-glass dimension from 23 sequenced hierarchical models. AB - The lower-critical dimension for the existence of the Ising spin-glass phase is calculated, numerically exactly, as dL=2.520 for a family of hierarchical lattices, from an essentially exact (correlation coefficent R2=0.999999) near linear fit to 23 different diminishing fractional dimensions. To obtain this result, the phase transition temperature between the disordered and spin-glass phases, the corresponding critical exponent yT, and the runaway exponent yR of the spin-glass phase are calculated for consecutive hierarchical lattices as dimension is lowered. PMID- 26382373 TI - Temporally correlated zero-range process with open boundaries: Steady state and fluctuations. AB - We study an open-boundary version of the on-off zero-range process introduced in Hirschberg et al. [Phys. Rev. Lett. 103, 090602 (2009)]. This model includes temporal correlations which can promote the condensation of particles, a situation observed in real-world dynamics. We derive the exact solution for the steady state of the one-site system, as well as a mean-field approximation for larger one-dimensional lattices, and also explore the large deviation properties of the particle current. Analytical and numerical calculations show that, although the particle distribution is well described by an effective Markovian solution, the probability of rare currents differs from the memoryless case. In particular, we find evidence for a memory-induced dynamical phase transition. PMID- 26382374 TI - Probing the existence of phase transitions in one-dimensional fluids of penetrable particles. AB - Phase transitions in one-dimensional classical fluids are usually ruled out by using van Hove's theorem. A way to circumvent the conclusions of the theorem is to consider an interparticle potential that is everywhere bounded. Such is the case of, e.g., the generalized exponential model of index 4 (GEM-4 potential), which in three dimensions gives a reasonable description of the effective repulsion between flexible dendrimers in a solution. An extensive Monte Carlo simulation of the one-dimensional GEM-4 model [S. Prestipino, Phys. Rev. E 90, 042306 (2014)] has recently provided evidence of an infinite sequence of low temperature cluster phases, however, also suggesting that upon pushing the simulation forward what seemed a true transition may eventually prove to be only a sharp crossover. We hereby investigate this problem theoretically by use of three different and increasingly sophisticated approaches (i.e., a mean-field theory, the transfer matrix of a lattice model of clusters, and the exact treatment of a system of point clusters in the continuum) to conclude that the alleged transitions of the one-dimensional GEM-4 system are likely just crossovers. PMID- 26382375 TI - Hyperdiffusion of quantum waves in random photonic lattices. AB - A quantum-mechanical analysis of hyperfast (faster than ballistic) diffusion of a quantum wave packet in random optical lattices is presented. The main motivation of the presented analysis is experimental demonstrations of hyperdiffusive spreading of a wave packet in random photonic lattices [L. Levi et al., Nature Phys. 8, 912 (2012)]. A rigorous quantum-mechanical calculation of the mean probability amplitude is suggested, and it is shown that the power-law spreading of the mean-squared displacement (MSD) is ~talpha, where 2=3.4 the system is always in the paramagnetic phase. PMID- 26382381 TI - Mean perimeter of the convex hull of a random walk in a semi-infinite medium. AB - We study various properties of the convex hull of a planar Brownian motion, defined as the minimum convex polygon enclosing the trajectory, in the presence of an infinite reflecting wall. Recently [Phys. Rev. E 91, 050104(R) (2015)], we announced that the mean perimeter of the convex hull at time t, rescaled by ?Dt, is a nonmonotonous function of the initial distance to the wall. In this article, we first give all the details of the derivation of this mean rescaled perimeter, in particular its value when starting from the wall and near the wall. We then determine the physical mechanism underlying this surprising nonmonotonicity of the mean rescaled perimeter by analyzing the impact of the wall on two complementary parts of the convex hull. Finally, we provide a further quantification of the convex hull by determining the mean length of the portion of the reflecting wall visited by the Brownian motion as a function of the initial distance to the wall. PMID- 26382382 TI - Crossover behavior in interface depinning. AB - We study the crossover scaling behavior of the height-height correlation function in interface depinning in random media. We analyze experimental data from a fracture experiment and simulate an elastic line model with nonlinear couplings and disorder. Both exhibit a crossover between two different universality classes. For the experiment, we fit a functional form to the universal crossover scaling function. For the model, we vary the system size and the strength of the nonlinear term and describe the crossover between the two universality classes with a multiparameter scaling function. Our method provides a general strategy to extract scaling properties in depinning systems exhibiting crossover phenomena. PMID- 26382383 TI - Inferring Levy walks from curved trajectories: A rescaling method. AB - An important problem in the study of anomalous diffusion and transport concerns the proper analysis of trajectory data. The analysis and inference of Levy walk patterns from empirical or simulated trajectories of particles in two and three dimensional spaces (2D and 3D) is much more difficult than in 1D because path curvature is nonexistent in 1D but quite common in higher dimensions. Recently, a new method for detecting Levy walks, which considers 1D projections of 2D or 3D trajectory data, has been proposed by Humphries et al. The key new idea is to exploit the fact that the 1D projection of a high-dimensional Levy walk is itself a Levy walk. Here, we ask whether or not this projection method is powerful enough to cleanly distinguish 2D Levy walk with added curvature from a simple Markovian correlated random walk. We study the especially challenging case in which both 2D walks have exactly identical probability density functions (pdf) of step sizes as well as of turning angles between successive steps. Our approach extends the original projection method by introducing a rescaling of the projected data. Upon projection and coarse-graining, the renormalized pdf for the travel distances between successive turnings is seen to possess a fat tail when there is an underlying Levy process. We exploit this effect to infer a Levy walk process in the original high-dimensional curved trajectory. In contrast, no fat tail appears when a (Markovian) correlated random walk is analyzed in this way. We show that this procedure works extremely well in clearly identifying a Levy walk even when there is noise from curvature. The present protocol may be useful in realistic contexts involving ongoing debates on the presence (or not) of Levy walks related to animal movement on land (2D) and in air and oceans (3D). PMID- 26382384 TI - Anomalous transport on regular fracture networks: Impact of conductivity heterogeneity and mixing at fracture intersections. AB - We investigate transport on regular fracture networks that are characterized by heterogeneity in hydraulic conductivity. We discuss the impact of conductivity heterogeneity and mixing within fracture intersections on particle spreading. We show the emergence of non-Fickian transport due to the interplay between the network conductivity heterogeneity and the degree of mixing at nodes. Specifically, lack of mixing at fracture intersections leads to subdiffusive scaling of transverse spreading but has negligible impact on longitudinal spreading. An increase in network conductivity heterogeneity enhances both longitudinal and transverse spreading and leads to non-Fickian transport in longitudinal direction. Based on the observed Lagrangian velocity statistics, we develop an effective stochastic model that incorporates the interplay between Lagrangian velocity correlation and velocity distribution. The model is parameterized with a few physical parameters and is able to capture the full particle transition dynamics. PMID- 26382385 TI - Non-Markovian work fluctuation theorem in crossed electric and magnetic fields. AB - The validity of the transient work fluctuation theorem for a charged Brownian harmonic oscillator embedded in a non-Markovian heat bath and under the action of crossed electric and magnetic fields is investigated. The aforementioned theorem is verified to be valid within the context of the generalized Langevin equation with an arbitrary memory kernel and arbitrary dragging in the potential minimum. The fluctuation-dissipation relation of the second kind is assumed to be valid and shows that the non-Markovian stochastic dynamics associated with the particle, in the absence of the external time-dependent electric field, reaches an equilibrium state, as is precisely demanded by such a relation. The Jarzynski equality in this problem is also analyzed. PMID- 26382386 TI - Internal noise-driven generalized Langevin equation from a nonlocal continuum model. AB - Starting with a micropolar formulation, known to account for nonlocal microstructural effects at the continuum level, a generalized Langevin equation (GLE) for a particle, describing the predominant motion of a localized region through a single displacement degree of freedom, is derived. The GLE features a memory-dependent multiplicative or internal noise, which appears upon recognizing that the microrotation variables possess randomness owing to an uncertainty principle. Unlike its classical version, the present GLE qualitatively reproduces the experimentally