bluuebunny/crossref_metadata_2025 huggingface dataset:
Two New Flavanols from Glycosmis pentaphylla and Their Cytotoxic Activities
Authors: Wang Jiangfeng , Zhao Bing , Zhang Feng , Zhang Qiongyu
Published: January 2016

Two new flavanols, (8S,9R)‐9,10‐dihydro‐5,9‐dihydroxy‐8‐(3,4,5‐trimethoxyphenyl)‐2H,8H‐benzo[1,2‐b:3,4‐b′]dipyran‐2‐one (1) and (2S,3R)‐3,4‐dihydro‐3,5‐dihydroxy‐2‐(3,4,5‐trimethoxyphenyl)‐2H,8H‐benzo[1,2‐b:3,4‐b′]dipyran‐8‐one (2), were isolated from the stems of Glycosmis pentaphylla. The structures of these compounds were determined by extensive spectroscopic (UV, IR, HR‐ESI‐MS, 1D‐ and 2D‐NMR) analyses. The cytotoxic activities of these compounds were evaluated using the MTT method. The results showed that compounds 1 and 2 exhibited considerable cytotoxic activities against HL‐60 and A549 cell lines.
In vitro Antioxidant Activity of Ubiquinone and Ubiquinol, Compared to Vitamin E
Authors: Cervellati Rinaldo , Greco Emanuela
Published: January 2016

Coenzyme Q10 (CoQ10) is the prevalent ubiquinone in human organism, largely present in its reduced form, ubiquinol (QH2), to which the antioxidant, free radical scavenger activity is ascribed by many authors. However, some studies indicate that also the oxidized form presents some effect in preventing the cellular oxidative stress. In this article four in vitro chemical test methods (TEAC, FRAP, DPPH, and BR) were used to assess the free radical scavenging power of CoQ10, QH2, and vitamin E. The results showed that CoQ10 is almost ineffective, while in three of the tests QH2 presents a higher antioxidant activity than vitamin E. From these results, it can be concluded that the interconversion CoQ10⇌QH2 leading to the prevalence of QH2 in biological tissues is responsible for the antioxidant action of coenzyme Q10 in living organisms.
Trichodermates A–F, New Cytotoxic Trichothecenes from the Plant Pathogenic Fungus Trichoderma sp.
Authors: Li Jiaying , Ren Jinwei , Bao Li , Jin Tao , Wang Wenzhao , Pei Yunfei , Liu Xingzhong , Li Erwei
Published: January 2016

Trichodermates A – F (1–6, resp.), six new trichothecene polyunsaturated octadioic acid esters, and (−)‐harzianum B (7) were isolated from the fermentation extract of Trichoderma sp., a plant pathogenic fungus isolated from stem rot of an unidentified tree in Thailand. The structures of 1–7 were elucidated by NMR experiments. The absolute configuration at C(12) in 3 was assigned by in situ dimolybdenum circular dichroism method, whereas that in 7 was deduced after hydrolysis of 7 to 8 via modified Mosher's method. Compounds 1 and 2 showed modest cytotoxic activities against the K562 (human myelogenous leukemia) cell line with IC50 values of 12.12 and 13.08 μM, respectively.
Chemical Constituents from the Fermented Mycelia of the Medicinal Fungus Xylaria nigripes
Authors: Xiong Juan , Huang Ya , Wu Xi‐Ying , Liu Xin‐Hua , Fan Hui , Wang Wei , Zhao Yun , Yang Guo‐Xun , Zhang Hai‐Yan , Hu Jin‐Feng
Published: January 2016

Nineteen compounds mainly including pyrrole‐containing alkaloids and phytosterols were isolated from the EtOH extract of the fermented mycelia of Xylaria nigripes, a precious medicinal fungus known as Wuling Shen in Chinese. On the basis of spectroscopic methods, the structures of the new naturally occurring compounds were determined to be (4S)‐3,4‐dihydro‐4‐(4‐hydroxybenzyl)‐3‐oxo‐1H‐pyrrolo[2,1‐c][1,4]oxazine‐6‐carbaldehyde (1), methyl (2S)‐2‐[2‐formyl‐5‐(hydroxymethyl)‐1H‐pyrrol‐1‐yl]‐3‐(4‐hydroxyphenyl)propanoate (2), and 3‐{4‐[(2R)‐(2,3‐dihydroxy‐3‐methylbutoxy]phenyl}‐7‐hydroxy‐4H‐chromen‐4‐one (3), respectively. The absolute configurations of 1 and 2 were deduced by the observed Cotton effects in their circular dichroism (CD) spectra, whereas that of the 1,2‐diol moiety in 3 was determined using the Snatzke's method. Their biological activities such as neuroprotective, anti‐neuroinflammatory, and cytotoxic properties were also reported.
One‐Pot Synthesis of 3‐Substituted 3,4‐Dihydro‐1,2,3‐benzotriazine Derivatives Based on the Reaction of o‐Bromobenzyl Azides with Butyllithium
Authors: Kobayashi Kazuhiro , Chikazawa Yuuki
Published: January 2016

An efficient one‐pot procedure for the preparation of 3‐substituted 3,4‐dihydro‐1,2,3‐benzotriazines 2, 3, and 4 from o‐bromobenzyl azides 1 is described. The reaction of these azides with BuLi in THF at −78° generates o‐lithiobenzyl azides via the Br/Li exchange. These lithium compounds immediately undergo intramolecular cyclization to give the corresponding (dihydro‐1,2,3‐benzotriazinyl)lithium intermediates, which are trapped with a variety of acylating agents or BnBr at N(3) exclusively to provide the desired products in moderate to good yields.
Examining subjective and physiological responses to norm violation using text‐based vignettes
Authors: Krumhuber Eva G. , Tsankova Elena , Kappas Arvid
Published: January 2016

