bluuebunny/crossref_metadata_2025 huggingface dataset:
New Device for the Treatment of Functional Ischemic Mitral Regurgitation: Proof of Concept in an In Vitro Model
Authors: Stock Sina , Scharfschwerdt Michael , Warnecke Rebecca Janina , Richardt Doreen , Tsvelodub Stanislav , Sievers Hans-Hinrich
Published: October 2018

Background Optimal surgical treatment of functional ischemic mitral regurgitation (FIMR) is still controversy. Due to the underlying pathophysiology, stand-alone ring annuloplasty is assumed with a high recurrence rate of mitral regurgitation, thus additional subvalvular repair techniques might improve the results. This in vitro study introduces a new device for subvalvular mitral valve repair.

Methods We developed a new device for subvalvular mitral valve repair, consisting of two frames for papillary muscle (PM) attachment, which are connected with two holding bars serving for fixation of the device on an annuloplasty ring. In the first experimental run, porcine mitral valves including the chordae tendineae and PMs were fixated on a holding device, consisting of a holding ring simulating mitral annulus dilation and height-adjustable frames for PM attachment simulating leaflet tethering. In vitro regurgitant volume was determined in a pulse duplicator. Afterward, the frames for PM attachment were replaced by our newly developed device and the measurements were repeated.

Results In the model simulating FIMR, the regurgitant volume was 44.3 ± 12.38 mL/stroke. After subvalvular reconstruction with our new device, the regurgitant volume was significantly reduced to 33.1 ± 11.68 mL/stroke (p = 0.009).

Conclusion In this specific in vitro model, our new device for subvalvular mitral valve reconstruction led to a significant reduction of the regurgitant volume, thus representing a promising technique to potentially improve the results of mitral reconstruction in ischemic functional mitral valve regurgitation. Additional studies are required to further investigate and improve our device.
A delay dynamic model of love affair with cautious partners
Authors: Matsumoto Akio , Szidarovszky Ferenc
Published: October 2018

We investigate love dynamics of two individuals in a delay love affair model in which both are assumed to be cautious, the most natural romantic style. The local stability analysis proves first that the steady state is fairly stable when there are no delays and second that solving the characteristic equation generates a set of positive delays for which the steady state loses stability. Through numerical analysis, we confirm the following three main results: (1) cyclic oscillations of love feeling emerge via Hopf bifurcation; (2) multiple delays cause the double edge effect implying that alternation of stability and instability repeatedly occurs; (3) complicated dynamics involving chaotic oscillations emerges and then merges to a limit cycle as the length of one delay increases with fixed values of the other delay.
Phylogeny of Hesionidae (Aciculata, Annelida), with four new species from deep-sea eastern Pacific methane seeps, and resolution of the affinity of Hesiolyra
Authors: Rouse Greg W. , Carvajal Jose Ignacio , Pleijel Fredrik
Published: October 2018

Hesionidae Grube, 1850 currently comprises over 175 species in 28 genera, placed in several subfamilies. Discoveries in recent years have largely been of deep-sea taxa. Here we describe a further four new hesionid species, mainly from methane ‘cold’ seeps at around 1000–1800 m depths off the Pacific coast of Costa Rica and new record of another species. Several of these taxa also occur at methane seeps in the Guaymas Basis (Mexico) and off the USA west coast (California and Oregon). The phylogenetic relationships within Hesionidae are reassessed via maximum parsimony and maximum likelihood analyses of DNA sequences from nuclear (18S rRNA and 28SrRNA) and mitochondrial (16SrRNA and Cytochrome c oxidase I) loci for the new samples. On the basis of these results, we refer one of the new species to Gyptis Marion & Bobretzky in Marion, 1874, one to Neogyptis Pleijel, Rouse, Sundkvist & Nygren, 2012, and two to Sirsoe Pleijel, 1998. The new species Gyptis robertscrippsi n. sp., Neogyptis jeffruoccoi n. sp., Sirsoe dalailamai n. sp. and Sirsoe munki n. sp. We refer to a collection of individuals from seeps ranging from Oregon to Costa Rica as Amphiduropsis cf. axialensis (Blake & Hilbig, 1990), even though this species was described from hydrothermal vents off Oregon. Neogyptis jeffruoccoi n. sp. was generally found living inside the solemyid clam Acharax johnsoni (Dall, 1891). The position of Hesiolyra bergi Blake, 1985 is resolved on the basis of newly-collected specimens from near the type locality and, as a result, Hesiolyrinae Pleijel, 1998 is synonymized with Gyptini Pleijel, 1998 (and Gyptinae Pleijel, 1998). http://zoobank.org/urn:lsid:zoobank.org:pub:9C0E88EE-34F8-4F25-9EC8-91797618AC86
mTORC1 signaling suppresses Wnt/β-catenin signaling through DVL-dependent regulation of Wnt receptor FZD level
Authors: Zeng Hao , Lu Bo , Zamponi Raffaella , Yang Zinger , Wetzel Kristie , Loureiro Joseph , Mohammadi Sina , Beibel Martin , Bergling Sebastian , Reece-Hoyes John , Russ Carsten , Roma Guglielmo , Tchorz Jan S. , Capodieci Paola , Cong Feng
Published: October 2018