measured fluctuations in the steady-state mean square displacement of scattering centers in a polyvinyl alcohol slab. The origin of the fluctuations is traced to nonlocal spatial interactions within the continuum, a phenomenon that is ubiquitous across a broad class of response regimes in solids and fluids. This renders the proposed GLE a potentially useful model in such cases. PMID- 26382387 TI - Modeling diffusion in colloidal suspensions by dynamical density functional theory using fundamental measure theory of hard spheres. AB - We study the dynamics of colloidal suspensions of hard spheres that are subject to Brownian motion in the overdamped limit. We obtain the time evolution of the self- and distinct parts of the van Hove function by means of dynamical density functional theory. The free-energy model for the hard-sphere fluid that we use is the very accurate White Bear II version of Rosenfeld's fundamental measure theory. However, in order to remove interactions within the self-part of the van Hove function, a nontrivial modification has to be applied to the free-energy functional. We compare our theoretical results with data that we obtain from dynamical Monte Carlo simulations, and we find that the latter are well described by our approach even for colloid packing fractions as large as 40%. PMID- 26382388 TI - Flow of wet granular materials: A numerical study. AB - We simulate dense assemblies of frictional spherical grains in steady shear flow under controlled normal stress P in the presence of a small amount of an interstitial liquid, which gives rise to capillary menisci, assumed isolated (pendular regime), and attractive forces, which are hysteretic: Menisci form at contact, but do not break until grains are separated by a finite rupture distance. The system behavior depends on two dimensionless control parameters, inertial number I and reduced pressure P*=aP/(piGamma), comparing confining forces ~a2P to meniscus tensile strength F0=piGammaa, for grains of diameter a joined by menisci with surface tension Gamma. We pay special attention to the quasistatic limit of slow flow and observe systematic, enduring strain localization in some of the cohesion-dominated (P*~0.1) systems. Homogeneous steady flows are characterized by the dependence of internal friction coefficient MU* and solid fraction Phi on I and P*. We also record normal stress differences, fairly small but not negligible and increasing for decreasing P*. The system rheology is moderately sensitive to saturation within the pendular regime, but would be different in the absence of capillary hysteresis. Capillary forces have a significant effect on the macroscopic behavior of the system, up to P* values of several units, especially for longer force ranges associated with larger menisci. The concept of effective pressure may be used to predict an order of magnitude for the strong increase of MU* as P* decreases but such a crude approach is unable to account for the complex structural changes induced by capillary cohesion, with a significant decrease of Phi and different agglomeration states and anisotropic fabric. Likewise, the Mohr-Coulomb criterion for pressure-dependent critical states is, at best, an approximation valid within a restricted range of pressures, with P*>=1. At small enough P*, large clusters of interacting grains form in slow flows, in which liquid bonds survive shear strains of several units. This affects the anisotropies associated with different interactions and the shape of function MU*(I), which departs more slowly from its quasistatic limit than in cohesionless systems (possibly explaining the shear banding tendency). PMID- 26382389 TI - Forced axial segregation in axially inhomogeneous rotating systems. AB - Controlling segregation is both a practical and a theoretical challenge. Using a novel drum design comprising concave and convex geometry, we explore, through the application of both discrete particle simulations and positron emission particle tracking, a means by which radial size segregation may be used to drive axial segregation, resulting in an order of magnitude increase in the rate of separation. The inhomogeneous drum geometry explored also allows the direction of axial segregation within a binary granular bed to be controlled, with a stable, two-band segregation pattern being reliably and reproducibly imposed on the bed for a variety of differing system parameters. This strong banding is observed to persist even in systems that are highly constrained in the axial direction, where such segregation would not normally occur. These findings, and the explanations provided of their underlying mechanisms, could lead to radical new designs for a broad range of particle processing applications but also may potentially prove useful for medical and microflow applications. PMID- 26382390 TI - Softening of stressed granular packings with resonant sound waves. AB - We perform numerical simulations of a two-dimensional bidisperse granular packing subjected to both a static confining pressure and a sinusoidal dynamic forcing applied by a wall on one edge of the packing. We measure the response experienced by a wall on the opposite edge of the packing and obtain the resonant frequency of the packing as the static or dynamic pressures are varied. Under increasing static pressure, the resonant frequency increases, indicating a velocity increase of elastic waves propagating through the packing. In contrast, when the dynamic amplitude is increased for fixed static pressure, the resonant frequency decreases, indicating a decrease in the wave velocity. This occurs both for compressional and for shear dynamic forcing and is in agreement with experimental results. We find that the average contact number Zc at the resonant frequency decreases with increasing dynamic amplitude, indicating that the elastic softening of the packing is associated with a reduced number of grain-grain contacts through which the elastic waves can travel. We image the excitations created in the packing and show that there are localized disturbances or soft spots that become more prevalent with increasing dynamic amplitude. Our results are in agreement with experiments on glass bead packings and earth materials such as sandstone and granite and may be relevant to the decrease in elastic wave velocities that has been observed to occur near fault zones after strong earthquakes, in surficial sediments during strong ground motion, and in structures during earthquake excitation. PMID- 26382391 TI - Granular flows on a dissipative base. AB - We study inclined channel flows of sand over a sensor-enabled composite geotextile fabric base that dissipates granular fluctuation energy. We record strain of the fabric along the flow direction with imbedded fiber-optic Bragg gratings, flow velocity on the surface by correlating grain position in successive images, flow thickness with the streamwise shift of an oblique laser light sheet, velocity depth profile through a transparent side wall using a high speed camera, and overall discharge rate. These independent measurements at inclinations between 33? and 37? above the angle of repose at 32.1+/-0.8? are consistent with a mass flow rate scaling as the 3/2 power of the flow depth, which is markedly different than flows on a rigid bumpy boundary. However, this power changes to 5/2 when flows are forced on the sand bed below its angle of repose. Strain measurements imply that the mean solid volume fraction in the flowing layer above the angle of repose is 0.268+/-0.033, independent of discharge rate or inclination. PMID- 26382392 TI - Emergence of traveling density waves in cyclic multiparticle transport. AB - Multiparticle flow through a cyclic array of K connected compartments with a preferential direction is found to be able to organize itself in traveling waves. This behavior is connected with the transition between uniform flow and cluster formation. When the bias in the system is large, the particles flow freely in the preferred direction, with all compartments being equally filled at all times. Conversely, when the bias is small the particles cluster together in one compartment. The transition between these two regimes is found to involve an intermediate state in which the flow exhibits a density peak traveling periodically around the system. We relate the emergence of this traveling wave to a Hopf bifurcation and analytically derive the critical value of the "symmetry parameter" at which this bifurcation occurs. This critical value proves to be independent of the number of compartments, but the width of the intermediate regime (and thus the chance of observing traveling wave solutions) decreases sharply with growing K. The reverse transition follows a different course and takes place at a significantly lower value of the symmetry parameter; it is an abrupt transition from a clustered state to a uniform flow without an intermediate regime of stable traveling waves. PMID- 26382393 TI - Grain-scale modeling of arbitrary fluid saturation in random packings. AB - We propose a model for increasing liquid saturation in a granular packing, which can account for liquid redistribution at saturation levels beyond the well studied capillary bridge regime. The model is capable of resolving and combining capillary bridges, menisci, and fully saturated pores to form local liquid clusters of any shape. They can exchange volume due to the local Laplace pressure gradient via a liquid film on the surfaces of grains. Local instabilities such as Haines jumps trigger the discontinuous evolution of the liquid front. The applicability of the model is demonstrated and compared to benchmark experiments on the level of individual liquid structures as well as on larger systems. PMID- 26382394 TI - Maximum entropy and the stress distribution in soft disk packings above jamming. AB - We show that the maximum entropy hypothesis