In this article, we describe a paradigm using text‐based vignettes for the study of social and cultural norm violation. Towards this aim, a range of scenarios depicting instances of norm violations was generated and tested with respect to their ability in evoking subjective and physiological responses. In Experiment 1, participants evaluated 29 vignettes on how upsetting, excusable and realistic the described behaviour appeared to be. Based on those ratings we selected and extended three norm violation vignettes for Experiment 2 in which participants' physiological responses were obtained in addition to their subjective ratings. In both studies, the vignettes were successful in eliciting negative responses to norm violations and were significantly affected by the perceivers' level of ethnocultural empathy. The trait measure of cultural empathy further predicted facial electromyography (EMG) activity at muscle sites associated with disgust (M. Levator Labii), thereby suggesting a potential moral response to norm‐violating scenarios. We discuss the methodological merits and implications of this vignettes paradigm for investigating perceived norm transgressions and make recommendations for future work.
The effect of increased microporosity on bone formation within silicate‐substituted scaffolds in an ovine posterolateral spinal fusion model
Authors: Coathup Melanie Jean , Blunn Gordon William , Campion Charlie , Ho Chih‐Yuan , Hing Karin Angela
Published: January 2016

This study compared the bone forming capacity of the same formulation of silicate‐substituted bone graft substitute materials with different microporosity in an instrumented posterolateral spinal fusion ovine model. Materials with a strut porosity of (i) 22.5% (SiCaP) or (ii) 36.0% (SiCaP(+)) were packed along either side of the spine. Bone apposition rates, % new bone formation, % bone‐implant contact, and % graft resorption were quantified at 8, 12, and 24 weeks post surgery. Computed Tomography (CT) was used to grade the formation of fusion bridges between vertebrae. Results showed no significant difference in bone apposition rates, % new bone formation, and % bone‐implant contact when the two materials were compared. However, at 8 weeks, a significantly higher CT score was obtained in the SiCaP(+) group (0.83 ± 0.17) when compared with the SiCaP group (0.17 ± 0.17; p = 0.027). Significantly less scaffold remained in the SiCaP(+) group at 12 weeks (p = 0.018). Both SiCaP and SiCaP(+) formulations augmented bone formation. Increasing the strut porosity did not significantly increase bone formation however, at 8 weeks it promoted the formation of more highly mineralized bone resulting in a significantly higher CT score, suggesting the bone tissue formed was more mature. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 805–814, 2017.
Study of smart antibacterial PCL‐xFe3O4 thin films using mouse NIH‐3T3 fibroblast cells in vitro
Authors: Pai B Ganesh , Kulkarni Ajay V. , Jain Shilpee
Published: January 2016

Surface energy plays a major role in prokaryotic and eukaryotic cell interactions with biomedical devices. In the present study, poly(ε‐caprolactone)‐xFe3O4 nanoparticles (PCL‐xFO NPs; x = 0, 10, 20, 30, 40, 60 wt% FO concentration in PCL) composite thin films were developed for skin tissue regeneration. The surface properties in terms of roughness, surface energy, wettability of the thin films were altered with the incorporation of Fe3O4 NPs. These thin films show antimicrobial properties and cyto‐compatibility with NIH 3T3 mouse embryonic fibroblast cells. The porosity and thickness of the films were controlled by varying RPM of the spin coater. Interestingly, at 1000 RPM the roughness of the film decreased with increasing concentrations of FO NPs in PCL, whereas the surface energy increased with increasing FO NPs concentrations. Furthermore, the spreading of NIH‐3T3 cells grown on PCL‐xFO thin films was less as compared to control (TCPS), however cells overcame this effect after 48 h of seeding and cells spread similarly to those grown on TCPS after 48 h. Also, the incorporation of FO NPs in thin films induced inner membrane permeabilization in E. coli bacteria leading to bacterial cell death. The viability of E. coli bacteria decreased with increasing concentration of FO NPs in PCL. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 795–804, 2017.
Neurotrophin-3 Induces BMP-2 and VEGF Activities and Promotes the Bony Repair of Injured Growth Plate Cartilage and Bone in Rats
Authors: Su Yu-Wen , Chung Rosa , Ruan Chun-Sheng , Chim Shek Man , Kuek Vincent , Dwivedi Prem P , Hassanshahi Mohammadhossein , Chen Ke-Ming , Xie Yangli , Chen Lin , Foster Bruce K , Rosen Vicki , Zhou Xin-Fu , Xu Jiake , Xian Cory J
Published: January 2016

