bluuebunny/crossref_metadata_2025 huggingface dataset:
Follow‐up of patients with refractory or relapsed multiple myeloma after allogeneic hematopoietic cell transplantation
Authors: Schneidawind Corina , Duerr‐Stoerzer Silke , Faul Christoph , Kanz Lothar , Weisel Katja , Bethge Wolfgang , Schneidawind Dominik
Published: May 2017

Background

The role of allogeneic hematopoietic cell transplantation (HCT) for the treatment of multiple myeloma is controversial. However, the introduction of proteasome inhibitors and immunomodulatory drugs might influence outcomes in case of relapse or refractory disease after allogeneic HCT.

Methods

We report 41 consecutive patients that underwent allogeneic HCT for the treatment of relapsed or refractory multiple myeloma.

Results

Three‐year event‐free survival (EFS) and overall survival (OS) of the whole cohort were 15% and 51%, respectively. In a subgroup analysis, allogeneic HCT after a second high‐dose chemotherapy with autologous stem cell support was associated with a decreased 3‐year EFS (6% vs 24%, P=.04) and OS (35% vs 64%, P=.09). In case of relapse or refractory disease after allogeneic HCT, the treatment with proteasome inhibitors or immunomodulatory drugs significantly improved survival (1‐year OS 79% vs 29%, P=.001).

Conclusion

The incorporation of proteasome inhibitors and immunomodulatory drugs into transplant protocols has the potential to improve outcomes and refine the role of allogeneic HCT for the treatment of multiple myeloma as a platform for long‐term disease control.
The relationship between initial route of heroin administration and speed of transition to daily heroin use
Authors: Hines Lindsey A. , Lynskey Michael , Morley Katherine I. , Griffiths Paul , Gossop Michael , Powis Beverly , Strang John
Published: May 2017

Introduction and Aims. The effect of heroin administration route on speed of transition to regular use is unknown. This paper aims to determine whether the speed of transition from initiation of heroin use to daily heroin use differs by route of administration (injecting, chasing/inhaling or snorting). Design and Methods. Privileged access interviewer survey of purposively selected sample of 395 current people who use heroin (both in and not in treatment) in London, UK (historical sample from 1991). Data on age and year of initiation, time from initiation to daily use and routes of administration were collected by means of a structured questionnaire. Generalised ordered logistic models were used to test the relationship between route of initial administration of heroin and speed of transition to daily heroin use. Analyses were adjusted for gender, ethnicity, daily use of other drug(s) at time of initiation, year of initiation and treatment status at interview. Results. After adjustment, participants whose initial administration route was injecting had a 4.71 (95% confidence interval 1.34–16.5) increase in likelihood of progressing to daily use within 1–3 weeks of initiation, compared to those whose initial administration route was non‐injecting. Discussion and Conclusions. The speed of transition from first use to daily heroin use is faster if the individual injects heroin at initiation of use. Those who initiate heroin use through injecting have a shorter time frame for intervention before drug use escalation. [Hines LA, Lynskey M, Morley KI, Griffiths P, Gossop M, Powis B, Strang J. The relationship between initial route of heroin administration and speed of transition to daily heroin use. Drug Alcohol Rev 2017;00:000‐000]
Defining Health Research for Development: The perspective of stakeholders from an international health research partnership in Ghana and Tanzania
Authors: Ward Claire Leonie , Shaw David , Anane‐Sarpong Evelyn , Sankoh Osman , Tanner Marcel , Elger Bernice
Published: May 2017

Objectives

The study uses a qualitative empirical method to define Health Research for Development. This project explores the perspectives of stakeholders in an international health research partnership operating in Ghana and Tanzania.

Methods

We conducted 52 key informant interviews with major stakeholders in an international multicenter partnership between GlaxoSmithKline (GSK, Vaccine Developer) and the global health nonprofit organisation PATH and its Malaria Vaccine Initiative program (PATH/MVI, Funder‐Development Partner), (RTS, S) (NCT00866619). The respondents included teams from four clinical research centres (two centres in Ghana and two in Tanzania) and various collaborating partners. This paper analyses responses to the question: What is Health Research for Development?

Results

Based on the stakeholders’ experience the respondents offered many ways of defining Health Research for Development. The responses fell into four broad themes: i) Equitable Partnerships; ii) System Sustainability; iii) Addressing Local Health Targets, and iv) Regional Commitment to Benefit Sharing.

Conclusion

Through defining Health Research for Development six key learning points were generated from the four result themes: 1) Ensure there is local research leadership working with the collaborative partnership, and local healthcare system, to align the project agenda and activities with local research and health priorities; 2) Know the country‐specific context ‐ map the social, health, legislative and political setting; 3) Define an explicit development component and plan of action in a research project; 4) Address the barriers and opportunities to sustain system capacity. 5) Support decentralised health system decision‐making to facilitate the translation pathway; 6) Govern, monitor and evaluate the development components of health research partnerships. Overall, equity and unity between partners are required to deliver health research for development.
A critique of the principle of ‘respect for autonomy’, grounded in African thought
Authors: Behrens Kevin G.
Published: May 2017