can successfully explain the distribution of stresses on compact clusters of particles within disordered mechanically stable packings of soft, isotropically stressed, frictionless disks above the jamming transition. We show that, in our two-dimensional case, it becomes necessary to consider not only the stress but also the Maxwell-Cremona force-tile area as a constraining variable that determines the stress distribution. The importance of the force-tile area had been suggested by earlier computations on an idealized force-network ensemble. PMID- 26382395 TI - Elasticity of frictionless particles near jamming. AB - We study the linear elastic response of harmonic disk packings near jamming via three types of probes: (i) point forcing, (ii) constrained homogeneous deformation of subregions of large systems, and (iii) unconstrained deformation of the full system subject to periodic boundary conditions. For the point forcing, our results indicate that the transverse component of the response is governed by a lengthscale xiT, which scales with the confining pressure, p, as xiT~p-0.25, while the longitudinal component is governed by xiL, which scales as xiL~p-0.4. The former scaling is precisely the transverse lengthscale, which has been invoked to explain the structure of normal modes near the density of states anomaly in sphere packings, while the latter is much closer to the rigidity length, l*~p-0.5, which has been invoked to describe the jamming scenario. For the case of constrained homogeneous deformation, we find that MU(R), the value of the shear modulus measured in boxes of size R, gives a value much higher than the continuum result for small boxes and recedes to its continuum limit only for boxes bigger than a characteristic length, which scales like p-0.5, precisely the same way as l*. Finally, for the case of unconstrained homogeneous deformation, we find displacement fields with power spectra, which are consistent with independent, uncorrelated Eshelby transformations. The transverse sector is amazingly invariant with respect to p and very similar to what is seen in Lennard Jones glasses. The longitudinal piece, however, is sensitive to p. It develops a plateau at long wavelength, the start of which occurs at a length that grows in the p->0 limit. Strikingly, the same behavior is observed both for applied shear and dilation. PMID- 26382396 TI - Stick-slip instabilities in sheared granular flow: The role of friction and acoustic vibrations. AB - We propose a theory of shear flow in dense granular materials. A key ingredient of the theory is an effective temperature that determines how the material responds to external driving forces such as shear stresses and vibrations. We show that, within our model, friction between grains produces stick-slip behavior at intermediate shear rates, even if the material is rate strengthening at larger rates. In addition, externally generated acoustic vibrations alter the stick-slip amplitude, or suppress stick-slip altogether, depending on the pressure and shear rate. We construct a phase diagram that indicates the parameter regimes for which stick-slip occurs in the presence and absence of acoustic vibrations of a fixed amplitude and frequency. These results connect the microscopic physics to macroscopic dynamics and thus produce useful information about a variety of granular phenomena, including rupture and slip along earthquake faults, the remote triggering of instabilities, and the control of friction in material processing. PMID- 26382397 TI - Stress partition and microstructure in size-segregating granular flows. AB - When a granular mixture involving grains of different sizes is shaken, sheared, mixed, or left to flow, grains tend to separate by sizes in a process known as size segregation. In this study, we explore the size segregation mechanism in granular chute flows in terms of the pressure distribution and granular microstructure. Therefore, two-dimensional discrete numerical simulations of bidisperse granular chute flows are systematically analyzed. Based on the theoretical models of J. M. N. T. Gray and A. R. Thornton [Proc. R. Soc. A 461, 1447] and K. M. Hill and D. S. Tan [J. Fluid Mech. 756, 54 (2014)], we explore the stress partition in the phases of small and large grains, discriminating between contact stresses and kinetic stresses. Our results support both gravity induced and shear-gradient-induced segregation mechanisms. However, we show that the contact stress partition is extremely sensitive to the definition of the partial stress tensors and, more specifically, to the way mixed contacts (i.e., involving a small grain and a large grain) are handled, making conclusions on gravity-induced segregation uncertain. By contrast, the computation of the partial kinetic stress tensors is robust. The kinetic pressure partition exhibits a deviation from continuum mixture theory of a significantly higher amplitude than the contact pressure and displays a clear dependence on the flow dynamics. Finally, using a simple approximation for the contact partial stress tensors, we investigate how the contact stress partition relates to the flow microstructure and suggest that the latter may provide an interesting proxy for studying gravity induced segregation. PMID- 26382398 TI - Shear-induced segregation of particles by material density. AB - Recently, shear rate gradients and associated gradients in velocity fluctuations (e.g., granular temperatures or kinetic stresses) have been shown to drive segregation of different-sized particles in a manner that reverses at relatively high solids fractions (>0.50). Here we investigate these effects in mixtures of particles differing in material density through computational and theoretical studies of particles sheared in a vertical chute where we vary the solids fraction from =0.2 to 0.6. We find that in sparse flows, =0.2 to 0.4, the heavier (denser) particles segregate to lower shear rates similarly to the heavier (larger) particles in mixtures of particles differing only in size. However, there is no segregation reversal at high f in mixtures of particles differing in density. At all solids fractions, heavier (denser) particles segregate to regions of lower shear rates and lower granular temperatures, in contrast with segregation of different-sized particles at high f, where the heavier (larger) particles segregate to the region of higher shear rates. Kinetic theory predicts well the segregation for both types of systems at low f but breaks down at higher f's. Our recently proposed mixture theory for high f granular mixtures captures the segregation trends well via the independent partitioning of kinetic and contact stresses between the two species. In light of these results, we discuss possible directions forward for a model framework that encompasses segregation effects more broadly in these systems. PMID- 26382399 TI - Optimizing a reconfigurable material via evolutionary computation. AB - Rapid prototyping by combining evolutionary computation with simulations is becoming a powerful tool for solving complex design problems in materials science. This method of optimization operates in a virtual design space that simulates potential material behaviors and after completion needs to be validated by experiment. However, in principle an evolutionary optimizer can also operate on an actual physical structure or laboratory experiment directly, provided the relevant material parameters can be accessed by the optimizer and information about the material's performance can be updated by direct measurements. Here we provide a proof of concept of such direct, physical optimization by showing how a reconfigurable, highly nonlinear material can be tuned to respond to impact. We report on an entirely computer controlled laboratory experiment in which a 6*6 grid of electromagnets creates a magnetic field pattern that tunes the local rigidity of a concentrated suspension of ferrofluid and iron filings. A genetic algorithm is implemented and tasked to find field patterns that minimize the force transmitted through the suspension. Searching within a space of roughly 10^{10} possible configurations, after testing only 1500 independent trials the algorithm identifies an optimized configuration of layered rigid and compliant regions. PMID- 26382400 TI - Stability of electrophoretic transport of ions. AB - We present an investigation of instability during electrophoretic transport of ions in a class of electrolytes called oscillating electrolytes. We analyze the onset of instability in electrophoretic transport in a binary electrolyte by modeling growth of small concentration disturbances over a base state with uniform acid and base concentrations. Our linear stability analysis shows that the growth rate of low wave-number concentration disturbances increases with an increase in wave number. Whereas, the growth rate of high wave-number disturbances decreases with increasing wave number due to the stabilizing effect of molecular diffusion. Our analysis also yields the scaling for growth rates and the wave number of most unstable mode with electric field. In addition, we show that the electrophoretic system exhibits instability only for a certain range of species concentrations. We also discuss the physical mechanism underlying the instability of transport process. We show that the instability is exhibited by those binary electrolytes that consist of a multivalent species with unusually high electrophoretic mobility in higher ionization states. Throughout, we provide verification of our linear stability analysis with full nonlinear simulations. PMID- 26382401 TI - Equivalence of Brownian dynamics and dynamic Monte Carlo simulations in multicomponent colloidal suspensions. AB - We propose a simple but powerful theoretical framework to quantitatively compare Brownian dynamics (BD) and dynamic Monte Carlo (DMC) simulations of