Injured growth plate is often repaired by bony tissue causing bone growth defects, for which the mechanisms remain unclear. Because neurotrophins have been implicated in bone fracture repair, here we investigated their potential roles in growth plate bony repair in rats. After a drill-hole injury was made in the tibial growth plate and bone, increased injury site mRNA expression was observed for neurotrophins NGF, BDNF, NT-3, and NT-4 and their Trk receptors. NT-3 and its receptor TrkC showed the highest induction. NT-3 was localized to repairing cells, whereas TrkC was observed in stromal cells, osteoblasts, and blood vessel cells at the injury site. Moreover, systemic NT-3 immunoneutralization reduced bone volume at injury sites and also reduced vascularization at the injured growth plate, whereas recombinant NT-3 treatment promoted bony repair with elevated levels of mRNA for osteogenic markers and bone morphogenetic protein (BMP-2) and increased vascularization and mRNA for vascular endothelial growth factor (VEGF) and endothelial cell marker CD31 at the injured growth plate. When examined in vitro, NT-3 promoted osteogenesis in rat bone marrow stromal cells, induced Erk1/2 and Akt phosphorylation, and enhanced expression of BMPs (particularly BMP-2) and VEGF in the mineralizing cells. It also induced CD31 and VEGF mRNA in rat primary endothelial cell culture. BMP activity appears critical for NT-3 osteogenic effect in vitro because it can be almost completely abrogated by co-addition of the BMP inhibitor noggin. Consistent with its angiogenic effect in vivo, NT-3 promoted angiogenesis in metatarsal bone explants, an effect abolished by co-treatment with anti-VEGF. This study suggests that NT-3 may be an osteogenic and angiogenic factor upstream of BMP-2 and VEGF in bony repair, and further studies are required to investigate whether NT-3 may be a potential target for preventing growth plate faulty bony repair or for promoting bone fracture healing. © 2016 American Society for Bone and Mineral Research.
Class I and IIa HDACs Mediate HIF-1α Stability Through PHD2-Dependent Mechanism, While HDAC6, a Class IIb Member, Promotes HIF-1α Transcriptional Activity in Nucleus Pulposus Cells of the Intervertebral Disc
Authors: Schoepflin Zachary R , Shapiro Irving M , Risbud Makarand V
Published: January 2016

The objective of this study was to determine the role of histone deacetylases (HDACs) in regulating HIF-1α protein stability and activity in nucleus pulposus (NP) cells. Treatment of NP cells with pan-HDAC inhibitor TSA resulted in decreased HIF-1α levels under both normoxia and hypoxia in a dose-dependent fashion. TSA-mediated HIF-1α degradation was rescued by concomitant inhibition of not only the 26S proteasome but also PHD2 function. Moreover, TSA treatment of PHD2−/− cells had little effect on HIF-1α levels, supporting the notion that inhibition of PHD2 function by HDACs contributed to HIF-1α stabilization. Surprisingly, class-specific HDAC inhibitors did not affect HIF-1α protein stability, indicating that multiple HDACs controlled HIF-1α stability by regulating HIF-1α-PHD2 interaction in NP cells. Interestingly, lower-dose TSA that did not affect HIF-1α stability decreased its activity and target gene expression. Likewise, rescue of TSA-mediated HIF-1α protein degradation by blocking proteasomal or PHD activity did not restore HIF-1 activity, suggesting that HDACs independently regulate HIF-1α stability and activity. Noteworthy, selective inhibition of HDAC6 and not of class I and IIa HDACs decreased HIF-1-mediated transcription under hypoxia to a similar extent as lower-dose TSA, contrasting the reported role of HDAC6 as a transcriptional repressor in other cell types. Moreover, HDAC6 inhibition completely blocked TSA effects on HIF-1 activity. HDAC6 associated with and deacetylated HSP90, an important cofactor for HIF-1 function in NP cells, and HDAC6 inhibition decreased p300 transactivation in NP cells. Taken together, these results suggest that although multiple class I and class IIa HDACs control HIF-1 stability, HDAC6, a class IIb HDAC, is a novel mediator of HIF-1 activity in NP cells possibly through promoting action of critical HIF-1 cofactors. © 2016 American Society for Bone and Mineral Research.
Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization
Authors: Lu Xuanyu , Fukumoto Satoshi , Yamada Yoshihiko , Evans Carla A , Diekwisch Thomas GH , Luan Xianghong
Published: January 2016

Matrix molecules such as the enamel-related calcium-binding phosphoprotein ameloblastin (AMBN) are expressed in multiple tissues, including teeth, bones, and cartilage. Here we have asked whether AMBN is of functional importance for timely long bone development and, if so, how it exerts its function related to osteogenesis. Adolescent AMBN-deficient mice (AMBNΔ5–6) suffered from a 33% to 38% reduction in femur length and an 8.4% shorter trunk spinal column when compared with WT controls, whereas there was no difference between adult animals. On a cellular level, AMBN truncation resulted in a shortened growth plate and a 41% to 49% reduction in the number of proliferating tibia chondrocytes and osteoblasts. Bone marrow stromal cells (BMSCs) isolated from AMBN mutant mice displayed defects in proliferation and differentiation potential as well as cytoskeleton organization. Osteogenesis-related growth factors, such as insulin-like growth factor 1 (IGF1) and BMP7, were also significantly (46% to 73%) reduced in AMBN-deficient BMSCs. Addition of exogenous AMBN restored cytoskeleton structures in AMBN mutant BMSCs and resulted in a dramatic 400% to 600% increase in BMP2, BMP7, and Col1A expression. Block of RhoA diminished the effect of AMBN on osteogenic growth factor and matrix protein gene expression. Addition of exogenous BMP7 and IGF1 rescued the proliferation and differentiation potential of AMBN-deficient BMSCs. Confirming the effects of AMBN on long bone growth, back-crossing of mutant mice with full-length AMBN overexpressors resulted in a complete rescue of AMBNΔ5–6 bone defects. Together, these data indicate that AMBN affects extracellular matrix production and cell adhesion properties in the long bone growth plate, resulting in altered cytoskeletal dynamics, increased osteogenesis-related gene expression, as well as osteoblast and chondrocyte proliferation. We propose that AMBN facilitates rapid long bone growth and an important growth spurt during the skeletogenesis of adolescent tooth-bearing vertebrates. © 2016 American Society for Bone and Mineral Research.
Regulation of Sclerostin Expression in Multiple Myeloma by Dkk-1: A Potential Therapeutic Strategy for Myeloma Bone Disease
Authors: Eda Homare , Santo Loredana , Wein Marc N , Hu Dorothy Z , Cirstea Diana D , Nemani Neeharika , Tai Yu-Tzu , Raines Sarah E , Kuhstoss Stuart Allen , Munshi Nikhil C , Kronenberg Henry M , Raje Noopur S
Published: January 2016

