ALBERT

Description: by Cedric Alaux, Samuel Soubeyrand, Alberto Prado, Mathilde Peruzzi, Alban Maisonnasse, Julien Vallon, Julie Hernandez, Pascal Jourdan, Yves Le Conte Honeybee colonies are increasingly exposed to environmental stress factors, which can lead to their decline or failure. However, there are major gaps in stressor risk assessment due to the difficulty of assessing the honeybee colony state and detecting abnormal events. Since stress factors usually induce a demographic disturbance in the colony (e.g. loss of foragers, early transition from nurse to forager state), we suggest that disturbances could be revealed indirectly by measuring the age- and task-related physiological state of bees, which can be referred to as biological age (an indicator of the changes in physiological state that occur throughout an individual lifespan). We therefore estimated the biological age of bees from the relationship between age and biomarkers of task specialization (vitellogenin and the adipokinetic hormone receptor). This relationship was determined from a calibrated sample set of known-age bees and mathematically modelled for biological age prediction. Then, we determined throughout the foraging season the evolution of the biological age of bees from colonies with low (conventional apiary) or high Varroa destructor infestation rates (organic apiary). We found that the biological age of bees from the conventional apiary progressively decreased from the spring (17 days) to the fall (6 days). However, in colonies from the organic apiary, the population aged from spring (13 days) to summer (18.5 days) and then rejuvenated in the fall (13 days) after Varroa treatment. Biological age was positively correlated with the amount of brood (open and closed cells) in the apiary with low Varroa pressure, and negatively correlated with Varroa infestation level in the apiary with high Varroa pressure. Altogether, these results show that the estimation of biological age is a useful and effective method for assessing colony demographic state and likely detrimental effects of stress factors.

Description: by Maganizo B. Chagomerana, William C. Miller, Jennifer H. Tang, Irving F. Hoffman, Bryna J. Harrington, Bethany DiPrete, Shaphil Wallie, Allan Jumbe, Laura Limarzi, Mina C. Hosseinipour Background In Malawi’s PMTCT Option B+ program, HIV-infected pregnant women who are already receiving ART are continued on their current therapy regimen without testing for treatment failure at the first antenatal care (ANC) visit. HIV RNA screening at ANC may identify women with treatment failure and ensure that viral suppression is maintained throughout the pregnancy. Methods We conducted a cross-sectional study of HIV-infected pregnant women who had been receiving ART for at least 6 months at the first ANC visit under the PMTCT Option B+ program at Bwaila Hospital in Lilongwe, Malawi from June 2015 to December 2017. Poisson regression models with robust variance were used to investigate the predictors of ART treatment failure defined as viral load ≥1000 copies/ml. Results The median age of 864 women tested for ART failure was 31.1 years (interquartile range: 26.9–34.5). The prevalence of treatment failure was 7.6% (95% confidence interval (CI): 6.0–9.6). CD4 cell count (adjusted prevalence ratio (aPR) = 0.57; 95% CI: 0.50–0.65) was strongly associated with treatment failure. Conclusion The low prevalence of treatment failure among women presenting for their first ANC in urban Malawi demonstrates success of Option B+ in maintaining viral suppression and suggests progress towards the last 90% of the UNAIDS 90-90-90 targets. Women failing on ART should be identified early for adherence counseling and may require switching to an alternative ART regimen.

Description: by Rie Matsushima-Nishiwaki, Noriko Yamada, Kouki Fukuchi, Osamu Kozawa A bioactive lipid, sphingosine 1-phosphate (S1P), acts extracellularly as a potent mediator, and is implicated in the progression of various cancers including hepatocellular carcinoma (HCC). S1P exerts its functions by binding to five types of specific receptors, S1P receptor 1 (S1PR1), S1PR2, S1PR3, S1PR4 and S1PR5 on the plasma membrane. However, the exact roles of S1P and each S1PR in HCC cells remain to be clarified. In the present study, we investigated the effect of S1P on the hepatocyte growth factor (HGF)-induced migration of human HCC-derived HuH7 cells, and the involvement of each S1PR. S1P dose-dependently reduced the HGF-induced migration of HuH7 cells. We found that all S1PRs exist in the HuH7 cells. Among each selective agonist for five S1PRs, CYM5520, a selective S1PR2 agonist, significantly suppressed the HGF-induced HuH7 cell migration whereas selective agonists for S1PR1, S1PR3, S1PR4 or S1PR5 failed to affect the migration. The reduction of the HGF-induced migration by S1P was markedly reversed by treatment of JTE013, a selective antagonist for S1PR2, and S1PR2- siRNA. These results strongly suggest that S1P reduces the HGF-induced HCC cell migration via S1PR2. Our findings may provide a novel potential of S1PR2 to therapeutic strategy for metastasis of HCC.

Description: by Mircea Zloteanu, Nigel Harvey, David Tuckett, Giacomo Livan The Sharing Economy (SE) is a growing ecosystem focusing on peer-to-peer enterprise. In the SE the information available to assist individuals (users) in making decisions focuses predominantly on community-generated trust and reputation information. However, how such information impacts user judgement is still being understood. To explore such effects, we constructed an artificial SE accommodation platform where we varied the elements related to hosts’ digital identity, measuring users’ perceptions and decisions to interact. Across three studies, we find that trust and reputation information increases not only the users’ perceived trustworthiness, credibility, and sociability of hosts, but also the propensity to rent a private room in their home. This effect is seen when providing users both with complete profiles and profiles with partial user-selected information. Closer investigations reveal that three elements relating to the host’s digital identity are sufficient to produce such positive perceptions and increased rental decisions, regardless of which three elements are presented. Our findings have relevant implications for human judgment and privacy in the SE, and question its current culture of ever increasing information-sharing.

Description: by Tucker Maxson, Candace D. Blancett, Amanda S. Graham, Christopher P. Stefan, Timothy D. Minogue Development and implementation of rapid antimicrobial susceptibility testing is critical for guiding patient care and improving clinical outcomes, especially in cases of sepsis. One approach to reduce the time-to-answer for antimicrobial susceptibility is monitoring the inhibition of DNA production, as differences in DNA concentrations are more quickly impacted compared to optical density changes in traditional antimicrobial susceptibility testing. Here, we use real-time PCR to rapidly determine antimicrobial susceptibility after short incubations with antibiotic. Application of this assay to a collection of 144 isolates in mock blood culture, covering medically relevant pathogens displaying high rates of resistance, provided susceptibility data in under 4 hours. This assay provided categorical agreement with a reference method in 96.3% of cases across all species. Sequencing of a subset of PCR amplicons showed accurate genus level identification. Overall, implementation of this method could provide accurate susceptibility results with a reduced time-to-answer for a number of medically relevant bacteria commonly isolated from blood culture.

Description: by Ágota Nagy, Levente Kovács, Zoltán Lipinszki, Margit Pál, Péter Deák In most Eukaryotes, ubiquitin either exists as free monoubiquitin or as a molecule that is covalently linked to other proteins. These two forms cycle between each other and due to the concerted antagonistic activity of ubiquitylating and deubiquitylating enzymes, an intracellular ubiquitin equilibrium is maintained that is essential for normal biological function. However, measuring the level and ratio of these forms of ubiquitin has been difficult and time consuming. In this paper, we have adapted a simple immunoblotting technique to monitor ubiquitin content and equilibrium dynamics in different developmental stages and tissues of Drosophila . Our data show that the level of total ubiquitin is distinct in different developmental stages, lowest at the larval-pupal transition and in three days old adult males, and highest in first instar larvae. Interestingly, the ratio of free mono-ubiquitin remains within 30–50% range of the total throughout larval development, but peaks to 70–80% at the larval-pupal and the pupal-adult transitions. It stays within the 70–80% range in adults. In developmentally and physiologically active tissues, the ratio of free ubiquitin is similarly high, most likely reflecting a high demand for ubiquitin availability. We also used this method to demonstrate the disruption of the finely tuned ubiquitin equilibrium by the abolition of proteasome function or the housekeeping deubiquitylase, Usp5. Our data support the notion that the ubiquitin equilibrium is regulated by tissue- and developmental stage-specific mechanisms.

Description: by Huirong Cheng, Pei Hu, Weihua Wen, Ling Liu Three arsenic species in urine are measured using an atomic absorption spectrophotometer. RT-PCR is performed to detect the expression levels of AS3MT, 3 miRNAs, and 17 relative mRNAs in 43 workers producing arsenic trioxide, 36 workers who stopped exposure to arsenic for 85 days, and 24 individuals as the control group. The concentrations of urinary arsenic are very high in workers. A negative correlation between AS3MT and MiR-5 48c-3p is found. There exist significant changes for most selected miRNAs and mRNAs in workers. There are no significant differences between workers who stopped exposure to arsenic and the control group for most miRNAs and mRNAs, but the MiR-5 48c-3p levels show significant changes. Similar positive correlations between the expression of AS3MT and all selected mRNAs are found. Negative correlations between the expression of MiR-5 48c-3p and many relative mRNAs are found as well. AS3MT and MiR-5 48c-3p may regulate arsenic methylation jointly, which when involved in a group of relative mRNAs may play roles in arsenic metabolism and epigenetic changes caused by this metabolism.

Description: by Xinyi Liu, Diane L. Lister, Zhijun Zhao, Cameron A. Petrie, Xiongsheng Zeng, Penelope J. Jones, Richard A. Staff, Anil K. Pokharia, Jennifer Bates, Ravindra N. Singh, Steven A. Weber, Giedre Motuzaite Matuzeviciute, Guanghui Dong, Haiming Li, Hongliang Lü, Hongen Jiang, Jianxin Wang, Jian Ma, Duo Tian, Guiyun Jin, Liping Zhou, Xiaohong Wu, Martin K. Jones

Description: by Jonas R. Kunst, Esther N. Phillibert It is well-established that experiences of discrimination influence immigrants’ acculturation. Yet, whereas a large body of research has demonstrated the role of discrimination by members of the dominant societal group, surprisingly little is known about how being discriminated by members of one’s own group relates to the way immigrants acculturate. With a sample of 162 African first- and second-generation immigrants living in Norway, the present research investigated the relationship between both types of discrimination, acculturation and psychological well-being. It did so, focusing on discrimination based on one’s skin tone, a type of discrimination Africans can experience from White as well as African individuals. Results showed that skin-tone discrimination by Whites was associated with a lower host culture orientation. By contrast, skin-tone discrimination by Africans was associated with a lower heritage culture orientation. Mediation analyses showed that the positive relationship of skin-tone discrimination by Whites and Africans with life satisfaction was mediated by a lower host and heritage culture orientation respectively. This indirect relationship did not reach significance with self-esteem as dependent variable. Participants’ actual skin tone was unrelated to experiences of skin-tone discrimination. We discuss our results in light of previous research and highlight potential limitations.

Description: by Christian Agebratt, Edvin Ström, Thobias Romu, Olof Dahlqvist-Leinhard, Magnus Borga, Per Leandersson, Fredrik H. Nystrom

Description: by Motoyasu Honma, Yuri Masaoka, Shinichi Koyama, Takeshi Kuroda, Akinori Futamura, Azusa Shiromaru, Yasuo Terao, Kenjiro Ono, Mitsuru Kawamura Parkinson's disease (PD) is associated with various cognitive impairments. However, the nature of cognitive modification in patients with PD remains to be elucidated. In the present study, we examined whether patients with PD could correct and maintain subjective time duration and line length estimation. After training sessions, in which participants repeatedly memorized either a duration or a length, we compared a learning performance in 20 PD patients with 20 healthy controls. In the case of duration in the PD patients, the learned durations immediately returned to baseline of pre-training within a few minutes. However, the patients’ ability to learn length estimation remained unimpaired. In contrast, healthy controls were able to retain the learned duration and length estimations. Time compression in PD's internal clock may become entrained to their altered duration estimation even after learning of accurate time duration. These deficits may be associated with disrupting cognitive modification in PD.

Description: by Greg Holmes, Lening Zhang, Joshua Rivera, Ryan Murphy, Claudia Assouline, Lorraine Sullivan, Todd Oppeneer, Ethylin Wang Jabs Activating mutations of fibroblast growth factor receptors (FGFRs) are a major cause of skeletal dysplasias, and thus they are potential targets for pharmaceutical intervention. BMN 111, a C-type natriuretic peptide analog, inhibits FGFR signaling at the level of the RAF1 kinase through natriuretic peptide receptor 2 (NPR2) and has been shown to lengthen the long bones and improve skull morphology in the Fgfr3 Y367C/+ thanatophoric dysplasia mouse model. Here we report the effects of BMN 111 in treating craniosynostosis and aberrant skull morphology in the Fgfr2c C342Y/+ Crouzon syndrome mouse model. We first demonstrated that NPR2 is expressed in the murine coronal suture and spheno-occipital synchondrosis in the newborn period. We then gave Fgfr2c C342Y/+ and Fgfr2c +/+ (WT) mice once-daily injections of either vehicle or reported therapeutic levels of BMN 111 between post-natal days 3 and 31. Changes in skeletal morphology, including suture patency, skull dimensions, and long bone length, were assessed by micro-computed tomography. Although BMN 111 treatment significantly increased long bone growth in both WT and mutant mice, skull dimensions and suture patency generally were not significantly affected. A small but significant increase in the relative length of the anterior cranial base was observed. Our results indicate that the differential effects of BMN 111 in treating various skeletal dysplasias may depend on the process of bone formation targeted (endochondral or intramembranous), the specific FGFR mutated, and/or the specific signaling pathway changes due to a given mutation.

Description: by Irineu Loturco, Bret Contreras, Ronaldo Kobal, Victor Fernandes, Neilton Moura, Felipe Siqueira, Ciro Winckler, Timothy Suchomel, Lucas Adriano Pereira The capacity to rapidly generate and apply a great amount of force seems to play a key role in sprint running. However, it has recently been shown that, for sprinters, the technical ability to effectively orient the force onto the ground is more important than its total amount. The force-vector theory has been proposed to guide coaches in selecting the most adequate exercises to comprehensively develop the neuromechanical qualities related to the distinct phases of sprinting. This study aimed to compare the relationships between vertically-directed (loaded and unloaded vertical jumps, and half-squat) and horizontally-directed (hip-thrust) exercises and the sprint performance of top-level track and field athletes. Sixteen sprinters and jumpers (including three Olympic athletes) executed vertical jumps, loaded jump squats and hip-thrusts, and sprinting speed tests at 10-, 20-, 40-, 60-, 100-, and 150-m. Results indicated that the hip-thrust is more associated with the maximum acceleration phase (i.e., from zero to 10-m; r = 0.93), whereas the loaded and unloaded vertical jumps seem to be more related to top-speed phases (i.e., distances superior to 40-m; r varying from 0.88 to 0.96). These findings reinforce the mechanical concepts supporting the force-vector theory, and provide coaches and sport scientists with valuable information about the potential use and benefits of using vertically- or horizontally-based training exercises.

Description: by Pei-Chun Kao, Michaela A. Pierro, Konstantina Booras Cognitive-motor interference, a negative influence on the performance of one or both tasks, is manifested when simultaneously performing a cognitive and a motor task. Motor fatigue reduces the ability of generating a required force level. However, little is known about the effects of motor fatigue on the cognitive-motor dual-tasking performance, an important capability during our daily lives. This study investigated how motor fatigue affects dual-task walking performance. Eighteen healthy younger adults walked on a treadmill under three different conditions: walking only, walking while receiving the Paced Auditory Serial Addition Test (PASAT) or a modified Stroop test before and after a lower-extremity fatiguing exercise. We computed dynamic margins of stability (MOS), step and joint kinematic variability, and short-term local divergence exponent (LDE) of the trunk motion. We found that subjects had similar values of short-term LDE during all conditions, indicating that local stability was not affected by the motor fatigue or dual-task conditions. Compared to the baseline, subjects had significantly greater mean MOS after the fatiguing exercise by walking with greater step length and width while having significantly greater gait variability. In contrast, subjects walked with similar mean MOS but significantly less gait variability during the dual-task conditions, indicating that subjects used different adaptive strategies when walking with motor fatigue and during dual-task conditions. There were no significant differences in the number of errors for the two cognitive tests before and after the fatiguing exercise. The current findings demonstrate that motor fatigue does not affect cognitive but motor performance in younger adults.

Description: by Insu Lee, Daegyu Kim, Ga-Lahm Park, Tae-Joon Jeon, Sun Min Kim When living tissues are injured, they undergo a sequential process of homeostasis, inflammation, proliferation and maturation, which is called wound healing. The working mechanism of wound healing has not been wholly understood due to its complex environments with various mechanical and chemical factors. In this study, we propose a novel in vitro wound healing model using a microfluidic system that can manipulate the topography of the wound bed. The topography of the extracellular matrix (ECM) in the wound bed is one of the most important mechanical properties for rapid and effective wound healing. We focused our work on the topographical factor which is one of crucial mechanical cues in wound healing process by using various nano-patterns on the cell attachment surface. First, we analyzed the cell morphology and dynamic cellular behaviors of NIH-3T3 fibroblasts on the nano-patterned surface. Their morphology and dynamic behaviors were investigated for relevance with regard to the recovery function. Second, we developed a highly reproducible and inexpensive research platform for wound formation and the wound healing process by combining the nano-patterned surface and a microfluidic channel. The effect of topography on wound recovery performance was analyzed. This in vitro wound healing research platform will provide well-controlled topographic cue of wound bed and contribute to the study on the fundamental mechanism of wound healing.

