bluuebunny/crossref_metadata_2025 huggingface dataset:
Arabidopsis R1R2R3-Myb proteins are essential for inhibiting cell division in response to DNA damage
Authors: Chen Poyu , Takatsuka Hirotomo , Takahashi Naoki , Kurata Rie , Fukao Yoichiro , Kobayashi Kosuke , Ito Masaki , Umeda Masaaki
Published: September 2017

Inhibition of cell division is an active response to DNA damage that enables cells to maintain genome integrity. However, how DNA damage arrests the plant cell cycle is largely unknown. Here, we show that the repressor-type R1R2R3-Myb transcription factors (Rep-MYBs), which suppress G2/M-specific genes, are required to inhibit cell division in response to DNA damage. Knockout mutants are resistant to agents that cause DNA double-strand breaks and replication stress. Cyclin-dependent kinases (CDKs) can phosphorylate Rep-MYBs in vitro and are involved in their proteasomal degradation. DNA damage reduces CDK activities and causes accumulation of Rep-MYBs and cytological changes consistent with cell cycle arrest. Our results suggest that CDK suppressors such as CDK inhibitors are not sufficient to arrest the cell cycle in response to DNA damage but that Rep-MYB-dependent repression of G2/M-specific genes is crucial, indicating an essential function for Rep-MYBs in the DNA damage response.
Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage
Authors: Zhao Xiurong , Ting Shun-Ming , Liu Chin-Hsuan , Sun Guanghua , Kruzel Marian , Roy-O’Reilly Meaghan , Aronowski Jaroslaw
Published: September 2017

Shortly after intracerebral hemorrhage, neutrophils infiltrate the intracerebral hemorrhage-injured brain. Once within the brain, neutrophils degranulate, releasing destructive molecules that may exacerbate brain damage. However, neutrophils also release beneficial molecules, including iron-scavenging lactoferrin that may limit hematoma/iron-mediated brain injury after intracerebral hemorrhage. Here, we show that the immunoregulatory cytokine interleukin-27 is upregulated centrally and peripherally after intracerebral hemorrhage. Data from rodent models indicate that interleukin-27 modifies neutrophil maturation in the bone marrow, suppressing their production of pro-inflammatory/cytotoxic products while increasing their production of beneficial iron-scavenging molecules, including lactoferrin. Finally, interleukin-27 or lactoferrin administration results in reduced edema, enhanced hematoma clearance, and improved neurological outcomes in an animal model of intracerebral hemorrhage. These results suggest that interleukin-27/lactoferrin-mediated modulations of neutrophil function may represent a therapeutically viable concept for the modification of neutrophils toward a “beneficial” phenotype for the treatment of intracerebral hemorrhage.
Determination of Quality Changes in Peaches Wrapped in Active Paper and Stored at Ambient Temperature in Summer
Authors: Du Xiao-long , Li Hui , Zhou Wei-hong , Liu Ying , Li Jian-long
Published: September 2017

Peaches are known for their palatable flavor and abundant nutrients. However, peaches are perishable, and the existing preservation techniques for peaches are still immature. To further extend the shelf life and prevent nutrient loss of perishable peaches under ambient temperature in summer (approximately 25–32 °C), we conducted experiments wrapping peaches (Prunus persica cv ‘Baihua’) in single- and composite-treated vegetal fibrous papers that contained calcium carbonate, phytic acid, Na-alginate and vitamin C. The pathogenic fungi that primarily caused peach decay during storage belonged to the genera of Penicillium, Botrytis, Aspergillus, Alternaria, and Rhizopus. After analyzing quality attributes, including weight loss, firmness, soluble sugar content, respiration rate, relative electric conductivity, malonaldehyde content, peroxidase activity and the decay index, we proved that vitamin C within the preservative paper greatly contributes to peach preservation. Combined with phytic acid and Na-alginate, the composite vitamin C preservative papers played significant roles in delaying fruit senescence, and 0.4% (w/v) vitamin C preservative paper with 1% Na-alginate could maintain quality and extend shelf life with the best effect. This preservation technique significantly postponed the respiration peak by 2–3 days and is a significant contribution to contemporary commercial production.
GATA3 regulates FLG and FLG2 expression in human primary keratinocytes
Authors: Zeitvogel Jana , Jokmin Neele , Rieker Samira , Klug Ilona , Brandenberger Christina , Werfel Thomas
Published: September 2017

GATA3 is a transcription factor with an important role in atopic diseases because of its role in the differentiation of Th2 lymphocytes. Moreover, GATA3 is expressed in keratinocytes and has a role in keratinocyte differentiation and the establishment of the epidermal barrier. In this study, we investigated the role of GATA3 in keratinocytes in the context of epidermal barrier integrity under inflammatory skin conditions. When analysing skin samples from atopic dermatitis and psoriasis patients or healthy controls, we detected decreased expression of GATA3 in the stratum spinosum and stratum granulosum of atopic dermatitis and psoriasis patients when compared to healthy controls. Our cell cultures experiments revealed that a downregulation in GATA3 by shRNA leads to a significant reduction of filaggrin mRNA under atopic dermatitis-like conditions in keratinocytes. Overexpression of GATA3 in keratinocytes reversed this effect and significantly upregulated filaggrin and, furthermore, filaggrin-2 mRNA expression. Our results demonstrate that GATA3 is involved in the regulation of filaggrin and filaggrin-2 expression during inflammatory conditions in the skin. Thus, GATA3 may be of special importance for the establishment and maintenance of an intact epidermal barrier, especially in atopic dermatitis.
Hemoglobin enhances miRNA-144 expression and autophagic activation mediated inflammation of microglia via mTOR pathway
Authors: Wang Zhenyu , Yuan Bangqing , Fu Fenlan , Huang Shaokuan , Yang Zhao
Published: September 2017