Sclerostin is a potent inhibitor of osteoblastogenesis. Interestingly, newly diagnosed multiple myeloma (MM) patients have high levels of circulating sclerostin that correlate with disease stage and fractures. However, the source and impact of sclerostin in MM remains to be defined. Our goal was to determine the role of sclerostin in the biology of MM and its bone microenvironment as well as investigate the effect of targeting sclerostin with a neutralizing antibody (scl-Ab) in MM bone disease. Here we confirm increased sclerostin levels in MM compared with precursor disease states like monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM. Furthermore, we found that a humanized MM xenograft mouse model bearing human MM cells (NOD-SCID.CB17 male mice injected intravenously with 2.5 million of MM1.S-Luc-GFP cells) demonstrated significantly higher concentrations of mouse-derived sclerostin, suggesting a microenvironmental source of sclerostin. Associated with the increased sclerostin levels, activated β-catenin expression levels were lower than normal in MM mouse bone marrow. Importantly, a high-affinity grade scl-Ab reversed osteolytic bone disease in this animal model. Because scl-Ab did not demonstrate significant in vitro anti-MM activity, we combined it with the proteasome inhibitor carfilzomib. Our data demonstrated that this combination therapy significantly inhibited tumor burden and improved bone disease in our in vivo MM mouse model. In agreement with our in vivo data, sclerostin expression was noted in marrow stromal cells and osteoblasts of MM patient bone marrow samples. Moreover, MM cells stimulated sclerostin expression in immature osteoblasts while inhibiting osteoblast differentiation in vitro. This was in part regulated by Dkk-1 secreted by MM cells and is a potential mechanism contributing to the osteoblast dysfunction noted in MM. Our data confirm the role of sclerostin as a potential therapeutic target in MM bone disease and provides the rationale for studying scl-Ab combined with proteasome inhibitors in MM. © 2016 American Society for Bone and Mineral Research.
Investigation of the Effect of Some Optically Active Imine Compounds on the Enzyme Activities of hCA‐I and hCA‐II under In Vitro Conditions: An Experimental and Theoretical Study
Authors: Tektas Osman , Akkemik Ebru , Baykara Haci
Published: January 2016

Inhibitors of carbonic anhydrase (hCA; EC 4.2.1.1) are used as medicines for many diseases. Therefore, they are very important. In this study, a known series of Schiff bases were synthesized and their effects on the activities of hCA‐I and hCA‐II, which are cytosolic isoenzymes of carbonic anhydrase, were investigated under in vitro conditions. The synthesized compounds (H1, H2, H3, and H4) were found to cause inhibition on enzyme activities of hCA‐1 and hCA‐II. IC50 values of H1, H2, H3, and H4 compounds were 140, 88, 201, and 271 μM for hCA‐I enzyme activity and 134, 251, 79, and 604 μM for hCA‐II enzyme activity, respectively. The synthesized Schiff bases were characterized by several methods, including 1H NMR, FT‐IR, elemental analysis, and polarimetric measurements. Correlation coefficient square values (R2) of comparison of the theoretical and experimental 1H NMR shifts for H1, H2, H3, and H4 compounds were found as 0.9781, 0.9814, 0.9758, and 0.8635, respectively.
Venous access for hematopoietic progenitor cell collection: An international survey by the ASFA HPC donor subcommittee
Authors: O'Leary Mandy Flannery , Dunbar Nancy M. , Kim Haewon C. , Draper Nicole L. , Linenberger Michael , Schwartz Joseph , Miller Yvette , Murtaugh Ally , West F. Bernadette , Fernando Leonor P. , Park Yara A.
Published: January 2016

Purpose:

Hematopoietic Progenitor Cell (HPC) collection by apheresis is performed in patients and donors to obtain HPCs for transplantation. Although studies have shown these procedures to be safe, successful collection cannot be performed without establishment of venous access. This project's objective was to ascertain the current practices of donor vein assessment and central venous catheter (CVC) usage. Methods: The American Society for Apheresis (ASFA) HPC subcommittee created an electronic survey about precollection vein assessment and line placement, care, and removal in autologous and allogeneic donors. It was distributed to >5,000 possible participants, with one response analyzed per institution. Results: One hundred centers performing autologous and/or allogeneic procedures provided adequate responses for analysis. Donor vein assessment is most often performed by apheresis staff more than 1 week prior to collection. For patients with questionable access, the next step performed most often is secondary assessment for autologous procedures and CVC placement for allogeneic procedures. Most centers use interventional radiology to place CVCs in jugular veins on collection day with placement verification through electronic medical records. Verbal and written postinsertion CVC care instructions are routinely provided. The apheresis team frequently provides postinsertion CVC care for autologous patients. Heparin is used most often for CVC lock. When used, tissue plasminogen activator is usually instilled for up to 60 min. Conclusion: These data summarize the largest single survey of donor vein assessment at institutions performing HPC collections by apheresis. The variations identified in donor venous access practice warrant further investigation and consensus to establish best practices. J. Clin. Apheresis 31:529–534, 2016. © 2015 Wiley Periodicals, Inc.
Switching Opioid‐Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics
Authors: Glue Paul , Cape Gavin , Tunnicliff Donna , Lockhart Michelle , Lam Fred , Gray Andrew , Hung Noelyn , Hung C. Tak , Harland Sarah , Devane Jane , Howes John , Weis Holger , Friedhoff Lawrence
Published: January 2016

The aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow‐release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12–24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half‐life of 59 hours. The most frequent treatment‐emergent non‐OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine.
Petersen Cores and the Oddness of Cubic Graphs
Authors: Jin Ligang , Steffen Eckhard
Published: January 2016

Let G be a bridgeless cubic graph. Consider a list of k 1‐factors of G. Let be the set of edges contained in precisely i members of the k 1‐factors. Let be the smallest over all lists of k 1‐factors of G. We study lists by three 1‐factors, and call with a ‐core of G. If G is not 3‐edge‐colorable, then . In Steffen (J Graph Theory 78 (2015), 195–206) it is shown that if , then is an upper bound for the girth of G. We show that bounds the oddness of G as well. We prove that . If , then every ‐core has a very specific structure. We call these cores Petersen cores. We show that for any given oddness there is a cyclically 4‐edge‐connected cubic graph G with . On the other hand, the difference between and can be arbitrarily big. This is true even if we additionally fix the oddness. Furthermore, for every integer , there exists a bridgeless cubic graph G such that .
Aggregate and hospital‐level impact of national guidelines on diagnostic resource utilization for children with pneumonia at children's hospitals
Authors: Parikh Kavita , Hall Matt , Blaschke Anne J. , Grijalva Carlos G. , Brogan Thomas V. , Neuman Mark I. , Williams Derek J. , Gerber Jeffrey S. , Hersh Adam L. , Shah Samir S.
Published: January 2016

BACKGROUND

National guidelines for the management of community‐acquired pneumonia (CAP) in children were published in 2011. These guidelines discourage most diagnostic testing for outpatients, as well as repeat testing for hospitalized patients who are improving. We sought to evaluate the temporal trends in diagnostic testing associated with guideline implementation among children with CAP.

METHODS

Children 1 to 18 years old who were discharged with pneumonia after emergency department (ED) evaluation or hospitalization from January 1, 2008 to June 30, 2014 at any of 32 children's hospitals participating in the Pediatric Health Information System were included. We excluded children with complex chronic conditions and those requiring intensive care or who underwent early pleural drainage. We compared use of diagnostic testing (blood culture, complete blood count [CBC], C‐reactive protein [CRP], and chest radiography [CXR]) before and after release of the guidelines, and assessed for temporal trends using interrupted time series analysis. We also calculated the cost impact of these changes on diagnostic utilization and evaluated the variability of the guideline's impact across hospitals.

RESULTS

Overall, 220,539 patients were included; 53% were male and the median age was 4 years (interquartile range, 2–7). For patients discharged from the ED with CAP, diagnostic utilization rates for blood culture, CBC, CRP, and CXR were higher after guideline publication compared with expected utilization rates without guidelines. In contrast, initial testing and repeat testing among patients hospitalized with CAP was lower after guideline publication. There were modest reductions in estimated costs associated with these changes. However, wide variability was observed in the impact of the guidelines across hospitals.

CONCLUSIONS

Publication of national pneumonia guidelines in 2011 was associated with modest changes in diagnostic testing for children with CAP. However, the changes varied across hospitals, and the financial impact was modest. Local implementation efforts are warranted to ensure widespread guideline adherence. Journal of Hospital Medicine 2016;11:317–323. © 2016 Society of Hospital Medicine
An assessment of ancient DNA preservation in Holocene–Pleistocene fossil bone excavated from the world heritage Naracoorte Caves, South Australia
Authors: Grealy Alicia , Macken Amy , Allentoft Morten E. , Rawlence Nicolas J. , Reed Elizabeth , Bunce Michael
Published: January 2016

Although there is a long history of research into the fossil deposits of the Naracoorte Caves (South Australia), ancient DNA (aDNA) has not been integrated into any palaeontological study from this World Heritage site. Here, we provide the first evidence of aDNA preservation in Holocene‐ and Pleistocene‐aged fossil bone from a deposit inside Robertson Cave. Using a combination of metabarcoding and shotgun next‐generation sequencing approaches, we demonstrate that aDNA from diverse taxa can be retrieved from bulk bone as old as 18 600 cal a BP. However, the DNA is highly degraded and contains a lower relative proportion of endogenous sequences in bone older than 8400 cal a BP. Furthermore, modelling of DNA degradation suggests that the decay rate is rapid, and predicts a very low probability of obtaining informative aDNA sequences from extinct megafaunal bones from Naracoorte (ca. 50 000 cal a BP). We also provide new information regarding the past faunal biodiversity of Robertson Cave, including families that have not been formerly described in the fossil record from here before. Collectively, these data demonstrate the potential for future aDNA studies to be conducted on material from Naracoorte, which will aid in the understanding of faunal turnover in southern Australia.
The onset of ultrashort pulse‐induced nanogratings
Authors: Zimmermann Felix , Plech Anton , Richter Sören , Tünnermann Andreas , Nolte Stefan
Published: January 2016

The fundamental formation process of nanogratings induced by focused ultrashort laser pulses inside the bulk of transparent materials is still object of intense debate. In particular the initial evolutionary steps, including the formation of anisotropic pores, alignment and arrangement in highly periodic grating planes could not been clarified up to now. To this end we have performed a comprehensive investigation of this process by optical retardance measurements, small‐angle X‐ray scattering, and focused ion beam milling in combination with scanning electron microscopy. The results show that the formation of nanogratings starts with isotropic, deterministic voids after the first incident laser pulse which start to elongate perpendicular to the laser scan direction with further illumination and the appearance of cracks along the scan direction. For increasing pulse overlap these cracks as well as randomly aligned voids build the template for the subsequent pore growth perpendicular to the laser polarization. The process of grating formation and subsequent period reduction occurs via increasing number of sheets and mutual realignment forming a more porous glass matrix.

