bluuebunny/crossref_metadata_2025 huggingface dataset:
Medicines optimization for patients with chronic kidney disease in the outpatient setting: the role of the clinical pharmacist
Authors: Schütze Alexander , Hohmann Carina , Haubitz Marion , Radziwill Roland , Benöhr Peter
Published: May 2021

Objectives

Medicines optimization (MO) in patients with chronic kidney disease (CKD) is at high risk at transition points of different ambulatory care levels such as nephrologists in outpatient clinics and general practitioners (GPs). We examined if adding a clinical pharmacist to the therapeutic team promotes implementation of nephrologists’ drug therapy recommendations by GPs’ and reduces drug-related problems (DRPs).

Methods

A prospective, controlled intervention study was conducted in the nephrology outpatient clinic of the Klinikum Fulda, Germany. The control and intervention phases took place successively. Patients with CKD stage 3–5 and at least one concomitant disease, for example, arterial hypertension or type-2 diabetes were recruited consecutively in three subgroups (naive, 1 contact, ≥2 contacts with nephrologist) from June 2015 to May 2019. GPs’ acceptance and frequency of DRPs without (control group [CG]) and with (intervention group [IG]) pharmacist’s interventions were compared after 6 months. Interventions include educational training events for GPs between control- and intervention phase, medication therapy management and pharmaceutical patient counselling.

Key findings

In total, 256 patients (CG = 160, IG = 96) were recruited into the study. GPs’ acceptance of nephrologists’ medication recommendations increased significantly among naive patients and those with one prior contact with the nephrologist (CG/IG: naive = 72.8%/95.5%, 1 contact = 81.1%/94.4%; P < 0.001). DRPs per patient were significantly reduced in all subgroups (P < 0.001).

Conclusions

Interdisciplinary collaboration between the nephrologist, GPs and clinical pharmacist resulted in better MO for patients with CKD.
A Brief History of Use of Animals in Biomedical Research and Perspective on Non-Animal Alternatives
Authors: Kinter Lewis B , DeHaven Ron , Johnson David K , DeGeorge Joseph J
Published: May 2021

Animals have been closely observed by humans for at least 17 000 years to gain critical knowledge for human and later animal survival. Routine scientific observations of animals as human surrogates began in the late 19th century driven by increases in new compounds resulting from synthetic chemistry and requiring characterization for potential therapeutic utility and safety. Statistics collected by the United States Department of Agriculture’s Animal and Plant Health Inspection Service and United Kingdom Home Office show that animal usage in biomedical research and teaching activities peaked after the mid-20th century and thereafter fell precipitously until the early 21st century, when annual increases (in the UK) were again observed, this time driven by expansion of genetically modified animal technologies. The statistics also show a dramatic transfer of research burden in the 20th and 21st centuries away from traditional larger and more publicly sensitive species (dogs, cats, non-human primates, etc) towards smaller, less publicly sensitive mice, rats, and fish. These data show that new technology can produce multi-faceted outcomes to reduce and/or to increase annual animal usage and to redistribute species burden in biomedical research. From these data, it is estimated that annual total vertebrate animal usage in biomedical research and teaching in the United States was 15 to 25 million per year during 2001–2018. Finally, whereas identification and incorporation of non-animal alternatives are products of, but not an integral component of, the animal research cycle, they replace further use of animals for specific research and product development purposes and create their own scientific research cycles, but are not necessarily a substitute for animals or humans for discovery, acquisition, and application of new (eg, previously unknown and/or unsuspected) knowledge critical to further advance human and veterinary medicine and global species survival.
Extremal density for sparse minors and subdivisions
Authors: Haslegrave John , Kim Jaehoon , Liu Hong
Published: May 2021

We prove an asymptotically tight bound on the extremal density guaranteeing subdivisions of bounded-degree bipartite graphs with a mild separability condition. As corollaries, we answer several questions of Reed and Wood on embedding sparse minors. Among others,

• $(1+o(1))t^2$ average degree is sufficient to force the $t\times t$ grid as a topological minor;

• $(3/2+o(1))t$ average degree forces every$t$-vertex planar graph as a minor, and the constant $3/2$ is optimal, furthermore, surprisingly, the value is the same for $t$-vertex graphs embeddable on any fixed surface;

• a universal bound of $(2+o(1))t$ on average degree forcing every$t$-vertex graph in any nontrivial minor-closed family as a minor, and the constant 2 is best possible by considering graphs with given treewidth.
Analytical Comparison of Pregnancy-Associated Plasma Protein-A (PAPP-A) Immunoassays for Biochemical Determination of Gestational Age
Authors: Buhimschi Irina A , Zhao Guomao , El Helou Yara , Frye Laura J , Winikoff Beverly , Raymond Elizabeth G
Published: May 2021

Background

Accurate pregnancy dating is critical for maternal and child health and for counseling on safe and effective abortion methods. While last menstrual period and first trimester ultrasound are often used together to determine gestational age (GA), they have limited accuracy and availability, respectively. Prior studies have shown that pregnancy-associated plasma protein-A (PAPP-A) increases exponentially during pregnancy and has the potential to serve as a biochemical marker of GA. We aimed to analyze the relationship between sonographically determined GA and serum PAPP-A concentration measured by different immunoassays and to derive cutoff levels informative for the 70 days GA commonly recommended limit for medical abortion in outpatient settings.

