bluuebunny/crossref_metadata_2025 huggingface dataset:
The Statistical Segment Length of DNA: Opportunities for Biomechanical Modeling in Polymer Physics and Next-Generation Genomics
Authors: Dorfman Kevin D.
Published: August 2017

The development of bright bisintercalating dyes for deoxyribonucleic acid (DNA) in the 1990s, most notably YOYO-1, revolutionized the field of polymer physics in the ensuing years. These dyes, in conjunction with modern molecular biology techniques, permit the facile observation of polymer dynamics via fluorescence microscopy and thus direct tests of different theories of polymer dynamics. At the same time, they have played a key role in advancing an emerging next-generation method known as genome mapping in nanochannels. The effect of intercalation on the bending energy of DNA as embodied by a change in its statistical segment length (or, alternatively, its persistence length) has been the subject of significant controversy. The precise value of the statistical segment length is critical for the proper interpretation of polymer physics experiments and controls the phenomena underlying the aforementioned genomics technology. In this perspective, we briefly review the model of DNA as a wormlike chain and a trio of methods (light scattering, optical or magnetic tweezers, and atomic force microscopy (AFM)) that have been used to determine the statistical segment length of DNA. We then outline the disagreement in the literature over the role of bisintercalation on the bending energy of DNA, and how a multiscale biomechanical approach could provide an important model for this scientifically and technologically relevant problem.
Stiffness Properties of Adventitia, Media, and Full Thickness Human Atherosclerotic Carotid Arteries in the Axial and Circumferential Directions
Authors: Hoffman Allen H. , Teng Zhongzhao , Zheng Jie , Wu Zheyang , Woodard Pamela K. , Billiar Kristen L. , Wang Liang , Tang Dalin
Published: August 2017

Arteries can be considered as layered composite material. Experimental data on the stiffness of human atherosclerotic carotid arteries and their media and adventitia layers are very limited. This study used uniaxial tests to determine the stiffness (tangent modulus) of human carotid artery sections containing American Heart Association type II and III lesions. Axial and circumferential oriented adventitia, media, and full thickness specimens were prepared from six human carotid arteries (total tissue strips: 71). Each artery yielded 12 specimens with two specimens in each of the following six categories; axial full thickness, axial adventitia (AA), axial media (AM), circumferential full thickness, circumferential adventitia (CA), and circumferential media (CM). Uniaxial testing was performed using Inspec 2200 controlled by software developed using labview. The mean stiffness of the adventitia was 3570 ± 667 and 2960 ± 331 kPa in the axial and circumferential directions, respectively, while the corresponding values for the media were 1070 ± 186 and 1800 ± 384 kPa. The adventitia was significantly stiffer than the media in both the axial (p = 0.003) and circumferential (p = 0.010) directions. The stiffness of the full thickness specimens was nearly identical in the axial (1540 ± 186) and circumferential (1530 ± 389 kPa) directions. The differences in axial and circumferential stiffness of media and adventitia were not statistically significant.
Myofibrils in Cardiomyocytes Tend to Assemble Along the Maximal Principle Stress Directions
Authors: Yuan Hongyan , Marzban Bahador , Kit Parker Kevin
Published: August 2017

The mechanisms underlying the spatial organization of self-assembled myofibrils in cardiac tissues remain incompletely understood. By modeling cells as elastic solids under active cytoskeletal contraction, we found a good correlation between the predicted maximal principal stress directions and the in vitro myofibril orientations in individual cardiomyocytes. This implies that actomyosin fibers tend to assemble along the maximal tensile stress (MTS) directions. By considering the dynamics of focal adhesion and myofibril formation in the model, we showed that different patterns of myofibril organizations in mature versus immature cardiomyocytes can be explained as the consequence of the different levels of force-dependent remodeling of focal adhesions. Further, we applied the mechanics model to cell pairs and showed that the myofibril organizations can be regulated by a combination of multiple factors including cell shape, cell–substrate adhesions, and cell–cell adhesions. This mechanics model can guide the rational design in cardiac tissue engineering where recapitulating in vivo myofibril organizations is crucial to the contractile function of the heart.
Functional vascularized lung grafts for lung bioengineering
Authors: Dorrello N. Valerio , Guenthart Brandon A. , O’Neill John D. , Kim Jinho , Cunningham Katherine , Chen Ya-Wen , Biscotti Mauer , Swayne Theresa , Wobma Holly M. , Huang Sarah X. L. , Snoeck Hans-Willem , Bacchetta Matthew , Vunjak-Novakovic Gordana
Published: August 2017

We propose a new approach to lung regeneration by replacement of damaged epithelium with full preservation of lung vasculature.
Tunable electroresistance and electro-optic effects of transparent molecular ferroelectrics
Authors: Zhang Zhuolei , Li Peng-Fei , Tang Yuan-Yuan , Wilson Andrew J. , Willets Katherine , Wuttig Manfred , Xiong Ren-Gen , Ren Shenqiang
Published: August 2017

A water-based approach grows molecular ferroelectric thin film with tunable electroresistance and electro-optic effect.
Perovskite nanocomposites as effective CO
2
-splitting agents in a cyclic redox scheme
Authors: Zhang Junshe , Haribal Vasudev , Li Fanxing
Published: August 2017