Significance

The Wnt/β-catenin signaling pathway plays prominent roles during embryonic development and adult tissue homeostasis by maintaining somatic stem cell functions. The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway has also been implicated in regulating stem cell functions in multiple tissue types. However, the crosstalk between these two pathways remains largely unclear. Herein, using in vitro cell lines, ex vivo organoids, and an in vivo mouse model, we made striking findings in support of a paradigm that mTORC1 signaling cell autonomously suppresses Wnt/β-catenin signaling through down-regulating the Wnt receptor FZD level to influence stem cell functions, with implications in the aging process.
Volatile loss following cooling and accretion of the Moon revealed by chromium isotopes
Authors: Sossi Paolo A. , Moynier Frédéric , van Zuilen Kirsten
Published: October 2018

Significance

With the exception of volatile elements, which are strongly depleted and isotopically fractionated, the Moon has chemical and isotopic signatures that are indistinguishable from Earth’s mantle. Reconciliation of these properties with Moon formation in a high-energy giant impact invokes evaporative loss of volatile elements, but at conditions that are poorly known. Chromium isotopic fractionation is sensitive to temperature variations and liquid–gas equilibration during evaporation. We measure an isotopic difference between Earth’s mantle and the Moon, consistent with the loss of a Cr-bearing, oxidized vapor phase in equilibrium with the proto-Moon. Temperatures of vapor loss required are much lower than predicted by recent models, implying that volatile elements were removed from the Moon following cooling rather than during a giant impact.
Globalization, national identity, and multiculturalism and multilingualism
Authors: Sun Wenyang , Rong Xue Lan
Published: October 2018

Language policies and practices play an important role in the increasingly multicultural and multilingual and globalized world. Using China, India, Japan, South Korea (Republic of Korea), and Singapore as examples, this paper examines how countries in Asian contexts have recently developed different language-planning orientations in order to build national identities, enhance global competitiveness, and navigate multiculturalism. By discussing the language-planning orientations (Ruíz 1984) that underlie different language policies and practices, we unpack the ideologies beneath the policies and teaching practices of official language(s), regional languages, dominating foreign languages, and the heritage languages of indigenous, immigrant, and migrant minority groups. We compare and contrast the three models for Ethnic and Linguistic Diversity backing the various language-planning orientations and ideologies, argue for the importance of human agency and minority language rights in language planning, and point out the potential dangers of the neoliberal promotion of English as a dominant foreign language.
Long-term dietary supplementation with the green tea cultivar Sunrouge prevents age-related cognitive decline in the senescence-accelerated mouse Prone8
Authors: Wasai Masafumi , Nonaka Haruna , Murata Motoki , Kitamura Ryo , Sato Yuka , Tachibana Hirofumi
Published: October 2018

A majority of the potential health benefits of green tea, including the potential to prevent cognitive decline, have been attributed to epigallocatechin gallate (EGCG). Sunrouge is a green tea cultivar that contains EGCG and several other bioactive components such as quercetin, myricetin, cyanidin and delphinidin. We compared the effects of Sunrouge and Yabukita, the most popular Japanese green tea cultivar, on cognitive function in the senescence-accelerated mouse Prone8. These mice were fed an experimental diet containing Sunrouge extract (SRE) or Yabukita extract (YBE). SRE feeding significantly prevented cognitive decline, whereas YBE feeding had little effect. Moreover, SRE feeding prevented elevation of the amyloid-β42 level while improving the gene expression of neprilysin and decreasing beta-site APP-cleaving enzyme 1 in the brain. These preventive effects of SRE against cognitive decline were attributed to the characteristic composition of Sunrouge and strongly suggest that consumption of this cultivar could protect against age-related cognitive decline.
A highly stable laccase from Bacillus subtilis strain R5: gene cloning and characterization
Authors: Basheer Saadia , Rashid Naeem , Akram Muhammad Sohail , Akhtar Muhammad
Published: October 2018

The gene encoding copper-dependent laccase from Bacillus subtilis strain R5 was cloned and expressed in Escherichia coli. Initially the recombinant protein was produced in insoluble form as inclusion bodies. Successful attempts were made to produce the recombinant protein in soluble and active form. The laccase activity of the recombinant protein was highly dependent on the presence of copper ions in the growth medium and microaerobic conditions during protein production. The purified enzyme exhibited highest activity at 55 °C and pH 7.0. The recombinant protein was highly thermostable, albeit from a mesophilic source, with a half-life of 150 min at 80 °C. Similar to temperature, the recombinant protein was stable in the presence of organic solvents and protein denaturants such as urea. Furthermore, the recombinant protein was successfully utilized for the degradation of various synthetic dyes reflecting its potential use in treatment of wastewater in textile industry.