Methods

We compared technical characteristics of 4 commercially available PAPP-A immunoassays and tested 120 maternal serum samples (GA range: 34–231 days) along with contrived pool samples and traceable quality controls. These characteristics included area under the receiver operator characteristic (AUROC) plot, sensitivity and specificity based on cutoffs defined by the Youden Index, and likelihood ratios.

Results

All 4 immunoassays had sensitivities and specificities ≥80%, and AUROC values ranging from 0.948 to 0.968. Marked differences among absolute PAPP-A values were noted depending on immunoassay. PAPP-A cutoff values at 70 days GA for each individual immunoassay were established along with procedural recommendations that increase equivalence among immunoassays.

Conclusions

Maternal serum PAPP-A levels correlated strongly with GA despite differences in immunoassay formats and absolute data output. Serum PAPP-A has biomarker potential for future development of a point-of-care test aimed at increasing access to medical abortion.
The ‘other’ bone sarcomas in Japan: a retrospective study of primary bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma, using data from the Bone Tumuor Registry in Japan
Authors: Nagano Akihito , Tsugita Masanori , Nishimoto Yutaka , Akiyama Haruhiko , Kawai Akira
Published: May 2021

Background

To date, no standard treatments for primary bone sarcomas other than those for osteosarcoma, Ewing sarcoma and chondrosarcoma have been developed.

Methods

The clinical characteristics and prognostic factors of 330 patients with primary bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma, listed in a nationwide tumour registry (Bone and Soft Tissue Tumor Registry in Japan) were investigated. The effects of adjuvant chemotherapy were determined by comparing the outcomes of patients with non-metastatic bone tumours who received surgery plus chemotherapy with those of patients who underwent surgery alone.

Results

The most common diagnosis was undifferentiated high-grade pleomorphic sarcoma. Axial site tumours (47.8%) and distant metastases at presentation (24.5%) were frequent. The 5-year overall and progression-free survival rates were 44.9 and 39.9%, respectively. Prognostic factor analysis identified surgery as an independent predictor of overall survival, and distant metastases at presentation was significant and independent predictor of both overall and progression-free survival. No significant difference in outcome was observed between patients treated with surgery alone and those treated with surgery plus chemotherapy (P = 0.71).

Conclusions

Patients with bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma without metastasis at presentation have a relatively good prognosis with definitive surgery; however, the benefit of adjuvant chemotherapy is unclear.
Large bilateral pulmonary arterial venous malformations treated with embolization and lingulectomy in a patient with hereditary hemorrhagic telangiectasia
Authors: Orovec Adele , French Daniel , Lightfoot Chris , Wallace Alison M
Published: May 2021

A 76-year-old woman with hereditary hemorrhagic telangiectasia presented to the emergency department with chest pain. Workup revealed multiple bilateral pulmonary arteriovenous malformations (PAVMs) with large aneurysmal venous outflow. A collaborative approach between interventional radiology and thoracic surgery was used in the treatment of these PAVMs.
The JCMT Gould Belt Survey: radiative heating by OB stars
Authors: Rumble D , Hatchell J , Kirk H , Pattle K
Published: May 2021

Radiative feedback can influence subsequent star formation. We quantify the heating from OB stars in the local star-forming regions in the James Clerk Maxwell Telescope (JCMT) Gould Belt Survey. Dust temperatures are calculated from 450/850 $\mu$m flux ratios from SCUBA-2 observations at the JCMT assuming a fixed dust opacity spectral index β = 1.8. Mean dust temperatures are calculated for each submillimetre clump along with projected distances from the main OB star in the region. Temperature versus distance is fitted with a simple model of dust heating by the OB star radiation plus the interstellar radiation field and dust cooling through optically thin radiation. Classifying the heating sources by spectral type, O-type stars produce the greatest clump average temperature rises and largest heating extent, with temperatures of over 40 K and significant heating out to at least 2.4 pc. Early-type B stars (B4 and above) produce temperatures of over 20 K and significant heating over 0.4 pc. Late-type B stars show a marginal heating effect within 0.2 pc. For a given projected distance, there is a significant scatter in clump temperatures that is due to local heating by other luminous stars in the region, projection effects, or shadowing effects. Even in these local, ‘low-mass’ star-forming regions, radiative feedback is having an effect on parsec scales, with 24 per cent of the clumps heated to at least 3 K above the 15 K base temperature expected from heating by only the interstellar radiation field, and a mean dust temperature for heated clumps of 24 K.
Jets, disc-winds, and oscillations in general relativistic, magnetically driven flows around black hole
Authors: Dihingia Indu K , Vaidya Bhargav , Fendt Christian
Published: May 2021