A methane-to-syngas selectivity of 96% and a CO yield of nearly 100% in CO
2
splitting were achieved over perovskite nanocomposites in a cyclic redox scheme.
Enhanced photovoltaic performance and stability with a new type of hollow 3D perovskite {en}FASnI
3
Authors: Ke Weijun , Stoumpos Constantinos C. , Zhu Menghua , Mao Lingling , Spanopoulos Ioannis , Liu Jian , Kontsevoi Oleg Y. , Chen Michelle , Sarma Debajit , Zhang Yongbo , Wasielewski Michael R. , Kanatzidis Mercouri G.
Published: August 2017

High-performance and good-stability hollow Sn-based perovskite solar cells using ethylenediammonium and formamidinium cations.
Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity
Authors: Komor Alexis C. , Zhao Kevin T. , Packer Michael S. , Gaudelli Nicole M. , Waterbury Amanda L. , Koblan Luke W. , Kim Y. Bill , Badran Ahmed H. , Liu David R.
Published: August 2017

Probing base editing outcomes leads to new C:G to T:A base editors with greater efficiency and product purity, and fewer indels.
β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease
Authors: Mittal Shuchi , Bjørnevik Kjetil , Im Doo Soon , Flierl Adrian , Dong Xianjun , Locascio Joseph J. , Abo Kristine M. , Long Elizabeth , Jin Ming , Xu Bing , Xiang Yang K. , Rochet Jean-Christophe , Engeland Anders , Rizzu Patrizia , Heutink Peter , Bartels Tim , Selkoe Dennis J. , Caldarone Barbara J. , Glicksman Marcie A. , Khurana Vikram , Schüle Birgitt , Park David S. , Riise Trond , Scherzer Clemens R.
Published: August 2017

Elucidating the risk of Parkinson's disease

High expression of the α-synuclein gene (
SNCA
) is a risk factor for Parkinson's disease (PD), but certain drugs may mitigate this risk. Mittal
et al.
ran a small-molecule screen to identify compounds that regulate levels of
SNCA
expression and found that several β2-adrenoreceptor (β2AR) agonists reduced them (see the Perspective by Snyder). These compounds modulated epigenetic marks at the
SNCA
gene, effectively suppressing
SNCA
transcription. The authors looked at the pharmaceutical history of more than 4 million Norwegians over an 11-year period and found a reduced risk of PD among those that were taking one of the β2AR agonists for other medical problems.

Science
, this issue p.
891
; see also p.
869
Global climatic drivers of leaf size
Authors: Wright Ian J. , Dong Ning , Maire Vincent , Prentice I. Colin , Westoby Mark , Díaz Sandra , Gallagher Rachael V. , Jacobs Bonnie F. , Kooyman Robert , Law Elizabeth A. , Leishman Michelle R. , Niinemets Ülo , Reich Peter B. , Sack Lawren , Villar Rafael , Wang Han , Wilf Peter
Published: August 2017

Leaf size, climate, and energy balance

Why does plant leaf size increase at lower latitudes, as exemplified by the evolutionary success of species with very large leaves in the tropics? Wright
et al.
analyzed leaf data for 7670 plant species, along with climatic data, from 682 sites worldwide. Their findings reveal consistent patterns and explain why earlier predictions from energy balance theory had only limited success. The authors provide a fully quantitative explanation for the latitudinal gradient in leaf size, with implications for plant ecology and physiology, vegetation modeling, and paleobotany.

Science
, this issue p.
917
A microtubule-organizing center directing intracellular transport in the early mouse embryo
Authors: Zenker J. , White M. D. , Templin R. M. , Parton R. G. , Thorn-Seshold O. , Bissiere S. , Plachta N.
Published: August 2017

How microtubules organize in embryos

Cell functions ranging from cell division to morphogenesis rely on microtubules, with microtubule-organizing centers serving as anchoring sites for their outgrowth. Although the centrosome organizes the microtubule cytoskeleton in most animal cells, this organelle is absent in early development. Using live-cell imaging, Zenker
et al.
found that the cells of the early mouse embryo are connected by stable microtubule bridges to direct the growth of microtubules within them. Microtubules emanating from the bridges help to guide transport of key proteins, including E-cadherin, to the cell membrane to control cell polarization during early development.

Science
, this issue p.
925
Response to Comment on “Active sites for CO
2
hydrogenation to methanol on Cu/ZnO catalysts”
Authors: Kattel Shyam , Ramírez Pedro J. , Chen Jingguang G. , Rodriguez José A. , Liu Ping
Published: August 2017

In their Comment on the our recent Report, Nakamura
et al
. argue that our x-ray photoelectron spectroscopy (XPS) analysis was affected by the presence of formate species on the catalyst surface. This argument is not valid because the reactant gases were evacuated at temperatures from 525 to 575 kelvin, conditions under which formate is not stable on the catalyst surface. An analysis of the XPS results obtained after exposing zinc oxide/copper (111) [ZnO/Cu(111)] surfaces to hydrogen (H
2
) and mixtures of carbon dioxide (CO
2
)/H
2
show an absence of carbon (C) 1s signal, no asymmetries in the oxygen (O) 1s peak, and a Zn:O intensity close to 1:1. Thus, the most active phase of these catalysts contained a ZnO-Cu interface.
Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19-9 blood markers
Authors: Kim Jungsun , Bamlet William R. , Oberg Ann L. , Chaffee Kari G. , Donahue Greg , Cao Xing-Jun , Chari Suresh , Garcia Benjamin A. , Petersen Gloria M. , Zaret Kenneth S.
Published: August 2017