Abbreviations: ABTS,2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid; CBB, Coomassie brilliant blue; SGZ, syringaldazine; DMP, 2,2-dimethoxy phenol.
Diversity, Not Randomness, Trumps Ability
Authors: Singer Daniel J.
Published: October 2018

A number of formal models, including a highly influential model from Hong and Page, purport to show that functionally diverse groups often beat groups of individually high-performing agents in solving problems. Thompson argues that in Hong and Page’s model, that the diverse groups are created by a random process explains their success, not the diversity. Here, I defend the diversity interpretation of the Hong and Page result. The failure of Thompson’s argument shows that to understand the value of functional diversity, we should be clearer about how we conceive of and measure that diversity.
Pressure effect at permeability and deformation of the hollow fiber membrane gas separation module
Authors: Laguntsov N I , Karaseva M D
Published: October 2018

In this paper, the deformation effect in the gas separation process of the hollow fiber membrane module is considered. A technique of gas permeability measurement in a commercial gas separation hollow fiber membrane module is provided. It is determined that permeability and selectivity are nonlinearly dependent on the pressure of the feed stream, this is justified by competing factors. The results of this work will allow introducing the membrane modules into hybrid gas separation units, in particular, into the drying unit of compressed gas.
The EVcouplings Python framework for coevolutionary sequence analysis
Authors: Hopf Thomas A , Green Anna G , Schubert Benjamin , Mersmann Sophia , Schärfe Charlotta P I , Ingraham John B , Toth-Petroczy Agnes , Brock Kelly , Riesselman Adam J , Palmedo Perry , Kang Chan , Sheridan Robert , Draizen Eli J , Dallago Christian , Sander Chris , Marks Debora S
Published: October 2018

Coevolutionary sequence analysis has become a commonly used technique for de novo prediction of the structure and function of proteins, RNA, and protein complexes. We present the EVcouplings framework, a fully integrated open-source application and Python package for coevolutionary analysis. The framework enables generation of sequence alignments, calculation and evaluation of evolutionary couplings (ECs), and de novo prediction of structure and mutation effects. The combination of an easy to use, flexible command line interface and an underlying modular Python package makes the full power of coevolutionary analyses available to entry-level and advanced users.

Availability and implementation

https://github.com/debbiemarkslab/evcouplings
Long noncoding RNA Hoxaas3 contributes to hypoxia-induced pulmonary artery smooth muscle cell proliferation
Authors: Zhang Hongyue , Liu Ying , Yan Lixin , Wang Siqi , Zhang Min , Ma Cui , Zheng Xiaodong , Chen He , Zhu Daling
Published: October 2018

Aims

Long noncoding RNAs (lncRNAs) are involved in the regulation of vascular smooth muscle cells and cardiovascular pathology. However, the contribution of lncRNAs to pulmonary hypertension (PH) remains largely unknown. The over-proliferation of pulmonary artery smooth muscle cells (PASMCs) causes pulmonary arterial smooth muscle hypertrophy and stenosis of the pulmonary vascular lumen, resulting in PH. Here, we investigated the biological role of a novel lncRNA, Hoxa cluster antisense RNA 3 (Hoxaas3), in the regulation of cell proliferation in PH.

Methods and results

Hoxaas3 was up-regulated in the lung vasculature of hypoxic mice and in PASMCs under hypoxic conditions. Histone H3 Lysine 9 acetylation of Hoxaas3 promoted gene expression. Moreover, high expression of Hoxaas3 was associated with cell proliferation and modulated cell cycle distribution by up-regulating Homeobox a3 at the mRNA and protein levels.

Conclusion

This study defined the role and mechanism of action of Hoxaas3 in the regulation of cell proliferation in PH, which should facilitate the development of new therapeutic strategies for the treatment of this disease.
Is Living Alone “Aging Alone”? Solitary Living, Network Types, and Well-Being
Authors: Djundeva Maja , Dykstra Pearl A , Fokkema Tineke
Published: October 2018

Objectives

When identifying older adults who may be at risk of being without necessary supports, policy makers and scholars tend to focus on those living alone, neglecting differences within that group. We examine how their social networks contribute to subjective well-being, why some of them fare better and compare their well-being to older adults coresiding with others.

Method

Data are from the fourth wave of the Survey of Health and Retirement in Europe (N = 53,383). A network typology for older people living alone (N = 10,047) is constructed using a latent class analysis. Using ordinary least squares (OLS) regressions, we examined differences in subjective well-being (life satisfaction, satisfaction with social network, depression) by network type, adding adults coresiding with others (N = 43,336) as comparison group.

Results

We find four social network types among older adults living alone. The likelihood of having “restricted” and “child-based” networks is greater in Eastern and Southern European countries, whereas the likelihood of having “friend-oriented” networks is greater in Western and Northern European countries. Across countries, only those with “restricted” networks tend to have the poorest well-being. Those with “diverse” networks have even better well-being than coresiding older adults.

Discussion

Our study shows the importance of drawing distinctions within the group of older adults living alone. Most (two thirds) are not vulnerable and at risk, but fare just as well or even better than peers who coreside with others. Country-level factors shape the opportunities to build satisfactory networks, but subjective well-being depends more strongly on individual resources, including social networks, than country-level factors.
Hospital admissions in the first year of life: inequalities over three decades in a southern Brazilian city
Authors: Wehrmeister Fernando C , Victora Cesar G , Horta Bernardo L , Menezes Ana M B , Santos Iná S , Bertoldi Andréa Dâmaso , da Silva Bruna G C , Barros Fernando C ,   Pelotas Cohorts Study Group, Barros Aluisio J D , Matijasevich Alicia , Bassani Diego G , Gonçalves Helen , Murray Joseph , Tovo-Rodrigues Luciana , Assunção Maria Cecilia F , Silveira Mariangela F , Domingues Marlos Rodrigues , Hallal Pedro R C
Published: October 2018

Background

Hospital admissions in infancy are declining in several countries. We describe admissions to neonatal intensive care units (NICU) and other hospitalizations over a 33-year period in the Brazilian city of Pelotas.