multicomponent colloidal suspensions. By extending our previous study focusing on monodisperse systems of rodlike colloids, here we generalize the formalism described there to multicomponent colloidal mixtures and validate it by investigating the dynamics in isotropic and liquid crystalline phases containing spherical and rodlike particles. In order to investigate the dynamics of multicomponent colloidal systems by DMC simulations, it is key to determine the elementary time step of each species and establish a unique timescale. This is crucial to consistently study the dynamics of colloidal particles with different geometry. By analyzing the mean-square displacement, the orientation autocorrelation functions, and the self part of the van Hove correlation functions, we show that DMC simulation is a very convenient and reliable technique to describe the stochastic dynamics of any multicomponent colloidal system. Our theoretical formalism can be easily extended to any colloidal system containing size and/or shape polydisperse particles. PMID- 26382402 TI - Equation of state for five-dimensional hyperspheres from the chemical-potential route. AB - We use the Percus-Yevick approach in the chemical-potential route to evaluate the equation of state of hard hyperspheres in five dimensions. The evaluation requires the derivation of an analytical expression for the contact value of the pair distribution function between particles of the bulk fluid and a solute particle with arbitrary size. The equation of state is compared with those obtained from the conventional virial and compressibility thermodynamic routes and the associated virial coefficients are computed. The pressure calculated from all routes is exact up to third density order, but it deviates with respect to simulation data as density increases, the compressibility and the chemical potential routes exhibiting smaller deviations than the virial route. Accurate linear interpolations between the compressibility route and either the chemical potential route or the virial one are constructed. PMID- 26382403 TI - Using the s ensemble to probe glasses formed by cooling and aging. AB - From length scale distributions characterizing frozen amorphous domains, we relate the s ensemble method with standard cooling and aging protocols for forming glass. We show that in a class of models where space-time scaling is in harmony with that of experiment, the spatial distributions of excitations obtained with the s ensemble are identical to those obtained through cooling or aging, but the computational effort for applying the s ensemble is generally many orders of magnitude smaller than that of straightforward numerical simulation of cooling or aging. We find that in contrast to the equilibrium ergodic state, a nonequilibrium length scale characterizes the anticorrelation between excitations and encodes the preparation history of glass states. PMID- 26382404 TI - Teorell instability in concentration polarization. AB - We investigate the development of electro-osmotic (Teorell) oscillations at a weakly charged microporous membrane without a preimposed transmembrane electrolyte concentration drop. This drop, necessary for the occurrence of oscillations, develops spontaneously as a result of concentration polarization in the solution layers adjacent to the membrane. A three-layer model comprising a membrane flanked by two diffusion layers is proposed and analyzed for galvano- and potentiostatic regimes of operation. PMID- 26382405 TI - Phase diagram and critical properties of Yukawa bilayers. AB - We study the ground-state Wigner bilayers of pointlike particles with Yukawa pairwise interactions, confined to the surface of two parallel hard walls at dimensionless distance eta. The model involves as limiting cases the unscreened Coulomb potential and hard spheres. The phase diagram of Yukawa particles, studied numerically by Messina and Lowen [Phys. Rev. Lett. 91, 146101 (2003)], exhibits five different staggered phases as eta varies from 0 to intermediate values. We present a lattice summation method using the generalized Misra functions which permits us to calculate the energy per particle of the phases with a precision much higher than usual in computer simulations. This allows us to address some tiny details of the phase diagram. Going from the hexagonal phase I to phase II is shown to occur at eta=0. All second-order phase transitions are proved to be of mean-field type. We also derive the asymptotic shape of critical lines close to the Coulomb and hard-spheres limits. In and close to the hard spheres limit, the dependence of the internal parameters of the present phases on eta is determined exactly. PMID- 26382406 TI - Strain fluctuations and elastic moduli in disordered solids. AB - Recently there has been a surge in interest in using video-microscopy techniques to infer the local mechanical properties of disordered solids. One common approach is to minimize the difference between particle vibrational displacements in a local coarse-graining volume and the displacements that would result from a best-fit affine deformation. Effective moduli are then inferred under the assumption that the components of this best-fit affine deformation tensor have a Boltzmann distribution. In this paper, we combine theoretical arguments with experimental and simulation data to demonstrate that the above does not reveal information about the true elastic moduli of jammed packings and colloidal glasses. PMID- 26382407 TI - Cooperativity and segregation in confined flows of soft binary glasses. AB - When a suspension containing particles of different sizes flows through a confined geometry a size gradient can be established, with large particles accumulating in the channel center. Such size separation driven by hydrodynamic interactions is expected to facilitate membrane filtration and may lead to the design of novel and innovative separation techniques. For this, a wide range of particle concentrations has to be investigated, in order to clarify whether shear induced migration can be utilized at concentrations close to or above the colloidal glass transition, where particle motion is severely hindered and hydrodynamic interactions are screened. We explore this scenario by studying the flow of binary mixtures of soft colloidal microgels, well above their liquid solid transition, through narrow microchannels. We find that, even though the flow becomes strongly heterogeneous, in both space and time, characterized by a large cooperativity length, size segregation still occurs. This suggests that even above the glass transition shear-induced diffusion could still be used as a fractionation mechanism, which is of great relevance for process intensification purposes. PMID- 26382409 TI - Adaptive elastic networks as models of supercooled liquids. AB - The thermodynamics and dynamics of supercooled liquids correlate with their elasticity. In particular for covalent networks, the jump of specific heat is small and the liquid is strong near the threshold valence where the network acquires rigidity. By contrast, the jump of specific heat and the fragility are large away from this threshold valence. In a previous work [Proc. Natl. Acad. Sci. USA 110, 6307 (2013)], we could explain these behaviors by introducing a model of supercooled liquids in which local rearrangements interact via elasticity. However, in that model the disorder characterizing elasticity was frozen, whereas it is itself a dynamic variable in supercooled liquids. Here we study numerically and theoretically adaptive elastic network models where polydisperse springs can move on a lattice, thus allowing for the geometry of the elastic network to fluctuate and evolve with temperature. We show numerically that our previous results on the relationship between structure and thermodynamics hold in these models. We introduce an approximation where redundant constraints (highly coordinated regions where the frustration is large) are treated as an ideal gas, leading to analytical predictions that are accurate in the range of parameters relevant for real materials. Overall, these results lead to a description of supercooled liquids, in which the distance to the rigidity transition controls the number of directions in phase space that cost energy and the specific heat. PMID- 26382408 TI - Evidence of slow Debye-like relaxation in the anti-inflammatory agent etoricoxib. AB - The origin of Debye-like relaxation in some hydrogen-bonded liquids is a matter of hot debate over the past decade. While a relatively clear picture of the issue has been established for monohydroxy alcohols, the Debye-type dynamics in other glass-forming systems still remains a not fully understood phenomenon. In this paper we present the results of dielectric measurements performed in the frequency interval 10(-1) to 10(9)Hz, both in the supercooled and normal liquid state of etoricoxib anti-inflammatory agent. Our investigations reveal the presence of slow Debye-like relaxation with features similar to that found for another active pharmaceutical ingredient, ibuprofen. Our results provide a fresh insight into the molecular nature of Debye-type relaxation in H-bonded pharmaceutically relevant materials and thus may stimulate the academic community for further discussion concerning the molecular dynamics of hydrogen-bonded fluids in general. PMID- 26382410 TI - Simple improvements to classical bubble nucleation models. AB - We revisit classical nucleation theory (CNT) for the homogeneous bubble nucleation rate and improve the classical formula using a correct prefactor in the nucleation rate. Most of the previous theoretical studies have used the constant prefactor determined by the bubble growth due to the evaporation process from the bubble surface. However, the growth of bubbles is also regulated by the thermal conduction, the viscosity, and the inertia of liquid