THBS2 and CA19-9 markers in human blood improve detection of pancreatic ductal adenocarcinoma.
Detecting human coronary inflammation by imaging perivascular fat
Authors: Antonopoulos Alexios S. , Sanna Fabio , Sabharwal Nikant , Thomas Sheena , Oikonomou Evangelos K. , Herdman Laura , Margaritis Marios , Shirodaria Cheerag , Kampoli Anna-Maria , Akoumianakis Ioannis , Petrou Mario , Sayeed Rana , Krasopoulos George , Psarros Constantinos , Ciccone Patricia , Brophy Carl M. , Digby Janet , Kelion Andrew , Uberoi Raman , Anthony Suzan , Alexopoulos Nikolaos , Tousoulis Dimitris , Achenbach Stephan , Neubauer Stefan , Channon Keith M. , Antoniades Charalambos
Published: August 2017

Adipocyte size and lipid content in perivascular adipose tissue are inversely associated with coronary inflammation and atherosclerotic plaque burden in human patients.
HIF activation causes synthetic lethality between the
VHL
tumor suppressor and the
EZH1
histone methyltransferase
Authors: Chakraborty Abhishek A. , Nakamura Eijiro , Qi Jun , Creech Amanda , Jaffe Jacob D. , Paulk Joshiawa , Novak Jesse S. , Nagulapalli Kshithija , McBrayer Samuel K. , Cowley Glenn S. , Pineda Javier , Song Jiaxi , Wang Yaoyu E. , Carr Steven A. , Root David E. , Signoretti Sabina , Bradner James E. , Kaelin William G.
Published: August 2017

Dysregulated H3K27 demethylase activity in pVHL-deficient cells increases dependence on the EZH1 H3K27 methyltransferase.
The Role of BAFF System Molecules in Host Response to Pathogens
Authors: Sakai Jiro , Akkoyunlu Mustafa
Published: August 2017

The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the “BAFF system molecules.” BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development.
Localization of Double-Strand Break Repair Proteins to Viral Replication Compartments following Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Hollingworth Robert , Horniblow Richard D. , Forrest Calum , Stewart Grant S. , Grand Roger J.
Published: August 2017

Double-strand breaks (DSBs) in DNA are recognized by the Ku70/80 heterodimer and the MRE11-RAD50-NBS1 (MRN) complex and result in activation of the DNA-PK and ATM kinases, which play key roles in regulating the cellular DNA damage response (DDR). DNA tumor viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV) are known to interact extensively with the DDR during the course of their replicative cycles. Here we show that during lytic amplification of KSHV DNA, the Ku70/80 heterodimer and the MRN complex consistently colocalize with viral genomes in replication compartments (RCs), whereas other DSB repair proteins form foci outside RCs. Depletion of MRE11 and abrogation of its exonuclease activity negatively impact viral replication, while in contrast, knockdown of Ku80 and inhibition of the DNA-PK enzyme, which are involved in nonhomologous end joining (NHEJ) repair, enhance amplification of viral DNA. Although the recruitment of DSB-sensing proteins to KSHV RCs is a consistent occurrence across multiple cell types, activation of the ATM-CHK2 pathway during viral replication is a cell line-specific event, indicating that recognition of viral DNA by the DDR does not necessarily result in activation of downstream signaling pathways. We have also observed that newly replicated viral DNA is not associated with cellular histones. Since the presence and modification of these DNA-packaging proteins provide a scaffold for docking of multiple DNA repair factors, the absence of histone deposition may allow the virus to evade localization of DSB repair proteins that would otherwise have a detrimental effect on viral replication.

IMPORTANCE
Tumor viruses are known to interact with machinery responsible for detection and repair of double-strand breaks (DSBs) in DNA, although detail concerning how Kaposi's sarcoma-associated herpesvirus (KSHV) modulates these cellular pathways during its lytic replication phase was previously lacking. By undertaking a comprehensive assessment of the localization of DSB repair proteins during KSHV replication, we have determined that a DNA damage response (DDR) is directed to viral genomes but is distinct from the response to cellular DNA damage. We also demonstrate that although recruitment of the MRE11-RAD50-NBS1 (MRN) DSB-sensing complex to viral genomes and activation of the ATM kinase can promote KSHV replication, proteins involved in nonhomologous end joining (NHEJ) repair restrict amplification of viral DNA. Overall, this study extends our understanding of the virus-host interactions that occur during lytic replication of KSHV and provides a deeper insight into how the DDR is manipulated during viral infection.
Importance of Resolving Fungal Nomenclature: the Case of Multiple Pathogenic Species in the
Cryptococcus
Genus
Authors: Hagen Ferry , Lumbsch H. Thorsten , Arsic Arsenijevic Valentina , Badali Hamid , Bertout Sebastien , Billmyre R. Blake , Bragulat M. Rosa , Cabañes F. Javier , Carbia Mauricio , Chakrabarti Arunaloke , Chaturvedi Sudha , Chaturvedi Vishnu , Chen Min , Chowdhary Anuradha , Colom Maria-Francisca , Cornely Oliver A. , Crous Pedro W. , Cuétara Maria S. , Diaz Mara R. , Espinel-Ingroff Ana , Fakhim Hamed , Falk Rama , Fang Wenjie , Herkert Patricia F. , Ferrer Rodríguez Consuelo , Fraser James A. , Gené Josepa , Guarro Josep , Idnurm Alexander , Illnait-Zaragozi María-Teresa , Khan Ziauddin , Khayhan Kantarawee , Kolecka Anna , Kurtzman Cletus P. , Lagrou Katrien , Liao Wanqing , Linares Carlos , Meis Jacques F. , Nielsen Kirsten , Nyazika Tinashe K. , Pan Weihua , Pekmezovic Marina , Polacheck Itzhack , Posteraro Brunella , de Queiroz Telles Flavio , Romeo Orazio , Sánchez Manuel , Sampaio Ana , Sanguinetti Maurizio , Sriburee Pojana , Sugita Takashi , Taj-Aldeen Saad J. , Takashima Masako , Taylor John W. , Theelen Bart , Tomazin Rok , Verweij Paul E. , Wahyuningsih Retno , Wang Ping , Boekhout Teun
Published: August 2017