Relativistic jets and disc-winds are typically observed in black hole X-ray binaries (BH-XRBs) and active galactic nuclei. However, many physical details of jet launching and the driving of disc winds from the underlying accretion disc are still not fully understood. In this study, we further investigate the role of the magnetic field strength and structure in launching jets and disc winds. In particular, we explore the connection between jet, wind, and the accretion disc around the central black hole. We perform axisymmetric general relativistic magneto-hydrodynamical simulations of the accretion-ejection system using adaptive mesh refinement. Essentially, our simulations are initiated with a thin accretion disc in equilibrium. An extensive parametric study by choosing different combinations of magnetic field strength and initial magnetic field inclination is also performed. Our study finds relativistic jets driven by the Blandford & Znajek mechanism and the disc-wind driven by the Blandford & Payne (BP) mechanism. We also find that plasmoids are formed due to the reconnection events, and these plasmoids advect with disc-winds. As a result, the tension force due to the poloidal magnetic field is enhanced in the inner part of the accretion disc, resulting in disc truncation and oscillation. These oscillations result in flaring activities in the jet mass flow rates. We find simulation runs with a lower value of the plasma-β, and lower inclination angle parameters are more prone to the formation of plasmoids and subsequent inner disc oscillations. Our models provide a possible template to understand spectral state transition phenomena in BH-XRBs.
Dissipation measures in weakly collisional plasmas
Authors: Pezzi O , Liang H , Juno J L , Cassak P A , Vásconez C L , Sorriso-Valvo L , Perrone D , Servidio S , Roytershteyn V , TenBarge J M , Matthaeus W H
Published: May 2021

The physical foundations of the dissipation of energy and the associated heating in weakly collisional plasmas are poorly understood. Here, we compare and contrast several measures that have been used to characterize energy dissipation and kinetic-scale conversion in plasmas by means of a suite of kinetic numerical simulations describing both magnetic reconnection and decaying plasma turbulence. We adopt three different numerical codes that can also include interparticle collisions: the fully kinetic particle-in-cell vpic, the fully kinetic continuum Gkeyll, and the Eulerian Hybrid Vlasov–Maxwell (HVM) code. We differentiate between (i) four energy-based parameters, whose definition is related to energy transfer in a fluid description of a plasma, and (ii) four distribution function-based parameters, requiring knowledge of the particle velocity distribution function. There is an overall agreement between the dissipation measures obtained in the PIC and continuum reconnection simulations, with slight differences due to the presence/absence of secondary islands in the two simulations. There are also many qualitative similarities between the signatures in the reconnection simulations and the self-consistent current sheets that form in turbulence, although the latter exhibits significant variations compared to the reconnection results. All the parameters confirm that dissipation occurs close to regions of intense magnetic stresses, thus exhibiting local correlation. The distribution function-based measures show a broader width compared to energy-based proxies, suggesting that energy transfer is co-localized at coherent structures, but can affect the particle distribution function in wider regions. The effect of interparticle collisions on these parameters is finally discussed.
The evolution of rapid optical/X-ray timing correlations in the initial hard state of MAXI J1820+070
Authors: Paice J A , Gandhi P , Shahbaz T , Veledina A , Malzac J , Buckley D A H , Charles P A , Rajwade K , Dhillon V S , Littlefair S P , Marsh T R , Uttley P , Vincentelli F M , Misra R
Published: May 2021

We report on a multiepoch campaign of rapid optical/X-ray timing observations of the superbright 2018 outburst of MAXI J1820+070, a black hole low-mass X-ray binary system. The observations spanned 80 d in the initial hard state and were taken with NTT/ULTRACAM and GTC/HiPERCAM in the optical (usgsrsiszs filters at time resolutions of 8–300 Hz) and with ISS/NICER in X-rays. We find (i) a growing anticorrelation between the optical and X-ray light curves, (ii) a steady, positive correlation at an optical lag of ∼0.2 s (with a longer lag at longer wavelengths) present in all epochs, and (iii) a curious positive correlation at negative optical lags in the last, X-ray softest epoch, with longer wavelengths showing a greater correlation and a more negative lag. To explain these, we postulate the possible existence of two synchrotron-emitting components – a compact jet and a hot flow. In our model, the significance of the jet decreases over the outburst, while the hot flow remains static (thus, relatively, increasing in significance). We also discuss a previously discovered quasi-periodic oscillation and note how it creates coherent optical time lags, stronger at longer wavelengths, during at least two epochs.
The surroundings of the Milky Way globular cluster NGC 6809
Authors: Piatti Andrés E
Published: May 2021

We study the outer regions of the Milky Way globular cluster NGC 6809 based on Dark Energy Camera observations, which reach nearly 6 mag below the cluster main-sequence (MS) turn-off. In order to unveil its fainter outermost structure, we built stellar density maps using cluster MS stars, once the contamination of field stars was removed from the cluster colour–magnitude diagram. We found that only the resulting stellar density map for the lightest stars exhibits some excesses of stars at opposite sides from the cluster centre that diminish soon thereafter at ∼ 0.32°.Studied globular clusters with apogalactic distances smaller than that of NGC 6809 (5.5 kpc) do not have observed tidal tails. The lack of detection of tidal tails in the studied inner globular cluster sample could be due to the reduced diffusion time of tidal tails by the kinematically chaotic nature of the orbits of these globular clusters, thus shortening the time interval during which the tidal tails can be detected. Further investigations with an enlarged cluster sample are needed to confirm whether chaotic and non-chaotic orbits are responsible for the existence of globular clusters with tidal tails and those with extra-tidal features that are different from tidal tails or without any signatures of extended stellar density profiles.
HD molecules at high redshift: cosmic ray ionization rate in the diffuse interstellar medium
Authors: Kosenko D N , Balashev S A , Noterdaeme P , Krogager J-K , Srianand R , Ledoux C
Published: May 2021