motion. These effects can decrease the prefactor significantly, especially when the liquid pressure is much smaller than the equilibrium one. The deviation in the nucleation rate between the improved formula and the CNT can be as large as several orders of magnitude. Our improved, accurate prefactor and recent advances in molecular dynamics simulations and laboratory experiments for argon bubble nucleation enable us to precisely constrain the free energy barrier for bubble nucleation. Assuming the correction to the CNT free energy is of the functional form suggested by Tolman, the precise evaluations of the free energy barriers suggest the Tolman length is ?0.3sigma independently of the temperature for argon bubble nucleation, where sigma is the unit length of the Lennard-Jones potential. With this Tolman correction and our prefactor one gets accurate bubble nucleation rate predictions in the parameter range probed by current experiments and molecular dynamics simulations. PMID- 26382411 TI - Molecular dynamics analysis of the velocity slip of a water and methanol liquid mixture. AB - The effect of methanol mixing on a nanoscale water flow was examined by using nonequilibrium molecular dynamics simulations of a Couette-type flow between nonpolarized smooth solid surfaces. Water and methanol molecules were uniformly mixed in the bulk, whereas at the solid-liquid interface methanol molecules showed a tendency to be adsorbed on the solid surface. Similar to a macroscale Couette flow, the shear stress exerted on the solid surface was equal to the shear stress in the liquid, showing that the mechanical balance holds in nanoscale. In addition, the shear stress in the liquid bulk was equal to the viscous stress which is a product of viscosity and velocity gradient. When more methanol molecules were adsorbed on the solid surface, the friction coefficient (FC) between solid and liquid was largely reduced with a small amount of methanol and that led to a remarkable decrease of the shear stress. The cause of the FC reduction was investigated in terms of the local rotational diffusion coefficient (RDC) near the solid surface, and it was shown that different from an existing model, the FC and local RDC were not simply inversely proportional to each other in the mixture system because the solid-liquid interfacial state was more complex. PMID- 26382412 TI - Role of heat generation and thermal diffusion during frontal photopolymerization. AB - Frontal photopolymerization (FPP) is a rapid and versatile solidification process that can be used to fabricate complex three-dimensional structures by selectively exposing a photosensitive monomer-rich bath to light. A characteristic feature of FPP is the appearance of a sharp polymerization front that propagates into the bath as a planar traveling wave. In this paper, we introduce a theoretical model to determine how heat generation during photopolymerization influences the kinetics of wave propagation as well as the monomer-to-polymer conversion profile, both of which are relevant for FPP applications and experimentally measurable. When thermal diffusion is sufficiently fast relative to the rate of polymerization, the system evolves as if it were isothermal. However, when thermal diffusion is slow, a thermal wavefront develops and propagates at the same rate as the polymerization front. This leads to an accumulation of heat behind the polymerization front which can result in a significant sharpening of the conversion profile and acceleration of the growth of the solid. Our results also suggest that a novel way to tailor the dynamics of FPP is by imposing a temperature gradient along the growth direction. PMID- 26382413 TI - Liquid-bridge breakup in contact-drop dispensing: Liquid-bridge stability with a free contact line. AB - The static stability of weightless liquid bridges with a free contact line with respect to axisymmetric and nonaxisymmetric perturbations is studied. Constant volume and constant-pressure stability regions are constructed in slenderness versus cylindrical volume diagrams for fixed contact angles. Bifurcations along the stability-region boundaries are characterized by the structure of axisymmetric bridge branches and families of equilibria. A wave-number definition is presented based on the pieces-of-sphere states at branch terminal points to classify equilibrium branches and identify branch connections. Compared with liquid bridges pinned at two equal disks, the free contact line breaks the equatorial and reflective symmetries, affecting the lower boundary of the constant-volume stability region where axisymmetric perturbations are critical. Stability is lost at transcritical bifurcations and turning points along this boundary. Our results furnish the maximum-slenderness stability limit for drop deposition on real surfaces when the contact angle approaches the receding contact angle. PMID- 26382414 TI - Creep rupture of fiber bundles: A molecular dynamics investigation. AB - The creep deformation and eventual breaking of polymeric samples under a constant tensile load F is investigated by molecular dynamics based on a particle representation of the fiber bundle model. The results of the virtual testing of fibrous samples consisting of 40000 particles arranged on Nc=400 chains reproduce characteristic stages seen in the experimental investigations of creep in polymeric materials. A logarithmic plot of the bundle lifetime tau versus load F displays a marked curvature, ruling out a simple power-law dependence of tau on F. A power law tau~F-4, however, is recovered at high load. We discuss the role of reversible bond breaking and formation on the eventual fate of the sample and simulate a different type of creep testing, imposing a constant stress rate on the sample up to its breaking point. Our simulations, relying on a coarse-grained representation of the polymer structure, introduce new features into the standard fiber bundle model, such as real-time dynamics, inertia, and entropy, and open the way to more detailed models, aiming at material science aspects of polymeric fibers, investigated within a sound statistical mechanics framework. PMID- 26382415 TI - Solidification of a disk-shaped crystal from a weakly supercooled binary melt. AB - The physics of ice crystal growth from the liquid phase, especially in the presence of salt, has received much less attention than the growth of snow crystals from the vapor phase. The growth of so-called frazil ice by solidification of a supercooled aqueous salt solution is consistent with crystal growth in the basal plane being limited by the diffusive removal of the latent heat of solidification from the solid-liquid interface, while being limited by attachment kinetics in the perpendicular direction. This leads to the formation of approximately disk-shaped crystals with a low aspect ratio of thickness compared to radius, because radial growth is much faster than axial growth. We calculate numerically how fast disk-shaped crystals grow in both pure and binary melts, accounting for the comparatively slow axial growth, the effect of dissolved solute in the fluid phase, and the difference in thermal properties between solid and fluid phases. We identify the main physical mechanisms that control crystal growth and show that the diffusive removal of both the latent heat released and the salt rejected at the growing interface are significant. Our calculations demonstrate that certain previous parametrizations, based on scaling arguments, substantially underestimate crystal growth rates by a factor of order 10-100 for low aspect ratio disks, and we provide a parametrization for use in models of ice crystal growth in environmental settings. PMID- 26382416 TI - Bridging transitions for spheres and cylinders. AB - We study bridging transitions between spherically and cylindrically shaped particles (colloids) of radius R separated by a distance H that are dissolved in a bulk fluid (solvent). Using macroscopics, microscopic density-functional theory, and finite-size scaling theory, we study the location and order of the bridging transition and also the stability of the liquid bridges, which determines spinodal lines. The location of the bridging transitions is similar for cylinders and spheres, so that at bulk coexistence, for example, the distance H_{b} at which a transition between bridged and unbridged configurations occurs is proportional to the colloid radius R. However, all other aspects, particularly the stability of liquid bridges, are very different in the two systems. Thus, for cylinders the bridging transition is typically strongly first-order, while for spheres it may be first-order, critical, or rounded as determined by a critical radius R_{c}. The influence of thick wetting films and fluctuation effects beyond mean field are also discussed in depth. PMID- 26382417 TI - Thermal response of cholesteric liquid crystal elastomers. AB - The effects of temperature variation on photonic properties of cholesteric liquid crystal elastomers (CLCEs) are investigated in mechanically unconstrained and constrained geometries. In the unconstrained geometry, cooling in the cholesteric state induces both a considerable shift of the selective reflection band to shorter wavelengths and a finite degree of macroscopic expansion in the two directions normal to the axis of the helical director configuration. The thermal deformation is driven by a change in orientational order of the underlying nematic structure S and the relation between the macroscopic strain and S is explained on the basis of the anisotropic Gaussian chain network model. The helical pitch varies with the film thickness in an affine manner under temperature variation. The CLCEs under the constrained geometry where thermal deformation is strictly prohibited show no shift of the reflection bands when subjected to temperature variation. This also reveals