Description: by Tilen Koklic, Iztok Urbančič, Irena Zdovc, Majda Golob, Polona Umek, Zoran Arsov, Goran Dražić, Štefan Pintarič, Martin Dobeic, Janez Štrancar Bacterial infections acquired in healthcare facilities including hospitals, the so called healthcare acquired or nosocomial infections, are still of great concern worldwide and represent a significant economical burden. One of the major causes of morbidity is infection with Methicillin Resistant Staphylococcus aureus (MRSA), which has been reported to survive on surfaces for several months. Bactericidal activity of copper-TiO 2 thin films, which release copper ions and are deposited on glass surfaces and heated to high temperatures, is well known even when illuminated with very weak UVA light of about 10 μW/cm 2 . Lately, there is an increased intrerest for one-dimensional TiO 2 nanomaterials, due to their unique properties, low cost, and high thermal and photochemical stability. Here we show that copper doped TiO 2 nanotubes produce about five times more ·OH radicals as compared to undoped TiO 2 nanotubes and that effective surface disinfection, determined by a modified ISO 22196:2011 test, can be achieved even at low intensity UVA light of 30 μW/cm 2 . The nanotubes can be deposited on a preformed surface at room temperature, resulting in a stable deposition resistant to multiple washings. Up to 10 3 microorganisms per cm 2 can be inactivated in 24 hours, including resistant strains such as Methicillin-resistant Staphylococcus aureus (MRSA) and Extended-spectrum beta-lactamase Escherichia coli ( E . coli ESBL). This disinfection method could provide a valuable alternative to the current surface disinfection methods.

Description: by Tim J. Sloan, Jonna Jalanka, Giles A. D. Major, Shanthi Krishnasamy, Sue Pritchard, Salah Abdelrazig, Katri Korpela, Gulzar Singh, Claire Mulvenna, Caroline L. Hoad, Luca Marciani, David A. Barrett, Miranda C. E. Lomer, Willem M. de Vos, Penny A. Gowland, Robin C. Spiller Background & aims Ingestion of poorly digested, fermentable carbohydrates (fermentable oligo-, di-, mono-saccharides and polyols; FODMAPs) have been implicated in exacerbating intestinal symptoms and the reduction of intake with symptom alleviation. Restricting FODMAP intake is believed to relieve colonic distension by reducing colonic fermentation but this has not been previously directly assessed. We performed a randomised controlled trial comparing the effect of a low FODMAP diet combined with either maltodextrin or oligofructose on colonic contents, metabolites and microbiota. Methods A parallel randomised controlled trial in healthy adults (n = 37). All subjects followed a low FODMAP diet for a week and supplemented their diet with either maltodextrin (MD) or oligofructose (OF) 7g twice daily. Fasted assessments performed pre- and post-diet included MRI to assess colonic volume, breath testing for hydrogen and methane, and stool collection for microbiota analysis. Results The low FODMAP diet was associated with a reduction in Bifidobacterium and breath hydrogen, which was reversed by oligofructose supplementation. The difference in breath hydrogen between groups post-intervention was 27ppm (95% CI 7 to 50, P

Description: by Geethika Reddi, Kali Pruss, Kathryn L. Cottingham, Ronald K. Taylor, Salvador Almagro-Moreno Vibrio cholerae O1, the etiological agent of cholera, is a natural inhabitant of aquatic ecosystems. Motility is a critical element for the colonization of both the human host and its environmental reservoirs. In this study, we investigated the molecular mechanisms underlying the chemotactic response of V . cholerae in the presence of some of its environmental reservoirs. We found that, from the several oligosaccharides found in mucin, two specifically triggered motility of V . cholerae O1: N -acetylneuraminic acid (Neu5Ac) and N -acetylglucosamine (GlcNAc). We determined that the compounds need to be internally catabolized in order to trigger motility of V . cholerae . Interestingly, the catabolism of Neu5Ac and GlcNAc converges and the production of one molecule common to both pathways, glucosamine-6-phosphate (GlcN-6P), is essential to induce motility in the presence of both compounds. Mutants unable to produce GlcN-6P show greatly reduced motility towards mucin. Furthermore, we determined that the production of GlcN-6P is necessary to induce motility of V . cholerae in the presence of some of its environmental reservoirs such as crustaceans or cyanobacteria, revealing a molecular link between the two distinct modes of the complex life cycle of V . cholerae . Finally, cross-species comparisons revealed varied chemotactic responses towards mucin, GlcNAc, and Neu5Ac for environmental (non-pathogenic) strains of V . cholerae , clinical and environmental isolates of the human pathogens Vibrio vulnificus and Vibrio parahaemolyticus , and fish and squid isolates of the symbiotic bacterium Vibrio fischeri . The data presented here suggest nuance in convergent strategies across species of the same bacterial family for motility towards suitable substrates for colonization.

Description: by Anne C. Wheeler, Camila V. Ventura, Ty Ridenour, Danielle Toth, Lucélia Lima Nobrega, Lana Claudia Silva de Souza Dantas, Camilla Rocha, Donald B. Bailey Jr., Liana O. Ventura The recent Zika outbreak and its link to microcephaly and other birth defects in infants exposed in utero have garnered widespread international attention. Based on the severity of birth defects the extent of impairment in these infants is expected to be profound; however, virtually nothing is known regarding the developmental and behavioral sequela of congenital Zika syndrome. This pilot study collected parent-reported patterns of development and sleep in 47 infants with confirmed congenital Zika syndrome who are being followed for clinical services at the Altino Ventura Foundation (FAV) in Recife, Brazil. With assistance from clinicians at FAV, caregivers completed Brazilian Portuguese versions of the Ages and Stages Questionnaire, 3 rd edition (ASQ-3) and the Brief Infant Sleep Questionnaire (BISQ). All infants were between 13–22 months of age at the time of the assessment. At 16 months of age, none of the children displayed age appropriate developmental skills. Most (~ 75%) mastered some communication and gross motor skills at around a 6–8-month level. Communication and gross motor skills were relative strengths for the sample, while problem-solving and fine motor skills were relative weaknesses. Sleep was noted to be a problem for around 18% of the sample. In utero exposure to the Zika virus will have lifelong consequences for affected children and their families. Understanding the developmental and behavioral trajectories of affected infants will help identify appropriate family supports to improve quality of life.

Description: by Veronique Deschodt-Arsac, Romain Lalanne, Beatrice Spiluttini, Claire Bertin, Laurent M. Arsac Introduction Heart rate variability biofeedback (HRV-BFB) training, a method whereby one controls an unusually low breathing rate to reach cardiac coherence, has been shown to reduce anxiety and improve cardiac autonomic markers in diseased people, but much less is known about HRV-BFB benefits in healthy people. Here we investigated potential benefits in young competitors experiencing stress during university examinations as well as persistence of benefits after HRV-BFB training cessation. Methods A group of sports students (n = 12) practiced 5-min HRV-BFB training twice a day for 5-weeks using URGOfeel ® (URGOTECH) and was compared to a control group (n = 6). University examinations occurred immediately after HRV-BFB training (Exam1), then 12-weeks later (Exam2). Anxiety markers and cardiac autonomic markers were assessed at baseline, Exam1 and Exam2. Principal Component Analyses (PCA) that combined all these markers were computed at Exam1 and Exam2 to emphasize covariations. Results At Exam 1, immediately after HRV-BFB training cessation, the experimental group demonstrated greater autonomic markers but similar states of anxiety when compared to the Control group. Twelve weeks later at Exam2, autonomic markers were greater and anxiety scores were lesser among the experimental group. PCA highlighted covariations only within cardiac autonomic markers at Exam1. Rather, variations in cardiac markers were associated with anxiety markers at Exam2. Conclusion Short sessions of HRV-BFB training for a brief period of 5 weeks bring substantial benefits to autonomic markers and anxiety levels in young competitors. Here beneficial effects persisted for 12 weeks. Dissociated profiles of anxiety and cardiac autonomic adaptations shed new light on the role of the amygdala in heart-brain interactions after cardiac coherence training.

Description: by Karina T. Barretto, Calvin M. Swanson, Christopher L. Nguyen, Douglas S. Annis, Stephane J. Esnault, Deane F. Mosher, Mats W. Johansson Periostin, which is induced by interleukin (IL)-13, is an extracellular matrix (ECM) protein that supports α M β 2 integrin-mediated adhesion and migration of IL-5-stimulated eosinophils. Transforming growth factor (TGF)-β-induced protein (TGFBI) is a widely expressed periostin paralog known to support monocyte adhesion. Our objective was to compare eosinophil adhesion and migration on TGFBI and periostin in the presence of IL-5-family cytokines. Eosinophil adhesion after 1 h and random motility over 20 h in the presence of various concentrations of IL-5, IL-3, or granulocyte macrophage-colony stimulating factor (GM-CSF) were quantified in wells coated with various concentrations of TGFBI or periostin. Results were compared to video microscopy of eosinophils. Cytokine-stimulated eosinophils adhered equivalently well to TGFBI or periostin in a coating concentration-dependent manner. Adhesion was blocked by anti-α M β 2 and stimulated at the lowest concentration by GM-CSF. In the motility assay, periostin was more potent than TGFBI, the coating-concentration effect was bimodal, and IL-3 was the most potent cytokine. Video microscopy revealed that under the optimal coating condition of 5 μg/ml periostin, most eosinophils migrated persistently and were polarized and acorn-shaped with a ruffling forward edge and granules gathered together, in front of the nucleus. On 10 μg/ml periostin or TGFBI, more eosinophils adopted a flattened pancake morphology with dispersed granules and nuclear lobes, and slower migration. Conversion between acorn and pancake morphologies were observed. We conclude that TGFBI or periostin supports two modes of migration by IL-5 family cytokine-activated eosinophils. The rapid mode is favored by intermediate protein coatings and the slower by higher coating concentrations. We speculate that eosinophils move by haptotaxis up a gradient of adhesive ECM protein and then slow down to surveil the tissue.

Description: by Lemmy Schakel, Dieuwke S. Veldhuijzen, Henriët van Middendorp, Pieter Van Dessel, Jan De Houwer, Rafael Bidarra, Andrea W. M. Evers There is initial support for the effectiveness of approach-avoidance trainings in altering food-related health behaviors. Furthermore, outcome expectancies induced by verbal suggestions might optimize the effectiveness of these interventions, as shown in placebo research. The present study investigated the effectiveness of a gamified approach-avoidance training on food-related outcomes and whether verbal suggestions could strengthen those effects. A total of 120 participants were randomly assigned to 1 of 4 conditions: serious gaming only, verbal suggestions only, serious gaming combined with verbal suggestions, or a gaming control condition. Virtual food preference and food choice were assessed with a food choice task, with pairs differing in healthiness or in healthiness and attractiveness. Implicit food preference was assessed with an Implicit Association Test and food intake with a bogus taste test. Participants in both serious gaming conditions made healthier food choices for pairs differing in healthiness and attractiveness and had healthier implicit food preferences compared to gaming control. No effects were found on food intake. These findings provide the first preliminary support for the effects of a gamified approach-avoidance training on virtual food choice and implicit food preference. Future studies should further elucidate these effects, also in other health domains such as physical activity.

Description: by Juan M. Castellote, Markus Kofler Objective To provide a neurophysiological tool for assessing sensorimotor pathways, which may differ for those involving distal muscles in simple tasks from those involving distal muscles in a kinetic chain task, or proximal muscles in both. Methods We compared latencies and magnitudes of motor responses in a reaction time paradigm in a proximal (biceps brachii, BB) and a distal (first dorsal interosseous, FDI) muscle following electrical stimuli used as imperative signal (IS) delivered to the index finger. These stimuli were applied during different motor tasks: simple tasks involving either one muscle, e.g. flexing the elbow for BB (FLEX), or pinching a pen for FDI (PINCH); combined tasks engaging both muscles by pinching and flexing simultaneously (PINCH-FLEX). Stimuli were of varying intensity and occasionally elicited a startle response, and a StartReact effect. Results In BB, response latencies decreased gradually and response amplitudes increased progressively with increasing IS intensities for non-startling trials, while for trials containing startle responses, latencies were uniformly shortened and response amplitudes similarly augmented across all IS intensities in both FLEX and PINCH-FLEX. In FDI, response latencies decreased gradually and response amplitudes increased progressively with increasing IS intensities in both PINCH and PINCH-FLEX for non-startling trials, but, unlike in BB for the simple task, in PINCH for trials containing startle responses as well. In PINCH-FLEX, FDI latencies were uniformly shortened and amplitudes similarly increased across all stimulus intensities whenever startle signs were present. Conclusions Our results suggest the presence of different sensorimotor pathways supporting a dissociation between simple tasks that involve distal upper limb muscles (FDI in PINCH) from simple tasks involving proximal muscles (BB in FLEX), and combined tasks that engage both muscles (FDI and BB in PINCH-FLEX), all in accordance with differential importance in the control of movements by cortical and subcortical structures. Significance Simple assessment tools may provide useful information regarding the differential involvement of sensorimotor pathways in the control of both simple and combined tasks that engage proximal and distal muscles.

Description: by Yuki Ideno, Kunihiko Hayashi, Junko Nakajima-Shimada, Yoko Onizuka, Mikiko Kishi, Tomomi Ueno, Shigeto Uchiyama Equol is one of the most active soy isoflavones. When the association between soy food intake in daily life and health outcomes is examined in epidemiological studies, it is important to define the equol-producing status of each individual. However, few studies have assessed equol-producing status without a soy challenge test. To determine a robust cutoff criterion for equol producer classification in observational studies, we conducted a urinary isoflavone concentration survey in daily life among women. Furthermore, we examined the association between eating habits regarding soy foods and equol-producing status. A total of 4,412 participants were included in the analyses. Urinary isoflavones were analyzed using a high-performance liquid chromatography method. We examined the distribution of the log 10 equol/daidzein ratios, finding a mixture of two normal distributions, corresponding to equol producer and non-producer subpopulations. Applying a finite mixture model, we estimated the means, standard deviations, and mixing proportions of these two distributions. The estimation was carried out using the SAS NLIN procedure. The optimal cutoff point for the log 10 equol/daidzein ratio in the study population was determined to be −1.42, according to the estimated parameters of the mixture distribution. Based on this criterion, 1,830 (41.5%) of the participants were identified as equol producers. Compared with non-consumers of soy foods, consumers of soy foods had significantly higher odds of being equol producers. Using log 10 -transformed equol/daidzein ratios ≥ −1.42 to define equol producers among Japanese women is reasonable and suitable for determining equol-producing status in epidemiological studies. We found that soy food eating habits were associated with equol-producing status. Further investigation is required to evaluate associations between equol-producing status in daily life and health outcomes. The results of this study suggest the best cutoff point to use in the definition of equol-producing status in daily life.

Description: by Ehsan Mirzakhalili, Bogdan I. Epureanu, Eleni Gourgou We propose a mathematical and computational model that captures the stimulus-generated Ca 2+ transients in the C . elegans ASH sensory neuron. The rationale is to develop a tool that will enable a cross-talk between modeling and experiments, using modeling results to guide targeted experimental efforts. The model is built based on biophysical events and molecular cascades known to unfold as part of neurons' Ca 2+ homeostasis mechanism, as well as on Ca 2+ signaling events. The state of ion channels is described by their probability of being activated or inactivated, and the remaining molecular states are based on biochemically defined kinetic equations or known biochemical motifs. We estimate the parameters of the model using experimental data of hyperosmotic stimulus-evoked Ca 2+ transients detected with a FRET sensor in young and aged worms, unstressed and exposed to oxidative stress. We use a hybrid optimization method composed of a multi-objective genetic algorithm and nonlinear least-squares to estimate the model parameters. We first obtain the model parameters for young unstressed worms. Next, we use these values of the parameters as a starting point to identify the model parameters for stressed and aged worms. We show that the model, in combination with experimental data, corroborates literature results. In addition, we demonstrate that our model can be used to predict ASH response to complex combinations of stimulation pulses. The proposed model includes for the first time the ASH Ca 2+ dynamics observed during both "on" and "off" responses. This mathematical and computational effort is the first to propose a dynamic model of the Ca 2+ transients' mechanism in C . elegans neurons, based on biochemical pathways of the cell's Ca 2+ homeostasis machinery. We believe that the proposed model can be used to further elucidate the Ca 2+ dynamics of a key C . elegans neuron, to guide future experiments on C . elegans neurobiology, and to pave the way for the development of more mathematical models for neuronal Ca 2+ dynamics.

Description: by Brittney M. Donovan, Nichole L. Nidey, Elizabeth A. Jasper, Jennifer G. Robinson, Wei Bao, Audrey F. Saftlas, Kelli K. Ryckman Biomarkers commonly assessed in prenatal screening have been associated with a number of adverse perinatal and birth outcomes. However, it is not clear whether first trimester measurements of prenatal screening biomarkers are associated with subsequent risk of gestational diabetes mellitus (GDM). We aimed to systematically review and statistically summarize studies assessing the relationship between first trimester prenatal screening biomarker levels and GDM development. We comprehensively searched PubMed/MEDLINE, EMBASE, CINAHL, and Scopus (from inception through January 2018) and manually searched the reference lists of all relevant articles. We included original, published, observational studies examining the association of first trimester pregnancy associated plasma protein-A (PAPP-A) and/or free β-human chorionic gonadotropin (free β-hCG) levels with GDM diagnosis. Mean differences were calculated comparing PAPP-A and free β-hCG multiples of median (MoM) levels between women who developed GDM and those who did not and were subsequently pooled using two-sided random-effects models. Our meta-analysis of 13 studies on PAPP-A and nine studies on free β-hCG indicated that first trimester MoM levels for both biomarkers were lower in women who later developed GDM compared to women who remained normoglycemic throughout pregnancy (MD -0.17; 95% CI -0.24, -0.10; MD -0.04; 95% CI -0.07–0.01). There was no evidence for between-study heterogeneity among studies on free β-hCG (I 2 = 0%). A high level of between-study heterogeneity was detected among the studies reporting on PAPP-A (I 2 = 90%), but was reduced after stratifying by geographic location, biomarker assay method, and timing of GDM diagnosis. Our meta-analysis indicates that women who are diagnosed with GDM have lower first trimester levels of both PAPP-A and free β-hCG than women who remain normoglycemic throughout pregnancy. Further assessment of the predictive capacity of these biomarkers within large, diverse populations is needed.