Methods

We analysed data from four population-based birth cohorts launched in 1982, 1993, 2004 and 2015, each including all hospital births in the calendar year. NICU and other hospital admissions during infancy were reported by the mothers in the perinatal interview and at the 12-month visit, respectively. We describe these outcomes by sex of the child, family income and maternal skin colour.

Results

In 1982, NICUs did not exist in the city; admissions into NICUs increased from 2.7% of all newborns in 1993 to 6.7% in 2015, and admission rates were similar in all income groups. Hospitalizations during the first year of life fell by 29%, from 23.7% in 1982 to 16.8% in 2015, and diarrhoea admissions fell by 95.2%. Pneumonia admissions fell by 46.3% from 1993 to 2015 (no data available for 1982). Admissions due to perinatal causes increased during the period. In the poorest income quintile, total admissions fell by 33% (from 35.7% to 23.9%), but in the richest quintile these remained stable at around 10%, leading to a reduction in inequalities. Over the whole period, children born to women with black or brown skin were 30% more likely to be admitted than those of white-skinned mothers.

Conclusions

Whereas NICU admissions increased, total admissions in the first year of life declined by nearly one-third. Socioeconomic disparities were reduced, but important gaps remain.
Putting a Number on Preferences: How Numerical Attitudes Are Shaped by Ideology and Equivalency Framing
Authors: Pedersen Rasmus T , Larsen Martin V
Published: October 2018

Numbers are ubiquitous in modern political communication and discussions. The relationship between numbers and policy attitudes is therefore a key issue for public opinion research. This article explores the degree to which voters can translate their ideological predispositions into numerical policy preferences. Further, we theorize and investigate how numerical framing can affect this translation of ideology into numerical preferences. Using a survey experiment, we show that voters’ ideological differences are reflected in their numerical preferences, but that they are also highly affected by numerical framing, specifically gain–loss framing and unit framing. These results have implications for our theoretical understanding of framing effects, and they suggest that politicians can markedly affect the attitudes of voters through strategic use of numerical framing.
The Calculus of Finite (Metric) Dissonances
Authors: Reale Steven
Published: October 2018

“Metric dissonance” is a term borrowed from the realm of pitch relationships, but many studies of metric dissonance draw primarily from a conception of dissonance based on the relative complexities of frequency ratios while downplaying the important syntactical aspect that dissonance plays in tonal music. This article develops existing models of metric dissonance, most notably that of Harald Krebs, by formalizing them through the calculus of finite differences, thereby introducing a methodology for quantifying metric dissonance. Such a formalization not only establishes a heuristic for comparing musical passages but also suggests an experiential model for hearing metrically dissonant music.
A Dihydroflavonol-4-Reductase-Like Protein Interacts with NFR5 and Regulates Rhizobial Infection in Lotus japonicus
Authors: Duan Liujian , Pei Junqing , Ren Yaping , Li Hao , Zhou Xiangzhen , Zhu Hui , Duanmu Deqiang , Wen Jiangqi , Mysore Kirankumar S. , Cao Yangrong , Zhang Zhongming
Published: October 2018

In almost all symbiotic interactions between rhizobia and leguminous plants, host flavonoid–induced synthesis of Nod factors in rhizobia is required to initiate symbiotic response in plants. In this study, we found that Lotus japonicus Nod factor receptor 5 (LjNFR5) might directly regulate flavonoid biosynthesis during symbiotic interaction with rhizobia. A yeast two-hybrid analysis revealed that a dihydroflavonol-4-reductase-like protein (LjDFL1) interacts with LjNFR5. The interaction between MtDFL1 and MtNFP, two Medicago truncatula proteins with homology to LjDFL1 and LjNFR5, respectively, was also shown, suggesting that interaction between these two proteins might be conserved in different legumes. LjDFL1 was highly expressed in root hairs and epidermal cells of root tips. Lotus ljdfl1 mutants and Medicago mtdfl1 mutants produced significantly fewer infection threads (ITs) than the wild-type control plants following rhizobial treatment. Furthermore, the roots of stable transgenic L. japonicus plants overexpressing LjDFL1 formed more ITs than control roots after exposure to rhizobia. These data indicated that LjDFL1 is a positive regulator of symbiotic signaling. However, the expression of LjDFL1 was suppressed by rhizobial treatment, suggesting that a negative feedback loop might be involved in regulation of the symbiotic response in L. japonicus.
Subfamily-Specific Specialization of RGH1/MLA Immune Receptors in Wild Barley
Authors: Maekawa Takaki , Kracher Barbara , Saur Isabel M. L. , Yoshikawa-Maekawa Makoto , Kellner Ronny , Pankin Artem , von Korff Maria , Schulze-Lefert Paul
Published: October 2018