We present a systematic study of deuterated molecular hydrogen (HD) at high redshift, detected in absorption in the spectra of quasars. We present four new identifications of HD lines associated with known $\rm H_2$-bearing Damped Lyman-α systems. In addition, we measure upper limits on the $\rm HD$ column density in 12 recently identified $\rm H_2$-bearing DLAs. We find that the new $\rm HD$ detections have similar $N({\rm HD})/N(\rm H_2)$ ratios as previously found, further strengthening a marked difference with measurements through the Galaxy. This is likely due to differences in physical conditions and metallicity between the local and the high-redshift interstellar media. Using the measured N(HD)/N(H2) ratios together with priors on the UV flux (χ) and number densities (n), obtained from analysis of $\rm H_2$ and associated C i lines, we are able to constrain the cosmic ray ionization rate (CRIR, ζ) for the new $\rm HD$ detections and for eight known HD-bearing systems where priors on n and χ are available. We find significant dispersion in ζ, from a few × 10−18 s−1 to a few × 10−15 s−1. We also find that ζ strongly correlates with χ – showing almost quadratic dependence, slightly correlates with Z, and does not correlate with n, which probably reflects a physical connection between cosmic rays and star-forming regions.
Enhanced Mutation Rate, Relaxed Selection, and the “Domino Effect” are associated with Gene Loss in Blattabacterium, A Cockroach Endosymbiont
Authors: Kinjo Yukihiro , Lo Nathan , Martín Paula Villa , Tokuda Gaku , Pigolotti Simone , Bourguignon Thomas
Published: May 2021

Intracellular endosymbionts have reduced genomes that progressively lose genes at a timescale of tens of million years. We previously reported that gene loss rate is linked to mutation rate in Blattabacterium, however, the mechanisms causing gene loss are not yet fully understood. Here, we carried out comparative genomic analyses on the complete genome sequences of a representative set of 67 Blattabacterium strains, with sizes ranging between 511 and 645 kb. We found that 200 of the 566 analyzed protein-coding genes were lost in at least one lineage of Blattabacterium, with the most extreme case being one gene that was lost independently in 24 lineages. We found evidence for three mechanisms influencing gene loss in Blattabacterium. First, gene loss rates were found to increase exponentially with the accumulation of substitutions. Second, genes involved in vitamin and amino acid metabolism experienced relaxed selection in Cryptocercus and Mastotermes, possibly triggered by their vertically inherited gut symbionts. Third, we found evidence of epistatic interactions among genes leading to a “domino effect” of gene loss within pathways. Our results highlight the complexity of the process of genome erosion in an endosymbiont.
ProLint: a web-based framework for the automated data analysis and visualization of lipid–protein interactions
Authors: Sejdiu Besian I , Tieleman D Peter
Published: May 2021

The functional activity of membrane proteins is carried out in a complex lipid environment. Increasingly, it is becoming clear that lipids are an important player in regulating or generally modulating their activity. A routinely used method to gain insight into this interplay between lipids and proteins are Molecular Dynamics (MD) simulations, since they allow us to study interactions at atomic or near-atomic detail as a function of time. A major bottleneck, however, is analyzing and visualizing lipid–protein interactions, which, in practice, is a time-demanding task. Here, we present ProLint (www.prolint.ca), a webserver that completely automates analysis of MD generated files and visualization of lipid–protein interactions. Analysis is modular allowing users to select their preferred method, and visualization is entirely interactive through custom built applications that enable a detailed qualitative and quantitative exploration of lipid–protein interactions. ProLint also includes a database of published MD results that have been processed through the ProLint workflow and can be visualized by anyone regardless of their level of experience with MD. The automated analysis, feature-rich visualization, database integration, and open-source distribution with an easy to install process, will allow ProLint to become a routine workflow in lipid–protein interaction studies.
Karl Barth
Authors: Tietz Christiane
Published: May 2021

From the beginning of his career, Swiss theologian Karl Barth (1886-1968) was often in conflict with the spirit of his times. While during the First World War German poets and philosophers became intoxicated by the experience of community and transcendence, Barth fought against all attempts to locate the divine in culture or individual sentiment. This freed him for a deep worldly engagement: he was known as “the red pastor,” was the primary author of the founding document of the Confessing Church, the Barmen Theological Declaration, and after 1945 protested the rearmament of the Federal Republic of Germany. Christiane Tietz compellingly explores the interactions between Barth's personal and political biography and his theology. Numerous newly-available documents offer insight into the lesser-known sides of Barth such as his long-term three-way relationship with his wife Nelly and his colleague Charlotte von Kirschbaum. This is an evocative portrait of a theologian who described himself as “God's cheerful partisan,” who was honored as a prophet and a genial spirit, was feared as a critic, and shaped the theology of an entire century as no other thinker.
Low light intensity delays vegetative phase change
Authors: Xu Mingli , Hu Tieqiang , Poethig R Scott
Published: May 2021