Intracerebral hemorrhage promotes autophagic activation of microglia and enhances neuroinflammation. MiRNAs are key factors to autophagy, contributed to negatively and posttranscriptionally regulate gene expression and function. However, the specific miRNAs involved in the intracerebral hemorrhage mediated microglia autophagic activation are unidentified. In this experiment, microglia was treated with hemoglobin. And then, miRNA-144 expression, autophagic activation and inflammation of microglia were detected. In addition, the mTOR target of miRNA-144 and its regulation were identified. Our data demonstrated that hemoglobin promoted miRNA-144 expression and autophagic activation mediated inflammation. Additionally, miRNA-144 targeted mTOR by directly interacting with the 3′ untranslated regions (UTRs), mutations of the binding sites abolish the miRNA-144 responsiveness. Overexpression of mTOR decreased autophagic activation and inflammation of microglia. Therefore, our results suggested that miRNA-144 contributed to hemoglobin mediated autophagic activation and inflammation of microglia via mTOR pathway. And miRNA based treatment provided novel therapeutical strategy for intracerebral hemorrhage.
Time-dependent effects of ipragliflozin on behaviour and energy homeostasis in normal and type 2 diabetic rats: continuous glucose telemetry analysis
Authors: Iuchi Hiroyuki , Sakamoto Masaya , Matsutani Daisuke , Suzuki Hirofumi , Kayama Yosuke , Takeda Norihiko , Minamisawa Susumu , Utsunomiya Kazunori
Published: September 2017

Sodium–glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote urinary glucose excretion. Conversely, they cause behavioural changes, such as hyperphagia, that result in a positive energy balance. The relationship between energy homeostasis and SGLT2 inhibitors-induced behavioural changes remains unclear. Here we show that ipragliflozin, a SGLT2 inhibitor, time-dependently affects behaviour and enhances energy expenditure in normal and type 2 diabetic Goto–Kakizaki (GK) rats, using continuous glucose telemetry. Alongside increased urinary glucose excretion, ipragliflozin increased total food and water intakes in normal and GK rats. In normal rats, ipragliflozin treatment acutely disturbed the circadian rhythms of food and water intakes, activity, and body temperature. Subsequently, these rhythms gradually returned towards a normal state. However, activity and body temperature remained suppressed. In GK rats, ipragliflozin did not affect circadian rhythms. Blood glucose values assessed by glucose telemetry were significantly reduced in both ipragliflozin-treated groups. Despite these behavioural and glycaemic changes, ipragliflozin significantly increased oxygen consumption during dark and light periods in both groups. Ipragliflozin reduced body weight in normal rats only. Thus, ipragliflozin decreases blood glucose beyond compensatory hyperphagia in normal and GK rats, resulting in enhanced basal energy expenditure, despite acutely altering circadian rhythms in normoglycaemic individuals.
Mucosa-associated lymphoid tissue lymphoma translocation 1 as a novel therapeutic target for rheumatoid arthritis
Authors: Lee Chang Hoon , Bae Su Jeong , Kim Miok
Published: September 2017

Emerging evidence suggests that mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) is a key regulator of inflammatory diseases; however, the pathological role of MALT1 in rheumatoid arthritis (RA) is not well understood. Consequently, this protein has not been therapeutically targeted for the treatment of RA. MALT1 plays a role in the paracaspase pathway, has proteolytic activity and is involved in the regulation of inflammatory responses. In this study, we found that the MALT1-targeting inhibitory small molecule, MALT1 selective inhibitor 2-chloro-N-[4-[5-(3,4-dichlorophenyl)-3-(2-methoxyethoxy)-1H-1,2,4-triazol-1-yl]phenylacetamide (MI-2) strongly suppresses the differentiation of monocytes into osteoclasts in the absence or presence of the inflammatory cytokine tumour necrosis factor α. Furthermore, MI-2 ameliorates pathologic bone erosion and synovitis in an in vivo mouse model of collagen-induced arthritis. Mechanistically, MI-2 blocked expression of the master osteoclast regulator – nuclear factor of activated T cells 1 (NFATc1) – by inhibiting nuclear factor κB (NF-κB), which is a critical regulator of NFATc1. These findings highlight the important regulatory role of MALT1 in the NF-κB–NFATc1-signalling axis during osteoclastogenesis and suggest that targeting MALT1 is a promising treatment option for rheumatoid arthritis.
A smart thermo- and pH-responsive microfiltration membrane based on three-dimensional inverse colloidal crystals
Authors: Yu Bing , Song Qianqian , Cong Hailin , Xu Xiaodan , Han Dongwei , Geng Zhongmin , Zhang Xiaoyan , Usman Muhammad
Published: September 2017

In this paper, a thermo- and pH-responsive microfiltration membrane was prepared based on three-dimensional (3D) inverse colloidal crystals (ICC). To manufacture the smart ICC membrane, the typical thermo-responsive N-isopropylacrylamide (NIPAM) and pH-responsive methacrylic acid (MAA) were polymerized inside silica colloidal crystals. The smart ICC membranes were characterized by SEM, IR and contact angle measurements. Moreover, the permeability of smart microfiltration membrane was carried out by the KCl diffusion tests. The result showed that effective diameter of the polymer ICC membrane can be reversible tuned by temperature and pH. Besides, the functional ICC membrane showed outstanding temperature- and pH-responsive gating property, which was applied to separate particles of different sizes. The savvy environment-responsive gating membranes have potential uses in filtration, separation, purification, sensor and other applications.
Deoxyribonuclease 1 reduces pathogenic effects of cigarette smoke exposure in the lung
Authors: King Paul T. , Sharma Roleen , O’Sullivan Kim M. , Callaghan Judy , Dousha Lovisa , Thomas Belinda , Ruwanpura Saleela , Lim Steven , Farmer Michael W. , Jennings Barton R. , Finsterbusch Michaela , Brooks Gavin , Selemidis Stavros , Anderson Gary P. , Holdsworth Stephen R. , Bardin Philip G.
Published: September 2017