The barley disease resistance (R) gene locus mildew locus A (Mla) provides isolate-specific resistance against the powdery mildew fungus Blumeria graminis hordei and has been introgressed into modern cultivars from diverse germplasms, including the wild relative Hordeum spontaneum. Known Mla disease resistance specificities to B. graminis hordei appear to encode allelic variants of the R gene homolog 1 (RGH1) family of nucleotide-binding domain and leucine-rich repeat (NLR) proteins. Here, we sequenced and assembled the transcriptomes of 50 H. spontaneum accessions representing nine populations distributed throughout the Fertile Crescent. The assembled Mla transcripts exhibited rich sequence diversity, linked neither to geographic origin nor population structure, and could be grouped into two similar-sized subfamilies based on two major N-terminal coiled-coil (CC) signaling domains that are both capable of eliciting cell death. The presence of positively selected sites located mainly in the C-terminal leucine-rich repeats of both MLA subfamilies, together with the fact that both CC signaling domains mediate cell death, implies that the two subfamilies are actively maintained in the population. Unexpectedly, known MLA receptor variants that confer B. graminis hordei resistance belong exclusively to one subfamily. Thus, signaling domain divergence, potentially as adaptation to distinct pathogen populations, is an evolutionary signature of functional diversification of an immune receptor.

[Formula: see text] Copyright © 2018 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Very early-onset inflammatory bowel disease: an integrated approach
Authors: Sullivan Kathleen E. , Conrad Maire , Kelsen Judith R.
Published: October 2018

Purpose of review

Immune dysregulation disorders are among the most rapidly growing set of inborn errors of immunity. One particular subset is the category where early-onset inflammatory bowel disease (IBD) is the most common manifestation. These disorders are being increasingly appreciated although there has been minimal effort to articulate a unified approach to their diagnosis and management. This review will cover current thinking and strategies related to diagnosis and management of very early-onset IBD.

Recent findings

There is an expanding set of monogenic causes of early-onset IBD. In many cases, the precise genetic cause dictates management. Lessons learned from the management of these monogenic conditions can sometimes be extrapolated to other refractory cases of IBD.

An integrated approach to diagnosis, risk analysis, and management can include diagnostic approaches not often utilized for traditional IBD such as whole exome sequencing. Management can also include nontraditional approaches such as targeted biologics or hematopoietic cell transplantation.
Redundant Information Is Sometimes More Beneficial Than Spatial Information to Understand Speech in Noise
Authors: Dieudonné Benjamin , Francart Tom
Published: October 2018

Objectives:

To establish a framework to unambiguously define and relate the different spatial effects in speech understanding: head shadow, redundancy, squelch, spatial release from masking (SRM), and so on. Next, to investigate the contribution of interaural time and level differences to these spatial effects in speech understanding and how this is influenced by the type of masking noise.

Design:

In our framework, SRM is uniquely characterized as a linear combination of head shadow, binaural redundancy, and binaural squelch. The latter two terms are combined into one binaural term, which we define as binaural contrast: a benefit of interaural differences. In this way, SRM is a simple sum of a monaural and a binaural term. We used the framework to quantify these spatial effects in 10 listeners with normal hearing. The participants performed speech intelligibility tasks in different spatial setups. We used head-related transfer functions to manipulate the presence of interaural time and level differences. We used three spectrally matched masker types: stationary speech-weighted noise, a competing talker, and speech-weighted noise that was modulated with the broadband temporal envelope of the competing talker.

Results:

We found that (1) binaural contrast was increased by interaural time differences, but reduced by interaural level differences, irrespective of masker type, and (2) large redundancy (the benefit of having identical information in two ears) could reduce binaural contrast and thus also reduce SRM.

Conclusions:

Our framework yielded new insights in binaural processing in speech intelligibility. First, interaural level differences disturb speech intelligibility in realistic listening conditions. Therefore, to optimize speech intelligibility in hearing aids, it is more beneficial to improve monaural signal-to-noise ratios rather than to preserve interaural level differences. Second, although redundancy is mostly ignored when considering spatial hearing, it might explain reduced SRM in some cases.
Factors Affecting Sound-Source Localization in Children With Simultaneous or Sequential Bilateral Cochlear Implants
Authors: Killan Catherine , Scally Andrew , Killan Edward , Totten Catherine , Raine Christopher
Published: October 2018

Objectives:

The study aimed to determine the effect of interimplant interval and onset of profound deafness on sound localization in children with bilateral cochlear implants, controlling for cochlear implant manufacturer, age, and time since second implant.

Design:

The authors conducted a retrospective, observational study using routinely collected clinical data. Participants were 127 bilaterally implanted children aged 4 years or older, tested at least 12 mo post- second implant. Children used implants made by one of three manufacturers. Sixty-five children were simultaneously implanted, of whom 43% were congenitally, bilaterally profoundly deaf at 2 and 4 kHz and 57% had acquired or progressive hearing loss. Sixty-two were implanted sequentially (median interimplant interval = 58 mo, range 3–143 mo) of whom 77% had congenital and 23% acquired or progressive bilateral profound deafness at 2 and 4 kHz. Children participated in a sound-source localization test with stimuli presented in a random order from five loudspeakers at –60, –30, 0, +30, and +60 degrees azimuth. Stimuli were prerecorded female voices at randomly roved levels from 65 to 75 dB(A). Root mean square (RMS) errors were calculated. Localization data were analyzed via multivariable linear regression models, one applied to the whole group and the other to just the simultaneously implanted children.