I give an account how the principle of ‘respect for autonomy’ dominates the field of bioethics, and how it came to triumph over its competitors, ‘respect for persons’ and ‘respect for free power of choice’. I argue that ‘respect for autonomy’ is unsatisfactory as a basic principle of bioethics because it is grounded in too individualistic a worldview, citing concerns of African theorists and other communitarians who claim that the principle fails to acknowledge the fundamental importance of understanding persons within the nexus of their communal relationships. I defend the claim that ‘respect for persons’ is a more appropriate principle, as it is able to acknowledge both individual decision making and the essential relationality of persons. I acknowledge that my preference for ‘respect for persons’ is problematic because of the important debate around the definition of ‘personhood’ in bioethics discourse. Relying on Thaddeus Metz's conception of moral status, I propose a relational definition of personhood that distinguishes between persons with agency and persons without agency, arguing that we have different moral obligations to these distinct categories of persons. I claim that this conception of personhood is better able to accommodate our moral intuitions than conventional approaches, and that it is able to do so without being speciesist or question‐begging.
H3Africa: An Africa exemplar? Exploring its framework on protecting human research participants
Authors: Nnamuchi Obiajulu
Published: May 2017

The Human Heredity and Health in Africa (H3Africa) Consortium is a conglomeration of research and infrastructure projects spread throughout Africa whose aim is to apply genomic methodology to diseases affecting the people in the region. Its operation is innovative in the sense that it is doing something new; that is, filling a hitherto existing void in genomic research capability of African scientists and infusing resources and manpower to institutions and investigators across Africa. But aside from developing and sustaining capacity in genomic research and biorepositories, H3Africa is also invested in developing appropriate ethical regulatory regime to govern research in these areas. This latter concern –research ethics governance – is the major subject of this paper. Specifically, the paper discusses protection of research participants as envisaged by H3Africa in the area of consent, safeguarding privacy, maintaining confidentiality of health information and sharing of data/biospecimens. The ultimate goal is to determine whether H3Africa initiatives and processes are consistent or at odds with international guidelines and best practices.
An Examination of European Firms’ Derivatives Usage: The Importance of Model Selection
Authors: Carroll Anthony , O'Brien Fergal , Ryan James
Published: May 2017

This paper investigates the determinants of foreign currency (FX) and interest rate (IR) derivatives usage for European non‐financial firms. We employ a Tobit model and a two‐part model which allows the determinants of the usage decision to differ from the extent of usage decision. We find FX derivatives usage is motivated by economies of scale and FX exposure, while IR derivatives usage is motivated by the magnitude and nature of firms’ debt. We also find that for IR derivatives the determinants of the usage decision differ from the determinants of the extent of usage decision.
Validation of the ultrasonographic assessment of the femoral trochlea epiphyseal cartilage in foals at osteochondrosis predilected sites with magnetic resonance imaging and histology
Authors: Martel G. , Forget C. , Gilbert G. , Richard H. , Moser T. , Olive J. , Laverty S.
Published: May 2017

Background

Noninvasive imaging tools are needed to screen foal femoropatellar joints to detect subclinical osteochondrosis lesions due to focal failure of endochondral ossification to enhance early management to optimise intrinsic healing events. Recently investigations employing 3T susceptibility‐weighted magnetic resonance imaging (3T SWI MRI) and CT have demonstrated their capacity for early osteochondrosis diagnosis, but these technologies are not practical for field screening. We postulate that ultrasonography is a valuable field tool for the detection of subclinical osteochondrosis lesions.

Objectives

The goals were to 1) describe the ultrasonographic features of the femoral trochlea of healthy and osteochondrosis‐predisposed neonatal foals, 2) validate the capacity of ultrasound to assess cartilage canal vascular archictecture and the ossification front and 3) evaluate field feasibility in a pilot study.

Study design

Experimental study.

Methods

Ultrasonographic evaluation of osteochondrosis predisposed (n = 10) and control (n = 6) femoral trochleas was performed ex vivo and compared with site‐matched histological sections and 3T SWI MRI. The articular and epiphyseal cartilage thickness, ossification front indentation and cartilage canal vascular archictecture were assessed at each ROI. Femoral trochleae of foals (n = 3) aged ≈ 1, 3 and 6 months were also evaluated with ultrasonography in field.

Results

Ultrasonographic measurements strongly correlated with the histological measurements. There was no difference in the cartilage thickness or ossification front indentation between control and osteochondrosis‐predisposed specimens. The cartilage canal vascular archictecture on ultrasonograms corresponded with the vessel pattern observed on site matched histology and 3T SWI MRI.

Main limitations

The number of specimens for study was limited and no early osteochondrosis lesions were present within the predilected group, but a field study is now underway.

Conclusion

Ultrasonographic examination of the femoral trochlea permitted accurate evaluation of cartilage thickness, cartilage canal vascular archictecture and ossification front indentation in young foals and is a promising, practical tool for screening subclinical osteochondrosis and monitoring and managing lesions at important clinical sites.
Platelet Rich Plasma for Chronic Synovitis Treatment in Patients with Haemophilia
Authors: Caviglia H. , Landro M. E. , Daffunchio C. , Galatro G. , Douglas Price A. L. , Salgado P. , Neme D.
Published: May 2017

Introduction

Haemophilic synovitis is caused by chronic accumulation of blood in the joint. Conservative treatment is insufficient to solve this pathology. Platelet‐rich plasma (PRP) has a high concentration of growth factors (GFs) that play a key role in regulation and stimulation of healing processes. The aim of this study was to describe the effect of PRP injection in chronic synovitis of the joints in patients with haemophilia (PWH).