the strong correlation between the macroscopic dimensions and the pitch of the helical director configuration. PMID- 26382418 TI - Flexoelectric polarization studies in bent-core nematic liquid crystals. AB - The flexoelectric polarization (Pf) of four bent-core nematic liquid crystals (LCs) has been measured using the pyroelectric effect. Hybrid aligned nematic cells are fabricated for measuring the pyroelectric response over the entire range of the nematic phase. It is found that the magnitude of flexoelectric polarization Pf and the sum of the flexoelectric coefficients |e1+e3| for the bent-core LCs studied here are three to six times higher than for the calamitics. Pf is found to depend on the transverse dipole moment of LC molecules. However, |e1+e3| values are by no means giant as |e3| alone had been reported for a bent core nematic system previously. The dependence of the sum of "splay and bend flexoelectric coefficients" is discussed in terms of the shape of the molecule and of the dipole moment directed normal to the molecular axis. PMID- 26382419 TI - Comparison of photoinduced reorientation of ortho-, meta-, and para-methyl red doped nematic liquid crystals on rubbed polyimide. AB - We compare the photoinduced reorientation of the easy axis on rubbed polyimide surfaces for the nematic E7 doped with three isomers of methyl red; ortho, meta, and para. Using optical techniques, the angle and the pitch of the director at the polymer surface were measured before, during, and after photoexcitation of the dye. Optical absorbances were also measured before and after photoexcitation. Extrapolation lengths, hence anchoring energies, were determined with the on/off application of a magnetic field for meta- and para-methyl red-doped nematics. Because of an elastic reorientation of the easy axis in the presence of the magnetic field, we could not determine the extrapolation length of the ortho methyl red-doped nematic. Our results confirm that photoinduced reorientation is facilitated by desorption of all dyes from the polymer surface. While there is little evidence of weak photoinduced adsorption of meta- and para-methyl red to the surface during photoexcitation, there is strong evidence of photoinduced adsorption of ortho-methyl red, which is long lasting. PMID- 26382420 TI - Clustering effects in ionic polymers: Molecular dynamics simulations. AB - Ionic clusters control the structure, dynamics, and transport in soft matter. Incorporating a small fraction of ionizable groups in polymers substantially reduces the mobility of the macromolecules in melts. These ionic groups often associate into random clusters in melts, where the distribution and morphology of the clusters impact the transport in these materials. Here, using molecular dynamic simulations we demonstrate a clear correlation between cluster size and morphology with the polymer mobility in melts of sulfonated polystyrene. We show that in low dielectric media ladderlike clusters that are lower in energy compared with spherical assemblies are formed. Reducing the electrostatic interactions by enhancing the dielectric constant leads to morphological transformation from ladderlike clusters to globular assemblies. Decrease in electrostatic interaction significantly enhances the mobility of the polymer. PMID- 26382421 TI - Time-dependent Ginzburg-Landau model for nonfrustrated linear ABC triblock terpolymers. AB - A time-dependent Ginzburg-Landau (TDGL) model is proposed to simulate the ordering of linear ABC triblock terpolymers. The model, in its current form, is applicable to nonfrustrated triblock systems, with the specific condition that chiAC?chiAB~chiBC. Simulations are presented that demonstrate the model's ability to evolve a wide variety of morphologies throughout time, including tetragonal, core-shell hexagonal, three-phase lamellar, and beads-in-lamellar phases. The model also incorporates an interaction term to study templated substrates for directed self-assembly. The efficiency of the TDGL model enables large-scale simulations that allow investigation of self-assembly, and directed self assembly, processes that may exhibit very small defect concentrations. PMID- 26382422 TI - Surface-adsorption-induced polymer translocation through a nanopore: Effects of the adsorption strength and the surface corrugation. AB - The surface corrugation plays an important role in single polymer diffusion on attractive surfaces. However, its effect on dynamics of surface adsorption induced polymer translocation through a nanopore is not clear. Using three dimensional Langevin dynamics simulations, we investigate the dynamics of a flexible polymer chain translocation through a nanopore induced by the selective adsorption of translocated segments onto the trans side of the membrane. The translocation probability Ptrans increases monotonically, while the mean translocation time tau has a minimum as a function of the adsorption strength E, which are explained from the perspective of the effective driving force for the translocation. With the surface being smoother, tau as well as the scaling exponent alpha of tau with the chain length N decreases. Finally, we show that the distributions of the translocation time are non-Gaussian even for strong adsorption at a moderate surface corrugation. A nearly Gaussian distribution of the translocation time is observed only for the smoothest surface we studied. PMID- 26382423 TI - Distribution of glass transition temperatures Tg in polystyrene thin films as revealed by low-energy muon spin relaxation: A comparison with neutron reflectivity results. AB - In a previous paper [Phys. Rev. E 83, 021801 (2011)] we performed neutron reflectivity (NR) measurements on a five-layer polystyrene (PS) thin film consisting of alternatively stacked deuterated polystyrene (dPS) and hydrogenated polystyrene (hPS) layers (dPS/hPS/dPS/hPS/dPS, ~100 nm thick) on a Si substrate to reveal the distribution of Tg along the depth direction. Information on the Tg distribution is very useful to understand the interesting but unusual properties of polymer thin films. However, one problem that we have to clarify is if there are effects of deuterium labeling on Tg or not. To tackle the problem we performed low-energy muon spin relaxation (MUSR) measurements on the above mentioned deuterium-labeled five-layer PS thin film as well as dPS and hPS single layer thin films ~100 nm thick as a function of muon implantation energy. It was found that the deuterium labeling had no significant effects on the Tg distribution, guaranteeing that we can safely discuss the unusual thin film properties based on the Tg distribution revealed by NR on the deuterium-labeled thin films. In addition, the MUSR result suggested that the higher Tg near the Si substrate is due to the strong orientation of phenyl rings. PMID- 26382424 TI - Poroelastic model for adsorption-induced deformation of biopolymers obtained from molecular simulations. AB - Molecular simulation of adsorption of water molecules in nanoporous amorphous biopolymers, e.g., cellulose, reveals nonlinear swelling and nonlinear mechanical response with the increase in fluid content. These nonlinearities result from hydrogen bond breakage by water molecules. Classical poroelastic models, employing porosity and pore pressure as basic variables for describing the "pore fluid," are not adequate for the description of these systems. There is neither a static geometric structure to which porosity can sensibly be assigned nor arrangements of water molecules that are adequately described by giving them a pressure. We employ molar concentration of water and chemical potential to describe the state of the "pore fluid" and stress-strain as mechanical variables. A thermodynamic description is developed using a model energy function having mechanical, fluid, and fluid-mechanical coupling contributions. The parameters in this model energy are fixed by the output of the initial simulation and validated with the results of further simulation. The poroelastic properties, e.g., swelling and mechanical response, are found to be functions both of the molar concentration of water and the stress. The basic fluid-mechanical coupling coefficient, the swelling coefficient, depends on the molar concentration of water and stress and is interpreted in terms of porosity change and solid matrix deformation. The difference between drained and undrained bulk stiffness is explained as is the dependence of these moduli on concentration and stress. PMID- 26382425 TI - Dynamics of polyelectrolyte solutions under a constant gradient of base concentration. AB - Phase-separation dynamics of weakly charged polyacid solutions under a constant gradient of base concentration is studied both theoretically and numerically. The time-evolution equation of polymer volume fraction is derived by assuming that the chemical equilibrium of the dissociation reaction is locally established. Numerical simulations of the system in contact with two reservoirs in which the base concentrations differ are performed. The numerical results show that the polymer volume fraction can be transported by the concentration gradient of the base, which leads to the dynamic behavior of mesophase domain structures. PMID- 26382426 TI - Feeding ducks, bacterial chemotaxis, and the Gini index. AB - Classic experiments on the distribution of ducks around separated food sources found consistency with the "ideal free" distribution in which the local population is proportional to the local supply rate. Motivated by this experiment and others, we examine the analogous problem in the microbial world: the distribution of chemotactic bacteria around multiple nearby food sources. In contrast to the optimization of uptake rate that may hold at the level of a single cell in a spatially varying nutrient field, nutrient consumption by a population of chemotactic cells will modify the