Our aim was to investigate if deoxyribonuclease (DNase) 1 is a potential therapeutic agent to reduce pathogenic effects of cigarette smoke exposure in the lung. Cigarette smoke causes protease imbalance with excess production of proteases, which is a key process in the pathogenesis of emphysema. The mechanisms responsible for this effect are not well-defined. Our studies demonstrate both in vitro and in vivo that cigarette smoke significantly increases the expression of neutrophil and macrophage extracellular traps with coexpression of the pathogenic proteases, neutrophil elastase and matrix metalloproteinases 9 and 12. This response to cigarette smoke was significantly reduced by the addition of DNase 1, which also significantly decreased macrophage numbers and lung proteolysis. DNase 1, a treatment currently in clinical use, can diminish the pathogenic effects of cigarette smoke.
Near-infrared light-mediated LA-UCNPs@SiO2-C/HA@mSiO2-DOX@NB nanocomposite for chemotherapy/PDT/PTT and imaging
Authors: Chen Yuhua , Zhang Feng , Wang Qian , Tong Ruihan , Lin Huiming , Qu Fengyu
Published: September 2017

Upon 980 nm light irradiation, multiple-emission can not only induce chemotherapy/PDT/PTT but also imaging.
Mono-, di- and tetrarhenium Fischer carbene complexes with thienothiophene substituents
Authors: Lamprecht Zandria , Radhakrishnan Shankara G. , Hildebrandt Alexander , Lang Heinrich , Liles David C. , Weststrate Nora-ann , Lotz Simon , Bezuidenhout Daniela I.
Published: September 2017

Syntheses, spectroelectrochemistry and molecular orbital analyses of mono- to multimetal Re(0) and Re(i) Fischer carbene complexes with condensed thienothienyl substituents.
Interplay between bulk self-assembly, interfacial and foaming properties in a catanionic surfactant mixture of varying composition
Authors: Ferreira José , Mikhailovskaya Alesya , Chenneviere Alexis , Restagno Frédéric , Cousin Fabrice , Muller François , Degrouard Jéril , Salonen Anniina , Marques Eduardo F.
Published: September 2017

Bulk nanostructures and foaming vary markedly with surfactant mixing ratio. Aggregates are unchanged inside foam and control foam drainage through solution viscosity.
Peptides mediating DNA transport on microtubules and their impact on non-viral gene transfer efficiency
Authors: Midoux Patrick , Pigeon Lucie , Gonçalves Cristine , Pichon Chantal
Published: September 2017

Synthetic vectors such as cationic polymers and cationic lipids remain attractive tools for non-viral gene transfer which is a complex process whose effectiveness relies on the ability to deliver a plasmid DNA (pDNA) into the nucleus of non-dividing cells. Once in the cytosol, the transport of pDNAs towards the nuclear envelope is strongly impaired by their very low cytosolic mobility due to their large size. To promote their movement towards the cell nucleus, few strategies have been implemented to exploit dynein, the microtubule’s (MT’s) motor protein, for propagation of cytosolic pDNA along the MTs towards the cell nucleus. In the first part of this review, an overview on MTs, dynein, dynein/virus interaction feature is presented followed by a summary of the results obtained by exploitation of LC8 and TCTEL1 dynein light chain association sequence (DLC-AS) for non-viral transfection. The second part dedicated to the adenoviral protein E3-14.7K, reports the transfection efficiency of polyplexes and lipoplexes containing the E3-14.7K-derived P79-98 peptide linked to pDNA. Here, several lines of evidence are given showing that dynein can be targeted to improve cytosolic pDNA mobility and accumulate pDNA near nuclear envelope in order to facilitate its transport through the nuclear pores. The linkage of various DLC-AS to pDNA carriers led to modest transfection improvements and their direct interaction with MTs was not demonstrated. In contrast, pDNA linked to the P79-98 peptide interacting with TCTEL1 via a cytosolic protein (fourteen seven K-interacting protein-1 (FIP-1)), interaction with MTs is evidenced in cellulo and transfection efficiency is improved.
Arizona Sonora Borders (ARSOBO) Hearing Health Program: A Cross Border Project for Inclusion
Authors: Dean James
Published: September 2017

Limited access to hearing health care, including hearing aids, is a universal and growing concern. This is particularly true in low- and middle-income countries, such as Mexico. Improving hearing health care equity within a large underserved infant to geriatric population in Mexico requires a foundation of trust and a culturally sensitive vision shared by all stakeholders. This article describes a cross-border hearing health care program that was integrated into an existing humanitarian project for individuals with disabilities. The program, called the Arizona Sonora Borders Projects for Inclusion (ARSOBO), based in Nogales, Sonora, Mexico, is building a “culture of health” in a border town divided by a fence. By crossing geographic, demographic, and social barriers, volunteers from Tucson, Arizona and Nogales, Sonora work to improve the quality of life for hearing impaired individuals, young and old.
Hybrid non‐uniform‐Q lossy filters with substrate integrated waveguide and microstrip resonators
Authors: Qiu Liang‐Feng , Wu Lin‐Sheng , Yin Wen‐Yan , Mao Jun‐Fa
Published: September 2017