Description: by Hsin-Hua Chen, Wen-Cheng Chao, Tsai-Ling Liao, Ching-Heng Lin, Der-Yuan Chen Objective To estimate the relative risk of autoimmune rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren’s syndrome (SS), dermatomyositis (DM) and polymyositis (PM), among patients with palindromic rheumatism (PR) compared with non-PR individuals. Methods The study utilized 2003–2013 claims data from the Taiwanese National Health Insurance Research Database. We identified 4,421 cases of PR from 2007 to 2012 and randomly chose 44,210 non-PR individuals who matched (1:10) for age, sex and the year of index date without prior history of RA, SLE, SSc, SS, DM, or PM. After adjusting for age, sex, and the Charlson comorbidity index, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard model to quantify the risk of RA, SLE, SS, DM and PM in PR patients compared with that in matched non-PR individuals. Results Among the 4,421 patients with PR, 569 (12.87%) developed RA, 269 (6.08%) developed SS, 113 (2.56%) developed SLE, 5 (0.11%) developed SSc, 8 (0.18%) developed PM, and 1 (0.02%) developed DM. After adjusting for potential confounders, the patients with PR had an increased risk of RA (HR, 118.76; 95% CI, 89.81–157.04), SS (HR, 59.57; 95% CI, 43.87–80.88), SLE (HR, 51.56; 95% CI, 32.96–80.66) PM (HR, 57.38; 95% CI, 6.90–476.83), and SSc (HR, 13.42; 95% CI, 3.79–47.55) but not of DM (HR, 3.44; 95% CI, 0.34–34.59). Conclusion Patients with PR had an increased risk of developing RA, SS, SLE, PM, and SSc.

Description: by Lin Yang, Xiaoyan Kong, Shuli Yang, Xinxing Dong, Jianfa Yang, Xiao Gou, Hao Zhang The Tibetan horse is a species endemic to the Tibetan plateau, with considerable economic value in the region. However, we currently have little genetic evidence to verify whether the breed originated in Tibet or if it entered the area via an ancient migratory route. In the present study, we analyzed the hypervariable segment I sequences of mitochondrial DNA (mtDNA) in 2,050 horses, including 290 individuals from five Tibetan populations and 1,760 from other areas across Asia. Network analysis revealed multiple maternal lineages in the Tibetan horse. Component analysis of sub-lineage F3 indicated that it decreased in frequency from east to west, a trend reflected both southward and northward from Inner Mongolia. Analysis of population genetics showed that the Deqen horse of eastern Tibet was more closely related to the Ningqiang horse of northern China than to other Tibetan horses or the Yunnan horse. These results indicated that the Tibetan horse migrated first from Central Asia to Mongolia, moved south to eastern Tibet (near Deqen), then finally westward to other regions of Tibet. We also identified a novel lineage K that mainly comprises Tibetan and Yunnan horses, suggesting autochthonous domesticated origin for some Tibetan horse breeds from local wild horses. In conclusion, our study demonstrated that modern Tibetan horse breeds originated from the introgression of local wild horses with exotic domesticated populations outside China.

Description: by Marya Plotkin, Dunstan Bishanga, Hussein Kidanto, Mary Carol Jennings, Jim Ricca, Amasha Mwanamsangu, Gaudiosa Tibaijuka, Ruth Lemwayi, Benny Ngereza, Mary Drake, Jeremie Zougrana, Neena Khadka, James A. Litch, Barbara Rawlins Background Globally, an estimated 2.7 million babies die in the neonatal period annually, and of these, about 0.7 million die from intrapartum-related events. In Tanzania 51,000 newborn deaths and 43,000 stillbirths occur every year. Approximately two-thirds of these deaths could be potentially prevented with improvements in intrapartum and neonatal care. Routine measurement of fetal intrapartum deaths and newborn deaths that occur in health facilities can help to evaluate efforts to improve the quality of intrapartum care to save lives. However, few examples exist of indicators on perinatal mortality in the facility setting that are readily available through health management information systems (HMIS). Methods From November 2016 to April 2017, health providers at 10 government health facilities in Kagera region, Tanzania, underwent refresher training on perinatal death classification and training on the use of handheld Doppler devices to assess fetal heart rate upon admission to maternity services. Doppler devices were provided to maternity services at the study facilities. We assessed the validity of an indicator to measure facility-based pre-discharge perinatal mortality by comparing perinatal outcomes extracted from the HMIS maternity registers to a gold standard perinatal death audit. Results Sensitivity and specificity of the HMIS neonatal outcomes to predict gold standard audit outcomes were both over 98% based on analysis of 128 HMIS–gold standard audit pairs. After this validation, we calculated facility perinatal mortality indicator from HMIS data using fresh stillbirths and pre-discharge newborn death as the numerator and women admitted in labor with positive fetal heart tones as the denominator. Further emphasizing the validity of the indicator, FPM values aligned with expected mortality by facility level, with lowest rates in health centers (range 0.3%– 0.5%), compared to district hospitals (1.5%– 2.9%) and the regional hospital (4.2%). Conclusion This facility perinatal mortality indicator provides an important health outcome measure that facilities can use to monitor levels of perinatal deaths occurring in the facility and evaluate impact of quality of care improvement activities.

Description: by Seung-Heon Shin, Mi-Kyung Ye, Dong-Won Lee, Mi-Hyun Che The essential oil of Chamaecyparis obtusa ( C . obtusa ), which is used in soap, toothpaste, and aromatic agents, has been known to have anti-inflammatory properties. In this study, we investigated the effects of microencapsulated C . obtusa essential oil on airborne fungus-induced dendritic cell (DC) activation and Th immune responses. We stimulated monocyte-derived DCs with Alternaria alternate and lipopolysaccharide (LPS). To determine the anti-inflammatory effects, we pre-treated DCs with various concentrations of microencapsulated C . obtusa essential oil and collected the supernatants to measure interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and we determined the expression of cell surface molecules. The effects of the essential oil on CD4 + T cells polarization was determine by culturing stimulated DCs and autologous CD4 + T cells. Alternaria enhanced the production of IL-6 and TNF-α from DCs, and pretreating DCs with 0.001, 0.01, and 0.05% of the essential oil significantly inhibited their production. Increased CD80 and CD86 expression by Alternaria was significantly inhibited with 0.05% of the essential oil. Alternaria -induced IL-5, IL-10, and interferon-gamma from CD4 + T cells were significantly inhibited with C . obtusa essential oil in a dose dependent manner. C . obtusa influenced both Alternaria - and LPS-induced Th1 and Th2 polarization of CD4 + T cells. These results suggest a novel pharmacological use for C . obtusa essential oil to treat inflammatory airway diseases.

Description: by P. Susthitha Menon, Fairus Atida Said, Gan Siew Mei, Dilla Duryha Berhanuddin, Akrajas Ali Umar, Sahbudin Shaari, Burhanuddin Yeop Majlis This work investigates the surface plasmon resonance (SPR) response of 50-nm thick nano-laminated gold film using Kretschmann-based biosensing for detection of urea and creatinine in solution of various concentrations (non-enzymatic samples). Comparison was made with the presence of urease and creatininase enzymes in the urea and creatinine solutions (enzymatic samples), respectively. Angular interrogation technique was applied using optical wavelengths of 670 nm and 785 nm. The biosensor detects the presence of urea and creatinine at concentrations ranging from 50–800 mM for urea samples and 10–200 mM for creatinine samples. The purpose of studying the enzymatic sample was mainly to enhance the sensitivity of the sensor towards urea and creatinine in the samples. Upon exposure to 670 nm optical wavelength, the sensitivity of 1.4°/M was detected in non-enzymatic urea samples and 4°/M in non-enzymatic creatinine samples. On the other hand, sensor sensitivity as high as 16.2°/M in urea-urease samples and 10°/M in creatinine-creatininase samples was detected. The enhanced sensitivity possibly attributed to the increase in refractive index of analyte sensing layer due to urea-urease and creatinine-creatininase coupling activity. This work has successfully proved the design and demonstrated a proof-of-concept experiment using a low-cost and easy fabrication of Kretschmann based nano-laminated gold film SPR biosensor for detection of urea and creatinine using urease and creatininase enzymes.

Description: by David A. Eavarone, Linah Al-Alem, Alexey Lugovskoy, Jillian M. Prendergast, Rawan I. Nazer, Jenna N. Stein, Daniel T. Dransfield, Jeff Behrens, Bo R. Rueda The expression of Sialyl-Tn (STn) in tumors is associated with metastatic disease, poor prognosis, and reduced overall survival. STn is expressed on ovarian cancer biomarkers including CA-125 (MUC16) and MUC1, and elevated serum levels of STn in ovarian cancer patients correlate with lower five-year survival rates. In the current study, we humanized novel anti-STn antibodies and demonstrated the retention of nanomolar (nM) target affinity while maintaining STn antigen selectivity. STn antibodies conjugated to Monomethyl Auristatin E (MMAE-ADCs) demonstrated in vitro cytotoxicity specific to STn-expressing ovarian cancer cell lines and tumor growth inhibition in vivo with both ovarian cancer cell line- and patient-derived xenograft models. We further validated the clinical potential of these STn-ADCs through tissue cross-reactivity and cynomolgus monkey toxicity studies. No membrane staining for STn was present in any organs of human or cynomolgus monkey origin, and the toxicity profile was favorable and only revealed MMAE-class associated events with none being attributed to the targeting of STn. The up-regulation of STn in ovarian carcinoma in combination with high affinity and STn-specific selectivity of the mAbs presented herein warrant further investigation for anti-STn antibody-drug conjugates in the clinical setting.

Description: by Laura K. Borkenhagen, Kerry A. Mallinson, Rick W. Tsao, Siaw-Jing Ha, Wei-Honn Lim, Teck-Hock Toh, Benjamin D. Anderson, Jane K. Fieldhouse, Sarah E. Philo, Kuek-Sen Chong, William G. Lindsley, Alejandro Ramirez, James F. Lowe, Kristen K. Coleman, Gregory C. Gray Background The large livestock operations and dense human population of Southeast Asia are considered a hot-spot for emerging viruses. Objectives To determine if the pathogens adenovirus (ADV), coronavirus (CoV), encephalomyocarditis virus (EMCV), enterovirus (EV), influenza A-D (IAV, IBV, ICV, and IDV), porcine circovirus 2 (PCV2), and porcine rotaviruses A and C (RVA and RVC), are aerosolized at the animal-interface, and if humans working in these environments are carrying these viruses in their nasal airways. Study This cross-sectional study took place in Sarawak, Malaysia among 11 pig farms, 2 abattoirs, and 3 animal markets in June and July of 2017. Pig feces, pig oral secretions, bioaerosols, and worker nasal wash samples were collected and analyzed via rPCR and rRT-PCR for respiratory and diarrheal viruses. Results In all, 55 pig fecal, 49 pig oral or water, 45 bioaerosol, and 78 worker nasal wash samples were collected across 16 sites. PCV2 was detected in 21 pig fecal, 43 pig oral or water, 3 bioaerosol, and 4 worker nasal wash samples. In addition, one or more bioaerosol or pig samples were positive for EV, IAV, and RVC, and one or more worker samples were positive for ADV, CoV, IBV, and IDV. Conclusions This study demonstrates that nucleic acids from a number of targeted viruses were present in pig oral secretions and pig fecal samples, and that several viruses were detected in bioaerosol samples or in the nasal passages of humans with occupational exposure to pigs. These results demonstrate the need for future research in strengthening viral surveillance at the human-animal interface, specifically through expanded bioaerosol sampling efforts and a seroepidemiological study of individuals with exposure to pigs in this region for PCV2 infection.

Description: by Vasileios Stavropoulos, Stefanos Mastrotheodoros, Tyrone L. Burleigh, Nicole Papadopoulos, Rapson Gomez Romantic development is a distinctive characteristic of puberty. However, a significant proportion of adolescents present with avoidant romantic attachment (ARA) tendencies, which have significant impact on their general adaptation. ARA variations have been suggested in relation to age, gender, engagement with a romantic partner and Excessive Internet Use (EIU) behaviours. In this longitudinal, two-wave study of a normative sample of 515 Greek adolescents at 16 and 18 years, ARA was assessed with the relevant subscale of the Experiences in Close Relationships-Revised and EIU with the Internet Addiction Test. A three-level hierarchical linear model found ARA tendencies to decrease between 16 and 18 while engagement in a romantic relationship and EIU were associated with lower and higher ARA tendencies respectively. Gender did not differentiate ARA severity either at the age of 16 or its changes over time. Results highlight the need of adopting a longitudinal-contextualized approach and provide implications for prevention and intervention initiatives in relation to the romantic development of adolescents.

Description: by David M. Brown, Sarah Jones, Zoe C. T. R. Daniel, Madelaine C. Brearley, Jo E. Lewis, Francis J. P. Ebling, Tim Parr, John M. Brameld Previously, we highlighted induction of an integrated stress response (ISR) gene program in skeletal muscle of pigs treated with a beta-adrenergic agonist. Hence we tested the hypothesis that the ER-stress inhibitor, sodium 4-phenylbutyrate (PBA), would inhibit Clenbuterol-mediated muscle growth and reduce expression of genes that are known indicators of an ISR in mice. Clenbuterol (1mg/kg/day) administered to C57BL6/J mice for 21 days increased body weight ( p

Description: by Charlotte Avet, Chantal Denoyelle, David L’Hôte, Florence Petit, Céline J. Guigon, Joëlle Cohen-Tannoudji, Violaine Simon Reproductive function is under the control of the neurohormone GnRH, which activates a G-protein-coupled receptor (GnRHR) expressed in pituitary gonadotrope cells. GnRHR activates a complex signaling network to regulate synthesis and secretion of the two gonadotropin hormones, luteinizing hormone and follicle-stimulating hormone, both regulating gametogenesis and steroidogenesis in gonads. Recently, in an attempt to identify the mechanisms underlying GnRHR signaling plasticity, we identified the first interacting partner of GnRHR, the proto-oncogene SET. We showed that SET binds to intracellular domains of GnRHR to enhance its coupling to cAMP pathway in αT3-1 gonadotrope cells. Here, we demonstrate that SET protein is rapidly regulated by GnRH, which increases SET phosphorylation state and decreases dose-dependently SET protein level. Our results highlight a post-translational regulation of SET protein involving the proteasome pathway. We determined that SET phosphorylation upon GnRH stimulation is mediated by PKC and that PKC mediates GnRH-induced SET down-regulation. Phosphorylation on serine 9 targets SET for degradation into the proteasome. Furthermore, a non-phosphorylatable SET mutant on serine 9 is resistant to GnRH-induced down-regulation. Altogether, these data suggest that GnRH-induced SET phosphorylation on serine 9 mediates SET protein down-regulation through the proteasome pathway. Noteworthy, SET down-regulation was also observed in response to pulsatile GnRH stimulation in LβT2 gonadotrope cells as well as in vivo in prepubertal female mice supporting its physiological relevance. In conclusion, this study highlights a regulation of SET protein by the neurohormone GnRH and identifies some of the mechanisms involved.

Description: by Wilson Mendoza, Dominick Mendola, Jang Kim, Charles Yarish, Alyssa Velloze, B. Greg Mitchell

Description: by Àngel Oliveras, Aina Baró, Laura Montesinos, Esther Badosa, Emilio Montesinos, Lidia Feliu, Marta Planas A collection of 36 lipopeptides were designed from the cecropin A-melittin hybrid peptide BP100 (H-Lys-Lys-Leu-Phe-Lys-Lys-Ile-Leu-Lys-Tyr-Leu-NH 2 ) previously described with activity against phytopathogenic bacteria. These lipopeptides were synthesized on solid-phase and screened for their antimicrobial activity, toxicity and proteolytic stability. They incorporated a butanoyl, a hexanoyl or a lauroyl group at the N-terminus or at the side chain of a lysine residue placed at each position of the sequence. Their antimicrobial activity and hemolysis depended on the fatty acid length and its position. In particular, lipopeptides containing a butanoyl or a hexanoyl chain exhibited the best biological activity profile. In addition, we observed that the incorporation of the acyl group did not induce the overexpression of defense-related genes in tomato. Best lipopeptides were BP370, BP378, BP381, BP387 and BP389, which were highly active against all the pathogens tested (minimum inhibitory concentration of 0.8 to 12.5 μM), low hemolytic, low phytotoxic and significantly stable to protease degradation. This family of lipopeptides might be promising functional peptides useful for plant protection.