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A New Generation Co‐Assembled Small Molecular Gel with Polyaniline: Exciting Mechanical, Electronic and Photovoltaic Properties
Authors: Chakraborty Priyadarshi , Bairi Partha , Nandi Arun K.
Published: January 2016

Folic acid (F), Fmoc‐protected phenylalanine (FP) and 5,5′‐(1,3,5,7‐tetraoxopyrrolo[3,4‐f]isoindole‐2,6‐diyl) diisophthalic acid (PMDIG) are used to produce co‐assembled gels with polyaniline(PANI). The formation of PANI inside the gel matrices are confirmed by FTIR and UV‐vis spectroscopy. UV‐vis spectra also exhibit the polaron band transitions of the doped PANI. Both F‐PANI and PMDIG‐PANI gels exhibit fibrillar network morphogy but the branching is more in the F‐PANI gel. The FP‐PANI gel however exhibits nanotubular morphology. The dc conductivity values of F‐PANI, FP‐PANI and PMDIG‐PANI xerogels are 0.14 × 10−4, 0.12 × 10−1 and 0.3 × 10−4 S/cm, respectively. The current–voltage (I–V) curves of the F‐PANI gel shows a negative differential resistance(NDR) property both at forward and backward bias. The I–V property of the FP‐PANI xerogel resembles to the behavior of a semiconductor‐metal junction and that of PMDIG‐PANI xerogel exhibits a signature of rectification property. A dye‐sensitized solar cell is also fabricated using the PMDIG‐PANI gel with a power conversion efficiency of 0.1%.
The Role of Molecular Interactions in Controlling Methanol Diffusion in Polyimides: A Time‐Resolved FTIR Spectroscopy Investigation
Authors: Musto Pellegrino , La Manna Pietro , Pannico Marianna
Published: January 2016

Polyimides are a well‐known class of high‐performance polymers with excellent properties and a wide range of applications, especially as membranes for gas and liquid separation. In this contribution a molecular level description of the methanol diffusion in three different polyimides is reported. Two commercial polyimides (PMDA‐ODA and Ultem 1000) and a third one synthetized ad‐hoc (6FDA‐ODA) were examined in detail by time‐resolved FTIR spectroscopy supplemented with gravimetric analysis. Complementary approaches were employed for the interpretation of the spectral data [difference spectroscopy (DS) and least‐squares curve fitting (LSCF)]. Information about the overall diffusivity, the interactions and the dynamics of the molecular species in the polymer/penetrant systems were provided.
Chiral Optical Response of Achiral and Enantiomeric Guests in Syndiotactic Polystyrene Films
Authors: Ianniello Graziella , Lepera Eugenia , Rizzo Paola
Published: January 2016

Circular dichroism of achiral (azulene and 4‐nitro‐aniline) and non‐racemic, enantiomeric molecules (carvone), being guests of s‐PS films crystallized with a non racemic guest, have been studied. Surprisingly the chiral response of the considered achiral guests is definitely higher than for the chirality‐inducing non‐racemic guest (carvone). This clearly indicates that the origin of the chiral‐optical response is extrinsic to the site of photon absorption. As for the circular dichroism of non‐racemic, enantiomeric guest molecules, after desorption and renewed absorption in sPS films, it has been observed that chiral response does not depend on their R or S molecular chirality but essentially only on the polymer host supramolecular chirality.
Nanoporous Semicrystalline Syndiotactic Polystyrene with Sulfonated Amorphous Phase, for a Fast and Efficient Removal of VOC Pollutant Traces From Water
Authors: Daniel Christophe , Pellegrino Marina , Borriello Anna , Venditto Vincenzo
Published: January 2016

Syndiotactic polystyrene films and aerogels with nanoporous crystalline phase and sulfonated amorphous phase have been prepared and characterized. The nanoporous nature of the crystalline phase confers to these materials a high solubility of volatile organic compounds (VOCs) from aqueous solutions even at low VOC concentrations while the sulfonation of the amorphous phase enhance the VOC sorption kinetics. These combined properties make these materials particularly interesting for a potential use as a sorption medium to remove traces of pollutants from water. Different aspects relative to the preparation, the structure and the transport properties of these innovative polymeric materials are described.
Cylindromatosis—A Protective Molecule against Liver Diseases
Authors: Hellerbrand Claus , Massoumi Ramin
Published: January 2016

Cylindromatosis (CYLD) is a deubiquitination enzyme involved in the regulation of different cellular processes including inflammation, fibrosis, and cancer. The function of CYLD is via deubiquitination of specific substrates in different signaling pathways including NF‐κB, Notch, and JNK. CYLD contributes to hepatic homeostasis and restoration upon liver injury. Mutation or disruption of the activity of CYLD in animals aggravates acute as well as chronic liver injury and promotes development and progression of hepatocellular cancer. This is mediated by a shift of the balance toward pro‐inflammatory, pro‐fibrogenic, and pro‐oncogenic pathways. In this review, we will explain the liver‐associated signaling pathways that CYLD regulates in hepatocytes and nonparenchymal liver cells under physiological and pathological conditions. We will also describe the most recent findings concerning CYLD‐mediated downstream signaling in the liver in situations such as injury, infection, inflammation, and cancer. Furthermore, we will discuss the potential of novel diagnostic tools and treatment strategies utilizing CYLD and its target genes.
Fructose and glucose combined with free fatty acids induce metabolic disorders in HepG2 cell: A new model to study the impacts of high‐fructose/sucrose and high‐fat diets in vitro
Authors: Zhao Liang , Guo Xiaoxuan , Wang Ou , Zhang Hongjuan , Wang Yong , Zhou Feng , Liu Jia , Ji Baoping
Published: January 2016

Scope

This work investigated the underlying mechanism of high‐fructose/sucrose and high‐fat diets, which rapidly induce metabolic syndrome in vivo, via a new cell model.