Three lossy filters with flat passband are proposed with substrate integrated waveguide (SIW) and microstrip resonators, designed with the non‐uniform‐Q method. By properly selecting the lower‐Q‐to‐higher‐Q ratio, the 0.2 dB bandwidth of the first filter is obtained to be 215 MHz (17% improvement), which is equivalent to a uniform unloaded Q‐factor of 820 at the cost of additional in‐band insertion loss (IL) of 0.5 dB, when compared with the full‐SIW filters. Further, two techniques are utilised to adjust the Q‐factor ratio. One method is implemented by mounting a resistor on each microstrip resonator to reduce its unloaded Q‐factor. Then, the 0.2 dB passband of 243 MHz is achieved for the second filter, equivalent to a uniform unloaded Q‐factor of 1420. The other method is realised by adjusting the Q‐factor due to radiation loss of microstrip resonators. By changing the input/output feeding structures, the 0.2 dB bandwidth of the third filter is enhanced by 32%, at the cost of minimum IL increased by 0.9 dB. The occupied area of the proposed planar hybrid filters is reduced by 15–21% and the passband flatness is much better than that of the uniform‐Q filter counterparts, as demonstrated by the simulated and measured results.
Performance of site diversity fade mitigation over Earth‐to‐space propagation link using rain cell measurements in a tropical Nigeria
Authors: Ojo Joseph S. , Ajewole Moses O. , Obagunle Romoke G.
Published: September 2017

The concept of site diversity is one of the fade mitigation techniques for radio communication system to overcome severe attenuation during an intense rainy condition. In this study, the performance of experimental findings during the three‐year rainy periods (2011–2013) at a tropical location, Akure (7.17°N, 5.18°E), Nigeria, using measurements from tipping bucket rain gauge network is presented to estimate and model site diversity fades mitigation over Earth–space links in the region. Time‐specified rain attenuation is generated from the micro‐rain cells over the site using Synthetic Storm Techniques by converting rain rate at the specified time and site into rain‐induced attenuation time‐series to obtain the diversity gain necessary to counter the severe rain events at Ku/Ka‐bands frequency. Based on the micro‐cell site diversity result, a modified site diversity gain prediction model has been proposed for different rainy periods: namely: onset, long‐rainy and cessation of rainy months. Results are compared with the existing site diversity models. The modified model which incorporated seasonal influences show improved estimation capability better than the International Telecommunication Union‐Recommendations (ITU‐R) diversity gain model for this location. The overall result will enhance the performance of radio signal transmission along Earth–space paths under intense rainy event in this tropical environment.
First Presentation of an Acquired Demyelinating Syndrome
Authors: Gottlieb-Smith Rachel , Waldman Amy
Published: September 2017

Acquired demyelinating syndromes (ADS) present with acute or subacute monofocal or polyfocal neurologic deficits localizing to the central nervous system. The clinical features of distinct ADS have been carefully characterized including optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. These disorders may all be monophasic disorders. Alternatively, optic neuritis, partial transverse myelitis, and acute disseminated encephalomyelitis may be first presentations of a relapsing or polyphasic neuroinflammatory disorder, such as multiple sclerosis or neuromyelitis optica. The clinical features of these disorders and the differential diagnosis are discussed in this article.
Organinteraktion Leber und Niere
Authors: Roedl Kevin , Jarczak Dominik , Fuhrmann Valentin
Published: September 2017

Alterations of the kidney function can be observed often in patients with liver diseases. Different mechanisms are leading to alterations in kidney funciton in these patients. New onset of kidney function alterations in patients with acute- or chronic liver disease often leads to acute kidney injury. This Review will inform you about the most importatant clinical interactions of the kidneys and the liver.
Geschlechtsspezifische Unterschiede in Verlauf und Therapie der chronischen Nierenerkrankung
Authors: Birgit Bader
Published: September 2017

Die geschlechtsspezifischen Unterschiede in der Prävalenz und der Progression der chronischen Nierenerkrankung sind noch wenig erforscht.
Noch geringer ist unser Wissen über die geschlechtsspezifischen Unterschiede beim Zugang zur medizinischen Versorgung. Letztlich hängt die
Gleichbehandlung der Frau von den aufgewandten Kosten für das Gesundheitswesen und dem gesellschaftlichen System ab.
Einfluss von Saxofon-Musik in der Behandlung von Hämodialysepatienten
Authors: Wiederhold Dietmar
Published: September 2017

Musiktherapeutische Maßnahmen gewinnen zunehmend als komplementäre und nicht pharmakologische Pflegeinterventionen an Bedeutung. Obwohl Musik
bereits bei Patienten an der Hämodialyse für ein emotionales Wohlbefinden, zur Reduzierung von Blutdruckschwankungen, Angst und Depressionen
angewendet wird, existieren zum Studienzeitpunkt keine klinischen Forschungsberichte, welche die therapeutischen Wirkungen evaluieren. Die
Studie zielte darauf ab, die Effekte von Live-Saxofon-Musik auf verschiedene physiologische Parameter sowie auf das Erleben von Schmerz, der
Stimmungslage und die Intensität von Juckreiz bei Hämodialysepatienten zu untersuchen.
E-Zigaretten in aller Munde? – Aktuelle repräsentative Daten zur Nutzung unter Jugendlichen und Erwachsenen
Authors: Schneider Sven , Görig Tatiana , Schilling Laura , Diehl Katharina
Published: September 2017

Hintergrund und Fragestellung Internationale Daten weisen auf einen Anstieg im E-Zigaretten-Konsum hin. In Deutschland jedoch gibt es bis dato große Defizite in der Berichterstattung aktueller Prävalenzen. Zur Behebung dieses Defizits sollen die vorliegenden Daten einen Beitrag liefern. Sie erlauben insbesondere eine simultane Differenzierung nach Nikotingehalt der E-Zigarette und nach dem Tabakrauchstatus der Nutzer.