Description: by The PLOS ONE staff

Description: by Fausto Petrelli, Chiara Lazzari, Raffaele Ardito, Karen Borgonovo, Alessandra Bulotta, Barbara Conti, Mary Cabiddu, Jody Filippo Capitanio, Matteo Brighenti, Mara Ghilardi, Luca Gianni, Sandro Barni, Vanesa Gregorc Background Patients with anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) have a higher risk of developing brain metastases (BMs) than patients with other NSCLC sub-types. ALK inhibitors have activity in BMs due to ALK+ NSCLC. We performed a systematic review of the literature with the aim of assessing the efficacy of ALK inhibitors on BMs. Material and methods A systematic search of the literature was performed using the databases Pubmed, EMBASE, Web of Science, The Cochrane Library, and SCOPUS. Relevant publications reporting activity of ALK inhibitors in NSCLC BMs were retrieved. Data were pooled using the number of events/number of evaluable patients according to fixed or random effect models. Intracranial tumour response was assessed through overall response rate (ORR), disease control rate (DCR: ORR + stable disease rate), median progression-free survival (PFS), and overall survival (OS). The primary endpoint was intracranial overall response rate (IC ORR). Results A total of 1,016 patients with BMs from 21 studies were analysed. In patients receiving ALK inhibitors in the first line setting, the pooled IC ORR was 39.17% (95%CI 13.1–65.2%), while the pooled IC ORR observed in further lines was 44.2% (95%CI 33.3–55.1%). Intracranial disease control rate (IC DCR) was 70.3% and 78.2% in naïve and pre-treated patients, respectively. Patients who had not received brain radiation attained an IC ORR of 49.0%. Conclusions Based on these data, ALK inhibitors are effective in both naive and pre-treated patients with similar IC ORR and IC DCR, irrespective of the line of therapy.

Description: by Steven Denyer, Abhiraj D. Bhimani, Steven Papastefan, Pouyan Kheirkhah, Tania Aguilar, Jack Zakrzewski, Clayton L. Rosinski, Akash S. Patel, Saavan Patel, Victoria Zakrzewski, Akop Seksenyan, Gail S. Prins, Ankit I. Mehta Vertebral compression fractures (VCFs) caused by metastatic malignancies or osteoporosis are devastating injuries with debilitating outcomes for patients. Minimally invasive kyphoplasty is a common procedure used for symptomatic amelioration. However, it fails in treating the underlying etiologies of VCFs. Use of systemic therapy is limited due to low perfusion to the spinal column and systemic toxicity. Localized delivery of drugs to the vertebral column can provide a promising alternative approach. A porcine kyphoplasty model was developed to study the magnetically guided drug delivery of systemically injected magnetic nanoparticles (MNPs). Jamshidi cannulated pedicle needles were placed into the thoracic vertebra and, following inflatable bone tamp expansion, magnetic bone cement was injected to the vertebral body. Histological analysis was performed after intravenous injection of MNPs. Qualitative analysis of harvested tissues revealed successful placement of magnetic cement into the vertebral body. Further quantitative analysis of histological sections of several vertebral bodies demonstrated enhanced accumulation of MNPs to regions that had magnetic cement injected during kyphoplasty compared to those that did not. By modifying the kyphoplasty bone cement to include magnets, thereby providing a guidance stimulus and a localizer, we were successfully able to guide intravenously injected magnetic nanoparticles to the thoracic vertebra. These results demonstrate an in-vivo proof of concept of a novel drug delivery strategy that has the potential to treat the underlying causes of VCFs, in addition to providing symptomatic support.

Description: by Maria Frølund, Arne Wikström, Peter Lidbrink, Waleed Abu Al-Soud, Niels Larsen, Christoffer Bugge Harder, Søren Johannes Sørensen, Jørgen Skov Jensen, Peter Ahrens Background Non-gonococcal urethritis (NGU) is a common syndrome in men. NGU may have several causes, but many cases are caused by sexually transmitted infections that may also cause complications in their female partners. Chlamydia trachomatis and Mycoplasma genitalium are the most common causes of NGU, but in up to 35% of the cases, none of the known viral or bacterial causes are found. Traditionally, pathogens have been detected using various culture techniques that may not identify all species present in the urethra. To address this, we used culture-independent methods for analysis of the male urethral microbiota. Methods This case-control study analysed first void urine samples, collected at STD clinics in Stockholm, Sweden from men with idiopathic urethritis (IU), i.e. negative for Neisseria gonorrhoeae , Chlamydia trachomatis , Mycoplasma genitalium , Ureaplasma urealyticum , Trichomonas vaginalis , adenovirus, and herpes simplex virus type 1 and -2 together with samples from men without urethritis. Forty-six controls and 39 idiopathic urethritis patients were analysed. Results The microbiota was highly diverse: None of the 302 operational taxonomic units (OTUs) found in negative controls and IU patients were found in all of the samples or even in all of the samples in one group. More than 50% of the OTUs were only found in one or two of the total of 85 samples. Still the most dominant 1/6 of the genera constituted 79% of the sequences.Hierarchical clustering in a heatmap showed no specific clustering of patients or controls.A number of IU patient samples were dominated by a single genus previously related to urethritis ( Gardnerella , Haemophilus , Ureaplasma ). Conclusion The male urethra contain a very diverse composition of bacteria, even in healthy controls. NGU may be caused by a number of different bacteria but more studies including a higher number of samples are needed for elucidation of the role of each species.

Description: by Yves Jackson, Adeline Paignon, Hans Wolff, Noelia Delicado Background Undocumented migrants endure adverse living conditions while facing barriers to access healthcare. Evidence is lacking regarding their healthcare needs, notably in regards to chronic diseases. Our goal was to investigate health conditions in undocumented migrants attended in primary care setting. Methods This study was conducted at the primary care outpatient clinic, Geneva University Hospitals, Switzerland. We retrospectively recorded and coded all medical conditions of a random sample of 731 undocumented migrants using the International Classification of Primary Care, 2nd version (ICPC-2). We dichotomized conditions as chronic or non-chronic and considered multimorbidity in the presence of three or more chronic conditions. Results Participants originated from 72 countries and were mainly female (65.5%) with a mean age of 42.4 (standard deviation [SD]: 11.4) years. They presented a mean of 2.9 (SD: 2.1; range: 1–17) health conditions. In multivariable analysis, the number of conditions was associated with female gender (p = 0.011) and older age (p

Description: by Kine Andenæs, Ida G. Lunde, Naiyereh Mohammadzadeh, Christen P. Dahl, Jan Magnus Aronsen, Mari E. Strand, Sheryl Palmero, Ivar Sjaastad, Geir Christensen, Kristin V. T. Engebretsen, Theis Tønnessen Pressure overload of the heart leads to cardiac remodeling that may progress into heart failure, a common, morbid and mortal condition. Increased mechanistic insight into remodeling is instrumental for development of novel heart failure treatment. Cardiac remodeling comprises cardiomyocyte hypertrophic growth, extracellular matrix alterations including fibrosis, and inflammation. Fibromodulin is a small leucine-rich proteoglycan that regulates collagen fibrillogenesis. Fibromodulin is expressed in the cardiac extracellular matrix, however its role in the heart remains largely unknown. We investigated fibromodulin levels in myocardial biopsies from heart failure patients and mice, subjected fibromodulin knock-out (FMOD-KO) mice to pressure overload by aortic banding, and overexpressed fibromodulin in cultured cardiomyocytes and cardiac fibroblasts using adenovirus. Fibromodulin was 3-10-fold upregulated in hearts of heart failure patients and mice. Both cardiomyocytes and cardiac fibroblasts expressed fibromodulin, and its expression was increased by pro-inflammatory stimuli. Without stress, FMOD-KO mice showed no cardiac phenotype. Upon aortic banding, left ventricles of FMOD-KO mice developed mildly exacerbated hypertrophic remodeling compared to wild-type mice, with increased cardiomyocyte size and altered infiltration of leukocytes. There were no differences in mortality, left ventricle dilatation, dysfunction or expression of heart failure markers. Although collagen amount and cross-linking were comparable in FMOD-KO and wild-type, overexpression of fibromodulin in cardiac fibroblasts in vitro decreased their migratory capacity and expression of fibrosis-associated molecules, i.e. the collagen-cross linking enzyme lysyl oxidase, transglutaminase 2 and periostin. In conclusion, despite a robust fibromodulin upregulation in clinical and experimental heart failure, FMOD-KO mice showed a relatively mild hypertrophic phenotype. In cultured cardiac fibroblasts, fibromodulin has anti-fibrotic effects.

Description: by Bruno Rossitto De Marchi, Tonny Kinene, James Mbora Wainaina, Renate Krause-Sakate, Laura Boykin The whitefly, Bemisia tabaci , is a species complex of more than 40 cryptic species and a major agricultural pest. It causes extensive damage to plants mainly by transmitting plant viruses. There is still a lack of genomic data available for the different whitefly species found in Brazil and their bacterial endosymbionts. Understanding the genetic and transcriptomic composition of these insect pests, the viruses they transmit and the microbiota is crucial to sustainable solutions for farmers to control whiteflies. Illumina RNA-Seq was used to obtain the transcriptome of individual whiteflies from 10 different populations from Brazil including Middle East-Asia Minor 1 (MEAM1), Mediterranean (MED) and New World 2 (NW2). Raw reads were assembled using CLC Genomics Workbench and subsequently mapped to reference genomes. We obtained whitefly complete mitochondrial genomes and draft genomes from the facultative bacterial endosymbiont Hamiltonella for further phylogenetic analyses. In addition, nucleotide sequences of the GroEL chaperonin gene from Hamiltonella from different populations were obtained and analysed. There was concordance in the species clustering using the whitefly complete mitogenome and the mtCOI gene tree. On the other hand, the phylogenetic analysis using the 12 ORF’s of Hamiltonella clustered the native species NW2 apart from the exotics MEAM1 and MED. In addition, the amino acid analysis of GroEL chaperonin revealed a deletion only in Hamiltonella infecting NW2 among whiteflies populations analysed which was further confirmed by PCR and Sanger sequencing. The genomic data obtained in this study will aid understanding the functions that Hamiltonella may have in whitefly biology and serve as a reference for further studies regarding whiteflies in Brazil.

Description: by Wen-Kai Yang, An-Di Hsu, Chao-Kai Kang, Ivan Pochou Lai, Pei-Shao Liao, Tsung-Han Lee FXYD proteins are the regulators of sodium-potassium ATPase (Na + /K + -ATPase, NKA). In teleosts, NKA is a primary driving force for the operation of many ion transport systems in the osmoregulatory organs (e.g. intestines). Hence, the purpose of this study was to determine the expression of FXYD proteins and NKA α-subunit in the intestines of two closely related medakas ( Oryzias dancena and O . latipes ), which came from different salinity habitats and have diverse osmoregulatory capabilities, to illustrate the association between NKA and FXYD proteins of two medaka species in response to salinity changes. The results showed that the fxyd12 mRNA was the most predominant in the intestines of both medakas. The association of FXYD12 and NKA in the intestines of the two medaka species was demonstrated via double immunofluorescent staining and co-immunoprecipitation. Upon salinity challenge, the localization of FXYD12 and NKA was similar in the intestines of the two medaka species. However, the expression profiles of intestinal FXYD12 and NKA (mRNA and protein levels), as well as NKA activity differed between the medakas. These results showed that FXYD12 may play a role in modulating NKA activity in the intestines of the two medakas following salinity changes in the maintenance of internal homeostasis. These findings contributed to knowledge of the expression and potential role of vertebrate FXYD12, the regulators of NKA, upon salinity challenge.

Description: by Raissa Prior Migliorini, Felipe Bortolotto Peters, Marina Ochoa Favarini, Carlos Benhur Kasper Information about resource partitioning among small cat species that live in sympatry in South America is fairly incomplete. Knowledge about feeding habits is essential for understanding the role of these predators in the environment, the impact on prey populations, and potential competition among themselves and with other carnivores. This study aimed to describe and compare the diet of four sympatric small cats in the grasslands of southern Brazil. We analysed the stomach contents of 37 Geoffroy’s cats ( Leopardus geoffroyi ), 27 margays ( Leopardus wiedii ), 14 pampas cats ( Leopardus colocola ), and 20 jaguarundis ( Herpailurus yagouaroundi ) obtained as road kill in the Brazilian Pampa in southern Brazil. Small mammals were the most representative class consumed by all cats, followed by Aves, Reptilia, and Amphibia. Some items, such as rodents Cavia aperea , Akodon sp., Oligoryzomys sp. and Passeriformes were consumed by all cat species. Niche overlap varied widely, from 10% (margay x jaguarundi) to 92% (jaguarundi x pampas cat). Niche breadth indicated that jaguarundi were the most specialized of the cats ( B sta = 0.24) in this region, with a diet closely associated to C . aperea . Margay consumed more items associated with arboreal behaviour than other cat species, but consumed more terrestrial items than arboreal ones. The pampas cat consumed mostly terrestrial species associated with open fields. Geoffroy’s cat consumed mammals found in a diversity of habitats, indicating high ecological flexibility. Species with more similarity in diet such as jaguarundi and pampas cat probably present temporal segregation in activity. In conclusion, despite their habitat and diet similarities, these four species explore distinct microhabitats by foraging different prey groups, what favor them to live in sympatry.

Description: by Cagan Urkup, Burcin Bozkaya, F. Sibel Salman The rapid growth of mobile payment and geo-aware systems as well as the resulting emergence of Big Data present opportunities to explore individual consuming patterns across space and time. Here we analyze a one-year transaction dataset of a leading commercial bank to understand to what extent customer mobility behavior and financial indicators can predict the use of a target product, namely the Individual Consumer Loan product. After data preprocessing, we generate 13 datasets covering different time intervals and feature groups, and test combinations of 3 feature selection methods and 10 classification algorithms to determine, for each dataset, the best feature selection method and the most influential features, and the best classification algorithm. We observe the importance of spatio-temporal mobility features and financial features, in addition to demography, in predicting the use of this exemplary product with high accuracy (AUC = 0.942). Finally, we analyze the classification results and report on most interesting customer characteristics and product usage implications. Our findings can be used to potentially increase the success rates of product recommendation systems.

Description: by Amparo Lázaro, Asier R. Larrinaga Seed size is a fundamental life-history trait for plants. A seed number/size trade-off is assumed because the resources invested in reproduction are limited; however, such a trade-off is not always observed. This could be a consequence of the method used for testing it, where the null hypothesis is dictated by common statistical practice, rather than being based on any underlying theory. Alternatively, there might be some population- and species-dependent variables that affect resource availability and, in turn, influence the presence and intensity of this trade-off. Using data on 42 herbs from two communities (lowland and alpine) from Southern Norway, we tested the validity of the classical linear model vs. two previously proposed models, based on resource competition, when assessing the existence of this trade-off at different levels. We also evaluated whether some species- (fruit aggregation, ovules/flower) and population-dependent (pollen limitation) variables could affect this trade-off. Classical linear modelling outperformed the other proposed functional models. Significant seed number/size relationships were negative in single-fruited species, whereas they were positive in species with infructescences of one-seeded fruits. Concordantly, fruit organization was the most influencing variable for the intra-specific trade-off in the lowland community. In the alpine community, species suffering higher pollen limitation showed more strongly negative slopes between seed size and seed number at the fruit/infructescence level. Across species, seed size and number were negatively related, although the relationship was significant in only one of the communities. No evidence of trade-off was found at the plant level. Linear models provide a flexible framework that allows coping with the variability in the seed number/size relationship. The emergence of the intra-specific relationship between seed number and size depends on species- and population-dependent variables, related to resource allocation and the pollination environment.

Description: by Sunitha Kodidela, Sabina Ranjit, Namita Sinha, Carole McArthur, Anil Kumar, Santosh Kumar Cytokines and chemokines circulate in plasma and may be transferred to distant sites, via exosomes. HIV infection is associated with dysregulation of cytokines and chemokines, which subsequently contribute to the pathogenesis of HIV. Alcohol and tobacco exposure, which are prevalent in HIV-infected individuals, may induce changes in the expression of cytokines and chemokines. Therefore, our aim in this study was to quantify plasma exosomal cytokines and chemokines that we expect to exacerbate toxicity or disease progression in HIV-positive drug abusers. We measured the levels of cytokines and chemokines in the plasma and plasma exosomes of 39 patients comprising six groups: HIV-negative and HIV-positive non drug abusers, HIV-negative and HIV-positive alcohol users, and HIV-negative and HIV positive tobacco smokers. We measured six cytokines (TNF-α, IL-1β, IL-8, IL-6, IL-1ra, IL-10) and two chemokines (MCP-1 and RANTES). All were present in exosomes of healthy subjects, but their levels varied between different study groups. HIV-positive alcohol drinkers had higher levels of plasma IL-8 compared to those of HIV-positive non-drinkers. The IL-1ra level was significantly higher in exosomes of non-HIV-infected alcohol drinkers compared to those of HIV-positive alcohol drinkers. Interestingly, the IL-10 level was higher in exosomes compared with their respective plasma levels in all study groups except HIV-positive non-alcohol drinkers. IL-10 was completely packaged in exosomes of HIV-positive smokers. HIV-positive smokers had significantly higher levels of plasma IL-8 compared with HIV-positive non-smokers and significantly higher exosomal IL-6 levels compared with HIV-negative subjects. HIV-positive smokers had significantly increased plasma levels of IL-1ra compared to HIV-positive non-smokers. The MCP-1 levels in the plasma of HIV-positive smokers was significantly higher than in either HIV-positive non-drug abusers or HIV-negative smokers. Overall, the findings suggest that plasma cytokines and chemokines are packaged in exosomes at varying degrees in different study groups. Exosomal cytokines and chemokines are likely to have a significant biological role at distant sites including cells in the brain.