Cryptococcosis is a major fungal disease caused by members of the
Cryptococcus gattii
and
Cryptococcus neoformans
species complexes. After more than 15 years of molecular genetic and phenotypic studies and much debate, a proposal for a taxonomic revision was made.
The Potential Therapeutic Agent Mepacrine Protects Caco-2 Cells against Clostridium perfringens Enterotoxin Action
Authors: Freedman John C. , Hendricks Matthew R. , McClane Bruce A.
Published: August 2017

Clostridium perfringens
enterotoxin (CPE) causes the gastrointestinal (GI) symptoms of a common bacterial food poisoning and several nonfoodborne human GI diseases. A previous study showed that, via an undetermined mechanism, the presence of mepacrine blocks CPE-induced electrophysiologic activity in artificial membranes. The current study now demonstrates that mepacrine also inhibits CPE-induced cytotoxicity in human enterocyte-like Caco-2 cells and that mepacrine does not directly inactivate CPE. Instead, this drug reduces both CPE pore formation and CPE pore activity in Caco-2 cells. These results suggest mepacrine as a therapeutic candidate for treating CPE-mediated GI diseases.
Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence
Authors: Schallig Henk DFH , Tinto Halidou , Sawa Patrick , Kaur Harparkash , Duparc Stephan , Ishengoma Deus S , Magnussen Pascal , Alifrangis Michael , Sutherland Colin J
Published: August 2017

Background

Management of uncomplicatedPlasmodium falciparummalaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia and changing parasite susceptibility to ACT in Africa have now been well documented. Strategies that retain current ACT as efficacious treatments are urgently needed.

Methods

We present an open-label, randomised three-arm clinical trial protocol in three African settings representative of varying malaria epidemiology to investigate whether prolonged ACT-based regimens using currently available formulations can eliminate potentially resistant parasites. The protocol investigates whether a sequential course of two licensed ACT in 1080 children aged 6–120 months exhibits superior efficacy against acuteP. falciparummalaria and non-inferior safety compared with standard single-course ACT given to 540 children. The primary endpoint is PCR-corrected clinical and parasitological response at day 42 or day 63 of follow-up. Persistence of PCR-detectable parasitaemia at day 3 is analysed as a key covariate. Secondary endpoints include gametocytaemia, occurrence of treatment-related adverse events in the double-ACT versus single-ACT arms, carriage of molecular markers of drug resistance, drug kinetics and patient adherence to treatment.

Discussion

This protocol addresses efficacy and safety of sequential ACT regimens inP. falciparummalaria in Africa. The approach is designed to extend the useful life of this class of antimalarials with maximal impact and minimal delay, by deploying licensed medicines that could be swiftly implemented as sequential double ACT by National Malaria Control Programmes, before emerging drug resistance in Africa becomes a major threat to public health.
Intersectoral approaches and integrated services in achieving the right to health for refugees upon resettlement: a scoping review protocol
Authors: Javadi Dena , Langlois Etienne V , Ho Shirley , Friberg Peter , Tomson Göran
Published: August 2017

Introduction

Global insecurity and climate change are exacerbating the need for improved management of refugee resettlement services. International standards hold states responsible for the protection of the right of non-citizens to an adequate standard of physical and mental health while recognising the importance of social determinants of health. However, programmes to protect refugees’ right to health often lack coordination and monitoring. This paper describes the protocol for a scoping review to explore barriers and facilitators to the integration of health services for refugees; the content, process and actors involved in protecting refugee health; and the extent to which intersectoral approaches are leveraged to protect refugees’ right to health on resettlement, especially for vulnerable groups such as women and children.

Methods and analysis

Peer-reviewed (through four databases including MEDLINE, Web of Science, Global Health and PsycINFO) and grey literature were searched to identify programmes and interventions designed to promote refugee health in receiving countries. Two reviewers will screen articles and abstract data. Two frameworks for integration and intersectoral action will be applied to understand how and why certain approaches work while others do not and to identify the actors involved in achieving success at different levels of integration as defined by these frameworks.