nutrient field, and the uptake rate will generally vary throughout the population. Through a simple model we study the distribution of resource uptake in the presence of chemotaxis, consumption, and diffusion of both bacteria and nutrients. Borrowing from the field of theoretical economics, we explore how the Gini index can be used as a means to quantify the inequalities of uptake. The redistributive effect of chemotaxis can lead to a phenomenon we term "chemotactic levelling," and the influence of these results on population fitness are briefly considered. PMID- 26382427 TI - Dynamic patterns in a two-dimensional neural field with refractoriness. AB - The formation of dynamic patterns such as localized propagating waves is a fascinating self-organizing phenomenon that happens in a wide range of spatially extended systems including neural systems, in which they might play important functional roles. Here we derive a type of two-dimensional neural-field model with refractoriness to study the formation mechanism of localized waves. After comparing this model with existing neural-field models, we show that it is able to generate a variety of localized patterns, including stationary bumps, localized waves rotating along a circular path, and localized waves with longer range propagation. We construct explicit bump solutions for the two-dimensional neural field and conduct a linear stability analysis on how a stationary bump transitions to a propagating wave under different spatial eigenmode perturbations. The neural-field model is then partially solved in a comoving frame to obtain localized wave solutions, whose spatial profiles are in good agreement with those obtained from simulations. We demonstrate that when there are multiple such propagating waves, they exhibit rich propagation dynamics, including propagation along periodically oscillating and irregular trajectories; these propagation dynamics are quantitatively characterized. In addition, we show that these waves can have repulsive or merging collisions, depending on their collision angles and the refractoriness parameter. Due to its analytical tractability, the two-dimensional neural-field model provides a modeling framework for studying localized propagating waves and their interactions. PMID- 26382429 TI - Conditions for positioning of nucleosomes on DNA. AB - Positioning of nucleosomes along a eukaryotic genome plays an important role in its organization and regulation. There are many different factors affecting the location of nucleosomes. Some can be viewed as preferential binding of a single nucleosome to different locations along the DNA and some as interactions between neighboring nucleosomes. In this study, we analyze positioning of nucleosomes and derive conditions for their good positioning. Using analytic and numerical approaches we find that, if the binding preferences are very weak, an interplay between the interactions and the binding preferences is essential for a good positioning of nucleosomes, especially on correlated energy landscapes. Analyzing the empirical energy landscape, we conclude that good positioning of nucleosomes in vivo is possible only if they strongly interact. In this case, our model, predicting long-length-scale fluctuations of nucleosomes' occupancy along the DNA, accounts well for the empirical observations. PMID- 26382428 TI - Diffusive transport through a model host-biofilm system. AB - Free-living biofilms have been subject to considerable attention, and basic physical principles for them are generally accepted. Many host-biofilm systems, however, consist of heterogeneous mixtures of aggregates of microbes intermixed with host material and are much less studied. Here we analyze a key property, namely reactive depletion, in such systems and argue that two regimes are possible: (1) a homogenizable mixture of biofilm and host that in important ways acts effectively like a homogeneous macrobiofilm and (2) a distribution of separated microbiofilms within the host with independent local microenvironments. PMID- 26382430 TI - Spatial evolution of tumors with successive driver mutations. AB - We study the influence of driver mutations on the spatial evolutionary dynamics of solid tumors. We start with a cancer clone that expands uniformly in three dimensions giving rise to a spherical shape. We assume that cell division occurs on the surface of the growing tumor. Each cell division has a chance to give rise to a mutation that activates an additional driver gene. The resulting clone has an enhanced growth rate, which generates a local ensemble of faster growing cells, thereby distorting the spherical shape of the tumor. We derive formulas for the abundance and diversity of additional driver mutations as function of time. Our model is semi-deterministic: the spatial growth of cancer clones is deterministic, while mutants arise stochastically. PMID- 26382431 TI - Effects of pore-size and shape distributions on diffusion pore imaging by nuclear magnetic resonance. AB - In medical imaging and porous media research, NMR diffusion measurements are extensively used to investigate the structure of diffusion restrictions such as cell membranes. Recently, several methods have been proposed to unambiguously determine the shape of arbitrary closed pores or cells filled with an NMR-visible medium by diffusion experiments. The first approach uses a combination of a long and a short diffusion-weighting gradient pulse, while the other techniques employ short gradient pulses only. While the eventual aim of these methods is to determine pore-size and shape distributions, the focus has been so far on identical pores. Thus, the aim of this work is to investigate the ability of these different methods to resolve pore-size and orientation distributions. Simulations were performed comparing the various pore imaging techniques employing different distributions of pore size and orientation and varying timing parameters. The long-narrow gradient profile is most advantageous to investigate pore distributions, because average pore images can be directly obtained. The short-gradient methods suppress larger pores or induce a considerable blurring. Moreover, pore-shape-specific artifacts occur; for example, the central part of a distribution of cylinders may be largely underestimated. Depending on the actual pore distribution, short-gradient methods may nonetheless yield good approximations of the average pore shape. Furthermore, the application of short gradient methods can be advantageous to differentiate whether pore-size distributions or intensity distributions, e.g., due to surface relaxation, are predominant. PMID- 26382432 TI - Complex kinetics of DNA condensation revealed through DNA twist tracing. AB - Toroid formation is an important mechanism for DNA condensation in cells. The length change during DNA condensation was investigated in previous single molecule experiments. However, DNA twist is key to understanding the topological kinetics of DNA condensation. In this study, DNA twist as well as DNA length was traced during the DNA condensation by the freely orbiting magnetic tweezers and the tilted magnetic tweezers combined with Brownian dynamics simulations. The experimental results disclose the complex relationship between DNA extension and backbone rotation. Brownian dynamics simulations show that the toroid formation follows a wiggling pathway which leads to the complex DNA backbone rotation as revealed in our experiments. These findings provide the complete description of multivalent cation-dependent DNA toroid formation under tension. PMID- 26382433 TI - Controlling the extent of viral genome release by a combination of osmotic stress and polyvalent cations. AB - While several in vitro experiments on viral genome release have specifically studied the effects of external osmotic pressure and of the presence of polyvalent cations on the ejection of DNA from bacteriophages, few have systematically investigated how the extent of ejection is controlled by a combination of these effects. In this work we quantify the effect of osmotic pressure on the extent of DNA ejection from bacteriophage lambda as a function of polyvalent cation concentration (in particular, the tetravalent polyamine spermine). We find that the pressure required to completely inhibit ejection decreases from 38 to 17 atm as the spermine concentration is increased from 0 to 1.5 mM. Further, incubation of the phage particles in spermine concentrations as low as 0.15 mM--the threshold for DNA condensation in bulk solution-is sufficient to significantly limit the extent of ejection in the absence of osmolyte; for spermine concentrations below this threshold, the ejection is complete. In accord with recent investigations on the packaging of DNA in the presence of a condensing agent, we observe that the self-attraction induced by the polyvalent cation affects the ordering of the genome, causing it to get stuck in a broad range of nonequilibrated structures. PMID- 26382434 TI - Model for calcium-mediated reduction of structural fluctuations in epidermis. AB - We propose a reaction-advection-diffusion model of epidermis consisting of two variables, the degree of differentiation and the calcium ion concentration, where calcium ions enhance differentiation. By analytically and numerically investigating this system, we show that a calcium localization layer formed beneath the stratum corneum helps reduce spatiotemporal fluctuations of the structure of the stratum corneum. In particular, spatially or temporally small scale fluctuations in the lower structure are suppressed and do not affect the upper structure, due to acceleration of differentiation by calcium ions. Analytical expressions for the reduction rate of fluctuation amplitudes are shown. PMID- 26382435 TI - Dynamic competition between transcription initiation and repression: Role of nonequilibrium steps in