Patients and methods

Nineteen patients with 28 joints were treated at our centre in Buenos Aires, Argentina between December 2014 and December 2015. Eighteen were Haemophilia type A (17 severe, one mild) and one was type B severe. Mean age was 26 years old. Chronic synovitis was present in two ankles, seven elbows and 19 knee joints. All affected joints were evaluated for range of motion (ROM), perimeter, Haemophilia Joint Health Score (HJHS), number of bleedings episodes and Visual Analogue Scale (VAS). Evaluations were before treatment and 3 and 6 months after treatment.

Results

A mean volume of 4 mL of PRP was injected into the joint cavity. The statistical analysis before and after treatments revealed a statistically significant (P < 0.001) decrease in the HJHS score. Decrease in joint bleeding episodes was also statistically significant (P < 0.001). All patients reported pain relief and VAS scores were statistically significant (P < 0.001). Joint perimeter also showed a statistically significant difference (P < 0.001). No complications were observed in any of the patients, either during blood collection or during PRP injection, even for inhibitor patients.

Conclusion

Platelet‐rich plasma is a useful, safe, and inexpensive treatment for chronic haemophilic synovitis.
First report on the safety and efficacy of an extended half‐life glycoPEGylated recombinant FVIII for major surgery in severe haemophilia A
Authors: Hampton K. , Chowdary P. , Dunkley S. , Ehrenforth S. , Jacobsen L. , Neff A. , Santagostino E. , Sathar J. , Takedani H. , Takemoto C. M. , Négrier C.
Published: May 2017

Background

N8‐GP (turoctocog alfa pegol) is an extended half‐life glycoPEGylated recombinant factor VIII (FVIII) product developed for the prevention and treatment of bleeds in haemophilia A patients.

Aim

This is a planned interim analysis of pathfinder™3, an international, open‐label, Phase 3 trial evaluating the efficacy and safety (including immunogenicity) of N8‐GP administered before, during and after major surgery in severe haemophilia A patients aged ≥12 years.

Methods

Sixteen patients who underwent 18 major surgical procedures (including synovectomy, joint replacement and ankle arthrodesis) were included here. Postoperative assessments were conducted daily for days 1–6, and once for days 7–14. Primary endpoint was N8‐GP haemostatic efficacy, assessed after completion of surgery using a four‐point scale (‘excellent’, ‘good’, ‘moderate’, ‘none’).

Results

Haemostasis was successful (rated ‘excellent’ or ‘good’) on completion of surgery in 17 (94.4%) procedures and rated as ‘moderate’ (5.6%) for one surgery in a patient with multiple comorbidities who needed an intraoperative N8‐GP dose (20.7 IU kg−1). In the postoperative period, three bleeds occurred (one during days 1–6; two during days 7–14); all were successfully treated with N8‐GP. Mean N8‐GP consumption on day of surgery was 80.0 IU kg−1; patients received a mean of 1.7 doses (median: 2, range: 1–3). No safety concerns were identified.

Conclusion

The data showed that N8‐GP was effective and well tolerated for the prevention and treatment of bleeds during major surgery; such FVIII products with extended half‐lives may modify current treatment schedules, enabling fewer infusions and earlier patient discharge.
Vitamin D Deficiency in Patients With Chronic Tension‐Type Headache: A Case‐Control Study
Authors: Prakash Sanjay , Rathore Chaturbhuj , Makwana Prayag , Dave Ankit , Joshi Hemant , Parekh Haresh
Published: May 2017

Objective

To see the interrelation between chronic tension‐type headache (CTTH) and serum vitamin D levels.

Background

Several studies have suggested an association between chronic pain and vitamin D deficiency. Anecdotal evidence suggests that vitamin D deficiency may be associated with tension‐type headache and migraine.

Methods

This case‐control study was carried out to examine the association between CTTH and serum 25‐hydroxy vitamin (25(OH) D) levels. One hundred consecutive adult (>18 years) patients with CTTH and 100 matched healthy controls were enrolled.

Results

The serum 25(OH) D levels were significantly lower in CTTH patients than in the controls (14.7 vs 27.4 ng/mL). The prevalence of vitamin D deficiency (serum 25 (OH) D < 20 ng/mL) was greater in patients with CTTH (71% vs 25%). CTTH patients had a significantly high prevalence of musculoskeletal pain (79% vs 57%), muscle weakness (29%vs 10%), muscle tenderness score (7.5 vs 1.9), and bone tenderness score (3.0 vs 0.8) in comparison to controls. CTTH patients with vitamin D deficient group (<20 ng/mL) had a higher prevalence of musculoskeletal pain (58% vs 31%), muscle weakness (38%vs 7%), muscle and bone tenderness score, associated fatigue (44% vs 17%) and more prolonged course (15.5 months vs 11.2 months). A strong positive correlation was noted between serum vitamin D levels and total muscle tenderness score (R2 = 0. 7365) and total bone tenderness score (R2 = 0. 6293).