Ethics and dissemination

Findings from the scoping review will be shared in relevant conferences and meetings. A brief will be created with lessons learnt from successful programmes to inform decision making in design of refugee programmes and services. Ethical approval is not required as human subjects are not involved.

Trial registration number

Registered on Open Science Framework athttps://osf.io/gt9ck/.
Update on dry cow therapy 2. measuring dry period performance
Authors: Biggs Andrew
Published: August 2017

This article, the second in a two‐part series on dry cow therapy, discusses practical approaches to targeting and justifying antibiotic dry cow therapy, with tips, tricks and challenges for initiating targeted/selective dry cow therapy on farm. The first part, published in the July/August issue of In Practice (Biggs 2017) described the evolution of knowledge around the dry period and provided an update on where knowledge, opinions and attitudes to antibiotic and non‐antibiotic approaches used in dry cow therapy have changed.
Workflow and factors associated with delay in the delivery of intra-arterial treatment for acute ischemic stroke in the MR CLEAN trial
Authors: Venema Esmee , Boodt Nikki , Berkhemer Olvert A , Rood Pleunie P M , van Zwam Wim H , van Oostenbrugge Robert J , van der Lugt Aad , Roos Yvo B W E M , Majoie Charles B L M , Lingsma Hester F , Dippel Diederik W J
Published: August 2017

Objective

The effect of intra-arterial treatment (IAT) for acute ischemic stroke is highly time-dependent. We investigated the delay of IAT and factors associated with such delay.

Methods

MR CLEAN was a randomized trial of IAT plus usual care versus usual care alone (n=500). With multivariable linear regression, we analyzed the effect of intravenous treatment, general anesthesia, off-hours and inter-hospital transfer on time to admission to the emergency department (ED) of the intervention center and time to treatment. Furthermore, we assessed compliance with a target of 75 min for time from ED to treatment, and calculated the potential absolute increase in the number of patients with a good outcome (modified Rankin Scale score ≤2) if this target had been achieved in all treated patients.

Results

Inter-hospital transfer prolonged time to ED by 140 min (95% CI 129 to 150) but reduced time from ED to treatment by 77 min (95% CI 64 to 91). Time from ED to treatment was increased by 19 min by general anesthesia (95% CI 5 to 33) and total time was increased by 23 min during off-hours (95% CI 6 to 40). The in-hospital target was achieved in 11.5% (22/192) of patients. Full compliance with the target time of 75 min from ED to treatment would have increased the proportion of patients with a good outcome by 7.6% (95% CI 6.7% to 8.5%).

Conclusion

Inter-hospital transfer is an important cause of delay in the delivery of IAT and every effort should be made to avoid transfers and reduce transfer-related delay. Furthermore, in-hospital workflow should be optimized to improve functional outcome after IAT.
Prolonged cerebral circulation time is more associated with symptomatic carotid stenosis than stenosis degree or collateral circulation
Authors: Hu Yong-Sin , Guo Wan-Yuo , Lee I-Hui , Chang Feng-Chi , Lin Chung-Jung , Lin Chun-Jen , Luo Chao-Bao , Wu Chih-Chun , Lee Han-Jui
Published: August 2017

Background and purpose

Current practice of revascularization for carotid stenosis (CS) primarily relies on symptoms and degree of stenosis. Other parameters, such as collateral circulation and cerebral circulation time (CCT), might influence the stroke risk in CS. This study was conducted to (1) investigate whether CCT is more associated with symptomatic CS than degree of stenosis and (2) elucidate the associations among the degree of stenosis, collateral status, and CCT.

Methods

From 2010 to 2016, 82 patients with unilateral CS were enrolled for DSA and divided into symptomatic and asymptomatic groups based on clinical presentation. CCT was defined as the difference between the time taken by the cavernous internal carotid artery and parietal vein to reach the maximal contrast medium intensities on lateral DSA. The degree of stenosis, collateral status, and CCT of the two groups were compared. Logistic regression analysis was performed to estimate the OR for symptomatic CS with the imaging variables.

Results

The symptomatic group had a significantly higher degree of stenosis and longer CCT. CCT (OR 1.95, p=0.013) was more associated with symptomatic CS than the degree of stenosis (OR 1.03, p=0.229), after adjustment for potential confounders—namely, age, sex, antithrombotic use, and collateral status. Symptomatic high grade CS with collaterals had a non-significantly shorter CCT than those without collaterals.

Conclusions

DSA derived CCT is more reflective of the hemodynamic differences between symptomatic and asymptomatic CS than degree of stenosis. Collaterals may not effectively reduce CCT in symptomatic high grade CS.
Impact of time to endovascular reperfusion on outcome differs according to the involvement of the proximal MCA territory
Authors: Hedderich Dennis M , Boeckh-Behrens Tobias , Friedrich Benjamin , Wiestler Benedikt , Wunderlich Silke , Zimmer Claus , Fischer Urs , Kleine Justus F , Kaesmacher Johannes
Published: August 2017

Background

The time interval between symptom onset and reperfusion is a major determinant of the benefit of endovascular therapy (ET) and patients’ outcome. The impact of time may be attenuated in patients with robust collaterals. However, not all regions in the middle cerebral artery (MCA) territory have access to collaterals.

Purpose

To evaluate if the involvement of the poorly collateralized proximal MCA territory has an impact on the degree of time dependency of patients’ outcome.