Methods and results

Glucose and/or fructose were used to induce the human hepatoma cell (HepG2) in the presence of palmitic acid, oleic acid, or combined fatty acids (CFA) for 24 h. The alterations in lipid and uric acid production, glucose metabolism, oxidative status, and related genes and proteins were monitored. The cell model that featured metabolic disorders was established by treatment of 10 mM glucose and 15 mM fructose plus 1 mM CFA. Results showed that palmitic acid mainly induced insulin resistance, oxidative stress, and triglyceride (TG) secretion, whereas oleic acid mainly contributed to intracellular TG. Fructose was mainly responsible for uric acid and cholesterol production. In addition, fructose synergistically elevated the intra‐ and extracellular TG and extracellular malonaldehyde with glucose and CFA. Regulations of genes and proteins associated with carbohydrate metabolism and lipogenesis partially explained the action of fructose in inducing the metabolic disorders in cell.

Conclusion

The combination of glucose, fructose, and CFA could successfully induce metabolic disorders in HepG2 cells, including dyslipidemia, insulin resistance, hyperuricemia, and oxidative stress.
Di(ethylene glycol) methyl ether methacrylate (DEGMEMA)‐derived gels align small organic molecules in methanol
Authors: García Manuela E. , Woodruff Shannon R. , Hellemann Erich , Tsarevsky Nicolay V. , Gil Roberto R.
Published: January 2016

Residual dipolar couplings (RDCs) constitute an important NMR parameter for structural elucidation in all areas of chemistry. In this study, di(ethylene glycol) methyl ether methacrylate (DEGMEMA)‐based gels are introduced as alignment media for the measurement of RDCs of small organic molecules in polar solvents such as methanol. The low viscosity of methanol permits the execution of J‐scaled BIRD HSQC experiments that yield very sharp lines in anisotropic conditions. The gels have excellent mechanical properties, and their compression and expansion in the swollen state can be reversed and performed multiple times. This process enables the easy loading and release of analytes. The excellent performance of these new aligning gels is demonstrated by analyzing the structure of the alkaloid retrorsine. Copyright © 2016 John Wiley & Sons, Ltd.
Rapid quantitative T2 mapping of the prostate using three‐dimensional dual echo steady state MRI at 3T
Authors: Dregely Isabel , Margolis Daniel A. J. , Sung Kyunghyun , Zhou Ziwu , Rangwala Novena , Raman Steven S. , Wu Holden H.
Published: January 2016

Purpose

To develop and evaluate a rapid three‐dimensional (3D) quantitative T2 mapping method for prostate cancer imaging using dual echo steady state (DESS) MRI at 3T.

Methods

In simulations, DESS‐T2 mapping in the presence of T1 and
variations was evaluated. In a phantom and in healthy volunteers (n = 4), 3D DESS‐T2 mapping was compared with a two‐dimensional turbo spin echo (TSE) approach. In volunteers and a pilot patient study (n = 29), quantitative T2 in normal prostate anatomical zones and in suspected cancerous lesions was evaluated.

Results

The simulated bias for DESS‐T2 was < 2% (5%) for typically observed T1 (
) variations. In phantoms and in vivo, high correlation of DESS‐T2 and TSE‐T2 (r2 = 0.98 and 0.88, P < 0.001) was found. DESS‐T2 in the normal peripheral zone and transition zone was 115 ± 26 ms and 64 ± 7 ms, respectively, in healthy volunteers and 129 ± 39 ms and 83 ± 12 ms, respectively, in patients. In suspected cancerous lesions, DESS‐T2 was 72 ± 14 ms, which was significantly decreased from the normal peripheral zone (P < 0.001) but not from the transition zone.

Conclusion

Rapid 3D T2 mapping in the entire prostate can be performed in 1 min using DESS MRI. Magn Reson Med 76:1720–1729, 2016. © 2016 International Society for Magnetic Resonance in Medicine
Noninvasive and repetitive measurement of cellular metabolite from human osteosarcoma cells (MG‐63) using 3.0 tesla proton (1H) MR spectroscopy
Authors: Kang Bok‐Man , Mun Chi‐Woong , Chun Song‐I , Kim Tae‐hyung , Son Doo‐Beum , Kim Hong‐Dae
Published: January 2016

Purpose

This study suggests a noninvasive and repetitive measurement method using 1H magnetic resonance spectroscopy to monitor changes in cellular metabolites within a single sample.

Methods

Longitudinal acquisition of cellular metabolites from three‐dimensional cultured human osteosarcoma (MG‐63) cells was conducted using 3.0 Tesla 1H MRS for 2 weeks at three time points: days 1, 7, and 14. During the MR spectroscopy (MRS) scan, cell specimen temperatures were kept constant at 37°C by a lab‐developed magnetic resonance compatible thermostatic device. A DNA assay and live/dead staining of the cell specimens were carried out at each time point to verify the MRS measurements.

Results

Cell viability in the proposed device did not significantly differ from that of cells in a conventional incubator (P = 0.946). Cell proliferation and choline concentration increased during the first week, but remained constant during the second week. Lactate did not change during the first week, but increased during the second week. Likewise, cell viability remained constant until day 7, then decreased.