Conclusion

Decreased serum 25(OHD) concentration was associated with CTTH. Intervention studies are required to find out if supplementation of vitamin D is effective in patients with CTTH.
From State Security Model to Selective + Residual Security Model: Health care regime shift in urban China
Authors: Yang Hui , Chen Hong‐lin
Published: May 2017

Based on the study of welfare states, welfare regime theory (WRT) has been widely applied to international and regional welfare regimes and to specific‐policy comparative studies. However, the health care system has often been neglected in this area of study. The current study promotes a health care regime approach that is influenced by WRT and incorporates analysis of the level of health care de‐commodification and health equity. Three types of health care regimes were identified in the development of the health care system in urban China: the State Medical Security Model, the Selective Medical Security Model and the Selective + Residual Medical Security Model. This approach provides useful policy implications for the health care reform currently taking place in China. In addition, this analysis contributes to theories in the comparative health policy literature.
A genetic analysis of meat compositions in Japanese Black cattle: Genetic parameters and sex influence
Authors: Onogi A. , Sasaki S. , Kobayashi M. , Ogino A. , Nozaki T. , Kurogi K. , Yasumori T. , Togashi K. , Iwata H.
Published: May 2017

Meat composition in beef is related to eating quality and food functionality. Genetic parameters for several meat compositions including free amino acid, peptide and sugar, however, remain poorly described. In this study, we estimated genetic parameters for 51 meat components, including free amino acids, peptides, sugars and fatty acid compositions, and two carcase traits in 1,354 heifers and 1,797 steers of Japanese Black cattle. Heritability estimates were generally equivalent to or moderately greater than those in previous studies of this breed. Genetic correlations between free amino acids, peptides and sugars and carcase traits were often negative, suggesting a trade‐off between traits. Using two‐trait animal models that treat records from the two sexes as different traits, we estimated sex‐specific heritabilities and cross‐sex genetic correlations which indicate the sex differences in genetic architecture. In these analyses, 12 traits showed significant heritability differences between sexes and cross‐sex genetic correlations occasionally deviated from unity. These results could be used to inform future breeding schemes and investigations of the genetic architecture of meat compositions in beef.
Effects of epicardial versus transvenous left ventricular lead placement on left ventricular function and cardiac perfusion in cardiac resynchronization therapy: A randomized clinical trial
Authors: van Dijk Vincent F. , Fanggiday Jim , Balt Jippe C. , Wijffels Maurits C.E.F. , Daeter Edgar J. , Kelder Johannes C. , Boersma Lucas V.A.
Published: May 2017

Introduction

Optimal left ventricular (LV) lead position in patients undergoing cardiac resynchronization therapy (CRT) is crucial to achieve an optimal effect on hemodynamics. Due to various difficulties, up to 30% of transvenous LV lead placements fail, or a suboptimal position is achieved. Surgical epicardial LV lead placement could be performed at a position anticipated to be the optimal site. This could have a more favorable effect, which may be expressed by increased improvement in left ventricular ejection fraction (LVEF) and cardiac perfusion.

The objective of this trial is to compare transvenous versus epicardial LV lead placement in CRT in a randomized fashion

Methods and results

Fifty‐two patients were randomized to either epicardial or transvenous approach. All patients received an ICD with CRT. Patients were followed for 6 months after device implant. Primary endpoint was the degree of change in cardiac perfusion measured by myocardial perfusion scintigraphy.

LVEF equally improved in both groups, from 24% to 36% in the transvenous group versus 25% to 35% in the epicardial group (P = 0.797). Cardiac perfusion, expressed as summed stress score, improved in both groups without a significant difference as well (P = 0.727). Complication rate was similar, respectively 6 and 7 patients had any complication. Admission time was significantly longer in the epicardial group with 2 (2–7) versus 3 (2–32) days (P <0.001).

Conclusion

Epicardial LV lead placement does not result in additional improvement of LVF or myocardial perfusion compared to the conventional transvenous in CRT.
Application of the 2015 ACC/AHA/HRS guidelines for risk stratification for sudden death in adult patients with asymptomatic pre‐excitation
Authors: Obeyesekere Manoj N. , Klein George J.
Published: May 2017

The management of the asymptomatic pre‐excited patient largely hinges on risk stratification and individual patient considerations and choice. A high threshold to treat patients may lead to a small overall risk of death while a low threshold clearly leads to increased invasive testing and ablation with associated cost and procedural risk. A firm recommendation to uniformly assess all by electrophysiology study or, alternatively, reassure all is inappropriate and unjustified by data as reflected in the recent guideline recommendations. The use of noninvasive and invasive parameters to identify the potentially at‐risk individual with surveillance for symptoms in those comfortable with this approach or ablation for those choosing this alternative for individual reasons remains the cornerstone of best practice.
Stellate ganglion blockade and bilateral cardiac sympathetic denervation in patients with life‐threatening ventricular arrhythmias
Authors: Cardona‐Guarache Ricardo , Padala Santosh K. , Velazco‐Davila Luis , Cassano Anthony , Abbate Antonio , Ellenbogen Kenneth A. , Koneru Jayanthi N.
Published: May 2017

Autonomic modulation is being increasingly employed as a strategy to treat ventricular arrhythmias refractory to beta‐blockers, antiarrhythmic drugs, and catheter‐based ablation procedures. We report 6 patients with refractory ventricular tachycardia (VT) or ventricular fibrillation (VF) treated with stellate ganglion blockade (SGB) and/or bilateral cardiac sympathetic denervation (CSD). Our case series emphasizes the concept that the cardiac sympathetic nerves are important targets in the management of ventricular arrhythmias. SGB and CSD can be effective in suppressing VT/VF and can be offered to patients with refractory ventricular arrhythmias as an adjunct to conventional therapy.
Targeting YAP in malignant pleural mesothelioma
Authors: Zhang Wen‐Qian , Dai Yu‐Yuan , Hsu Ping‐Chih , Wang Hui , Cheng Li , Yang Yi‐Lin , Wang Yu‐Cheng , Xu Zhi‐Dong , Liu Shu , Chan Geraldine , Hu Bin , Li Hui , Jablons David M. , You Liang
Published: May 2017