Plants that develop under low light (LL) intensity often display a phenotype known as the “shade tolerance syndrome (STS)”. This syndrome is similar to the phenotype of plants in the juvenile phase of shoot development, but the basis for this similarity is unknown. We tested the hypothesis that the STS is regulated by the same mechanism that regulates the juvenile vegetative phase by examining the effect of LL on rosette development in Arabidopsis (Arabidopsis thaliana). We found that LL prolonged the juvenile vegetative phase and that this was associated with an increase in the expression of the master regulators of vegetative phase change, miR156 and miR157, and a decrease in the expression of their SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL) targets. Exogenous sucrose partially corrected the effect of LL on seedling development and miR156 expression. Our results suggest that the response of Arabidopsis to LL is mediated by an increase in miR156/miR157 expression and by factors that repress SPL gene expression independently of miR156/miR157, and is caused in part by a decrease in carbohydrate production. The effect of LL on vegetative phase change does not require the photoreceptors and transcription factors responsible for the shade avoidance syndrome, implying that light intensity and light quality regulate rosette development through different pathways.
#ChurchInAction: more than a hashtag, it is an activism
Authors: Macaraan Willard Enrique R
Published: May 2021

In a letter to the editor, the authors have explored how the social media hashtag #ChurchInAction has become a narrative of the Philippine Church's social engagement with the poor during the pandemic and the public perception of its dynamism. But I argue that there is more to it than its perceived meaning. The hashtag plays a more political role as a symbol of activism against the emerging anti-church sentiment at the onset of intense lockdowns during the pandemic. More than just a display of Church prosocial engagement, the #ChurchInAction is embedded with connective and collective identity as in any activism against the critics of the Catholic institution.
The Rise of Neo-Abolitionism in Europe: Exploring the role of the Neoliberalism–Vulnerability–Security Nexus in the Prostitution Policies of the United Kingdom, Spain, France, and Ireland
Authors: Rubio Grundell Lucrecia
Published: May 2021

This article explains the rise of neo-abolitionism in Europe with reference to the intersection that it enables between the gender and sexual politics of neoliberalism, vulnerability, and security. Analyzing the recent adoption of neo-abolitionist prostitution policies in the United Kingdom, Spain, France, and Ireland, it contends that neo-abolitionism offers a suitable response to the needs that globalized neoliberalism creates for European states, allowing them to extend their control, disguise their moral agenda, and reproduce their material and normative foundations, guaranteeing the reproduction of the population and accumulation of wealth while reasserting their sovereignty and political identity as progressive in gender and sexual terms.
Impact of successive spring frosts on leaf phenology and radial growth in three deciduous tree species with contrasting climate requirements in central Spain
Authors: Rubio-Cuadrado Álvaro , Camarero J Julio , Rodríguez-Calcerrada Jesús , Perea Ramón , Gómez Cristina , Montes Fernando , Gil Luis
Published: May 2021

Rear-edge tree populations forming the equatorward limit of distribution of temperate species are assumed to be more adapted to climate variability than central (core) populations. However, climate is expected to become more variable and the frequency of climate extremes is forecasted to increase. Climatic extreme events such as heat waves, dry spells and spring frosts could become more frequent, and negatively impact and jeopardize rear-edge stands. To evaluate these ideas, we analyzed the growth response of trees to successive spring frosts in a mixed forest, where two temperate deciduous species, Fagus sylvatica L. (European beech) and Quercus petraea (Matt.) Liebl. (sessile oak), both at their southernmost edge, coexist with the Mediterranean Quercus pyrenaica Willd. (Pyrenean oak). Growth reductions in spring-frost years ranked across species as F. sylvatica > Q. petraea > Q. pyrenaica. Leaf flushing occurred earlier in F. sylvatica and later in Q. pyrenaica, suggesting that leaf phenology was a strong determinant of spring frost damage and stem growth reduction. The frost impact depended on prior climate conditions, since warmer days prior to frost occurrence predisposed to frost damage. Autumn Normalized Difference Vegetation Index data showed delayed leaf senescence in spring-frost years and subsequent years as compared with pre-frost years. In the studied forest, the negative impact of spring frosts on Q. petraea and especially on F. sylvatica growth, was considerably higher than the impacts due to drought. The succession of four spring frosts in the last two decades determined a trend of decreasing resistance of radial growth to frosts in F. sylvatica. The increased frequency of spring frosts might prevent the expansion and persistence of F. sylvatica in this rear-edge Mediterranean population.
The Autophagy-Related Gene CpAtg4 Is Required for Fungal Phenotypic Traits, Stress Tolerance, and Virulence in Cryphonectria parasitica
Authors: Li Ru , Zhao Lijiu , Li Shuangcai , Chen Fengyue , Qiu Jinfeng , Bai Lingyun , Chen Baoshan
Published: May 2021