Methods

Patients with MCA occlusions treated with ET and involvement/sparing of the proximal striatocapsular MCA territory (SC+/SC−, each n=97) were matched according to their symptom onset to reperfusion times (SORTs). Correlation and impact of time on outcome was evaluated with strata of SC+/SC− using multivariate logistic regression models (LRMs), including interaction terms. Discharge National Institute of Health Stroke Scale (NIHSS-DIS) score <5 and discharge modified Rankin Scale (mRS-DIS) score ≤2 were prespecified outcome measures.

Results

A stronger correlation between all outcome measures (NIHSS-DIS/ΔNIHSS/mRS-DIS) and SORTs was found for SC+ patients than for SC−patients. SORTs were significant variables in LRMs for mRS-DIS score ≤2 and NIHSS-DIS score <5 in SC+ but not in SC− patients. Interaction of SC+ and SORTs was significant in LRMs for both endpoints.

Conclusion

Time dependency of outcome after ET is more pronounced if parts of the proximal MCA territory are affected. This may reflect the lack of collateralization in the striatocapsular region and a more stringent cell death with time. If confirmed, this finding may affect the selection of patients based on different time windows according to the territory at risk.
Tongue lacerations in a geriatric dog after bilateral inferior alveolar nerve blocks with bupivacaine
Authors: Chau Arthur Yuk Kong
Published: August 2017

This report describes a 13‐year‐old, 41.5 kg, male neutered, Rhodesian ridgeback that had lacerated its tongue on postanaesthetic recovery after administration of bilateral inferior alveolar nerve blocks (IANBs). IANBs are a commonly used locoregional anaesthesia technique for oral and dental procedures. An often‐mentioned complication is tongue laceration; however, there are no case reports of such events in the literature for cats or dogs. To the author’s knowledge, this is the first case report of such an event. This complication was attributed to the administration of bilateral IANBs using 1.5 ml of 0.5 per cent bupivacaine per block. Other differentials included lateral tongue positioning on extubation, emergence delirium or dysphoria and a presumptive degenerative myelopathy.
Operant conditioning facilitates safe induction and appropriate positioning for molar extraction under general anaesthetic in an Asian elephant (Elephas maximus)
Authors: Asquith‐Barnes Holly A , Sambrook Lee , Masters Nicholas J , Kertesz Peter , Molenaar Fieke M
Published: August 2017

An Asian elephant (Elephas maximus) suffering from dental malocclusion was anaesthetised for dental treatment using etorphine. The main risks of the procedure were trauma, associated with falls during sedation, and malpositioning, preventing access to the oral cavity. To reduce these risks the elephant was trained, using operant conditioning, to lie down in the required position and accept hand injections. Induction was straightforward and no repositioning was required under anaesthesia. One molar was extracted and another reshaped to improve occlusion and prevent soft tissue trauma. The anaesthetic was reversed within two hours of induction, and the elephant was manually assisted by the keepers to stand up. Operant conditioning proved invaluable during this procedure by improving staff and animal safety by enabling controlled hand injection of potent opioids instead of remote injection; allowing correct positioning prior to induction, greatly reducing anaesthetic time; and allowing a swift‐assisted recovery post reversal.
An infectious bronchitis virus Mass‐like strain from Brazil causing kidney damage and tropism in a broiler flock
Authors: Fernando Filipe Santos , Kasmanas Thaiane Coelho , Lopes Priscila Diniz , Montassier Helio José , Assayag Mário Sérgio
Published: August 2017

In this case, the authors showed an infectious bronchitis virus (IBV) strain from Massachusetts (Mass) genotype with nephropathogenic characteristics. This virus has great importance for causing damage to poultry production related to feed conversion, association with secondary infections and carcass condemnation in the slaughterhouse. IBV comprises several genotypes, and among these genotypes some pathogenic characteristics are specific, such as the strong pathogenesis of some Mass strains for the respiratory tract. However, the authors isolated IBV/Brazil/NUP/0316 strain and showed that when isolated from broilers it causes mild to moderate renal damage, besides presenting high amino acid sequence identity with other pathogenic strains isolated in countries far from Brazil.
DERIVATIVE PRICING WITH COLLATERALIZATION AND FX MARKET DISLOCATIONS
Authors: MORENI NICOLA , PALLAVICINI ANDREA
Published: August 2017

We present a general derivation of an arbitrage-free pricing framework for multiple-currency collateralized products. We include the impact on option pricing of the policy adopted to fund in foreign currency, so that we are able to price contracts with cash flows and/or collateral accounts expressed in foreign currencies inclusive of funding costs originating from dislocations in the foreign exchange market. Then, we apply these results to price cross-currency swaps under different market situations to understand how to implement a feasible curve bootstrap procedure. We present the main practical problems arising from the way the market is quoting liquid instruments: uncertainties about collateral currencies and renotioning features. We discuss the theoretical requirements to implement curve bootstrapping and the approximations usually taken to practically implement the procedure. We also provide numerical examples based on real market data.
SIEVE ESTIMATION OF THE MINIMAL ENTROPY MARTINGALE MARGINAL DENSITY WITH APPLICATION TO PRICING KERNEL ESTIMATION
Authors: BELOMESTNY DENIS , HÄRDLE WOLFGANG KARL , KRYMOVA EKATERINA
Published: August 2017