Description: by Mian Zhou, Monowar Aziz, Manhendar Ochani, Weng-Lang Yang, Archna Sharma, Ping Wang Decrease of CD4 T cell numbers causes immunosuppression in sepsis. We previously showed the beneficial role of ghrelin in sepsis. We hypothesize that the protective outcome of ghrelin in sepsis is mediated partially through the restoration of CD4 T cells’ proliferation. Sepsis was induced in mice by cecal ligation and puncture (CLP). The percentage of CD4 T cells in spleen was assessed by flow cytometry and their proliferation was determined by carboxyfluorescein succinimidyl ester (CSFE). Compared to sham mice, the percentages of splenic CD4 T cells were reduced by 20%, 21%, and 29% at day 1, 2 and 3 after CLP, respectively. Human ghrelin was given to 3 day septic mice by s . c . injection at 5 and 24 h after CLP. Treatment with ghrelin restored the loss of CD4 T cells by increasing their proliferation in septic mice. The expression of cyclin D1 and B1 was significantly increased, while the expression of p57 was decreased in ghrelin-treated mice compared to vehicle-treated mice in sepsis. Treatment with human ghrelin significantly increased the p-AKT levels in the spleen compared to vehicle-treated septic mice. Human ghrelin plays an important role in reestablishing the proliferation of CD4 T cells and serves as a promising therapeutic agent in sepsis.

Description: by Ann Machablishvili, Giorgi Chakhunashvili, Khatuna Zakhashvili, Irakli Karseladze, Olgha Tarkhan-Mouravi, Mari Gavashelidze, Tamar Jashiashvili, Lela Sabadze, Paata Imnadze, Rodney S. Daniels, Burcu Ermetal, John W. McCauley Background Influenza epidemiological and virologic data from Georgia are limited. We aimed to present Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) surveillance data and characterize influenza viruses circulating in the country over three influenza seasons. Methods We analyzed sentinel site ILI and SARI data for the 2014–2017 seasons in Georgia. Patients’ samples were screened by real-time RT-PCR and influenza viruses isolated were characterized antigenically by haemagglutination inhibition assay and genetically by sequencing of HA and NA genes. Results 32% (397/1248) of ILI and 29% (581/1997) of SARI patients tested were positive for influenza viruses. In 2014–2015 the median week of influenza detection was week 7/2015 with B/Yamagata lineage viruses dominating (79%); in 2015–2016—week 5/2016 was the median with A/H1N1pdm09 viruses prevailing (83%); and in 2016–2017 a bimodal distribution of influenza activity was observed—the first wave was caused by A/H3N2 (55%) with median week 51/2016 and the second by B/Victoria lineage viruses (45%) with median week 9/2017. For ILI, influenza virus detection was highest in children aged 5–14 years while for SARI patients most were aged 〉15 years and 27 (4.6%) of 581 SARI cases died during the three seasons. Persons aged 30–64 years had the highest risk of fatal outcome, notably those infected with A/H1N1pdm09 (OR 11.41, CI 3.94–33.04, p

Description: by Juan Pablo Gutierrez, Sebastian Garcia-Saiso, Belkis M. Aracena Objective This study aimed to estimate the magnitude of the association between overall household health expenditures & the presence of members with a chronic disease in the household. Research design & methods This was a cross-sectional analysis of a probabilistic household survey, which gathered data on previously diagnosed type 2 diabetes mellitus and hypertension as well as health expenditure in Mexico. From an analytic sample of 44,000 households, we identified those having at least one member with diabetes or hypertension and determined their health expenditure. Using matching procedures, we compared these data with those of households lacking such individuals. Results We found that 24% of the households had at least one member who had been diagnosed with diabetes, hypertension, or both. Households with such members reported health expenditures that were 25%–34% ( P

Description: by Hong Li, Manuel Zeitelhofer, Ingrid Nilsson, Xicong Liu, Laura Allan, Benjamin Gloria, Angelo Perani, Carmel Murone, Bruno Catimel, A. Munro Neville, Fiona E. Scott, Andrew M. Scott, Ulf Eriksson PDGF-CC is a member of the platelet-derived growth factor (PDGF) family that stimulates PDGFRα phosphorylation and thereby activates intracellular signalling events essential for development but also in cancer, fibrosis and neuropathologies involving blood-brain barrier (BBB) disruption. In order to elucidate the biological and pathological role(s) of PDGF-CC signalling, we have generated high affinity neutralizing monoclonal antibodies (mAbs) recognizing human PDGF-CC. We determined the complementarity determining regions (CDRs) of the selected clones, and mapped the binding epitope for clone 6B3. Using the monoclonal 6B3, we determined the expression pattern for PDGF-CC in different human primary tumours and control tissues, and explored its ability to neutralize PDGF-CC-induced phosphorylation of PDGFRα. In addition, we showed that PDGF-CC induced disruption of the blood-retinal barrier (BRB) was significantly reduced upon intraperitoneal administration of a chimeric anti-PDGF-CC antibody. In summary, we report on high affinity monoclonal antibodies against PDGF-CC that have therapeutic efficacy in vivo .

Description: by Sofia Shevtsov, Keren Nevo-Dinur, Lior Faigon, Laure D. Sultan, Michal Zmudjak, Mark Markovits, Oren Ostersetzer-Biran Mitochondria are key sites for cellular energy metabolism and are essential to cell survival. As descendants of eubacterial symbionts (specifically α-proteobacteria), mitochondria contain their own genomes (mtDNAs), RNAs and ribosomes. Plants need to coordinate their energy demands during particular growth and developmental stages. The regulation of mtDNA expression is critical for controlling the oxidative phosphorylation capacity in response to physiological or environmental signals. The mitochondrial transcription termination factor (mTERF) family has recently emerged as a central player in mitochondrial gene expression in various eukaryotes. Interestingly, the number of mTERFs has been greatly expanded in the nuclear genomes of plants, with more than 30 members in different angiosperms. The majority of the annotated mTERFs in plants are predicted to be plastid- or mitochondria-localized. These are therefore expected to play important roles in organellar gene expression in angiosperms. Yet, functions have been assigned to only a small fraction of these factors in plants. Here, we report the characterization of mTERF22 (At5g64950) which functions in the regulation of mtDNA transcription in Arabidopsis thaliana . GFP localization assays indicate that mTERF22 resides within the mitochondria. Disruption of mTERF22 function results in reduced mtRNA accumulation and altered organelle biogenesis. Transcriptomic and run-on experiments suggest that the phenotypes of mterf22 mutants are attributable, at least in part, to altered mitochondria transcription, and indicate that mTERF22 affects the expression of numerous mitochondrial genes in Arabidopsis plants.

Description: by Akram Bakkour, Rotem Botvinik-Nezer, Neta Cohen, Ashleigh M. Hover, Russell A. Poldrack, Tom Schonberg The maintenance of behavioral change over the long term is essential to achieve public health goals such as combatting obesity and drug use. Previous work by our group has demonstrated a reliable shift in preferences for appetitive foods following a novel non-reinforced training paradigm. In the current studies, we tested whether distributing training trials over two consecutive days would affect preferences immediately after training as well as over time at a one-month follow-up. In four studies, three different designs and an additional pre-registered replication of one sample, we found that spacing of cue-approach training induced a shift in food choice preferences over one month. The spacing and massing schedule employed governed the long-term changes in choice behavior. Applying spacing strategies to training paradigms that target automatic processes could prove a useful tool for the long-term maintenance of health improvement goals with the development of real-world behavioral change paradigms that incorporate distributed practice principles.

Description: by David E. Goldsbury, Sarsha Yap, Marianne F. Weber, Lennert Veerman, Nicole Rankin, Emily Banks, Karen Canfell, Dianne L. O’Connell Background Cancer care represents a substantial and rapidly rising healthcare cost in Australia. Our aim was to provide accurate population-based estimates of the health services cost of cancer care using large-scale linked patient-level data. Methods We analysed data for incident cancers diagnosed 2006–2010 and followed to 2014 among 266,793 eligible participants in the 45 and Up Study. Health system costs included Medicare and pharmaceutical claims, inpatient hospital episodes and emergency department presentations. Costs for cancer cases and matched cancer-free controls were compared, to estimate monthly/annual excess costs of cancer care by cancer type, before and after diagnosis and by phase of care (initial, continuing, terminal). Total costs incurred in 2013 were also estimated for all people diagnosed in Australia 2009–2013. Results 7624 participants diagnosed with cancer were matched with up to three controls. The mean excess cost of care per case was AUD$1,622 for the year before diagnosis, $33,944 for the first year post-diagnosis and $8,796 for the second year post-diagnosis, with considerable variation by cancer type. Mean annual cost after the initial treatment phase was $4,474/case and the mean cost for the last year of life was $49,733/case. In 2013 the cost for cancers among people in Australia diagnosed during 2009–2013 was ~$6.3billion (0.4% of Gross Domestic Product; $272 per capita), with the largest costs for colorectal cancer ($1.1billion), breast cancer ($0.8billion), lung cancer ($0.6billion) and prostate cancer ($0.5billion). Conclusions The cost of cancer care is substantial and varies by cancer type and time since diagnosis. These findings emphasise the economic importance of effective primary and secondary cancer prevention strategies.

Description: by Yi Guo, Jiang Bian, Qian Li, Trevor Leavitt, Eric I. Rosenberg, Thomas W. Buford, Megan D. Smith, Heather K. Vincent, François Modave Background Cardiorespiratory fitness (CRF) is the only major risk factor that is not routinely assessed in the clinical setting, for preventive medicine. A valid and practical CRF test is needed for use in the clinics. The objective of this study is to demonstrate the validity of a 3-minute squat test to assess CRF in primary care. Methods A cross-sectional study in which the participants performed both the Ruffier squat test and the Balke maximal treadmill test. The study was conducted in a clinical setting from September 2016 to March 2017. We recruited a convenient sample of 40 adults between 18 and 64 years from the general U.S. population. Participants completed 30 squats in 45 seconds, paced by a metronome. Heart rate was measured at rest (P1), immediately after the test (P2), one minute after the test (P3). V˙O2max was measured using the Balke maximal treadmill fitness test. Results Of the 40 participants, there were 18 men and 22 women. Mean age was 31.2 years (SD = 9.9). We found that the best V˙O2max predictors were HR features P 1/ height and ( P 2– P 3)/ age 3 . Our best-performing model using these two features predicted individuals’ CRF levels with an adjusted R 2 of 0.637, sensitivity of 0.79, and specificity of 0.56. Conclusions The study provided strong evidence for the validity of the squat test in the clinical setting. Further, the equation of our model along with V˙O2max normative tables provides an efficient and easy way to assess CRF in a primary care setting.

Description: by Primo Proietti, Massimo Trabalza Marinucci, Alberto Marco Del Pino, Roberto D’Amato, Luca Regni, Gabriele Acuti, Elisabetta Chiaradia, Carlo Alberto Palmerini Selenium (Se) is an essential element in human and animal diets, based upon a widespread range of beneficial effects that are primarily due to its antioxidant properties. While Se can be associated to anti-cancer and anti-diabetic activities, reproductive efficiency, and enhancement of the immune system, the mechanistic details of the corresponding biological processes are still largely elusive. To avoid deficiencies and increase bioavailability, Se it is generally supplied to livestock through Se-supplemented feeds or forage plants fertilized with inorganic Se. While the relationship between Ca 2+ and ROS (reactive oxygen species) is well known, only a few studies have addressed the possible involvement of Se in the control of cytosolic Ca 2+ in oxidative stress. The results on Ca 2+ homeostasis were obtained adding exogenous Se in the form of SeO 4 2- to sheep lymphomonocytes cultured in vitro . In particular, Se strongly attenuated 1mM H 2 O 2 -induced alteration of intracellular [Ca 2+ ] C as well as the entry of extracellular Ca 2+ into the cells with comparable EC50 values for sodium selenate accounting to 1.72 and 2.28 mM, respectively. In an ex vivo trial, it was observed that Ca 2+ homeostasis can effectively be rescued in sheep lymphomonocytes exposed in vivo to a Se concentration of approximately 1.9 mM, that was achieved by feeding sheep with olive leaves previously sprayed with 500 mg/plant Na-selenate. Thus the results obtained suggest that the mode of action of selenium markedly influenced Ca 2+ -related signaling events. Furthermore, results clearly reveal that the protective effect of Se on Ca 2+ homeostasis under oxidative challenge can be clearly and effectively achieved through an appropriate dietary regimen obtained also in a circular economy logic using pruning of olive trees treated to reduce tree drought stress.

Description: by Rabab Rashwan, Julius F. Varano della Vergiliana, Sally M. Lansley, Hui Min Cheah, Natalia Popowicz, James C. Paton, Grant W. Waterer, Tiffany Townsend, Ian Kay, Jeremy S. Brown, Y. C. Gary Lee Pleural infection/empyema is common and its incidence continues to rise. Streptococcus pneumoniae is the commonest bacterial cause of empyema in children and among the commonest in adults. The mesothelium represents the first line of defense against invading microorganisms, but mesothelial cell responses to common empyema pathogens, including S . pneumoniae , have seldom been studied. We assessed mesothelial cell viability in vitro following exposure to common empyema pathogens. Clinical isolates of S . pneumoniae from 25 patients with invasive pneumococcal disease and three reference strains were tested. All potently induced death of cultured mesothelial cells (MeT-5A) in a dose- and time-dependent manner (〉90% at 10 7 CFU/mL after 24 hours). No significant mesothelial cell killing was observed when cells were co-cultured with Staphylococcus aureus , Streptococcus sanguinis and Streptococcus milleri group bacteria. S . pneumoniae induced mesothelial cell death via secretory product(s) as cytotoxicity could be: i) reproduced using conditioned media derived from S . pneumoniae and ii) in transwell studies when the bacteria and mesothelial cells were separated. No excess cell death was seen when heat-killed S . pneumoniae were used. Pneumolysin, a cytolytic S . pneumoniae toxin, induced cell death in a time- and dose-dependent manner. S . pneumoniae lacking the pneumolysin gene (D39 ΔPLY strain) failed to kill mesothelial cells compared to wild type (D39) controls, confirming the necessity of pneumolysin in D39-induced mesothelial cell death. However, pneumolysin gene mutation in other S . pneumoniae strains (TIGR4, ST3 and ST23F) only partly abolished their cytotoxic effects, suggesting different strains may induce cell death via different mechanisms.

Description: by Ming-Tzer Lin, Chao-Lun Lai, Pei-Lin Lee, Min-Huei Shen, Chong-Jen Yu, Chi-Tai Fang, Chi-Ling Chen Background The present study aimed to test if the temporal sequence between sleep apnea (SA) diagnosis and incident myocardial infarction (MI) was associated with the long-term mortality and cardiovascular event in a community-based cohort. Methods We retrieved data from 9,453 incident MI patients between Jan. 1 st 2000 and Dec. 31 st 2012 from the Taiwan National Health Insurance Research Database. The study subjects included 207 MI patients with SA (SA-MI), further stratified into 110 with pre-existing SA before MI (SA-bMI) and 96 diagnosed with SA after MI (SA-pMI). The median follow-up period was 4.2 years. Propensity-score-matched controls were selected from 9,246 non-SA MI patients (non-SA-MI). The association of SA and outcomes including all-cause mortality and major adverse cardiac and cerebrovascular events (MACCEs) were analyzed by a Cox proportional hazards model. Results The result showed that SA was not associated with mortality regardless of the timing of SA diagnosis. SA-pMI was associated with increased risk of MACCEs (Hazard ratio [HR]: 1.412, 95% confidence interval [CI]: 1.037~1.923, p = 0.029) including re-MI or revascularization and ischemic heart disease hospitalization. Such an association was most significant for SA diagnosed within one year after MI (HR: 2.029, 95% CI: 1.265~3.254, p = 0.003), which was not seen in patients treated with continuous positive airway pressure (CPAP). Conclusion The temporal sequence and the time interval between SA diagnosis and incident MI was associated with the cardiovascular events after MI, especially within one year after MI. Early assessment for the presence of SA after incident MI and early CPAP intervention may reduce the risk of further adverse cardiovascular events.

Description: by Thomas LeBrun, Peter Schuck, Ren Wei, Justine S. Yoon, Xianghui Dong, Nicole Y. Morgan, Jeffrey Fagan, Huaying Zhao Analytical ultracentrifugation (AUC) is a first-principles based method for studying macromolecules and particles in solution by monitoring the evolution of their radial concentration distribution as a function of time in the presence of a high centrifugal field. In sedimentation velocity experiments, hydrodynamic properties relating to size, shape, density, and solvation of particles can be measured, at a high hydrodynamic resolution, on polydisperse samples. In a recent multilaboratory benchmark study including data from commercial analytical ultracentrifuges in 67 laboratories, the calibration accuracy of the radial dimension was found to be one of the dominant factors limiting the accuracy of AUC. In the present work, we develop an artifact consisting of an accurately calibrated reflective pattern lithographically deposited onto an AUC window. It serves as a reticle when scanned in AUC control experiments for absolute calibration of radial magnification. After analysis of the pitch between landmarks in scans using different optical systems, we estimate that the residual uncertainty in radial magnification after external calibration with the radial scale artifact is ≈0.2 %, of similar magnitude to other important contributions after external calibration such as the uncertainty in temperature and time. The previous multilaboratory study had found many instruments with errors in radial measurements of 1 % to 2 %, and a few instruments with errors in excess of 15 %, meaning that the use of the artifact developed here could reduce errors by 5-to 10-fold or more. Adoption of external radial calibration is thus an important factor for assuring accuracy in studies related to molecular hydrodynamics and particle size measurements by AUC.