Autophagy is an evolutionarily ancient process wherein cells are able to break down intracellular contents to support normal physiology and development. Autophagosome formation is regulated by several different proteins, including the key cysteine protease Atg4. The contribution of Atg4 protein in the pathogenic fungus Cryphonectria parasitica, which causes blight in chestnut plants, has not been completely understood. In this context, we aimed to investigate the role of Atg4 during autophagy formation and their contribution to nonautophagic events in C. parasitica. By complementation assay, we determined that the CpAtg4 gene from C. parasitica was able to functionally complement the deletion of yeast Atg4. Using a yeast two-hybrid assay system, we confirmed that CpAtg4 and CpAtg8 directly interact with one another, and amino acids 377 to 409 of CpAtg4 were identified as being responsible for its binding with CpAtg8. The deletion mutant of CpAtg4 did not demonstrate positive monodansylcadaverine staining, which indicated that CpAtg4 is required for autophagy in C. parasitica. Moreover, the ΔCpAtg4 strain exhibited a decrease in aerial hyphae formation and sporulation, and reduction in virulence on apple and chestnut stem. The ΔCpAtg4 strains were also more sensitive to H2O2 and Congo red-induced stress. We further determined that amino acids 377 to 409 of CpAtg4 were essential for the function of CpAtg4 in vivo. Together, our findings indicated that CpAtg4 is required for the autophagy formation, fungal phenotypic traits, stress tolerance, and virulence in C. parasitica.
Guttation Fluids Containing Pseudomonas amygdali pv. lachrymans Are a Potential Source of Secondary Infection in Cucumber
Authors: Zhang Shengping , Wang Yanan , Hu Tongle , Wang Shutong , Che Hanmei , Cao Keqiang , Meng Xianglong
Published: May 2021

Guttation is a common feature of cucumber leaves under high relative humidity conditions; however, little is known about the role of guttation in the transmission of Pseudomonas amygdali pv. lachrymans, which is the pathogen of cucumber angular leaf spot disease. In this study, experimental evidence for the transmission of P. amygdali pv. lachrymans inside cucumber plants and through guttation was provided, and the results proved that P. amygdali pv. lachrymans can be transmitted from the bottom leaf to the upper leaves inside the plant and excreted from the upper leaves through guttation. After that, the third leaf of cucumber was inoculated with P. amygdali pv. lachrymans bacterial suspension, P. amygdali pv. lachrymans was detected on the fifth leaf, the petiole, and the stem and in guttation drops. Healthy cucumber seedlings were infected by P. amygdali pv. lachrymans in the guttation droplets, indicating that guttation fluids containing P. amygdali pv. lachrymans could become a potential source of secondary infection. The results from this study verified the hypothesis that guttation is a potential route for P. amygdali pv. lachrymans excretion from cucumber plants and may be a source of secondary transmission under high relative humidity.
Iron Superoxide Dismutase is Upregulated in Response to Antibiotic Challenge in Multi‐Drug Resistant Acinetobacter baumannii
Authors: Damo Steven , Pattanayek Rekha , Amoah Kofi , Boone RaNashia , Mittal Anisha , Teran Adriana , Whitehead Briana , Mandape Sammed , Pratap Siddharth , Davis Jamaine , Dent Lemuel , Marshall Dana , Gaddy Jennifer A.
Published: May 2021

Acinetobacter baumannii is an opportunistic gram‐negative human pathogen. Underscoring the threat to global health is the observation of isolates of A. baumannii that are resistant to all known antibiotics. Multidrug resistant A. baumannii is a leading cause of nosocomial infections and can lead to increased mortality and length of stay. To address this public health problem, there is a need to develop new therapeutics. Our approach is to identify potential drug targets by characterizing molecular mechanisms that contribute to the antibiotic resistance of A. baumannii. To achieve this, we leverage a collated bank of 247 isolates (72% are multi‐drug resistant) of A. baumannii from patients at Nashville General Hospital. Isolate MMC4 (Meharry Medical College Isolate 4) is resistant to >25 antibiotics and hence represents an ideal system for dissecting the molecular origins of antibiotic resistance. Here we report the identification of superoxide dismutase B (SodB) as an important antibiotic resistance factor along with its biochemical characterization and high‐resolution crystal structure. Isolate MMC4 was subjected to proteomic analysis in the presence and absence of antibiotic challenge using multidimensional protein identification technology. SodB showed the greatest differential protein expression, a greater than 40 fold increase in response to antibiotic challenge. SodB is an enzyme that protects bacteria from oxidative stress by dismutating highly reactive superoxide radicals. While the superoxide dismutase family has been extensively studied, little is known about A. baumannii SodB. We expressed SodB recombinantly from E. coli and purified it to >95% homogeneity. We evaluated the activity of SodB using a tetrazolium salt assay and established it is an iron dependent enzyme using inductively coupled plasma – optical emission spectrometry. We also determined the structure of SodB with iron bound to 1.45 angstroms resolution. The crystal belonged to the C121 monoclinic space group with unit cell sides (angstroms) and angles (degrees) 97.28, 40.74, 76.63 and 90, 123, 90, respectively. In total, these data establish the importance of protection from oxidative stress in antibiotic resistant A. baumannii and provide the first steps for a structure‐based drug design approach to target inhibition of SodB as a therapeutic strategy.