Methodik und Material Datenbasis bildet das Nationale Krebshilfe-Monitoring NCAM. Hier wurden in der ersten Welle 3000 Personen im Alter von 14 bis 45 Jahren telefonisch befragt. Berichtet werden Punktschätzer, Konfidenzintervalle sowie Determinanten des Konsums.

Ergebnisse Insgesamt hatten 20 % der Befragten schon einmal eine E-Zigarette genutzt, davon griffen 80 % auf nikotinhaltige Liquids zurück. Männer, jüngere Personen, Personen mit Migrationshintergrund und Personen mit niedrigem Bildungsstand hatten eher schon einmal E-Zigaretten genutzt als die jeweiligen Referenzgruppen. Die Hälfte aller Jemalsnutzer von E-Zigaretten rauchte auch Tabakzigaretten. Rund ein Drittel aller Jemalsnutzer hatte noch nie Tabakprodukte konsumiert.

Folgerungen und Diskussion Als Zielgruppen für zukünftige Präventionsmaßnahmen ergaben sich zum einen Jugendliche, da die jüngsten Befragten die höchsten Prävalenzen aufwiesen, sowie Nie-Raucher, da ein Drittel der E-Zigarettennutzer noch nie Tabakzigaretten geraucht hatte. Beide Gruppen erscheinen ebenfalls als relevante Zielgruppe, deren Einstieg in die Nutzung von E-Zigaretten verhindert werden sollte.
SOP Allgemeine Methodik der Myografie
Authors: Bischoff Christian , Schulte-Mattler Wilhelm
Published: September 2017

Die Elektromyografie dient der Untersuchung von Patienten mit neuromuskulären Erkrankungen mittels konzentrischer Nadelelektroden. In dieser SOP wird eine standardisierte Verfahrensweise mit technischen Details vorgestellt. Ein Überblick über die wichtigsten elektromyografischen Befunde bietet Unterstützung bei der Interpretation der Messergebnisse. Abschließend werden Besonderheiten der Einzelfaser-EMG erläutert.
Palliative Therapies for Congenital Heart Disease with Ductus Dependent Pulmonary Circulation
Authors: Yuan Shi-Min
Published: September 2017

In neonates, the management of ductus dependent pulmonary circulation is challenging. There have been three palliative therapies for this lesion: the modified Blalock-Taussig shunt, ductal stenting and prostaglandin E infusions, for maintaining the ductal patency before definite operations. Debates remain with regard to the indications and disadvantages of three palliative therapies. The aim of this article is to give a brief review of these three palliative therapies.
Die Bedeutung von Natriumhydrogenkarbonat
Authors: Stradtmann Herbert
Published: September 2017

Der Säure-Basen-Haushalt und Körperfunktionen sind eng verknüpft. Eine metabolische Azidose (mA) hat viele negative Auswirkungen, auch auf
die Nierenfunktion. Die mA ist in ihren unterschiedlichen Schweregraden mittels Blutgasanalyse leicht zu enttarnen. Ein Standardbikarbonat
von unter 22 mmol/l gilt als kritisch und sollte Anlass sein, die Ursachen zu suchen, diese zu behandeln und gegen die Azidose vorzugehen.
Am besten eignen sich orale, magensaftresistente Natriumhydrogenkarbonat-Präparate.
Hidden Relaxation Channels in Aqueous Methylene Blue after Functionalization of Graphene Oxide Probed by Transient Absorption Spectroscopy
Authors: Ke Da , Sui Lai-zhi , Liu Dun-li , Wang Yu-su , Li Su-yu , Jiang Yuan-fei , Chen An-min , Jin Ming-xing
Published: September 2017

The mixture of graphene oxide (GO) and dye molecules may provide some new applications due to unique electronic, optical, and structural properties. Methylene blue (MB), a typical anionic dye, can attach on GO via π-π stacking and electrostatic interaction, and the molecule removal process on GO has been observed. However, it remains unclear about the ultrafast carrier dynamics and the internal energy transfer pathways of the system which is composed of GO and MB. We have employed ultrafast optical pump-probe spectroscopy to investigate the excited dynamics of the GO-MB system dispersed in water by exciting the samples at 400 nm pump pulse. The pristine MB and GO dynamics are also analyzed in tandem for a direct comparison. Utilizing the global analysis to fit the measured signal via a sequential model, five lifetimes are acquired: (0.61±0.01) ps, (3.52±0.04) ps, (14.1±0.3) ps, (84±2) ps, and (3.66±0.08) ns. The ultrafast dynamics corresponding to these lifetimes was analyzed and the new relaxation processes were found in the GO-MB system, compared with the pristine MB. The results reveal that the functionalization of GO can alter the known decay pathways of MB via the energy transfer from GO to MB in system, the increased intermediate state, and the promoted energy transfer from triplet state MB to ground state oxygen molecules dissolved in aqueous sample.
Robust mechanobiological behavior emerges in heterogeneous myosin systems
Authors: Egan Paul F. , Moore Jeffrey R. , Ehrlicher Allen J. , Weitz David A. , Schunn Christian , Cagan Jonathan , LeDuc Philip
Published: September 2017

Significance

Myosin proteins operate in complex coordinated systems to power muscle. There is a diversity of myosins that enable muscle responses with tuned force–velocity characteristics. Myosin structures may be altered and repurposed for nanotechnologies. We developed a computational model to compare myosin systems when multiple myosin types operate together (i.e. heterogeneous) or only a single type is present (i.e. homogeneous). The model predicts that modifying myosin chemical attachment and detachment rates may improve the robustness of a system to operate for a broad range of force conditions. In vitro experiments were conducted for force-loaded heterogeneous systems to validate computational predictions. The model suggests that in comparison with homogenous systems, heterogeneous systems have potentially advantageous and unique trade-offs for system robustness.
IntPred: a structure-based predictor of protein–protein interaction sites
Authors: Northey Thomas C , Barešić Anja , Martin Andrew C R
Published: September 2017

Motivation

Protein–protein interactions are vital for protein function with the average protein having between three and ten interacting partners. Knowledge of precise protein–protein interfaces comes from crystal structures deposited in the Protein Data Bank (PDB), but only 50% of structures in the PDB are complexes. There is therefore a need to predict protein–protein interfaces in silico and various methods for this purpose. Here we explore the use of a predictor based on structural features and which exploits random forest machine learning, comparing its performance with a number of popular established methods.