Description: by Giorgi Chakhunashvili, Abram L. Wagner, Laura E. Power, Cara B. Janusz, Ann Machablishvili, Irakli Karseladze, Olgha Tarkhan-Mouravi, Khatuna Zakhashvili, Paata Imnadze, Gregory C. Gray, Benjamin Anderson, Matthew L. Boulton Background Severe Acute Respiratory Infection (SARI) causes substantial mortality and morbidity worldwide. The country of Georgia conducts sentinel surveillance to monitor SARI activity and changes in its infectious etiology. This study characterizes the epidemiology of SARI in Georgia over the 2015/16 and 2016/17 influenza seasons, compares clinical presentations by etiology, and estimates influenza vaccine effectiveness using a test-negative design. Methods SARI cases were selected through alternate day systematic sampling between September 2015 and March 2017 at five sentinel surveillance inpatient sites. Nasopharyngeal swabs were tested for respiratory viruses and Mycoplasma pneumoniae using a multiplex diagnostic system. We present SARI case frequencies by demographic characteristics, co-morbidities, and clinical presentation, and used logistic regression to estimate influenza A vaccine effectiveness. Results 1,624 patients with SARI were identified. More cases occurred in February (28.7%; 466/1624) than other months. Influenza was the dominant pathogen in December-February, respiratory syncytial virus in March-May, and rhinovirus in June-November. Serious clinical symptoms including breathing difficulties, ICU hospitalization, and artificial ventilation were common among influenza A and human metapneumovirus cases. For influenza A/H3, a protective association between vaccination and disease status was observed when cases with unknown vaccination status were combined with those who were unvaccinated (OR: 0.53, 95% CI: 0.30, 0.97). Conclusions Multi-pathogen diagnostic testing through Georgia’s sentinel surveillance provides useful information on etiology, seasonality, and demographic associations. Influenza A and B were associated with more severe outcomes, although the majority of the population studied was unvaccinated. Findings from sentinel surveillance can assist in prevention planning.

Description: by Qian Cai, Fang Li, Yunxian Zhou Background Despite the increasing number of Crohn's disease patients self-administering nasogastric feeding as enteral nutrition support therapy, no studies have reported the experiences of self-administering nasogastric feeding from the perspective of these patients. Objectives To explore the initial trigger factors for the self-administration of nasogastric feeding by Crohn’s disease patients and to understand the experiences of self-administration of nasogastric feeding, its effects on various aspects of life and work, and relevant challenges and coping mechanisms encountered during this therapy in order to improve the understanding of this group of patients among medical staff and the public. Design This study adopted a descriptive qualitative method. Crohn's disease patients from several tertiary hospitals in Hangzhou, Zhejiang, were recruited to participate through purposive sampling combined with maximum variation and the snowballing technique. Data were collected using semi-structured interviews and analyzed using the conventional content analysis method. Results A total of 11 Crohn's disease patients were interviewed. Four themes and eight subthemes emerged from the analysis: rejecting the self-administration of nasogastric feeding (being afraid of inserting the nasogastric tube, having concerns about nasogastric feeding), accepting the reality of nasogastric feeding (health being the most important, followed by having sources of support), nasogastric feeding as a double-edged sword (the disturbances and efficacies of nasogastric feeding), and nasogastric feeding as a part of life (becoming accustomed to tube insertion and taking nasogastric feeding for granted). Conclusions Apart from suffering from physical discomfort, diet and body image disturbances, and inconveniences in daily life, Crohn's disease patients who self-administered nasogastric feeding faced many psychological challenges. Many of these patients eventually adjusted to a life with nasogastric feeding, but not everyone achieved this state. Therefore, health care providers, including physicians and nurses, and the general public should collaborate to help these patients adapt to their “new lives” as soon as possible.

Description: by Tao Li, Hongyun Wang, Xiubo Xia, Shoujun Cao, Jiangang Yao, Lili Zhang Root-knot nematodes (RKNs; Meloidogyne spp.) are obligate endoparasites that infect many crops and cause severe yield losses. In this research, we studied the effect of Welsh onion, grown as a companion plant, on the resistance of cucumber plants to RKN infection and analyzed the most abundant components of Welsh onion root exudates. The results showed that, when grown with Welsh onion as a companion plant, cucumber roots had 77.0% fewer root knots and egg masses than the control cucumber roots. Welsh onion root exudates were collected and extracted with chloroform, ethyl ether, n -butanol and ethyl acetate. High concentrations of the extracts from the Welsh onion root exudates decreased the hatchability of RKN eggs. In particular, the inhibitory effect of the n -butanol extract was significant and the hatchability of RKN eggs did not exceed 10%. Gas chromatographic–mass spectrometric analysis revealed that the most abundant component in the n -butanol extract was 4-hydroxy-benzeneethanol. Treatment with 1.2 mM 4-hydroxy-benzeneethanol decreased egg hatchability to 40%, whereas treatment with 9.6 mM or a higher concentration of 4-hydroxy-benzeneethanol decreased egg hatchability to less than 10%. In addition, 1.2 mM or a higher concentration of 4-hydroxy-benzeneethanol decreased the activity of the second-stage juvenile (J2). Higher 4-hydroxy-benzeneethanol concentrations (9.8 and 19.2 mM) were lethal to RKNs to some extent, with death rates greater than 50% at 48 h of treatment. The present results suggest that cultivation with Welsh onion as a companion plant may represent an alternative to the application of synthetic nematicides, with fewer side effects. We confirmed that 4-hydroxy-benzeneethanol is a natural effective nematicide.

Description: by Puja Kohli, Pedro V. Staziaki, Sumbal A. Janjua, Daniel A. Addison, Travis R. Hallett, Orla Hennessy, Richard A. P. Takx, Michael T. Lu, Florian J. Fintelmann, Marc Semigran, Robert S. Harris, Bartolome R. Celli, Udo Hoffmann, Tomas G. Neilan Heart Failure (HF) and chronic obstructive pulmonary disease (COPD) are morbid diseases that often coexist. In patients with coexisting disease, COPD is an independent risk factor for readmission and mortality. However, spirometry is often inaccurate in those with active heart failure. Therefore, we investigated the association between the presence of emphysema on computed tomography (CT) and readmission rates in smokers admitted with heart failure (HF). The cohort included a consecutive group of smokers discharged with HF from a tertiary center between January 1, 2014 and April 1, 2014 who also had a CT of the chest for dyspnea. The primary endpoint was any readmission for HF before April 1, 2016; secondary endpoints were 30-day readmission for HF, length of stay and all-cause mortality. Over the study period, there were 225 inpatient smokers with HF who had a concurrent chest CT (155 [69%] males, age 69±11 years, ejection fraction [EF] 46±18%, 107 [48%] LVEF of 〈 50%). Emphysema on CT was present in 103 (46%) and these were older, had a lower BMI, more pack-years, less diabetes and an increased afterload. During a follow-up of 2.1 years, there were 110 (49%) HF readmissions and 55 (24%) deaths. When separated by emphysema on CT, any readmission, 30-day readmission, length of stay and mortality were higher among HF patients with emphysema. In multivariable regression, emphysema by CT was associated with a two-fold higher (adjusted HR 2.11, 95% CI 1.41–3.15, p 〈 0.001) risk of readmission and a trend toward increased mortality (adjusted HR 1.70 95% CI 0.86–3.34, p = 0.12). In conclusion, emphysema by CT is a frequent finding in smokers hospitalized with HF and is associated with adverse outcomes in HF. This under recognized group of patients with both emphysema and heart failure may benefit from improved recognition and characterization of their co-morbid disease processes and optimization of therapies for their lung disease.

Description: by Christian Akem Dimala, Hannah Blencowe, Simeon Pierre Choukem Background With increasing adverse cardiovascular disease (CVD) outcomes in HIV/AIDS patients, the possible contribution of antiretroviral therapy (ART) to the prevailing CVD epidemic in sub-Saharan Africa (SSA) through its effect on CVD risk factors has rather been under investigated. This study aimed to assess the extent to which ART is associated with hypertension, diabetes mellitus (DM) and dyslipidemia in SSA. Methods This is a systematic review and meta-analysis of studies from SSA, published between January 1946 and December 2017, from Medline, Embase, Africa-wide Information, the Cochrane library, African Index and Medicus databases. Both observational and interventional studies with comparable ART-treated and ART-naïve populations were selected and data was extracted from eligible studies. Pooled estimates of the effect of ART on the outcomes of interest (hypertension, diabetes and abnormal lipid profiles) were obtained using random effects meta-analysis, and meta-regression analysis was used to explore between-study heterogeneity. Results Twenty cross-sectional studies were included involving 5386 participants. There was no association between ART use and hypertension (OR: 1.9, 95%CI: 0.96–3.76, n = 8, I 2 = 73.8%) and DM (OR: 2.53, 95%CI: 0.87–7.35, n = 8, I 2 = 73.8%). ART use was associated with high total cholesterol (OR: 3.85, 95%CI: 2.45–6.07, n = 8, I 2 = 67.0%), high triglycerides (OR: 1.46, 95%CI: 1.21–1.75, n = 14, I 2 = 10.0%) and high LDL-cholesterol (OR: 2.38, 95%CI: 1.43–3.95, n = 11, I 2 = 87.6%). ART was associated with rather lower odds of having low HDL-cholesterol (OR: 0.53, 95%CI: 0.32–0.87, n = 8, I 2 = 78.2%). There was evidence of between-study heterogeneity for all outcomes except high triglycerides. Conclusions ART appears to be associated with CVD risk in HIV/AIDS patients in SSA only through dyslipidemia but not through hypertension and DM, however, high quality and robust research in SSA is mandated to accurately ascertain the actual contribution of ART to the CVD burden in this part of the world. Nevertheless, HIV/AIDS patients should still benefit from systematic CVD screening alongside their regular care services. Trial registration Prospero Registration - CRD42016042306.

Description: by Glenn D. Bell, Yi Yang, Euphemia Leung, Geoffrey W. Krissansen Messenger RNA (mRNA) transfection is a developing field that has applications in research and gene therapy. Potentially, mRNA transfection can be mediated efficiently by cell-penetrating peptides (CPPs) as they may be modified to target specific tissues. However, whilst CPPs are well-documented to transfect oligonucleotides and plasmids, mRNA transfection by CPPs has barely been explored. Here we report that peptides, including a truncated form of protamine and the same peptide fused to the CPP Xentry (Xentry-protamine; XP), can transfect mRNAs encoding reporter genes into human cells. Further, this transfection is enhanced by the anti-malarial chloroquine (CQ) and the toll-like receptor antagonist E6446 (6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole), with E6446 being 〉5-fold more potent than CQ at enhancing this transfection. Finally, E6446 facilitated the transfection by XP of mRNA encoding the cystic fibrosis transmembrane regulator, the protein mutated in cystic fibrosis. As such, these findings introduce E6446 as a novel transfection enhancer and may be of practical relevance to researchers seeking to improve the mRNA transfection efficiency of their preferred CPP.

Description: by Alexandra Grosse, Claudia Grosse, Irene Lang Purpose The aim of this study was to evaluate the vascular and parenchymal CT imaging findings, including vessel and cardiac chamber diameter measurements, in patients newly diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). The CT imaging findings were correlated with hemodynamic measurements and patient outcome. Methods Vascular and parenchymal CT findings were assessed on retrospectively ECG-gated MDCT angiography scans in 76 patients newly diagnosed with CTEPH. The diameters of the right and left ventricle (dRV, dLV), the right and left atrium (dRA, dLA), the ascending aorta (dAA), the right and left pulmonary arteries (drPA, dlPA), and the main pulmonary artery (dPA) were measured on axial CT scans. The CT imaging findings were correlated with demographic and hemodynamic data and adverse patient outcome due to right heart failure (RHF). Results The majority of patients showed chronic PE, mosaic perfusion, disparity in segmental vessel size, parenchymal densities, bronchial dilatation, and bronchial collaterals in CT. Mean pulmonary artery pressure (mPAP) was not significantly different in patients with and those without chronic PE, mosaic perfusion, disparity in segmental vessel size, parenchymal densities, bronchial dilatation, and bronchial collaterals. Mean PAP showed significant correlations with the CT metrics of dRV/dLV ratio, dRA, dRV, dPA and dPA/dAA ratio, but no correlation with the central thrombi score. By backward linear regression, the dPA/dAA ratio independently correlated with mPAP. Patients who died of RHF tended to have a higher frequency of exclusively chronic peripheral PE and greater dRV/dLV ratios on presenting CT scans compared with survivors. Conclusion The majority of patients newly diagnosed with CTEPH show vascular signs of chronic PE, mosaic perfusion, parenchymal densities, disparity in segmental vessel size, bronchial dilatation, and bronchial collaterals on presenting CT scans. Particularly CTEPH patients with exclusively chronic peripheral PE and increased dRV/dLV ratios seem to be at risk of adverse outcome due to RHF.

Description: by Sayak Bhattacharya, Pablo A. Iglesias Chemotaxis, the migration of cells in the direction of a chemical gradient, is of utmost importance in various biological processes. In recent years, research has demonstrated that the underlying mechanism that controls cell migration is an excitable network. One of the properties that characterizes excitability is the presence of a threshold for activation. Here, we show that excitable systems possess noise filtering capabilities that enable faster and more efficient directed migration compared to other systems that also include a threshold, such as ultrasensitive switches. We demonstrate that this filtering ability is a consequence of the varying responses of excitable systems to step and pulse stimuli. Whereas the response to step inputs is determined solely by the magnitude of the stimulus, for pulse stimuli, the response depends on both the magnitude and duration of the stimulus. We then show that these two forms of threshold behavior can be decoupled from one another, allowing finer control in chemotaxis. Finally, we use a simple model of chemotaxis to demonstrate that cells that rely on an excitable system display faster and more effective directed migration that a hypothetical cell guided by an ultra-sensitive switch.

Description: by Pooja Muralidharan, Swapnalee Sarmah, James A. Marrs Fetal alcohol spectrum disorder caused by prenatal alcohol exposure includes ocular abnormalities (microphthalmia, photoreceptor dysfunction, cataracts). Zebrafish embryos exposed to ethanol from gastrulation through somitogenesis show severe ocular defects, including microphthalmia and photoreceptor differentiation defects. Ethanol-treated zebrafish had an enlarged ciliary marginal zone (CMZ) relative to the retina size and reduced Müller glial cells (MGCs). Ethanol exposure produced immature photoreceptors with increased proliferation, indicating cell cycle exit failure. Signaling mechanisms in the CMZ were affected by embryonic ethanol exposure, including Wnt signaling in the CMZ, Notch signaling and neurod gene expression. Retinoic acid or folic acid co-supplementation with ethanol rescued Wnt signaling and retinal differentiation. Activating Wnt signaling using GSK3 inhibitor (LSN 2105786; Eli Lilly and Co.) restored retinal cell differentiation pathways. Ethanol exposed embryos were treated with Wnt agonist, which rescued Wnt-active cells in the CMZ, Notch-active cells in the retina, proliferation, and photoreceptor terminal differentiation. Our results illustrate the critical role of Wnt signaling in ethanol-induced retinal defects.

Description: by Jussi O. T. Sipilä, Jussi P. Posti, Jori O. Ruuskanen, Päivi Rautava, Ville Kytö Background The age-standardized incidence of stroke has decreased globally but, for reasons unknown, conflicting results have been observed regarding trend in incidence of major stroke subtypes in young adults. We studied these trends among people of working age in a population-based setting in Finland, where cardiovascular risk factor profiles have developed favorably. Methods All hospitalizations for stroke in 2004–2005 and 2013–2014 for persons 18–64 years of age were identified from a national register. The search included all hospitals that provide acute stroke care on mainland Finland. Results Hospitalizations for both intracerebral hemorrhage (ICH; -15.2%; p = 0.0008) and subarachnoid hemorrhage (SAH; -26.5%; p

Description: by Wai-Ming To, Peter K. C. Lee, King-Hang Lam Smart and sustainable buildings save energy and material resources and provide a comfortable environment that enhances their occupants’ well-being and productivity. It is therefore crucial to understand how building professionals, including designers, engineers, and contractors, view smart and sustainable buildings and what drives them towards smart and sustainable building technologies. This study identifies salient smart and sustainable building features from building professionals’ perspective and explores what determines building professionals’ intention to use such building technologies. Responses from 543 Hong Kong’s building professionals identify that intelligent security, intelligent and responsive fresh air supply, and intelligent and responsive thermal control are among the most important features of smart and sustainable buildings. Results of structural equation modeling grounded on an extended technology acceptance model indicate that facilitating condition and job relevance are related to perceived ease of use while subjective norm pertaining to image and perceived ease of use are predictors of perceived usefulness. Facilitating condition, perceived ease of use and perceived usefulness jointly influence building professionals’ intention to use smart and sustainable building technologies.

Description: by Souheil Hallit, Benedicte Leynaert, Marie Christine Delmas, Steffi Rocchi, Jacques De Blic, Christophe Marguet, Emeline Scherer, Marie Noelle Dufourg, Corinne Bois, Gabriel Reboux, Laurence Millon, Marie Aline Charles, Chantal Raherison

Description: by Wei-Wei Wang, Chao Zheng, Wan-Jun Hao, Chun-Lei Ma, Jian-Qiang Ma, De-Jiang Ni, Liang Chen Tea plant ( Camellia sinensis (L) O. Kuntze) respond to herbivore attack through large changes in defense related metabolism and gene expression. Ectropis oblique (Prout) is one of the most devastating insects that feed on tea leaves and tender buds, which can cause severe production loss and deteriorate the quality of tea. To elucidate the biochemicals and molecular mechanism of defense against tea geometrid (TG), transcriptome and metabolome of TG interaction with susceptible (SG) and resistance (RG) tea genotypes were analyzed by using UPLC-Q-TOF-MS, GC-MS, and RNA-seq technologies. This revealed that jasmonic acid was highly induced in RG, following a plethora of secondary metabolites involved in defense against TG could be induced by jasmonic acid signaling pathway. However, the constitutively present of salicylic acid in SG might be a suppressor of jasmonate signaling and thus misdirect tea plants against TG. Furthermore, flavonoids and terpenoids biosynthesis pathways were highly activated in RG to constitute the chemical barrier on TG feeding behavior. In contrast, fructose and theanine, which can act as feeding stimulants were observed to highly accumulate in SG. Being present in the major hub, 39 transcription factors or protein kinases among putative candidates were identified as master regulators from protein-protein interaction network analysis. Together, the current study provides a comprehensive gene expression and metabolite profiles, which can shed new insights into the molecular mechanism of tea defense against TG. The candidate genes and specific metabolites identified in the present study can serve as a valuable resource for unraveling the possible defense mechanism of plants against various biotic stresses.