Malignant mesothelioma is an aggressive cancer that is resistant to current therapy. The poor prognosis of mesothelioma has been associated with elevated Yes‐associated protein (YAP) activity. In this study, we evaluated the effect of targeting YAP in mesothelioma. First, we comprehensively studied YAP activity in five mesothelioma cell lines (211H, H2052, H290, MS‐1 and H2452) and one normal mesothelial cell line (LP9). We found decreased phospho‐YAP to YAP protein ratio and consistently increased GTIIC reporter activity in 211H, H2052 and H290 compared to LP9. The same three cell lines (IC50s < 1 μM) were more sensitive than LP9 (IC50 = 3.5 μM) to the YAP/TEAD inhibitor verteporfin. We also found that verteporfin significantly reduced YAP protein level, mRNA levels of YAP downstream genes and GTIIC reporter activity in the same three cell lines, indicating inhibition of YAP signaling by verteporfin. Verteporfin also impaired invasion and tumoursphere formation ability of H2052 and H290. To validate the effect of specific targeting YAP in mesothelioma cells, we down‐regulated YAP by siRNA. We found siYAP significantly decreased YAP transcriptional activity and impaired invasion and tumoursphere formation ability of H2052 and H290. Furthermore, forced overexpression of YAP rescued GTIIC reporter activity and cell viability after siYAP targeting 3′UTR of YAP. Finally, we found concurrent immunohistochemistry staining of ROCK2 and YAP (P < 0.05). Inhibition of ROCK2 decreased GTIIC reporter activity in H2052 and 211H suggesting that Rho/ROCK signaling also contributed to YAP activation in mesothelioma cells. Our results indicate that YAP may be a potential therapeutic target in mesothelioma.
P2X7 receptor inhibition attenuated sympathetic nerve sprouting after myocardial infarction via the NLRP3/IL‐1β pathway
Authors: Yin Jie , Wang Yu , Hu Hesheng , Li Xiaolu , Xue Mei , Cheng Wenjuan , Wang Ye , Li Xinran , Yang Na , Shi Yugen , Yan Suhua
Published: May 2017

Mounting evidence supports the hypothesis that inflammation modulates sympathetic sprouting after myocardial infarction (MI). The myeloid P2X7 signal has been shown to activate the nucleotide‐binding and oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome, a master regulator of inflammation. We investigated whether P2X7 signal participated in the pathogenesis of sympathetic reinnervation after MI, and whether NLRP3/interleukin‐1β (IL‐1β) axis is involved in the process. We explored the relationship between P2X7 receptor (P2X7R) and IL‐1β in the heart tissue of lipopolysaccharide (LPS)‐primed naive rats. 3′‐O‐(4‐benzoyl) benzoyl adenosine 5′‐triphosphate (BzATP), a P2X7R agonist, induced caspase‐1 activation and mature IL‐1β release, which was further neutralized by a NLRP3 inhibitor (16673‐34‐0). MI was induced by coronary artery ligation. Following infarction, a marked increase in P2X7R was localized within infiltrated macrophages and observed in parallel with an up‐regulation of NLRP3 inflammasome levels and the release of IL‐1β in the left ventricle. The administration of A‐740003 (a P2X7R antagonist) significantly prevented the NLRP3/IL‐1β increase. A‐740003 and/or Anakinra (an IL‐1 receptor antagonist) significantly reduced macrophage infiltration as well as macrophage‐based IL‐1β and NGF (nerve growth factor) production and eventually blunted sympathetic hyperinnervation, as assessed by the immunofluorescence of tyrosine hydroxylase (TH) and growth‐associated protein 43 (GAP 43). Moreover, the use of Anakinra partly attenuated sympathetic sprouting. This indicated that the effect of P2X7 on neural remodelling was mediated at least partially by IL‐1β. The arrhythmia score of programmed electric stimulation was in accordance with the degree of sympathetic hyperinnervation. In vitro studies showed that BzATP up‐regulated secretion of nerve growth factor (NGF) in M1 macrophages via IL‐1β. Together, these data indicate that P2X7R contributes to neural and cardiac remodelling, at least partly mediated by NLRP3/IL‐1β axis. Therapeutic interventions targeting P2X7 signal may be a novel approach to ameliorate arrhythmia following MI.
Combination of biochemical and mechanical cues for tendon tissue engineering
Authors: Testa Stefano , Costantini Marco , Fornetti Ersilia , Bernardini Sergio , Trombetta Marcella , Seliktar Dror , Cannata Stefano , Rainer Alberto , Gargioli Cesare
Published: May 2017

Tendinopathies negatively affect the life quality of millions of people in occupational and athletic settings, as well as the general population. Tendon healing is a slow process, often with insufficient results to restore complete endurance and functionality of the tissue. Tissue engineering, using tendon progenitors, artificial matrices and bioreactors for mechanical stimulation, could be an important approach for treating rips, fraying and tissue rupture. In our work, C3H10T1/2 murine fibroblast cell line was exposed to a combination of stimuli: a biochemical stimulus provided by Transforming Growth Factor Beta (TGF‐β) and Ascorbic Acid (AA); a three‐dimensional environment represented by PEGylated‐Fibrinogen (PEG‐Fibrinogen) biomimetic matrix; and a mechanical induction exploiting a custom bioreactor applying uniaxial stretching. In vitro analyses by immunofluorescence and mechanical testing revealed that the proposed combined approach favours the organization of a three‐dimensional tissue‐like structure promoting a remarkable arrangement of the cells and the neo‐extracellular matrix, reflecting into enhanced mechanical strength. The proposed method represents a novel approach for tendon tissue engineering, demonstrating how the combined effect of biochemical and mechanical stimuli ameliorates biological and mechanical properties of the artificial tissue compared to those obtained with single inducement.
The roar of the lionfishes Pterois volitans and Pterois miles
Authors: Beattie M. , Nowacek D. P. , Bogdanoff A. K. , Akins L. , Morris J. A.
Published: May 2017