Results:

Mean RMS error was 25.4 degrees (SD = 12.5 degrees) with results ranging from perfect accuracy to chance level (0–62.7 degrees RMS error). Compared with simultaneous implantation, an interimplant interval was associated with worse localization by 1.7 degrees RMS error per year (p < 0.001). Compared with congenital deafness, each year with hearing thresholds better than 90 dB HL at 2 and 4 kHz bilaterally before implantation led to more accurate localization by 1.3 degrees RMS error (p < 0.005). Every year post-second implant led to better accuracy by 1.6 degrees RMS error (p < 0.05). Med-El was associated with more accurate localization than Cochlear by 5.8 degrees RMS error (p < 0.01) and with more accurate localization than Advanced Bionics by 9.2 degrees RMS error (p < 0.05).

Conclusions:

Interimplant interval and congenital profound hearing loss both led to worse accuracy in sound-source localization for children using bilateral cochlear implants. Interimplant delay should therefore be minimized for children with bilateral profound hearing loss. Children presenting with acquired or progressive hearing loss can be expected to localize better via bilateral cochlear implants than their congenitally deaf peers.
Mapping 241Am Spatial Distribution Within Anatomical Bone Structures Using Digital Autoradiography
Authors: Tabatadze George , Miller Brian W. , Tolmachev Sergei Y.
Published: October 2018

Digital autoradiography with the ionizing radiation quantum imaging detector is used at the US Transuranium and Uranium Registries for visualizing the microdistribution of alpha particles from 241Am and quantifying the activity. The radionuclide spatial distribution was investigated within cortical and trabecular regions of bone samples from US Transuranium and Uranium Registries case 0846. Multiple specimens from the humerus proximal end, humerus proximal shaft, and clavicle acromial end were embedded in plastic, and 100‐μm-thick sections were taken and imaged using the ionizing radiation quantum imaging detector. The detector images were superimposed on the anatomical structure images to visualize 241Am distribution in cortical bone, trabecular bone, and trabecular spongiosa. Activity concentration ratios were used to characterize 241Am distribution within different bone regions. The trabecular-to-cortical bone and trabecular-spongiosa-to-cortical bone activity concentration ratios were quantified in both humerus and clavicle. The ionizing radiation quantum imaging detector results were in agreement with those obtained from radiochemical analysis of the remaining bone specimens. The results were compared with International Commission on Radiological Protection default biokinetic model predictions. Digital autoradiography was proven to be an effective method for microscale heterogeneous distribution studies where traditional counting methods are impractical.
Preganglionic Parasympathetic Denervation Rabbit Model for Innervation Studies
Authors: Toshida Hiroshi , Suto Chikako
Published: October 2018

Purpose:

Tear secretion from the main lacrimal gland (LG) is mainly regulated by parasympathetic nerves. We performed several innervation studies to investigate lacrimation.

Methods:

In male rabbits, we performed a retrograde dye-tracing study of LG innervation, evaluated preganglionic parasympathetic denervation, and administered glial cell–derived neurotrophic factor (GDNF) in the surgical area after parasympathetic denervation.

Results:

Accumulation of fluorescent dye was observed in the pterygopalatine ganglion cells on the same side as the dye injection into the main LG. Fewer stained cells were observed in the cervical and trigeminal ganglia. After parasympathetic denervation surgery, tear secretion was decreased, and fluorescein and rose bengal staining scores were increased at day 1 after surgery and remained increased for 3 months on the denervated side only. Most of the effects in rabbits with parasympathetic denervation were not recovered by administration of GDNF.

Conclusions:

The main LG is primarily innervated by parasympathetic nerves to stimulate tear secretion. After preganglionic parasympathetic denervation, lacrimation was decreased, resulting in dry eyes, and this was maintained for at least 3 months. Administration of GDNF only minimally altered the effects of denervation.
Fuchs Endothelial Corneal Dystrophy Through the Prism of Oxidative Stress
Authors: Jurkunas Ula V.
Published: October 2018

The corneal endothelium (CE) is vital for maintaining the water balance and clarity of the cornea. The CE is a cell layer that is particularly susceptible to aging because of its postmitotic arrest, high metabolic activity involving pumping of ions, and lifelong exposure to ultraviolet light. Despite gradual age-related cell loss, a sufficient number of CE cells are preserved during the lifespan of an individual. However, in conditions such as Fuchs endothelial corneal dystrophy (FECD), permanent loss of CE cells leads to corneal edema and loss of vision requiring corneal transplantation. FECD is a genetic and oxidative stress disorder manifested by abnormal cell–matrix interactions and expedited cellular aging culminating in cellular death. Because the endothelium has minimal replicative capacity in vivo and an inability to replace its genome, it is particularly prone to cumulative DNA damage acquired throughout life. In FECD, the underlying genetic defects make the CE genome even more vulnerable to this damage, to the point of causing mitochondrial dysfunction, mitochondrial membrane potential loss, and excessive mitophagy activation. Endogenous and exogenous intracellular stressors alter the synthetic footprint of CE cells, leading to endothelial–mesenchymal transition and secretion of aberrant extracellular matrix (in the form of guttae), resembling scar formation in other organs. In turn, the guttae or endothelial scars contribute to a vicious cycle of FECD pathogenesis and, by further inducing endothelial–mesenchymal transition and oxidant–antioxidant imbalance, perpetuate the molecular changes of the degenerating endothelium.
Group B Streptococcal Neonatal and Early Infancy Infections in Iceland, 1976–2015
Authors: Björnsdóttir Erla S. , Martins Elisabete R. , Erlendsdóttir Helga , Haraldsson Gunnsteinn , Melo-Cristino José , Ramirez Mário , Kristinsson Karl G.
Published: October 2018