Description: by Polina Gundorova, Rena A. Zinchenko, Irina A. Kuznetsova, Elena A. Bliznetz, Anna A. Stepanova, Aleksander V. Polyakov Phenylketonuria is an inherited disease caused by mutations in the phenylalanine hydroxylase gene PAH . Different PAH pathogenic variants occur in different ethnic groups with various frequencies and the incidence of the disease itself varies from country to country. In the Caucasus region of Russia, some ethnoses are geographically and culturally isolated from each other. The tradition of monoethnic marriages may cause decreased genetic variability in those populations. In the Karachay-Cherkess Republic (Russia), the highest incidence of phenylketonuria in the world has been detected (1:850 newborns) in the region and 1:332 among the titular nation Karachays. Here, we showed that this phenomenon is due to the widespread prevalence of the p.Arg261* variant. Its allele frequency among Karachay patients with PKU was 68.4% and the carrier frequency in Karachays was 1:16 healthy individuals. PAH haplotype analysis showed a unique common origin. The founder haplotype and mutation “age” were estimated by analyzing the linkage disequilibrium between p.Arg261* and extragenic short tandem repeat loci. The p.Arg261* variant occurred in the Karachays population 10.2 ± 2.7 generations ago (275 ± 73 years) and its spread occurred in parallel with the growth of the population.

Description: by Nicolas Clementy, Bruno Garcia, Clémentine André, Arnaud Bisson, Nazih Benhenda, Bertrand Pierre, Anne Bernard, Laurent Fauchier, Eric Piver, Dominique Babuty Introduction Mechanisms of maintenance of both atrial fibrillation and structural left ventricular disease are known to include fibrosis. Galectin-3, a biomarker of fibrosis, is elevated both in patients with heart failure and persistent atrial fibrillation. We sought to find whether galectin-3 has a prognostic value in patients with heart failure and a reduced left ventricular ejection fraction undergoing ablation of persistent atrial fibrillation. Methods Serum concentrations of galectin-3 were determined in a consecutive series of patients with an ejection fraction ≤40%, addressed for ablation of persistent atrial fibrillation. Responders to ablation were patients in sinus rhythm and with an ejection fraction ≥50% at 6 months. A combined endpoint of heart failure hospitalization, transplantation and/or death was used at 12 months. Results Seventy-five patients were included (81% male, age 63±10 years, ejection fraction 34±7%, galectin-3 21±12 ng/mL). During follow-up, eight patients were hospitalized for decompensated heart failure, 1 underwent heart transplantation, and 4 died; 50 patients were considered as responders to ablation. After adjustment, galectin-3 level independently predicted both 6-month absence of response to ablation (OR = 0.89 per unit increase, p = 0.002). Patients with galectin-3 levels

Description: by Jungchan Park, Jeayoun Kim, Ji Hye Kwon, Soo Jung Park, Jeong Jin Min, Sangmin Maria Lee, Hyeon-Cheol Gwon, Young Tak Lee, Myungsoo Park, Seung Hwa Lee Perioperative use of β-blocker has been encouraged in patients undergoing non-cardiac surgery despite weak evidence, especially in patients without left ventricular systolic dysfunction (LVSD) or heart failure (HF). This study evaluated the effects of perioperative β-blocker on clinical outcomes after non-cardiac surgery among coronary revascularized patients without LVSD or HF. Among a total of 503 patients with a history of coronary revascularization (either by percutaneous coronary intervention or coronary arterial bypass grafts) undergoing non-cardiac surgery, those without severe LVSD defined by ejection fraction over 30% or HF were evaluated. The primary outcome was a composite of death, myocardial infarction, repeat revascularization, and stroke during 1-year follow-up. Perioperative β-blocker was used in 271 (53.9%) patients. During 1-year follow-up, we found no significant difference in primary outcome between the two groups on multivariate analysis (hazard ratio [HR], 1.01; confidence interval [CI] 95%, 0.56–1.82; P = 0.963). The same result was shown in propensity-matched population (HR, 1.25; CI 95%, 0.65–2.38; P = 0.504). In coronary revascularized patients without severe LVSD or HF, perioperative β-blocker use may not be associated with postoperative clinical outcome of non-cardiac surgery. Larger registry data is needed to support this finding.

Description: by Hiroyuki Motoyama, Akihiro Tamori, Shoji Kubo, Sawako Uchida-Kobayashi, Shigekazu Takemura, Shogo Tanaka, Satoko Ohfuji, Yuga Teranishi, Ritsuzo Kozuka, Etsushi Kawamura, Atsushi Hagihara, Hiroyasu Morikawa, Masaru Enomoto, Yoshiki Murakami, Norifumi Kawada

Description: by Michihito Tagawa, Chihiro Kurashima, Satoshi Takagi, Naoya Maekawa, Satoru Konnai, Genya Shimbo, Kotaro Matsumoto, Hisashi Inokuma, Keiko Kawamoto, Kazuro Miyahara B cell high grade lymphoma is the most common hematopoietic malignancy in dogs. Although the immune checkpoint molecules, programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and immune checkpoint inhibitors have been evaluated for the treatment of various human lymphoid malignancies, the expression of those molecules and their relationship with prognosis remain unknown in canine lymphoma. The objective of this study was to evaluate the expression of costimulatory molecules on peripheral blood lymphocytes and tumor infiltrating lymphocytes, in addition to associated ligand expression in the lymph nodes of patients with B cell multicentric high grade lymphoma. Eighteen patients diagnosed with B cell high grade lymphoma and nine healthy control dogs were enrolled. Flow cytometric analysis revealed that the expression of PD-1 on CD4+ peripheral and tumor infiltrating lymphocytes and CTLA-4 on CD4+ peripheral lymphocytes was significantly higher in the lymphoma group than in the control group. The expression level of CD80 mRNA was significantly lower in the lymphoma group than in the control group. In contrast, there were no significant differences in PD-L1 , PD-L2 , and CD86 expression between the groups. Dogs with CTLA-4 levels below the cutoff values, which were determined based on receiver operating characteristic curves, on peripheral CD4+, CD8+, and tumor infiltrating CD4+ lymphocytes had significantly longer survival than dogs with values above the cutoff. Although it is uncertain whether the expression of immune checkpoint molecules affect the biological behavior of canine lymphoma, one possible explanation is that PD-1 and CTLA-4 might be associated with the suppression of antitumor immunity in dogs with B cell high grade lymphoma, particularly through CD4+ T cells.

Description: by Wei Zhang, Keren Chen, Xueqing Zhang, Chunhe Guo, Yaosheng Chen, Xiaohong Liu Background Recently, three-dimensional (3D) imaging techniques have been used to detect viral invasion and the appearance of specialized structures established in virus-infected cells. These methods have had a positive impact in the field of virology and helped to further our knowledge of how viruses invade cells. Nearly all positive-strand RNA viruses propagate their viral genomes in part through intracellular membranes. Porcine reproductive and respiratory syndrome virus (PRRSV), an Arterivirus, accumulates viral RNA that forms replication complexes (RCs) in infected cells. In this study, using immunofluorescence and electron microscopy (EM), we dissected PRRSV-induced membrane structures in infected cells and determined the correlations between PRRSV particles and vesicles stimulated by PRRSV to understand the structural and dynamic aspects of PRRSV infection. Methods We identified the appropriate time point by determining the 50% tissue culture infectious dose (TCID50) and using qRT-PCR and Western blotting. The co-localization of viruses and organelles was determined by immunofluorescence and immune-electron microscopy (IEM). The ultrastructure of cells infected by PRRSV was observed using EM and electron tomography (ET). Results In our study, we found that PRRSV dsRNA was located at the endoplasmic reticulum (ER) and autophagosomes; in addition, the N protein was located at the mitochondria, ER and autophagosomes. Vesicles induced by PRRSV appeared at 16 hours post-infection (h.p.i.) and increased in size with time during the infection period. In addition, our findings demonstrated that the virus vesicles originated from the ER, and these two organelle structures connected with each other to form a reticulovesicular network (RVN) that provided a site for virus replication and assembly. Conclusion Our results revealed that membrane vesicles induced by PRRSV were derived from the ER. The vesicles may provide a location for PRRSV replication and assembly.

Description: by Deogratius Bintabara, Stephen M. Kibusi Introduction A hidden determinant such as intimate partner violence victimization has been associated with under-five morbidity and mortality. However, there is lack of information regarding which exactly age group of under-five is more vulnerable to morbidity when their mothers exposed to intimate partner violence victimization. This study aimed to determine the effect of mothers’ exposure to intimate partner violence victimization on age groups specific under-five morbidity that could lead to mortality. Material and methods The current study pooled and analyzed data from 2010 and 2016 Tanzania Demographic Health Survey datasets. We used a stratified multilevel modeling to assess the association between under-five morbidity and intimate partner violence victimization according to age groups. The Statistical approach using Stata 14 was used to adjust for clustering effect and weighted the estimates to correct for non-responses and disproportionate sampling employed during designing of the surveys. Results A total of 13,639 singleton live-births babies within three years prior to interview dates from the ever-married women were included in the analysis. We found a significant reduction of the three main symptoms of under-five morbidity namely; a cough with difficult or fast breathing from 21.7 to 15.7%, fever from 22.5 to 18.3%, and diarrhoea from 15.5 to 12.7% for the survey years from 2010 to 2016 respectively ( P

Description: by Ana María Vásquez, Ana Catalina Medina, Alberto Tobón-Castaño, Maritza Posada, Gabriel Jaime Vélez, Ana Campillo, Iveth J. González, Xavier Ding Background Pregnancy poses specific challenges for the diagnosis of Plasmodium falciparum infection due to parasite sequestration in the placenta, which translates in low circulation levels in peripheral blood. The aim of this study is to assess the performance of a new highly sensitive rapid diagnostic test (HS-RDT) for the detection of malaria in peripheral and placental blood samples from pregnant women in Colombia. Methods This is a retrospective study using 737 peripheral and placental specimens collected from pregnant women in Colombian malaria-endemic regions. Light microscopy (LM), conventional rapid diagnostic tests (Pf/Pv RDT and Pf RDT), and HS-RDT testing were performed. Diagnostic accuracy endpoints of LM, HS-RDT and RDTs were compared with nested polymerase chain reaction (nPCR) as the reference test. Results In comparison with nPCR, the sensitivity of HS-RDT, Pf RDT, Pf/Pv RDT and LM to detect infection in peripheral samples was 85.7% (95% CI = 70.6–93.7), 82.8% (95% CI = 67.3–91.9), 77.1% (95% CI = 61.0–87.9) and 77.1% (95% CI = 61.0–87.9) respectively. The sensitivity to detect malaria in asymptomatic women, was higher with HS-RDT, where LM and Pf/Pv RDT missed half of infections detected by nPCR, but differences were not significant. Overall, specificity was similar for all tests (〉99.0%). In placental blood, the prevalence of infection by P . falciparum by nPCR was 2.8% (8/286), by HS-RDT was 1% and by conventional RDTs (Pf RDT and Pf/Pv RDT) and LM was 0.7%. The HS-RDT detected placental infections in peripheral blood that were negative by LM and Pf/Pv RDT, however the number of positive placentas was low. Conclusions The sensitivity of HS-RDT to detect P . falciparum infections in peripheral and placental samples from pregnant women was slightly better compared to routinely used tests during ANC visits and at delivery. Although further studies are needed to guide recommendations on the use of the HS-RDT for malaria case management in pregnancy, this study shows the potential value of this test to diagnose malaria in pregnancy in low-transmission settings.

Description: by Yue Ding, Kathleen Gray, Alexander Forrence, Xiaoqin Wang, Juan Huang Tonal working memory (WM) refers to the maintenance and the online manipulation of tonal information and has been suggested to involve different mechanisms than verbal WM. Previous research has suggested that verbal WM performance is determined by the duration instead of the number of verbal materials. We investigated in the present study to what degree that the number and the duration of notes in a sequence influence the tonal WM in participants with or without professional musical training. The forward tonal discrimination task in Experiment 1 tested the maintenance of the tonal information and the backward N-back tonal task in Experiment 2 probed the running memory span of tonal information. Results show that the number of notes, but not the duration of notes in a tone sequence significantly affects tonal WM performance for both musicians and non-musicians. In addition, within a minimum musical context, musicians outperformed non-musicians in the N-back tonal task but not the forward tone sequence discrimination task. These findings indicate that the capacity of tonal WM is determined by the number of notes but not the duration of notes in a sequence to be memorized, suggesting a different mechanism underlying tonal WM from verbal WM. Furthermore, the present study demonstrated that N-back tonal task is a quantitative and sensitive measure of the effect of musical training on tonal WM.

Description: by Mark P. Miller, Raymond J. Davis, Eric D. Forsman, Thomas D. Mullins, Susan M. Haig Landscape genetics investigations examine how the availability and configuration of habitat influence genetic structure of plants and animals. We used landscape genetics to evaluate the role that forest connectivity plays in determining genetic structure of the federally-threatened Northern Spotted Owl ( Strix occidentalis caurina ) using genotypes of 339 Northern Spotted Owls obtained for 10 microsatellite loci. Spatial clustering analyses identified a distinct genetic cluster at the southern extent of the region examined. This cluster could not be linked to landscape connectivity patterns and suggested that post-Pleistocene processes were involved with its development rather than contemporary landscape configuration. We also compared matrices of pairwise inter-individual genetic distances with resistance distances derived from a circuit-theory based framework. Resistance distances were obtained for an idealized raster map that reflected continuous unimpeded dispersal habitat across the landscape along with five empirically-derived raster maps reflecting the 1870’s, 1940’s, 1986, 1994, and 2012. Resistance distances from the idealized map served as surrogates for linear geographic distances. Relative to idealized conditions, resistance distances were ~250% higher in the 1940’s and ~200% higher from 1986 onward. Resistance distances from the 1870’s were ~40% higher than idealized conditions. Inter-individual genetic distances were most highly correlated with resistance distances from the idealized map rather than any of the empirical maps. Two hypotheses explain our results. First, our results may reflect temporal lags between the onset of large-scale habitat alterations and their novel effects on genetic structure in long-lived species such as Northern Spotted Owls. Second, because Northern Spotted Owls disperse over long distances, our results may indicate that forest habitat has never been sufficiently fragmented to the point where connectivity was disrupted. The second hypothesis could indicate that forest management practices mandated by the Northwest Forest Plan succeeded with one of its primary goals. However, our results do not represent a complete portrayal of the status of Northern Spotted Owls given detection of significant population declines and bottlenecks in other studies. Future investigations based on computer simulations may help distinguish between hypotheses.

Description: by Bruno Merk, Dzianis Litskevich The successful implementation of disarmament treaties of the last centuries has led to significant amounts of weapon-grade Plutonium which are currently stored in high security storage facilities. Disposing this Plutonium should be seen as ‘good housekeeping’ avoiding unnecessary costs and the hazards of storing this material indefinitely. In addition, the disarmament is only brought to a successful end when the Plutonium isn’t available for the production of new weapons anymore. We propose a disruptive approach for Plutonium disposition and demonstrate the feasibility in a neutronic study. Burning of weapon-grade Plutonium in a molten salt fast reactor is significantly more efficient than in the studied other reactors, while efficient process design has the potential to reduce the security concerns significantly. The proposed system could turn about 1.25 tons of weapon-grade Plutonium into electric energy worth £ 0.5 to 1 billion/year, depending on the electricity price while avoiding the hassle and eliminating the risk of high security Plutonium storage. In conclusion, burning of the weapon-grade Plutonium resulting from disarmament could be an economically very attractive approach to reduce the nuclear threat.

Description: by Adolfo Paolin, Lisa Spagnol, Giuseppe Battistella, Diletta Trojan Microbiological contamination of retrieved tissues is a critical aspect of allograft safety and tissue banks must continuously implement decontamination procedures to minimize tissue contamination. In this study we compared the decontamination efficacy of a new antibiotic cocktail (cocktail B: BASE medium with Gentamicin, Meropenem and Vancomycin) with the cocktail previously adopted at Treviso Tissue Bank Foundation (FBTV) (cocktail A: RPMI medium with Ceftazidime, Lincomycin, Polymyxin B and Vancomycin). Two decontamination steps were carried out, the first immediately after retrieval, the second after processing. The contamination rate was calculated before processing (Time 1) and cryopreservation (Time 2) for total tissues, musculoskeletal tissues and cardiovascular tissues, and the bacterial species involved were analyzed. Cocktail A was used to decontaminate 3548 tissues, of which 266 were cardiovascular and 3282 musculoskeletal tissues. For cocktail A, total tissue contamination was 18.6% at Time 1 and 0.9% at Time 2, with 15.7% contaminated musculoskeletal tissues at Time 1 and 0.4% at Time 2, respectively, while cardiovascular tissues were 50% contaminated at Time 1 and 6.4% at Time 2. Cocktail B was used to decontaminate 3634 tissues of which 318 were cardiovascular and 3316 musculoskeletal tissues. For cocktail B, total tissue contamination was 8.6% at Time 1 and 0.2% at Time 2, with 7.6% contaminated musculoskeletal tissues at Time 1 and 0.03% at Time 2, respectively. Contamination of cardiovascular tissues was 20.4% at Time 1 and 1.9% at Time 2. Intergroup and intragroup contamination rates decreased statistically significantly (p

Description: by The PLOS ONE Staff

Description: by Juan J. Martínez, María C. de Aranzamendi, Enrique H. Bucher The monk parakeet ( Myiopsitta monachus ) is a South American species unique among parrots; it builds communal stick nests that allow independence from tree or cliff cavities required by most parrots. As a very successful invasive species, it has expanded into several countries around the world. Questions remain around the factors that allowed this species to be such a successful invader in its native range as in other countries, and particularly the extent that evolutionary processes may be involved in adapting to new areas. Along with this line of analysis, we focused on assessing whether morphological characteristics are sufficiently heritable, and therefore responsive to selection. As the first step in this direction, we have estimated heritability of monk parakeet in six external morphological traits considered of potential adaptability value. Samples were obtained in the province of Córdoba in central Argentina. Data from seven microsatellites were used to determine the familial relationships among individuals. Heritabilities and genetic correlations were estimated by means of animal models. We found evidence for significant heritability in the six traits measured, particularly in weight, tarsus length and bill width. We also found evidence of maternal effects on morphological traits, particularly in the traits with lower heritability: wing length, bill length and tail length. Genetic correlations between traits were significant and associated with phenotypic correlations, suggesting that these traits are constrained in terms of evolutionary potential, whereas the amount of additive genetic variance in weight, tarsus length and bill width indicate that these traits could be responsive to selection.