Through the analysis of acoustic recordings of captive Pterois spp., this study has confirmed anecdotal evidence that Pterois spp. are soniferous. This report of sound production in Pterois spp. provides the foundation for future research into their specific acoustic capabilities including sound production mechanisms, the role of social behaviour and applied techniques for controlling and monitoring invasive Pterois spp. in the tropical and temperate western Atlantic Ocean.
Validation of a KHV antibody enzyme‐linked immunosorbent assay (ELISA)
Authors: Bergmann S M , Wang Q , Zeng W , Li Y , Wang Y , Matras M , Reichert M , Fichtner D , Lenk M , Morin T , Olesen N J , Skall H F , Lee P‐Y , Zheng S , Monaghan S , Reiche S , Fuchs W , Kotler M , Way K , Bräuer G , Böttcher K , Kappe A , Kielpinska J
Published: May 2017

Koi herpesvirus (KHV) causes KHV disease (KHVD). The virus is highly contagious in carp or koi and can induce a high mortality. Latency and, in some cases, a lack of signs presents a challenge for virus detection. Appropriate immunological detection methods for anti‐KHV antibodies have not yet been fully validated for KHV. Therefore, it was developed and validated an enzyme‐linked immunosorbent assay (ELISA) to detect KHV antibodies. The assay was optimized with respect to plates, buffers, antigens and assay conditions. It demonstrated high diagnostic and analytical sensitivity and specificity and was particularly useful at the pond or farm levels. Considering the scale of the carp and koi industry worldwide, this assay represents an important practical tool for the indirect detection of KHV, also in the absence of clinical signs.
Effects on Greenhouse Gas Emissions of Introducing Electric Vehicles into an Electricity System with Large Storage Capacity
Authors: Garcia Rita , Freire Fausto , Clift Roland
Published: May 2017

Under some circumstances, electric vehicles (EVs) can reduce overall environmental impacts by displacing internal combustion engine vehicles (ICEVs) and by enabling more intermittent renewable energy sources (RES) by charging with surplus power in periods of low demand. However, the net effects on greenhouse gas (GHG) emissions of adding EVs into a national or regional electricity system are complex and, for a system with significant RES, are affected by the presence of storage capacity, such as pumped hydro storage (PHS). This article takes the Portuguese electricity system as a specific example, characterized by relatively high capacities of wind generation and PHS. The interactions between EVs and PHS are explored, using life cycle assessment to compare changes in GHG emissions for different scenarios with a fleet replacement model to describe the introduction of EVs. Where there is sufficient storage capacity to ensure that RES capacity is exploited without curtailment, as in Portugal, any additional demand, such as introduction of EVs, must be met by the next marginal technology. Whether this represents an average increase or decrease in GHG emissions depends on the carbon intensity of the marginal generating technology and on the fuel efficiency of the ICEVs displaced by the EVs, so that detailed analysis is needed for any specific energy system, allowing for future technological improvements. A simple way to represent these trade‐offs is proposed as a basis for supporting strategic policies on introduction of EVs.
Driving reversible redox reactions at solid–liquid interfaces with the electron beam of a transmission electron microscope
Authors: AHMAD NABEEL , WANG GUILLAUME , NELAYAH JAYSEN , RICOLLEAU CHRISTIAN , ALLOYEAU DAMIEN
Published: May 2017

Liquid‐cell transmission electron microscopy (LCTEM) has opened up a new way to study chemical reactions at the interface between solids and liquids. However, understanding the effects of the electron beam in the liquid cell has been clearly identified as one of the most important challenges to assess correctly and quantitatively LCTEM data. Here we show that the electron beam can be used to drive reversible deposition/dissolution cycles of copper shells over gold nanoparticles in methanol. Besides revealing the influence of irreversible processes on the kinetic of growth/etching cycles, this study of nanostructure behaviour as a function of the dose rate highlights the possibility to switch the oxidising or reducing nature of liquid environment only with the electron beam. The chemical and electronic processes possibly involved in these tunable redox reactions are qualitatively discussed together with their possible impacts on electrochemical LCTEM experiments.
Membrane protein stoichiometry studied in intact mammalian cells using liquid‐phase electron microscopy
Authors: DE JONGE N.
Published: May 2017