cell-to-cell heterogeneity. AB - Transcriptional repression may cause transcriptional noise by a competition between repressor and RNA polymerase binding. Although promoter activity is often governed by a single limiting step, we argue here that the size of the noise strongly depends on whether this step is the initial equilibrium binding or one of the subsequent unidirectional steps. Overall, we show that nonequilibrium steps of transcription initiation systematically increase the cell-to-cell heterogeneity in bacterial populations. In particular, this allows also weak promoters to give substantial transcriptional noise. PMID- 26382436 TI - Interplay between stochasticity and negative feedback leads to pulsed dynamics and distinct gene activity patterns. AB - Gene expression is an inherently stochastic process that depends on the structure of the biochemical regulatory network in which the gene is embedded. Here we study the dynamical consequences of the interplay between stochastic gene switching and the widespread negative feedback regulatory loop in a simple model of a biochemical regulatory network. Using a simplified hybrid simulation approach, in which only the gene activation is modeled stochastically, we find that stochasticity in gene switching by itself can induce pulses in the system, providing also analytical insights into their origin. Furthermore, we find that this simple network is able to reproduce both exponential and peaked distributions of gene active and inactive times similar to those that have been observed experimentally. This simplified hybrid simulation approach also allows us to link these patterns to the dynamics of the system for each gene state. PMID- 26382437 TI - Wing-pitch modulation in maneuvering fruit flies is explained by an interplay between aerodynamics and a torsional spring. AB - While the wing kinematics of many flapping insects have been well characterized, understanding the underlying sensory, neural, and physiological mechanisms that determine these kinematics is still a challenge. Two main difficulties in understanding the physiological mechanisms arise from the complexity of the interaction between a flapping wing and its own unsteady flow, as well as the intricate mechanics of the insect wing hinge, which is among the most complicated joints in the animal kingdom. These difficulties call for the application of reduced-order approaches. Here this strategy is used to model the torques exerted by the wing hinge along the wing-pitch axis of maneuvering fruit flies as a damped torsional spring with elastic and damping coefficients as well as a rest angle. Furthermore, we model the air flows using simplified quasistatic aerodynamics. Our findings suggest that flies take advantage of the passive coupling between aerodynamics and the damped torsional spring to indirectly control their wing-pitch kinematics by modulating the spring parameters. The damped torsional-spring model explains the changes measured in wing-pitch kinematics during roll correction maneuvers through modulation of the spring damping and elastic coefficients. These results, in conjunction with the previous literature, indicate that flies can accurately control their wing-pitch kinematics on a sub-wing-beat time scale by modulating all three effective spring parameters on longer time scales. PMID- 26382438 TI - Effect and evolution of gene expression noise on the fitness landscape. AB - Gene expression is a stochastic process that affects cellular and population fitness. Noise in gene expression can enhance fitness by increasing cell to cell variability as well as the time cells spend in favorable expression states. Using a stochastic model of gene expression together with a fitness function that incorporates the costs and benefits of gene expression in a stressful environment, we show that the fitness landscape is shaped by gene expression noise in more complex ways than previously anticipated. We find that mutations modulating the properties of expression noise enable cell populations to optimize their position on the fitness landscape. Additionally, we find that low levels of expression noise evolve under conditions where the fitness benefits of expression exceed the fitness costs, and that high levels of expression noise evolve when the expression costs exceed the fitness benefits. The results presented in this study expand our understanding of the interplay between stochastic gene expression and fitness in selective environments. PMID- 26382439 TI - Metapopulation dynamics in a complex ecological landscape. AB - We propose a general model to study the interplay between spatial dispersal and environment spatiotemporal fluctuations in metapopulation dynamics. An ecological landscape of favorable patches is generated like a Levy dust, which allows to build a range of patterns, from dispersed to clustered ones. Locally, the dynamics is driven by a canonical model for the time evolution of the population density, consisting of a logistic expression plus multiplicative noises. Spatial coupling is introduced by means of two spreading mechanisms: diffusion and selective dispersal driven by patch suitability. We focus on the long-time population size as a function of habitat configurations, environment fluctuations, and coupling schemes. We obtain the conditions, that the spatial distribution of favorable patches and the coupling mechanisms must fulfill, to grant population survival. The fundamental phenomenon that we observe is the positive feedback between environment fluctuations and spatial spread preventing extinction. PMID- 26382440 TI - Up and down translocation events and electric double-layer formation inside solid state nanopores. AB - We present a theoretical study of nanorod translocation events through solid state nanopores of different sizes which result in positive or negative ion conductance changes. Using theoretical models, we show that positive conductance changes or up events happen for nanopore diameters smaller than a transition diameter dt, and negative conductance changes or down events occur for nanopore diameters larger than dt. We investigate the underlying physics of such translocation phenomena and describe the significance of the electric double layer effects for nanopores with small diameters. Furthermore, for nanopores with large diameters, it is shown that a geometric model, formulated based on the nanoparticle blockade inside the nanopore, provides a straightforward and reasonably accurate prediction of ion conductance change. Based on this concept, we also implement a method to distinguish and detect nanorods of different sizes by focusing solely on the sign and not the exact value of the conductance change. PMID- 26382441 TI - Ribosome utilizes the minimum free energy changes to achieve the highest decoding rate and fidelity. AB - The performance of ribosome translation can be characterized by two factors, the translation rate and fidelity. Here, we provide analytical studies of the effect of the near-cognate tRNAs on the two factors. It is shown that the increase of the concentration of the near-cognate tRNAs relative to that of the cognate tRNA has negative effects on the ribosome translation by reducing both the translation rate and the translation fidelity. The effect of the near-cognate ternary complexes on the translation rate results mainly from the initial selection phase, whereas the proofreading phase has a minor effect. By contrast, the effect of the near-cognate ternary complexes on the fidelity results almost equally from the two phases. By using two successive phases, the initial selection and the proofreading, the ribosome can achieve higher translation fidelity than the product of the fidelity when only the initial selection is included and when only the proofreading is included, especially at the large ratio of the concentration of the near-cognate tRNAs compared to that of the cognate tRNA. Moreover, we study the changes of the free energy landscape in the tRNA decoding step. It is found that the rate constants of the tRNA decoding step measured experimentally give the minimum energy changes for the ribosomal complex to attain the optimal performance with both the highest decoding rate and fidelity and/or with the maximum value of the decoding fitness function. This suggests that the ribosome has evolved to utilize the minimum free energy changes gained from the conformational changes of the ribosome, EF-Tu, and tRNA to achieve the optimal performance in the tRNA decoding. PMID- 26382442 TI - Fast sparsely synchronized brain rhythms in a scale-free neural network. AB - We consider a directed version of the Barabasi-Albert scale-free network model with symmetric preferential attachment with the same in- and out-degrees and study the emergence of sparsely synchronized rhythms for a fixed attachment degree in an inhibitory population of fast-spiking Izhikevich interneurons. Fast sparsely synchronized rhythms with stochastic and intermittent neuronal discharges are found to appear for large values of J (synaptic inhibition strength) and D (noise intensity). For an intensive study we fix J at a sufficiently large value and investigate the population states by increasing D. For small D, full synchronization with the same population-rhythm frequency fp and mean firing rate (MFR) fi of individual neurons occurs, while for large D partial synchronization with fp> (: ensemble-averaged MFR) appears due to intermittent discharge of individual neurons; in particular, the case of fp>4 is referred to as sparse synchronization. For the case of partial and sparse synchronization, MFRs of individual neurons vary depending on their degrees. As D passes a critical value D* (which is determined by employing an order parameter), a transition to unsynchronization occurs due to the destructive role of noise to spoil the pacing between sparse spikes. For D