Background:

Despite a risk-based peripartum chemoprophylaxis approach in Iceland since 1996,Streptococcus agalactiae[group B streptococci (GBS)] remains an important cause of early-onset [<7 days, early-onset disease (EOD)] and late-onset disease (LOD; 7 days to 3 months).

Methods:

We studied GBS invasive disease in children <1 year in Iceland in 1976–2015. Bacteria (n = 98) were characterized by susceptibility to a panel of antimicrobials, capsular serotyping, resistance genes, surface protein and pilus-locus profiling and multilocus sequence typing.

Results:

Both EOD and LOD increased during the early years, but while EOD subsequently decreased from 0.7/1000 live births in 1991–1995 to 0.2/1000 in 2011–2015, LOD showed a nonsignificant decrease from its peak value of 0.6/1000 in 2001–2005 to 0.4/1000 in 2006–2015. Serotype III was the most frequently found (n = 48), represented mostly by the hypervirulent lineage CC17/III/rib/PI-1+PI-2b (62%), but also by CC19/III/rib/PI-1+PI-2a (35%) frequently associated with colonization. Serotype Ia (n = 22) was represented by CC23/Ia/eps/PI-2a (68%) and CC7/Ia/bca/PI-1+PI-2b (23%) of possible zoonotic origin. Resistance to erythromycin and clindamycin was increasingly detected in the last years of the study (5 of the 9 cases were isolated after 2013), including representatives of a multiresistant CC17/III/rib/PI-2b sublineage described recently in other countries and expressing resistance to erythromycin, clindamycin and streptomycin.

Conclusions:

The risk-based chemoprophylaxis adopted in Iceland possibly contributed to the decline of EOD but has had limited effect on LOD. GBS causing neonatal and early infancy invasive infections in Iceland are genetically diverse, and the recent emergence of antimicrobial resistant lineages may reduce the choices for prophylaxis and therapy of these infections.
Renin–Angiotensin Inhibition and Outcomes in Nursing Home Residents With Heart Failure
Authors: Arundel Cherinne , Sheriff Helen M. , Lam Phillip H. , Mohammed Selma F. , Jones Linda G. , Jurgens Corrine Y. , Morgan Charity J. , Faselis Charles , Allman Richard M. , Fonarow Gregg C. , Ahmed Ali
Published: October 2018

Background:

Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs-ARBs) improve outcomes in heart failure (HF). Less is known about this association in nursing home (NH) residents.

Methods:

Of the 8024 hospitalized HF patients, 542 were NH residents, of whom 250 received ACEIs-ARBs. We assembled a propensity score–matched cohort of 157 pairs of NH residents receiving and not receiving ACEIs-ARBs balanced on 29 baseline characteristics (mean age, 83 years, 74% women, 17% African American), in which we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with ACEI-ARB use. We then checked for interaction in a matched cohort of 5130 patients (378 were NH residents) assembled from the 8024 patients.

Results:

Among 314 matched NH residents, HRs (95% CIs) for 30-day all-cause readmission, HF readmission, and all-cause mortality were 0.78 (0.47–1.28), 0.68 (0.29–1.60), and 1.26 (0.70–2.27), respectively. Respective HRs (95% CIs) at 1 year were 0.76 (0.56–1.02), 0.68 (0.42–1.09), and 1.04 (0.78–1.38). Among 5130 matched patients, ACEI-ARB use was associated with a significantly lower risk of all outcomes at both times, with no significant interactions, except for 1-year mortality, which was only significant in the non-NH subgroup (P for interaction, 0.026).

Conclusions:

We found no evidence that the use of ACEIs or ARBs is associated with improved outcomes in patients with HF in the NH setting. However, we also found no evidence that this association is different in NH residents with HF versus non-NH patients with HF. Future larger studies are needed to demonstrate effectiveness of these drugs in the NH setting.
Detection of IDH1 and IDH2 Mutation in Formalin-fixed Paraffin-embedded Gliomas Using Allele-specific COLD-PCR and Probe Melting Curve Analysis
Authors: Zhang Qing , Liu Kun , Yang Wensheng , Shao Wei , Liu Dan , Lan Haitao , Ji Tianhai
Published: October 2018