Receptor membrane proteins in the plasma membranes of cells respond to extracellular chemical signals by conformational changes, spatial redistribution, and (re‐)assembly into protein complexes, for example, into homodimers (pairs of the same protein type). The functional state of the proteins can be determined from information about how subunits are assembled into protein complexes. Stoichiometric information about the protein complex subunits, however, is generally not obtained from intact cells but from pooled material extracted from many cells, resulting in a lack of fundamental knowledge about the functioning of membrane proteins. First, functional states may dramatically differ from cell to cell on account of cell heterogeneity. Second, extracting the membrane proteins from the plasma membrane may lead to many artefacts. Liquid‐phase scanning transmission electron microscopy (STEM), in short liquid STEM, is a new technique capable of determining the locations of individual membrane proteins within the intact plasma membranes of cells in liquid. Many tens of whole cells can readily be imaged. It is possible to analyse the stoichiometry of membrane proteins in single cells while accounting for heterogenic cell populations. Liquid STEM was used to image epidermal growth factor receptors in whole COS7 cells. A study of the dimerisation of the HER2 protein in breast cancer cells revealed the presence of rare cancer cells in which HER2 was in a different functional state than in the bulk cells. Stoichiometric information about receptors is essential not only for basic science but also for biomedical application because they present many important pharmaceutical targets.
Sociophonetic variation in a long‐term language contact situation: /l/‐darkening in Welsh‐English bilingual speech
Authors: Morris Jonathan
Published: May 2017

This study investigates /l/‐darkening in the Welsh and English speech of bilinguals in North Wales. Although it is claimed that /l/ is dark in all syllable positions in northern varieties of both languages, there have been no quantitative investigations of this feature which consider cross‐linguistic phonetic differences, the differing nature of language contact between North East and North West Wales, and differences in the way both languages are acquired by speakers. The dataset of 32 Welsh‐English bilinguals, aged 16–18, was stratified by speaker sex, home language, and area. Tokens of /l/ in word‐initial onset and word‐final coda positions were analysed acoustically. The results show cross‐linguistic differences in onset position and that such differences were found to be greater in the speech of female speakers. Differences were also found between the two areas. These results are discussed with reference to the influence of extra‐linguistic factors on speech production and the possible social meaning associated with dark /l/.
Discourses of cultural heritage in times of crisis: The case of the Parthenon Marbles
Authors: Angouri Jo , Paraskevaidi Marina , Wodak Ruth
Published: May 2017

The paper focuses on the commodification and politicisation of cultural heritage using as a case study the ongoing debate on the return of the Parthenon Marbles from the U.K. to Greece, recently reignited by the press release for the movie The Monuments Men in 2014. Greece has been in the throes of a severe financial crisis for over six years with the ever imminent threat of Grexit constantly disputed. In parallel with this ongoing turmoil, discourses of Greek antiquity have been persistently prominent in the media. In this context, we problematise the complex nexus of relationships between the financial crisis, national identity and cultural heritage. We combine the Discourse‐Historical Approach and Interactional Sociolinguistics drawing data from an online forum, and investigate how the users negotiate pro‐/anti‐return positions and make the financial crisis relevant in the argumentation process. The analysis shows that history, identity, value, and debt are recontextualised in relation to the Parthenon sculptures. The analysis identifies an underlying process of value trade off and brings the current political and economic environment to the fore. We close the paper by foregrounding the implications of our study and provide directions for further research.
Bilateral plantar geographic lesions
Authors: Fernández‐Crehuet Pablo , Ruiz‐Villaverde Ricardo
Published: May 2017

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Encapsulation of ritonavir in solid lipid nanoparticles: in-vitro anti-HIV-1 activity using lentiviral particles
Authors: Javan Farzaneh , Vatanara Alireza , Azadmanesh Kayhan , Nabi-Meibodi Mohsen , shakouri Mehdi
Published: May 2017

Objectives

In this study, ritonavir was entrapped into solid lipid nanoparticles (SLNs) employing two production methods. The prepared SLNs were characterized and antiretroviral activity was investigated for more efficient formulation.

Methods

Ritonavir-loaded SLNs were produced by solvent emulsification evaporation (SE) and double emulsion methods (DE), and the effects of Tween80 and poloxamer188 as external phase surfactant were compared. Prepared SLNs were characterized in terms of size, surface charge, entrapment efficiency (EE), release profile and thermal behaviour. Moreover, the activity of drug-loaded SLNs was investigated on the lentiviral-based pseudo-HIV-1 particles.

Key findings

The average size of negatively charged SLNs was 170–250 nm with polydispersity index (PDI) of 0.2. The most EE% was about 53.2% achieved by DE method in the presence of poloxamer188. It was found that addition of poloxamer188 in the process led to increased entrapment efficiency and particle size. The in-vitro antiviral experiment showed ritonavir SLNs can actively maintain inhibition of virus production as well as free drug.

Conclusions

In this study, we showed the SLNs not only can encapsulate ritonavir efficiently but also can maintain its antiviral activity and modulate drug release as promising nanocarrier.
The dynamics of texture perception of hard solid food: A review of the contribution of the temporal dominance of sensations technique
Authors: Fiszman Susana , Tarrega Amparo
Published: May 2017

The present paper reviews the use of temporal dominance of sensations (TDS) sensory methodology in relation to texture evaluation. From more than 100 papers initially screened, 28 dealing with the texture of hard solid foods that require mastication were selected. The attributes evaluated by TDS were comprehensively analyzed and the phases of the mastication period in which they occurred were studied. The relation between these attributes and the initial mechanical food properties, the particle size, shape, and aggregation of the increasingly destroyed food structure, and the evolving properties of the bolus through to swallowing were also examined. Results from complementary techniques used alongside TDS, both sensory and nonsensory, were also analyzed. The contribution of TDS methodology to understanding the texture construct is shown to be reliable and suggestions are made for future lines of research.