Results

On an independent test set of obligate and transient complexes, our IntPred predictor performs well (MCC = 0.370, ACC = 0.811, SPEC = 0.916, SENS = 0.411) and compares favourably with other methods. Overall, IntPred ranks second of six methods tested with SPPIDER having slightly better overall performance (MCC = 0.410, ACC = 0.759, SPEC = 0.783, SENS = 0.676), but considerably worse specificity than IntPred. As with SPPIDER, using an independent test set of obligate complexes enhanced performance (MCC = 0.381) while performance is somewhat reduced on a dataset of transient complexes (MCC = 0.303). The trade-off between sensitivity and specificity compared with SPPIDER suggests that the choice of the appropriate tool is application-dependent.

Availability and implementation

IntPred is implemented in Perl and may be downloaded for local use or run via a web server at www.bioinf.org.uk/intpred/.

Supplementary information

Supplementary data are available at Bioinformatics online.
High Rates of Occult Hepatitis B Virus Infection in HIV-Positive Individuals Initiating Antiretroviral Therapy in Botswana
Authors: Ryan Kathleen , Anderson Motswedi , Gyurova Ivayla , Ambroggio Lilliam , Moyo Sikhulile , Sebunya Teresa , Makhema Joseph , Marlink Richard , Essex Max , Musonda Rosemary , Gaseitsiwe Simani , Blackard Jason T
Published: September 2017

Background

Hepatitis B surface antigen (HBsAg)–negative but hepatitis B virus (HBV) DNA-positive infection—known as occult hepatitis B infection (OBI)—occurs in 1% to >15% of HIV-positive individuals in the United States and South Africa, respectively. However, there are no data on OBI from Botswana, a country known to be hyperendemic for chronic HBV infection and to have a significant HIV burden.

Methods

Two hundred seventy-two adults enrolled in an HIV treatment study of tenofovir/emtricitabine as the nucleoside backbone who were previously determined to be HBsAg negative were tested for HBV DNA at baseline and 1 year after initiation of highly active antiretroviral therapy (HAART).

Results

HBV DNA was detected in 72 of 272 (26.5%). Six individuals (8.3%) had HBV DNA levels greater than 200 IU/mL, and the highest viral load was 3280 IU/mL. Of 65 participants with OBI evaluated at 12 months after initiating HAART, only 1 (1.5%) had detectable HBV DNA.

Conclusions

Occult HBV infection is quite common in HIV-infected patients in Botswana, although its impact on the course of HIV disease progression is unknown. The suppression of occult HBV DNA levels by tenofovir/emtricitabine suggests an effective therapeutic option, although the long-term suppressive abilities remain unstudied.
Indications for CT-Angiography of the Vertebral Arteries After Trauma
Authors: Drain Joseph P. , Weinberg Douglas S. , Ramey James S. , Moore Timothy A. , Vallier Heather A.
Published: September 2017

Study Design.

Retrospective.

Objective.

The purpose of this project is to identify factors that predict vertebral artery injury (VAI) in an effort to assess risks and benefits of computed tomography angiography (CT-A) of the neck in the trauma setting. We seek to develop guidelines for practitioners to stratify patients at medium/high risk of VAI from those who are at low risk.

Summary of Background Data.

VAI and blunt carotid injury (BCI) together comprise blunt cerebrovascular injury (BCVI). More is known about risk factors for BCI than for VAI, but the neurovascular complications associated with VAI are similarly disastrous. With increasing frequency, trauma providers are using CT-A to screen for BCVI; this test carries risks that include radiation exposure and nephrotoxicity, in addition to higher cost of treatment and longer hospital stay.

Methods.

Trauma patients seen over 4 months at an urban, level 1 trauma were analyzed. BCVI screening was conducted in 144/1854 (7.77%) patients. Presence of VAI and several clinical characteristics were recorded. Univariate analysis and binomial logistic regression analysis were conducted at a 95% significance level.

Results.

VAI was diagnosed in 0.49% of the study population. Univariate analysis determined six factors associated with positive VAI screening. Regression analysis showed four factors that independently predicted VAI: female sex, decreased Glasgow Coma Scale, cervical spine (c-spine) fracture, and concurrent BCI. A positive c-spine physical examination trended toward predicting VAI without achieving significance.

Conclusion.

Several independent predictors of VAI were identified. This study highlights the importance of identifying patients at a higher risk for VAI and indicating CT-A of the neck versus those who are at low risk and can be evaluated without undergoing advanced imaging, as CT-A appears unnecessary for most trauma patients.

Level of Evidence: 3
Minimally Invasive Palmaris Longus Abductorplasty for Severe Carpal Tunnel Syndrome
Authors: Chung Sze-Ryn , Yap Robert Tze-Jin , Tuck Andrew Yam Kean
Published: September 2017

Camitz abductorplasty is the most commonly used tendon transfer in patients with severe carpal tunnel syndrome with significant muscle wasting and loss of opposition. This procedure requires a long incision in the palm to harvest a strip of palmar aponeurosis to lengthen the palmaris longus tendon, allowing it to reach the abductor pollicis brevis insertion. Several complications have been attributed to this extensive dissection in the palm. We describe a minimally invasive palmaris longus abductorplasty using a strip of free flexor carpi radialis tendon graft to achieve the necessary length. This can be done together with carpal tunnel release in patients with severe carpal tunnel syndrome.
Systemic therapy in advanced melanoma: integrating targeted therapy and immunotherapy into clinical practice
Authors: Silva Inês P. , Long Georgina V.
Published: September 2017

Purpose of review

Here we review the results from relevant phase III trials and discuss treatment strategies for challenging subgroups of melanoma patients.