Description: by Aya Wakabayashi, Takashi Ishiguro, Yotaro Takaku, Yosuke Miyahara, Naho Kagiyama, Noboru Takayanagi Background To elucidate the characteristics of pneumonia in rheumatoid arthritis (RA) patients and to assess whether pneumonia in RA patients differs from that in non-RA patients. Methods We retrospectively divided pneumonia patients into two groups, those with RA and those without RA, and compared the two groups. We evaluated the risk factors for mortality with univariate and multivariate logistic regression analysis. Results Among 1549 patients, 71 had RA. The RA patients with pneumonia were 71.0±8.9 years old, 54.9% were female, 40.9% had a smoking history, and 71.8% had underlying respiratory disease. Female sex, non-smoker, and respiratory comorbidities were statistically more frequent in the RA patients than non-RA patients. The most frequent causative microbial agents of pneumonia in the RA patients were Streptococcus pneumoniae , Pseudomonas aeruginosa , Haemophilus influenzae , Mycoplasma pneumoniae , and influenza virus, whereas those of pneumonia in non-RA patients were S . pneumoniae , influenza virus, M . pneumoniae , Legionella spp., P . aeruginosa , H . influenzae , and Moraxella catarrhalis . Polymicrobial infection were identified as etiologies more frequently in the RA patients than non-RA patients. Although the severity of pneumonia did not differ between the two groups, mortality was statistically higher in the RA patients than non-RA patients. Multivariate analysis showed RA to be an independent risk factor for mortality. Conclusions P . aeruginosa , H . influenzae , M . catarrhalis , and polymicrobial infection were statistically more frequent etiologies of pneumonia in the RA patients than non-RA patients. RA itself was found to be an independent risk factor for mortality from pneumonia.

Description: by Jungwon Yoon, Jong Wook Kim, Beakcheol Jang This paper describes the web-based automated disease-related topic extraction system, called to DiTeX, which monitors important disease-related topics and provides associated information. National disease surveillance systems require a considerable amount of time to inform people of recent outbreaks of diseases. To solve this problem, many studies have used Internet-based sources such as news and Social Network Service (SNS). However, these sources contain many intentional elements that disturb extracting important topics. To address this challenge, we employ Natural Language Processing and an effective ranking algorithm, and develop DiTeX that provides important disease-related topics. This report describes the web front-end and back-end architecture, implementation, performance of the ranking algorithm, and captured topics of DiTeX. We describe processes for collecting Internet-based data and extracting disease-related topics based on search keywords. Our system then applies a ranking algorithm to evaluate the importance of disease-related topics extracted from these data. Finally, we conduct analysis based on real-world incidents to evaluate the performance and the effectiveness of DiTeX. To evaluate DiTeX, we analyze the ranking of well-known disease-related incidents for various ranking algorithms. The topic extraction rate of our ranking algorithm is superior to those of others. We demonstrate the validity of DiTeX by summarizing the disease-related topics of each day extracted by our system. To our knowledge, DiTeX is the world’s first automated web-based real-time service system that extracts and presents disease-related topics, trends and related data through web-based sources. DiTeX is now available on the web through http://epidemic.co.kr/media/topics.

Description: by Mark A. Schmidt, Holly C. Groom, Allison L. Naleway, Christianne Biggs, S. Bianca Salas, Kayoko Shioda, Zachary Marsh, Judy L. Donald, Aron J. Hall Background This study presents a novel methodology for estimating all-age, population-based incidence rates of norovirus and other pathogens that contribute to acute gastroenteritis in the United States using an integrated healthcare delivery system as a surveillance platform. Methods All cases of medically attended acute gastroenteritis within the delivery system were identified from April 1, 2014 through September 30, 2016. A sample of these eligible patients were selected to participate in two phone-based surveys and to self-collect a stool sample for laboratory testing. To ascertain household transmission patterns, information on household members with acute gastroenteritis was gathered from participants, and symptomatic household members were contacted to participate in a survey and provide stool sample as well. Results 54% of individuals who met enrollment criteria agreed to participate, and 76% of those individuals returned a stool sample. Among household members, 85% of eligible individuals agreed to participate, and 68% of those returned a stool sample. Participant demographics were similar to those of the eligible population, although minority racial/ethnic groups were somewhat underrepresented in the final sample. Conclusions This study demonstrates the feasibility of conducting acute infectious disease research within an integrated health care delivery system. The surveillance, sampling, recruitment, and data collection methods described here are broadly applicable to conduct baseline and epidemiological assessments, as well as for other research requiring representative samples of stool specimens.

Description: by Vadim Osadchiy, Jennifer S. Labus, Arpana Gupta, Jonathan Jacobs, Cody Ashe-McNalley, Elaine Y. Hsiao, Emeran A. Mayer Objective A growing body of preclinical and clinical literature suggests that brain-gut-microbiota interactions play an important role in human health and disease, including hedonic food intake and obesity. We performed a tripartite network analysis based on graph theory to test the hypothesis that microbiota-derived fecal metabolites are associated with connectivity of key regions of the brain’s extended reward network and clinical measures related to obesity. Methods DTI and resting state fMRI imaging was obtained from 63 healthy subjects with and without elevated body mass index (BMI) (29 males and 34 females). Subjects submitted fecal samples, completed questionnaires to assess anxiety and food addiction, and BMI was recorded. Results The study results demonstrate associations between fecal microbiota-derived indole metabolites (indole, indoleacetic acid, and skatole) with measures of functional and anatomical connectivity of the amygdala, nucleus accumbens, and anterior insula, in addition to BMI, food addiction scores (YFAS) and anxiety symptom scores (HAD Anxiety). Conclusions The findings support the hypothesis that gut microbiota-derived indole metabolites may influence hedonic food intake and obesity by acting on the extended reward network, specifically the amygdala-nucleus accumbens circuit and the amygdala-anterior insula circuit. These cross sectional, data-driven results provide valuable information for future mechanistic studies.

Description: by Todd R. Sponholtz, Ramachandran S. Vasan Few studies of the health impact of the built environment have examined downstream outcomes, such as cardiovascular disease. We analyzed the neighborhood-level proportional variance in the 10- and 30-year Framingham risk scores (FRS) in the Framingham Heart Study. Our analysis included 3,103 Offspring- and Generation 3 cohort participants 20–74 years old, inhabiting private residences in Massachusetts geocoded to neighborhoods (defined as 2000 US Census block groups) containing the residences of ≥5 participants. The outcome variables were log-transformed to mitigate the effects of the non-normal distributions. In order to remove the possible effects of neighborhood clustering by age and sex, we analyzed residuals of the transformed FRS regressed upon age and sex. Neighborhood-level intraclass correlations (ICCs) and 95% confidence intervals (CIs) of age- and sex-independent, log-transformed FRS were estimated using multilevel linear regression. Individual- and neighborhood-level variables were then added to models to evaluate their influence on ICCs. Analyses were repeated stratified by sex. Among 2,888 participants living in 187 neighborhoods, 1.73% (95% CI: 0.62, 4.72%) of the variance in 10-year FRS was explained at the neighborhood level. The neighborhood ICC was 2.70% (95% CI: 0.93, 7.56) among women but 0.23% (95% CI: 0.00, 99.47%) among men. In the analysis of the neighborhood-level variances in 30-year FRS among 2,317 participants residing in 164 neighborhoods, the ICCs were 3.31% (95% CI: 1.66, 6.47%), 6.47% (95% CI: 3.22, 12.58), and 0.74% (95% CI: 0.01, 33.31), among all participants, women, and men, respectively. In our homogenous middle-class white population in Massachusetts, residential neighborhoods explained a small proportion of the variance in CVD risk.

Description: by Georgiana-Aura Giurgea, Andrea Heuberger, Jamil Babayev, Susanne Winkler, Oliver Schlager, Irene M. Lang, Mariann Gyöngyösi Objectives This matched-cohort retrospective study investigated the long-term (9-year) safety and efficacy outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and primary percutaneous coronary intervention (pPCI) with Genous (n = 102) versus TAXUS Liberté (n = 101) stents in 2006–2008. Background In the era of off-label use of drug-eluting stents for pPCI in patients with STEMI, the use of first-generation Genous stents (endothelial progenitor cell capture stents that have a passive coating and accelerate re-endothelialization) was proposed. Methods The primary endpoint was 9-year major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, re-infarction, target vessel revascularization (TVR), and stroke. The secondary endpoints were the separate primary endpoint events at pre-defined time-points (in-hospital, 6 months, and yearly) and stent thrombosis. Time-dependent 9-year composite MACCE, all-cause death, and TVR were compared using Kaplan-Meier estimates and multivariate Cox regression models. Results Propensity score analysis confirmed the comparability of the groups. Patients in the Genous and TAXUS groups had 7 and 1 acute definitive stent thrombosis events, respectively (p

Description: by Gillian Wheater, Mohsen Elshahaly, Kamran Naraghi, Stephen P. Tuck, Harish K. Datta, Jacob M. van Laar Data describing the effect of in vivo B cell depletion on general bone loss in patients with rheumatoid arthritis (RA) are limited. Given the pathogenetic role of B cells in RA, it is tempting to speculate that B cell depletion might have a beneficial effect on bone loss. We prospectively investigated the changes in bone mineral density (BMD), bone turnover, inflammation and disease activity before and after rituximab in 45 RA patients over a 12 month period, 36 patients of whom completed the study and were included in the analysis. There was no significant change in our primary endpoint; lumbar spine BMD after 12 months. However, we found a significant decrease in neck of femur (mean -0.017 g/cm 2 , 95% CI -0.030, -0.004 p = 0.011) and total femur BMD (mean -0.016 g/cm 2 , 95% CI -0.025, -0.007 p = 0.001). Additionally, there was a significant increase in procollagen type 1 amino-terminal propeptide (P1NP) and bone specific alkaline phosphatase (BAP); biomarkers of bone formation (median change from baseline to 12 months; P1NP 11.3 μg/L, 95% CI -1.1, 24.8 p = 0.025; BAP 2.5 μg/L, 95% CI 1.2, 3.6 p = 0.002), but no significant change in bone resorption or osteocyte markers. The fall in BMD occurred despite improvement in disease control. Post-menopausal women had the lowest mean lumbar spine, femoral and forearm BMD at baseline and after 12 months, additionally they had a higher level of bone turnover throughout the study. In conclusion, BMD was maintained at the lumbar spine and forearm, but fell at the femur sites. A high prevalence of vitamin D deficiency was observed and these patients had lower BMD and evidence of higher bone turnover.

Description: by Samson Gebremedhin Background In developing countries lacking functional vital registration system, statistical models are being increasingly used for estimating maternal mortality ratio (MMR). Yet, most of the models have limited applicability at sub-country level. This paper introduces a new model for estimating MMR at national and sub-national levels based on maternal health-related indicators. Further, it applies the model for explaining sub-national variations of MMR in Ethiopia. Methods Country level data on MMR and other nine potential predictors of maternal death were extracted from 248 national Demographic and Health Surveys and other related surveys conducted in 80 low- and middle-income countries since 1990. Additional data were obtained from the World Bank and the World Health Organization databases. The potential model predictors were: contraceptive prevalence rate (CPR); utilizations of antenatal care (ANC), health institution delivery (HID), Caesarian section (CS) and postnatal care (PNC); and prevalence of maternal anemia, thinness (Body Mass Index (BMI 〈 18.5 kg/m 2 ), short stature (height less than 145 cms) and HIV. Stepwise Generalized Estimating Equation (GEE) with Negative Log-binomial link was employed to model MMR as a function of the covariates. Results The ultimate model comprised six significant predictors and the equation is provided as: Ln (MMR) = 6 . 464–0 . 013(CPR)– 0 . 006(HID)– 0 . 003(PNC)– 0 . 027(CS rate) + 0 . 060(HIV prevalence) + 0 . 011 (thinness prevalence) . The variation explained by the model was 54.3%) and the mean (±SD) relative standard error (8.6±2.6%) suggested the model has a reasonable precision. Application of the model to describe sub-national variation of maternal mortality in Ethiopia indicated, in 2016 the highest MMRs per 100,000 live births were in Somali (805) and Afar (795) regions. Between 2000 and 2016, all the regions of Ethiopia have significantly reduced MMRs; yet the rate of decline was lower in the aforementioned two regions. Oromiya region contributed for 46% of all maternal deaths in Ethiopia. Conclusion In developing countries lacking dependable maternal mortality data; the model can be used to estimate national and sub-national MMR with reasonable accuracy and precision.

Description: by Tadamichi Akagi, Linda M. Zangwill, Takuhei Shoji, Min Hee Suh, Luke J. Saunders, Adeleh Yarmohammadi, Patricia Isabel C. Manalastas, Rafaella C. Penteado, Robert N. Weinreb Purpose To evaluate microvasculature dropout in the optic disc (Mvd-D) using optical coherence tomography angiography (OCTA) and investigate factors associated with Mvd-D in primary open-angle glaucoma (POAG) eyes. Methods One hundred twenty-three eyes of 123 POAG patients were included from the Diagnostic Innovations in Glaucoma Study. The 3.0×3.0-mm optic nerve head OCTA scans were acquired using a spectral-domain OCT instrument. Images with whole-signal-mode were evaluated. Eyes were classified into 3 categories (Mvd-D, pseudo-Mvd-D, and no Mvd-D). Mvd-D and pseudo-Mvd-D had complete loss of OCTA signals on the temporal side of the optic disc on the en face projection image. They were distinguished base on the visualization of the anterior lamina cribrosa in the horizontal B-scans of that area. No Mvd-D was defined when no complete signal loss of OCTA signals was observed. Covariates including focal lamina cribrosa defects assessed by swept-source OCT and microvasculature dropout in the parapapillary region (Mvd-P) were analyzed. Results Forty-two, 37, and 44 eyes were identified as having Mvd-D, pseudo-Mvd-D, and no Mvd-D, respectively. The eyes with Mvd-D showed significantly lower intraocular pressure, worse visual field mean deviation, larger cup-to-disc ratio, thinner circumpapillary retinal nerve fiber layer (cpRNFL), and lower circumpapillary vessel density within the RNFL than the eyes with pseudo-Mvd-D or the eyes without Mvd-D. Multivariable logistic regression analysis showed significant associations of Mvd-D with larger cup-to-disc ratio (OR, 1.08; P = 0.001), worse visual field mean deviation (OR, 1.09; P = 0.048), higher prevalence of focal lamina cribrosa defect (OR, 9.05; P = 0.002), and higher prevalence of Mvd-P (OR, 10.33; P

Description: by Paul O’Callaghan, Yvette Zarb, Fredrik Noborn, Johan Kreuger The exocyst is a molecular tether that retains secretory vesicles at the plasma membrane prior to SNARE-mediated docking and fusion. However, individual exocyst complex components (EXOCs) may also function independently of exocyst assembly. Alternative splice variants of EXOC mRNA and paralogs of EXOC genes have been described and several have been attributed functions that may be independent of the exocyst complex. Here we describe a novel splice variant of murine Exoc3l2 , which we term Exoc3l2a . We discuss possible functional implications of the resulting domain excision from this isoform of EXOC3L2 based on structural similarities with its paralog M-Sec (EXOC3L3), which is implicated in tunneling nanotube formation. The identification of this Exoc3l2 splice variant expands the potential for subunit diversity within the exocyst and for alternative functionality of this component independently of the exocyst.

Description: by Derek Timm, Jacob T. Cain, Ryan D. Geraets, Katherine A. White, Seung yon Koh, Tammy Kielian, David A. Pearce, Michelle L. Hastings, Jill M. Weimer CLN3 -Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3 Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion. Identification of reproducible biomarker(s) to facilitate longitudinal monitoring of disease progression and provide readouts for therapeutic response has remained elusive. One factor that has complicated the identification of suitable biomarkers in this mouse model has been that variations in animal husbandry appear to significantly influence readouts. In the current study, we cross-compared a number of biological parameters in blood from Cln3 Δex7/8 mice and control, non-disease mice on the same genetic background from multiple animal facilities in an attempt to better define a surrogate marker of CLN3 -Batten disease. Interestingly, we found that significant differences between Batten and non-disease mice found at one site were generally not maintained across different facilities. Our results suggest that colony variation in the Cln3 Δex7/8 mouse model of CLN3 -Batten disease can influence potential biomarkers of the disease.