Practical applications

The literature on the temporal dominance of sensations method is constantly increasing. The present review examines the application of this method to the dynamics of texture perception of hard solid foods. The key texture attributes perceived in each phase of mastication, together with their relation to the initial food structure, gradual comminution, and bolus formation, will shed light on the usefulness of this methodology for food texture appraisal.
Effect of whole wheat flour on the quality, texture profile, and oxidation stability of instant fried noodles
Authors: Cao Xinlei , Zhou Sumei , Yi Cuiping , Wang Li , Qian Haifeng , Zhang Hui , Qi Xiguang
Published: May 2017

The effects of whole wheat flour (WWF) on pasting properties of instant fried noodle dry mix and quality of final product were investigated in this research. Refined wheat flour in the recipe for instant‐fried noodle was replaced by WWF at different levels. The peak and final viscosities were significantly and negatively correlated to WWF substitution level. With increasing WWF level, the hardness, cohesiveness, adhesiveness, and resilience values of instant fried noodles decreased by 11.63, 16.23, 16.67, 20.00%, respectively. WWF darkened noodle's surface color and increased its oil content (26.63%). A porous and less uniformed structure of the WWF instant fried noodles was observed by a scanning electron microscope. Moreover, the WWF incorporation lowered peroxide values of the instant fried noodles during storage. In conclusion, even though the oil content increased, WWF was helpful to inhibit the oil oxidation and produce instant fried noodles with softer texture and less sticky surface.

Practical applications

Refined wheat flour in the recipe for instant‐fried noodle was replaced by whole wheat flour (WWF), which is rich in dietary fibers, vitamins, and other bioactive compounds. The addition of WWF delayed the retrogradation tendency of starch in the dry mix. WWF‐added instant noodles had softer texture, less sticky surface, and lower peroxide value. Based on the results of this study, the refined wheat flour in the recipe for instant‐fried noodle could be partially replaced by WWF to make noodles with better texture profile and higher consumer acceptance.
Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment‐naïve, noncirrhotic HCV genotype 3‐infected patients
Authors: Gane E. , Nahass R. , Luketic V. , Asante‐Appiah E. , Hwang P. , Robertson M. , Wahl J. , Barr E. , Haber B.
Published: May 2017

Elbasvir (EBR; HCV NS5A inhibitor) and grazoprevir (GZR; HCV NS3/4A protease inhibitor) are approved as a fixed‐dose combination to treat patients chronically infected with HCV genotypes 1 and 4. During the development programme and supported by in vitro potency, the efficacy of EBR+GZR was assessed in HCV GT3‐infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18 weeks of EBR+GZR with ribavirin (RBV) in treatment‐naïve, noncirrhotic HCV GT3‐infected patients. Randomized patients received open‐label EBR (50 mg once daily) + GZR (100 mg once daily) + RBV. The primary efficacy objective was to evaluate the sustained virologic response rates 12 weeks after the end of all study therapy (SVR12). SVR12 rates (95% confidence interval) were 45.0% (23.1, 68.5) and 57.1% (34.0, 78.2) after treatment with EBR+GZR+RBV for 12 weeks or 18 weeks, respectively. On‐treatment virologic failure was observed in 41% (17 of 41) of patients. At virologic failure, resistance‐associated substitutions (RASs) with a >five‐fold shift in potency occurred in the NS3 region in six (35%) patients and in the NS5A region in 16 (94%) patients. The most common RAS at virologic failure was Y93H in NS5A which was identified in 13 of 17 (76%) patients. The efficacy of EBR+GZR+RBV was suboptimal in HCV GT3‐infected patients due to a high rate of on‐treatment virologic failure and treatment‐emergent RASs which demonstrates an inadequate barrier to the development of GT3 resistance. However, rapid viral clearance demonstrated the antiviral activity of EBR+GZR+RBV in GT3‐infected patients.clinicaltrials.gov: NCT01717326.
Vitamin D deficiency causes rickets in an urban informal settlement in Kenya and is associated with malnutrition
Authors: Jones Kelsey D. J. , Hachmeister C. Ulrich , Khasira Maureen , Cox Lorna , Schoenmakers Inez , Munyi Caroline , Nassir H. Samira , Hünten‐Kirsch Barbara , Prentice Ann , Berkley James A.
Published: May 2017

The commonest cause of rickets worldwide is vitamin D deficiency, but studies from sub‐Saharan Africa describe an endemic vitamin D‐independent form that responds to dietary calcium enrichment. The extent to which calcium‐deficiency rickets is the dominant form across sub‐Saharan Africa and in other low‐latitude areas is unknown. We aimed to characterise the clinical and biochemical features of young children with rickets in a densely populated urban informal settlement in Kenya. Because malnutrition may mask the clinical features of rickets, we also looked for biochemical indices of risk in children with varying degrees of acute malnutrition. Twenty one children with rickets, aged 3 to 24 months, were identified on the basis of clinical and radiologic features, along with 22 community controls, and 41 children with either severe or moderate acute malnutrition. Most children with rickets had wrist widening (100%) and rachitic rosary (90%), as opposed to lower limb features (19%). Developmental delay (52%), acute malnutrition (71%), and stunting (62%) were common. Compared to controls, there were no differences in calcium intake, but most (71%) had serum 25‐hydroxyvitamin D levels below 30 nmol/L. These results suggest that rickets in young children in urban Kenya is usually driven by vitamin D deficiency, and vitamin D supplementation is likely to be required for full recovery. Wasting was associated with lower calcium (p = .001), phosphate (p < .001), 25‐hydroxyvitamin D (p = .049), and 1,25‐dihydroxyvitamin D (p = 0.022) levels, the clinical significance of which remain unclear.