We study the problem of nonparametric estimation of the risk-neutral densities from options data. The underlying statistical problem is known to be ill-posed and needs to be regularized. We propose a novel regularized empirical sieve approach for the estimation of the risk-neutral densities which relies on the notion of the minimal martingale entropy measure. The proposed approach can be used to estimate the so-called pricing kernels which play an important role in assessing the risk aversion over equity returns. The asymptotic properties of the resulting estimate are analyzed and its empirical performance is illustrated.
Stratigraphy of deformed Permian carbonate reefs in Saraburi Province, Thailand
Authors: Dew Romana E. C. , King Rosalind , Collins Alan S. , Morley Christopher K. , Arboit Francesco , Glorie Stijn
Published: August 2017

Kilometre-scale thrusts affect the stratigraphic order of the sedimentary rocks that form the Khao Khwang Platform in central Thailand. The effect of these thrusts requires detailed analysis to unravel the original distribution of the sedimentary units and their associated facies. The Khao Khwang Platform comprises three carbonate-dominated units identified previously as the Phu Phe, Khao Khad and Khao Khwang Formations. These carbonates are intercalated with clastic, mixed siliciclastic and carbonate sequences: the Sap Bon, Pang Asok and Nong Pong Formations. The palaeogeography of the area prior to the Indosinian Orogeny is poorly known and has herein been investigated by combining structural reconstructions, microfacies and biostratigraphy in the Saraburi area. A stratigraphic model for the Yakhtashian–Midian carbonate platform palaeogeography using the well-developed exposed sections of the Khao Khwang Platform, located in the Saraburi Province of Thailand, is presented. This has revealed the presence of several separate carbonate platforms dominated by four major Middle Permian facies (peritidal, platform interior, algal reef and basin slope), which are dated using foraminifera and algae. This model integrates recent structural studies and considers their impact on the present-day distribution of the facies in terms of platform development using biostratigraphy and detailed microfacies analysis.

Supplementary material:
Characteristic images of the six facies, high-resolution stratigraphic logs, a timescale correlation chart and a table detailing the common fossils identified in this study are available at
https://doi.org/10.6084/m9.figshare.c.3861796
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Creatine (methyl-d3) dilution in urine for estimation of total body skeletal muscle mass: accuracy and variability vs. MRI and DXA
Authors: Clark Richard V. , Walker Ann C. , Miller Ram R. , O’Connor-Semmes Robin L. , Ravussin Eric , Cefalu William T.
Published: August 2017

A noninvasive method to estimate muscle mass based on creatine ( methyl-d3) (D3-creatine) dilution using fasting morning urine was evaluated for accuracy and variability over a 3- to 4-mo period. Healthy older (67- to 80-yr-old) subjects ( n = 14) with muscle wasting secondary to aging and four patients with chronic disease (58–76 yr old) fasted overnight and then received an oral 30-mg dose of D3-creatine at 8 AM ( day 1). Urine was collected during 4 h of continued fasting and then at consecutive 4- to 8-h intervals through day 5. Assessment was repeated 3–4 mo later in 13 healthy subjects and 1 patient with congestive heart failure. Deuterated and unlabeled creatine and creatinine were measured using liquid chromatography–tandem mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by whole body MRI and 24-h urine creatinine, and lean body mass (LBM) was measured by dual-energy X-ray absorptiometry (DXA). D3-creatinine urinary enrichment from day 5 provided muscle mass estimates that correlated with MRI for all subjects ( r = 0.88, P < 0.0001), with less bias [difference from MRI = −3.00 ± 2.75 (SD) kg] than total LBM assessment by DXA, which overestimated muscle mass vs. MRI (+22.5 ± 3.7 kg). However, intraindividual variability was high with the D3-creatine dilution method, with intrasubject SD for estimated muscle mass of 2.5 kg vs. MRI (0.5 kg) and DXA (0.8 kg). This study supports further clinical validation of the D3-creatine method for estimating muscle mass.

NEW & NOTEWORTHY Measurement of creatine ( methyl-d3) (D3-creatine) and D3-creatinine excretion in fasted morning urine samples may be a simple, less costly alternative to MRI or dual-energy X-ray absorptiometry (DXA) to calculate total body muscle mass. The D3-creatine enrichment method provides estimates of muscle mass that correlate well with MRI, and with less bias than DXA. However, intraindividual variability is high with the D3-creatine method. Studies to refine the spot urine sample method for estimation of muscle mass may be warranted.
Single passive leg movement assessment of vascular function: contribution of nitric oxide
Authors: Broxterman Ryan M. , Trinity Joel D. , Gifford Jayson R. , Kwon Oh Sung , Kithas Andrew C. , Hydren Jay R. , Nelson Ashley D. , Morgan David E. , Jessop Jacob E. , Bledsoe Amber D. , Richardson Russell S.
Published: August 2017