Conclusion

The proposed MRS technique results in a survivable environment for longitudinal studies of cells and provides a new way to measure metabolomic changes over time in single specimens of cells. Magn Reson Med 76:1912–1918, 2016. © 2016 International Society for Magnetic Resonance in Medicine
On the accuracy and precision of cardiac magnetic resonance T2 mapping: A high‐resolution radial study using adiabatic T2 preparation at 3 T
Authors: Bano Wajiha , Feliciano Hélène , Coristine Andrew J. , Stuber Matthias , van Heeswijk Ruud B.
Published: January 2016

Purpose

The goal of this study was to characterize the accuracy and precision of cardiac T2 mapping as a function of different factors including low signal‐to‐noise ratio (SNR), imaging in systole, and off‐resonance frequencies.

Methods

Bloch equation and Monte Carlo simulations were used to determine the influence of SNR and the choice of T2 preparation echo time (TET2prep) increments on the accuracy and precision of high‐resolution radial cardiac T2 mapping at 3.0 T. Healthy volunteers were scanned to establish the difference in precision and inter‐ and intraobserver variability between T2 mapping in diastole and systole, as well as the effect of SNR and off‐resonance frequencies on the accuracy of T2 maps.

Results

The simulations demonstrated that a TET2prep increment of ∼0.75 times the T2 value of interest optimally increases the precision of the T2 fit. Systolic T2 maps were found to have a higher precision (P = 0.002), but similar inter‐ and intraobserver variability compared with diastolic T2 maps, whereas off‐resonance frequencies beyond ± 100 Hz cause a significant decrease in both accuracy and precision (P < 0.05).

Conclusion

This evaluation of the accuracy and precision of cardiac T2 mapping characterizes the major vulnerabilities of the technique and will help guide protocol definition of studies that include T2 mapping. Magn Reson Med 77:159–169, 2017. © 2016 Wiley Periodicals, Inc.
Thermal noise variance of a receive radiofrequency coil as a respiratory motion sensor
Authors: Andreychenko A. , Raaijmakers A.J.E. , Sbrizzi A. , Crijns S.P.M. , Lagendijk J.J.W. , Luijten P.R. , van den Berg C.A.T.
Published: January 2016

Purpose

Development of a passive respiratory motion sensor based on the noise variance of the receive coil array.

Methods

Respiratory motion alters the body resistance. The noise variance of an RF coil depends on the body resistance and, thus, is also modulated by respiration. For the noise variance monitoring, the noise samples were acquired without and with MR signal excitation on clinical 1.5/3 T MR scanners. The performance of the noise sensor was compared with the respiratory bellow and with the diaphragm displacement visible on MR images. Several breathing patterns were tested.

Results

The noise variance demonstrated a periodic, temporal modulation that was synchronized with the respiratory bellow signal. The modulation depth of the noise variance resulting from the respiration varied between the channels of the array and depended on the channel's location with respect to the body. The noise sensor combined with MR acquisition was able to detect the respiratory motion for every k‐space read‐out line.

Conclusion

Within clinical MR systems, the respiratory motion can be detected by the noise in receive array. The noise sensor does not require careful positioning unlike the bellow, any additional hardware, and/or MR acquisition. Magn Reson Med 77:221–228, 2017. © 2016 Wiley Periodicals, Inc.
Cost efficiency of mobile in‐network caching
Authors: Zhang Nan , Kimmerlin Maël , Costa‐Requena Jose , Hämmäinen Heikki
Published: January 2016

Mobile data volume is growing with an annual compound rate of 61% between 2014 and 2019. To cope with the data volume growth, a more dynamic and flexible network is needed. Caching has been deployed by both mobile network operators and content providers to reduce the load on centralized data centers and gateways. In addition, software‐defined networking (SDN) is a prominent solution to more flexibly and efficiently utilize the available network resources, especially in the mobile backhaul. However, installation of cache servers into the network means additional capital expenditure (CAPEX) and their daily operations incur operational expenses (OPEX). Thus, the change in cost of deploying and operating in‐network caching compared with data center caching is modeled in this paper using a Finnish Long‐Term Evolution reference network. In addition, this paper simulates both the SDN‐optimized in‐network caching system and data center caching, the results of which are utilized in the cost model. The simulation results show that, on average, in‐network caching compared with caching only in data centers reduces traffic load by 45% in the network and 6% in the gateways. The cost modeling indicates that in‐network caching reduces network‐related CAPEX by 1.53% and OPEX by 0.49% compared with caching only in data centers. Copyright © 2015 John Wiley & Sons, Ltd.
Review 10 trends impacting distance and continuing education, Part 2
Authors: Scull Reed , Thorup Jennifer , Howell Scott L.
Published: January 2016

Part of maintaining a leadership role involves spotting, synthesizing and analyzing trends that will impact the work of distance and continuing education. In last month's issue, we explained four top trends impacting distance and continuing education. In our second installment of the article, we describe six more trends you should know about for effective planning and program delivery.
Learn how Brandman University created a successful recruitment strategy
Authors: Racen Lindsay Amanda
Published: January 2016

Shelly Neal, Ph.D., is the vice chancellor of strategic initiatives at Brandman University, a nonprofit institution with a rich heritage of academic excellence and more than 50 years of experience serving nontraditional and adult students. Her division, which began as a one‐woman show at the school's San Diego campus ten years ago, has grown to a team of more than 30 professionals who are dedicated to building enrollments by creating strategic community and corporate partnerships.