Recent findings

Targeted therapies induce rapid responses in the majority of BRAF-mutant patients, however, 50% of these responders will develop resistance within approximately 13 months. In contrast, inhibitors of checkpoints on T cells, particularly inhibitors of PD-1, induce responses in 40–55% of patients (monotherapy or whenever combined with anti-CTLA-4), and these responses tend to be durable. Data from subgroup analyses of large clinical trials, as well as patient-centred factors, help guide clinicians in their choice of first-line therapy.

Immune checkpoint inhibitors and MAP kinase pathway-targeted therapies have revolutionized the management of advanced melanoma, and significantly prolong the overall survival of patients with this disease. The median overall survival is over 2 years for both anti-PD-1-based therapy and combined BRAF and MEK inhibition. Without head-to-head comparison data for either therapy, choice of first-line drug treatment is difficult.
Care patterns and changes in treatment for nonmetastatic breast cancer in 2013–2014 versus 2005: a population-based high-resolution study
Authors: Guevara Marcela , Burgui Rosana , Díaz-González Jorge , Salgado Esteban , Vicente Francisco , Moreno-Iribas Conchi , Urbina María J. , Córdoba Alicia , de Miguel Concepción , Ardanaz Eva
Published: September 2017

Studies on recent trends in patterns of care for breast cancer patients are scarce. This study aims to examine the patterns and trends in the treatment of women with nonmetastatic breast cancer according to major recommended treatment options. A population-based study was carried out in Navarra, Spain, including all women with a primary invasive nonmetastasized breast cancer, diagnosed in 2005 and in 2013–2014. We compared patients’ characteristics and treatment patterns between periods. Factors associated with receipt of recommended treatment were examined by multivariate logistic regression. Of the 719 patients included, 90% received guideline-adherent locoregional treatment. Over the two periods, there was an increasing use of sentinel lymph node biopsy as opposed to axillary lymph node dissection as the first axillary procedure. Among women with oestrogen receptor-positive tumours, 96% received endocrine therapy. The proportion of high-risk patients who were treated with chemotherapy increased between the two periods from 65 to 74% (P=0.079) and, among patients with human epidermal growth factor receptor 2-positive tumours, the receipt of targeted treatment increased from 37 to 72% (P<0.001). The main factors associated independently with a lower probability of receiving recommended treatment were age 70 years or older for all treatment modalities and comorbidity for locoregional treatment and chemotherapy. The proportion of women with breast cancer who received treatment according to recent European guidelines in Navarra has increased from 2005 to 2013–2014, resulting in a high level of adherence to standard care. Most failures in adherence to these standards are related to older age or comorbidities.
Academic Developmental-Behavioral Pediatric Faculty at Developmental-Behavioral Pediatric Research Network Sites: Changing Composition and Interests
Authors: Roizen Nancy , Stein Ruth E. K. , Silver Ellen J. , High Pamela , Augustyn Marilyn C. , Blum Nathan J.
Published: September 2017

Objective:

To obtain and review workforce data, given the critical demand for developmental pediatricians (DPs).

Methods:

Survey of demographics and professional activities of DP physician faculty at Developmental-Behavioral Pediatric (DBP) Research Network fellowship training sites.

Results:

Of the eligible providers at 12 centers, 76% (n = 50) completed surveys. They were on average 50 years old and mostly female (86%), white (82%), and working full time (74%). Full timers reported a mean 50.2-hour week made up of clinical work (23.2 hours), supervision (5.9 hours), research (8.8 hours), administration (5.2 hours), teaching (1.5 hours), advocacy (1.1 hours), and other (4.3 hours). Compared with those >10 years out of training, the 20 physicians (40%) ≤10 years out of fellowship were more likely to be nonwhite (p = .003). Overall faculty interest/expertise (I/E) was highest in autism (90%) and attention deficit hyperactivity disorder (ADHD; 86%). Those ≤10 years out of fellowship had more I/E in autism (p = .05) and less in chronic illness (p = .06) and parenting (p = .06). DPs practiced most frequently in a General DBP Clinic (74%), followed by clinics specific for: Autism (36%), Toddlers (22%), ADHD (20%), Infants (18%) and Preschoolers (16%). Common clinics were Autism (9), syndrome specific (9), ADHD (6), and School-Aged (5).

Conclusion:

Developmental pediatrician faculty in DBP training sites feed the pipeline of much needed DP physicians. This survey provides baseline information on the professional activities of DP faculty and found changing demographics and I/E as well as a wide variety of clinic types.
Disparities in access to care in marginalized populations
Authors: Silberholz Elizabeth A. , Brodie Nicola , Spector Nancy D. , Pattishall Amy E.
Published: September 2017

Purpose of review

The current article reviews recent literature related to three groups whose health is affected by barriers to the healthcare system: refugee and immigrant populations; youth who are lesbian, gay, bisexual, transgender, queer, or questioning; and those with mental health problems.

Recent findings

Refugee and immigrant populations are increasing worldwide, and recent work has focused on improving their access to mental, dental, and preventive care. Lesbian, gay, bisexual, transgender, queer, or questioning youth have unique healthcare needs but frequently lack a support system and may not be forthcoming about their sexuality or sex identity. A rising number of children are being diagnosed with mental health disorders, but due to multiple factors, youth are not receiving the care they need.