Support or Funding Information

This work was funded by National Science Foundation HRD1547757, National Institutes of Health R25MD010396 and R01HD090061, and Office of Medical Research, Department of Veterans Affairs IK2BX001701.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effectiveness of the Premature Infant Oral Motor Intervention on Feeding Performance, Duration of Hospital Stay, and Weight of Preterm Neonates in Neonatal Intensive Care Unit
Authors: Thabet Amina Mohamed , Sayed Zahra Ahmed
Published: May 2021

Background

Most preterm neonates are unable to achieve independent oral feeding and are fed using tubes. Premature infant oral motor intervention (PIOMI) is effective in initiating early oral feeding and reducing hospital stays.

Objective

This study aimed to evaluate the effectiveness of PIOMI on feeding performance, duration of hospital stay, and weight of preterm neonates in the neonatal intensive care unit (NICU).

Methods

This was a parallel randomized controlled trial conducted in Egypt. Sixty preterm neonates born between 30 and 34 weeks of gestation were randomly selected (30 in the study group and 30 in the control group). The study was conducted at the NICU in Sohag, Egypt, over 3 months from October to December 2019. Two tools were used: demographic data of preterm neonates according to gestational age, sex, weight, and diagnosis, and PIOMI.

Results

Among the preterm neonates in the study group, full oral feeding was achieved significantly earlier (P = .03), milk leakage decreased significantly (P = .001), weight was significantly higher (P = .018), and the duration of hospital stay was significantly lower (P = .014) than that in the control group.

Conclusion

Premature infant oral motor intervention was effective in improving preterm neonates' feeding performance, reducing the duration of hospital stay, and increasing their weight. This study recommended that a training program for nurses in the NICU about PIOMI for preterm neonates be conducted, along with training of the parents to use PIOMI and the implementation of policies in the NICU to conduct PIOMI as a part of daily routine preterm neonatal care.
Critical Care Nurses' Qualitative Reports of Experiences With Physician Behaviors, Nursing Issues, and Other Obstacles in End-of-Life Care
Authors: Beckstrand Renea L. , Willmore Elizabeth E. , Macintosh Janelle L.B. , Luthy Karlen E. (Beth)
Published: May 2021

Background

Critical care nurses (CCNs) frequently provide end of life (EOL) care in intensive care units (ICUs). Obstacles to EOL care in ICUs exist and have been previously published along with reports from CCNs. Further data exploring obstacles faced during ICU EOL care may increase awareness of common EOL obstacles. Research focusing on obstacles related to physician behaviors and nursing issues (and others) may provide improvement of care.

Objective

The aim of this study was to gather first-hand data from CCNs regarding obstacles related to EOL care.

Methods

A random, geographically dispersed sample of 2000 members of the American Association of Critical-Care Nurses was surveyed. Responses from an item asking CCNs to tell us of the obstacles they experience providing EOL care to dying patients were analyzed.

Results

There were 104 participants who provided 146 responses to this item reflecting EOL obstacles. These obstacles were divided into 11 themes; 6 physician-related obstacles and 5 nursing- and other related obstacles. Major EOL ICU barrier themes were inadequate physician communication, physicians giving false hope, poor nurse staffing, and inadequate EOL care education for nurses.

Discussion and Conclusion

Poor physician communication was the main obstacle noted by CCNs during ICU EOL care, followed by physicians giving false hope. Heavy patient workloads with inadequate staffing were also a major barrier in CCNs providing EOL care.
An Ethics Early Action Protocol to Promote Teamwork and Ethics Efficacy
Authors: Pavlish Carol L. , Brown-Saltzman Katherine , Robinson Ellen M. , Henriksen Joan , Warda Umme Shefa , Farra Christopher , Chen Belinda , Jakel Patricia
Published: May 2021

Background

Moral dilemmas and ethical conflicts occur in critical care. Negative consequences include misunderstandings, mistrust, patient and family suffering, clinician moral distress, and patient safety concerns. Providing an opportunity for team-based ethics assessments and planning could improve communication and reduce moral distress.

Objectives

The aims of this study were to explore whether an early action ethics intervention affects intensive care unit (ICU) clinicians' moral distress, ethics self-efficacy, and perceptions of hospital climate and to compare nurses' and physicians' scores on moral distress, ethics self-efficacy, and ethical climate at 3 time points.

Methods

Intensive care unit nurses and physicians were asked to complete surveys on moral distress, ethics self-efficacy, and ethical climate before implementing the ethics protocol in 6 ICUs. We measured responses to the same 3 surveys at 3 and 6 months after the protocol was used.

Results

At baseline, nurses scored significantly higher than physicians in moral distress and significantly lower in ethics self-efficacy. Plot graphs revealed that nurses' and physicians' outcome scores trended toward one another. At 3 and 6 months post intervention, nurse and physician scores changed differently in moral distress and ethics self-efficacy. When examining nurse and physician scores separately over time, we found nurses' scores in moral distress and moral distress frequency decreased significantly over time and ethics self-efficacy and ethics climate increased significantly over time. Physicians' scores did not change significantly.