Many tumors, especially gliomas, contain an isocitrate dehydrogenase (IDH) mutation that can be used for clinical diagnosis and prognosis. Our study aimed to develop a new reliable detection assay for IDH1 and IDH2 mutations for clinical diagnosis based on the allele-specific (AS) coamplification with lower denaturing-polymerase chain reaction (COLD-PCR) and probe melting curve analysis (PMCA). The method includes 3 elements allowing for the sensitive detection of low-abundance mutations: (1) PCR amplification of the target fragments with AS primers; (2) COLD-PCR; and (3) PMCA for differentiating the different mutations after amplification. We conducted a blinded study with 45 paraffin-embedded gliomas specimens and 13 fresh specimens screened for IDH mutations using Sanger sequencing. Concordance between the results of our AS-COLD-PCR/PMCA assay and Sanger sequencing was 100%. Our assay appeared to be superior to direct sequencing with a much higher sensitivity of 0.4% mutations. In summary, our assay is a cost-effective, convenient, and sensitive method for detecting IDH mutations and could be applied in the clinical setting to assess small brain biopsies.
Multidrug-resistant Gram-negative infection in solid organ transplant recipients: implications for outcome and treatment
Authors: Silva Jose Tiago , Fernández-Ruiz Mario , Aguado Jose Maria
Published: October 2018

Purpose of review

Solid organ transplantation (SOT) is the best therapeutic option for both acute and chronic end-stage diseases. The development of more potent and safer immunosuppressants and the improvement of prophylactic practices have significantly diminished the morbidity and mortality associated with rejection and opportunistic infections. However, infections produced by multidrug-resistant (MDR) Gram-negative bacilli (GNB) have recently emerged as a significant threat.

Recent findings

The Spanish Society of Transplantation (SET), the Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI) have recently published their recommendations concerning the management of MDR GNB infections in SOT recipients. We review this guideline, and also the most recent available evidence, focusing on donor-derived infections, colonized recipients and therapeutic approaches.

Overall, donor and recipient colonization is associated with an increased risk of infection by MDR GNB, although none of these circumstances constitutes an absolute contraindication to transplantation. SOT recipients with risk factors for MDR GNB infection should receive an empirical treatment which includes potentially active antibiotics. Targeted therapy should be adjusted according to antimicrobial susceptibility testing and severity of infection.
Current management of Gram-negative septic shock
Authors: Vincent Jean-Louis , Mongkolpun Wasineenart
Published: October 2018

Purpose of review

Sepsis is a common condition in critically ill patients and associated with high morbidity and mortality. Sepsis is the result of infection by many potential pathogens, including Gram-negative bacteria. There are no specific antisepsis therapies and management relies largely on infection control and organ support, including hemodynamic stabilization. We discuss these key aspects and briefly mention potential immunomodulatory strategies.

Recent findings

New aspects of sepsis management include the realization that early treatment is important and that fluids and vasopressor agents should be administered simultaneously to insure rapid restoration of an adequate perfusion pressure to limit development and worsening of organ dysfunction. New immunomodulatory therapies, both suppressive and stimulatory, are being tested.

Early diagnosis enabling rapid treatment can optimize outcomes. The multiple components of adequate sepsis management necessitate a team approach.
The ligand-mediated affinity of escort proteins determines the directionality of lipophilic cargo transport
Authors: Cheng Yi-Yun , Huang Yun-Fang , Lin Hsin-Hui , Wayne Chang Wun-Shaing , Lyu Ping-Chiang
Published: October 2018

Intracellular cargo transport is a highly dynamic process. In eukaryotic cells, the uptake and release of lipophilic ligands are executed by escort proteins. However, how these carriers control the directionality of cargo trafficking remains unclear. Here, we have elucidated the unliganded structure of an archetypal fatty acid-binding protein (FABP) and found that it possesses stronger binding affinity than its liganded counterpart towards empty nanodiscs. Titrating unliganded FABP and nanodiscs with long-chain fatty acids (LCFAs) rescued the broadening of FABP cross-peak intensities in HSQC spectra due to decreased protein-membrane interaction. Crystallographic studies revealed that the tails of bound LCFAs obstructed the charged interfaces of the FABP–nanodisc complexes. We conclude that the lipophilic ligands, by taking advantage of escort proteins with high conformational homogeneity and nanodiscs as the third interaction partner involved in this transport study, participate directly in the control of their own transportation in an irreversible, unidirectional fashion.
BioModelos: a collaborative online system to map species distributions
Authors: Velásquez-Tibatá Jorge , Olaya-Rodríguez María H. , López-Lozano Daniel , Gutiérrez César , González Iván , Londoño-Murcia y María C.
Published: October 2018

Information on species distribution is recognized as a crucial input for biodiversity conservation and management. To that end, considerable resources have been dedicated towards increasing the quantity and availability of species occurrence data, boosting their use in species distribution modeling and online platforms for their dissemination. Currently, those platforms face the challenge of bringing biology into modeling by making informed decisions that result in meaningful models. Here we describe BioModelos, a modeling approach supported by an online system and a core team, whereby a network of experts contributes to the development of species distribution models by assessing the quality of occurrence data, identifying potentially limiting environmental variables, establishing species’ accessible areas and validating qualitatively modeling predictions. Models developed through BioModelos become publicly available once validated by experts, furthering their use in conservation applications. This approach has been implemented in Colombia since 2013 and it currently consist of a network of nearly 500 experts that collaboratively contribute to enhance the knowledge on the distribution of a growing number of species and where it has aided the development of several decision support products such as national risk assessments and biodiversity compensation manuals. BioModelos is an example of operationalization of an essential biodiversity variable at a national level through the implementation of a research infrastructure that enhances the value of open access species data.