Pediatric healthcare providers should be aware of the unique challenges faced by youth displaced from their country of origin, who are lesbian, gay, bisexual, or transgender or are questioning their sexuality or sex identity, and who struggle with mental health disorders. Toolkits, other educational resources, and novel technological advances can assist pediatricians in ensuring optimal health care of these at-risk groups.
Atypical Exit Wound in High-Voltage Electrocution
Authors: Parakkattil Jamshid , Kandasamy Shanmugam , Das Siddhartha , Devnath Gerard Pradeep , Chaudhari Vinod Ashok , Shaha Kusa Kumar
Published: September 2017

Electrocution fatality cases are difficult to investigate. High-voltage electrocution burns resemble burns caused by other sources, especially if the person survives for few days. In that case, circumstantial evidence if correlated with the autopsy findings helps in determining the cause and manner of death. In addition, the crime scene findings also help to explain the pattern of injuries observed at autopsy. A farmer came in contact with a high-voltage transmission wire and sustained superficial to deep burns over his body. A charred and deeply scorched area was seen over the face, which was suggestive of the electric entry wound. The exit wound was present over both feet and lower leg and was atypical in the form of a burnt area of peeled blistered skin, charring, and deep scorching. The injuries were correlated with crime scene findings, and the circumstances that lead to his electrocution are discussed here.
Decision-Making in Pediatric Transport Team Dispatch Using Script Concordance Testing*
Authors: Rajapreyar Prakadeshwari , Marcdante Karen , Zhang Liyun , Simpson Pippa , Meyer Michael T.
Published: September 2017

Objectives:

Our objective was to compare decision-making in dispatching pediatric transport teams by Medical Directors of pediatric transport teams (serving as experts) to that of Pediatric Intensivists and Critical Care fellows who often serve as Medical Control physicians. Understanding decision-making around team composition and dispatch could impact clinical management, cost effectiveness, and educational needs.

Design:

Survey was developed using Script Concordance Testing guidelines. The survey contained 15 transport case vignettes covering 20 scenarios (45 questions). Eleven scenarios assessed impact of intrinsic patient factors (e.g., procedural needs), whereas nine assessed extrinsic factors (e.g., weather).

Setting:

Pediatric Critical Care programs accredited by the Accreditation Council for Graduate Medical Education (the United States).

Subjects:

Pediatric Intensivists and senior Critical Care fellows at Pediatric Critical Care programs were the target population with Transport Medical Directors serving as the expert panel.

Interventions:

None.

Measurements and Main Results:

Survey results were scored per Script Concordance Testing guidelines. Concordance within groups was assessed using simple percentage agreement. There was little concordance in decision-making by Transport Medical Directors (median Script Concordance Testing percentage score [interquartile range] of 33.9 [30.4–37.3]). In addition, there was no statistically significant difference between the median Script Concordance Testing scores among the senior fellows and Pediatric Intensivists (31.1 [29.6–33.2] vs 29.7 [28.3–32.3], respectively; p = 0.12). Transport Medical Directors were more concordant on reasoning involving intrinsic patient factors rather than extrinsic factors (10/21 vs 4/24).

Conclusions:

Our study demonstrates pediatric transport team dispatch decision-making discordance by pediatric critical care physicians of varying levels of expertise and experience. Script Concordance Testing at a local level may better elucidate standards in medical decision-making within pediatric critical care physicians. The development of a curriculum, which provides education and trains our workforce on the logistics of pediatric transport team dispatch, would help standardize practice and evaluate outcomes based on decision-making.
Early Exercise in Critically Ill Youth and Children, a Preliminary Evaluation: The wEECYCLE Pilot Trial*
Authors: Choong Karen , Awladthani Saif , Khawaji Adeeb , Clark Heather , Borhan ASM , Cheng Ji , Laskey Sam , Neu Charmaine , Sarti Aimee , Thabane Lehana , Timmons Brian W. , Zheng Katina , Al-Harbi Samah
Published: September 2017

Objectives:

To determine the feasibility of conducting a full trial evaluating the efficacy of early mobilization using in-bed cycling as an adjunct to physiotherapy, on functional outcomes in critically ill children.

Design:

Single center, pilot, randomized controlled trial.

Setting:

Twelve-bed tertiary care, medical-surgical PICU at McMaster Children’s Hospital, Hamilton, ON, Canada.

Patients:

Children 3–17 years old who were limited to bed-rest with an expected PICU stay of at least 48 hours. Patients were excluded if they were at their baseline level of function, already mobilizing out of bed or expected to do so within 24 hours.

Interventions:

Patients were randomized in a 2:1 ratio to early mobilization using in-bed cycling in addition to usual care physiotherapy (cycling arm) or to usual care physiotherapy alone (control). Usual care was according to institutional practice guidelines. The primary outcome was feasibility and safety.

Measurements and Main Results:

Thirty patients were enrolled (20 to the cycling and 10 to control) over a 12-month period, at a 93.7% consent rate. The median (interquartile range) time from PICU admission to mobilization was 1.5 days (1–3) in the cycling arm and 2.5 days (2–7) in the control arm. Total duration of mobilization therapy in PICU was 210 (152–380) and 136 minutes (42–314 min) in cycling and control arms, respectively. Total number of PICU days mobilized was 5.0 (3–6) with cycling and 2.5 (2–4.8) with usual care. No adverse events occurred in either arm. The main threat to feasibility of mobilization was the availability of physiotherapists or research personnel.

Conclusions:

Early mobilization is safe and feasible in the PICU. In-bed cycling may facilitate greater duration and intensity of mobilization, in critically ill children. A full-scale randomized controlled trial is warranted to evaluate the efficacy of this intervention on PICU-acquired morbidities and functional outcomes in this population.