Discussion

This study indicates that routine, team-based ethics assessment and planning opens a space for sharing information, which could decrease nurses' moral distress and increase their ethics self-efficacy. This, in turn, can potentially promote teamwork and reduce burnout.
The Impact of a Multidisciplinary Education Program for Intensive Care Unit Staff Regarding Ventilator Care Bundle on the Frequency of Ventilator-Associated Events
Authors: Adiyeke Esra , Koc Betul Ilbey , Coskun Nilufer , Bakan Nurten , Sen Erman , Turan Adem , Ozturk Hande
Published: May 2021

Background

Ventilator bundles have been reported to reduce the risk of ventilator-associated pneumonia. However, data concerning the role of the education of the intensive care unit (ICU) staff regarding the items in the bundle and the importance to adhere to its items on the development of ventilator-associated events (VAEs) are limited. This study aimed to compare the frequency of VAEs in subjects admitted to the ICU before and after the education of the ICU staff.

Methods

A total of 105 subjects were enrolled in this retrospective study. The ICU staff, including the physicians, respiratory therapists, and nurses, received a 2-day educational lecture regarding items in the bundle as well as the need to adhere to its items. The study population was divided into two according to the admission date: subjects who were admitted before the education of the ICU staff regarding the ventilator bundle (preeducation) and subjects who were admitted after the education of the ICU staff regarding the ventilator bundle (posteducation). The difference in VAE rate in subjects admitted before and after bundle training was the primary outcome measure of this study.

Results

The bundle compliance rates presented by days were significantly higher in the posteducation group compared with the preeducation group. Moreover, the frequency of VAEs was significantly lower in posteducation subjects compared with preeducation subjects (4.7% vs 19.0%, P = .042). Ventilator-associated event rate was also lower in posteducation subjects compared with preeducation subjects (2.5/1000 vs 9.8/1000 ventilator days). There were no significant differences among the groups with respect to ICU mortality.

Conclusion

The educational intervention performed in this study not only increased the adherence to the ventilator care bundle but also led to a significant reduction in the rate of the VAEs in patients receiving mechanical ventilator support in the ICU.
Independent association of palpitation with vasomotor symptoms and anxiety in middle-aged women
Authors: Enomoto Haruka , Terauchi Masakazu , Odai Tamami , Kato Kiyoko , Iizuka Makoto , Akiyoshi Mihoko , Miyasaka Naoyuki
Published: May 2021

Objective:

Palpitation, or the sensation of rapid or irregular heartbeats, is common in menopausal women; however, the precise underlying mechanisms are unknown. We aimed to investigate factors associated with palpitation in middle-aged women.

Methods:

Medical records of 394 women aged 40 to 59 years (108 premenopausal, 85 perimenopausal, and 201 postmenopausal) were analyzed cross-sectionally. Palpitation severity was estimated based on responses to the Menopausal Symptom Scale. Effects of background characteristics, including age, menopausal status, body composition, cardiovascular parameters, basal metabolism, physical fitness, lifestyle factors, vasomotor, and psychological symptoms on palpitation were assessed using multivariate logistic regression analysis. The association between autonomic nervous system activity and palpitation was also analyzed in 198 participants.

Results:

Prevalence of palpitation by severity was as follows: none, 26.4%; mild, 32.7%; moderate, 29.4%; severe, 11.4%. In univariate analyses, the more severely the women were affected by palpitation, 1) the higher their systolic blood pressure, 2) the less exercise they performed, 3) the lower they scored in the sit-and-reach test, 4) the higher their vasomotor symptoms score in the Menopausal Health Related-Quality of Life questionnaire, and 5) the higher their Hospital Anxiety and Depression Scale. Multiple logistic regression analysis revealed that moderate to severe palpitation was independently associated with the vasomotor symptom score (adjusted odds ratio [95% confidence interval]: 1.18 [1.07-1.31]) and Hospital Anxiety and Depression Scale anxiety subscale score (1.19 [1.12-1.27]).

Conclusions:

Rapid or irregular heartbeats are highly prevalent in middle-aged women. It is not associated with age, menopausal status, heart rate, arrhythmia, autonomic nervous system activity, caffeine, or alcohol consumption, but with vasomotor symptoms and anxiety.
Free-floating and spinning thrombus of the basilar artery
Authors: Kim Keon-Yeup , Lee Sang-Hun
Published: May 2021

Rationale:

Free-floating thrombi in the intracranial artery are rare. We report a case of a free-floating and spinning thrombus caused by turbulent flow distal to the basilar artery stenosis. We compare thrombus changes in a series of images according to time and describe the approach to treatment and thrombosis resolution.

Patient concerns:

A 55-year-old man presented to the emergency department on March 21, 2020, with left-sided weakness, bilateral limb ataxia, and a one-day history of dysarthria. Brain magnetic resonance imaging showed multifocal infarctions in the pons and cerebellum with severe basilar stenosis.

Diagnoses:

Digital subtraction angiography showed severe focal stenosis. A relatively large oval-shaped mobile thrombus was observed spinning due to turbulent flow at the distal portion of the stenosis.

Interventions:

We administered a combination antithrombotic regimen of warfarin and clopidogrel for 50 days.

Outcomes:

No thrombus was observed on the third follow-up digital subtraction angiography.

Lessons:

No previous study has directly observed a mobile thrombus in the intracranial artery using digital subtraction angiography. We used a combination antithrombotic strategy, which was effective after long-term, rather than short-term, use.