The assessment of passive leg movement (PLM)-induced leg blood flow (LBF) and vascular conductance (LVC) is a novel approach to assess vascular function that has recently been simplified to only a single PLM (sPLM), thereby increasing the clinical utility of this technique. As the physiological mechanisms mediating the robust increase in LBF and LVC with sPLM are unknown, we tested the hypothesis that nitric oxide (NO) is a major contributor to the sPLM-induced LBF and LVC response. In nine healthy men, sPLM was performed with and without NO synthase inhibition by intra-arterial infusion of NG-monomethyl-l-arginine (l-NMMA). Doppler ultrasound and femoral arterial pressure were used to determine LBF and LVC, which were characterized by the peak change (ΔLBFpeak and ΔLVCpeak) and area under the curve (LBFAUC and LVCAUC). l-NMMA significantly attenuated ΔLBFpeak [492 ± 153 (l-NMMA) vs. 719 ± 238 (control) ml/min], LBFAUC [57 ± 34 (l NMMA) vs. 147 ± 63 (control) ml], ΔLVCpeak [4.7 ± 1.1 (l-NMMA) vs. 8.0 ± 3.0 (control) ml·min−1·mmHg−1], and LVCAUC [0.5 ± 0.3 (l-NMMA) vs. 1.6 ± 0.9 (control) ml/mmHg]. The magnitude of the NO contribution to LBF and LVC was significantly correlated with the magnitude of the control responses ( r = 0.94 for ΔLBFpeak, r = 0.85 for LBFAUC, r = 0.94 for ΔLVCpeak, and r = 0.95 for LVCAUC). These data establish that the sPLM-induced hyperemic and vasodilatory response is predominantly (~65%) NO-mediated. As such, sPLM appears to be a promising, simple, in vivo assessment of NO-mediated vascular function and NO bioavailability.

NEW & NOTEWORTHY Passive leg movement (PLM), a novel assessment of vascular function, has been simplified to a single PLM (sPLM), thereby increasing the clinical utility of this technique. However, the role of nitric oxide (NO) in mediating the robust sPLM hemodynamic responses is unknown. This study revealed that sPLM induces a hyperemic and vasodilatory response that is predominantly NO-mediated and, as such, appears to be a promising simple, in vivo, clinical assessment of NO-mediated vascular function and, therefore, NO bioavailability.
UBC-Nepal Expedition: acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea level and high altitude
Authors: Tymko Michael M. , Tremblay Joshua C. , Steinback Craig D. , Moore Jonathan P. , Hansen Alex B. , Patrician Alexander , Howe Connor A. , Hoiland Ryan L. , Green Daniel J. , Ainslie Philip N.
Published: August 2017

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g., shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that 1) at rest, SNA would be elevated and FMD would be reduced at HA compared with sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344 m) and HA (5,050 m) in 14 participants during mild lower-body negative pressure (LBNP; −10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants ( n = 5). Our findings were 1) at rest, SNA was elevated ( P < 0.01), and absolute FMD was reduced ( P = 0.024), but relative FMD remained unaltered ( P = 0.061), at HA compared with SL; and 2) despite significantly altering SNA with LBNP (+60.3 ± 25.5%) and LBPP (−37.2 ± 12.7%) ( P < 0.01), FMD was unaltered at SL ( P = 0.448) and HA ( P = 0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA.

NEW & NOTEWORTHY The role of the sympathetic nervous system on endothelial function remains unclear. We used lower-body negative and positive pressure to manipulate sympathetic nervous activity at sea level and high altitude and measured brachial endothelial function via flow-mediated dilation. We found that acutely altering sympathetic nervous activity had no effect on endothelial function.
Skeletal muscle contractile properties in a novel murine model for limb girdle muscular dystrophy 2i
Authors: Rehwaldt Jordan D. , Rodgers Buel D. , Lin David C.
Published: August 2017

Limb-girdle muscular dystrophy (LGMD) 2i results from mutations in fukutin-related protein and aberrant α-dystroglycan glycosylation. Although this significantly compromises muscle function and ambulation, the comprehensive characteristics of contractile dysfunction are unknown. Therefore, we quantified the in situ contractile properties of the medial gastrocnemius in young adult P448L mice, an affected muscle of a novel model of LGMD2i. Normalized maximal twitch force, tetanic force, and power were significantly smaller in P448L mice, compared with sex-matched, wild-type mice. These differences were consistent with the replacement of contractile fibers by passive tissue. The shape of the active force-length relationships were similar in both groups, regardless of sex, consistent with an intact sarcomeric structure in P448L mice. Passive force-length curves normalized to maximal isometric force were steeper in P448L mice, and passive elements contribute disproportionately more to total contractile force in P448L mice. Sex differences were mostly noted in the force-velocity curves, as normalized values for maximal and optimal velocities were significantly slower in P448L males, compared with wild-type, but not in P448L females. This suggests that the dystrophic phenotype, which may include possible changes in cross-bridge kinetics and fiber-type proportions, progresses more quickly in P448L males. These results together indicate that active force and power generation are compromised in both sexes of P448L mice, while passive forces increase. More importantly, the results identified several functional markers of disease pathophysiology that could aid in developing and assessment of novel therapeutics for LGMD2i and possibly other dystroglycanopathies as well.

NEW & NOTEWORTHY Comprehensive assessments of muscle contractile function have, until now, never been performed in an animal model for any dystroglycanopathy. This study suggests that skeletal muscle contractile properties are significantly compromised in a recently developed model for limb-girdle muscular dystrophy 2i, the P448L mouse. It further identifies novel pathological markers of muscle function that are suitable for developing therapeutics and for better understanding of disease pathogenesis.