bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro models of multiple system atrophy from primary cells to induced pluripotent stem cells
Authors: Abati Elena , Di Fonzo Alessio , Corti Stefania
Published: March 2018

Multiple system atrophy (MSA) is a rare neurodegenerative disease with a fatal outcome. Nowadays, only symptomatic treatment is available for MSA patients. The hallmarks of the disease are glial cytoplasmic inclusions (GCIs), proteinaceous aggregates mainly composed of alpha‐synuclein, which accumulate in oligodendrocytes. However, despite the extensive research efforts, little is known about the pathogenesis of MSA. Early myelin dysfunction and alpha‐synuclein deposition are thought to play a major role, but the origin of the aggregates and the causes of misfolding are obscure. One of the reasons for this is the lack of a reliable model of the disease. Recently, the development of induced pluripotent stem cell (iPSC) technology opened up the possibility of elucidating disease mechanisms in neurodegenerative diseases including MSA. Patient specific iPSC can be differentiated in glia and neurons, the cells involved in MSA, providing a useful human disease model. Here, we firstly review the progress made in MSA modelling with primary cell cultures. Subsequently, we focus on the first iPSC‐based model of MSA, which showed that alpha‐synuclein is expressed in oligodendrocyte progenitors, whereas its production decreases in mature oligodendrocytes. We then highlight the opportunities offered by iPSC in studying disease mechanisms and providing innovative models for testing therapeutic strategies, and we discuss the challenges connected with this technique.
Qiliqiangxin attenuates hypoxia‐induced injury in primary rat cardiac microvascular endothelial cells via promoting HIF‐1α‐dependent glycolysis
Authors: Wang Yanyan , Han Xueting , Fu Mingqiang , Wang Jingfeng , Song Yu , Liu Yuan , Zhang Jingjing , Zhou Jingmin , Ge Junbo
Published: March 2018

Protection of cardiac microvascular endothelial cells (CMECs) against hypoxia injury is an important therapeutic strategy for treating ischaemic cardiovascular disease. In this study, we investigated the effects of qiliqiangxin (QL) on primary rat CMECs exposed to hypoxia and the underlying mechanisms. Rat CMECs were successfully isolated and passaged to the second generation. CMECs that were pre‐treated with QL (0.5 mg/mL) and/or HIF‐1α siRNA were cultured in a three‐gas hypoxic incubator chamber (5% CO2, 1% O2, 94% N2) for 12 hours. Firstly, we demonstrated that compared with hypoxia group, QL effectively promoted the proliferation while attenuated the apoptosis, improved mitochondrial function and reduced ROS generation in hypoxic CMECs in a HIF‐1α‐dependent manner. Meanwhile, QL also promoted angiogenesis of CMECs via HIF‐1α/VEGF signalling pathway. Moreover, QL improved glucose utilization and metabolism and increased ATP production by up‐regulating HIF‐1α and a series of glycolysis‐relevant enzymes, including glucose transport 1 (GLUT1), hexokinase 2 (HK2), 6‐phosphofructokinase 1 (PFK1), pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Our findings indicate that QL can protect CMECs against hypoxia injury via promoting glycolysis in a HIF‐1α‐dependent manner. Lastly, the results suggested that QL‐dependent enhancement of HIF‐1α protein expression in hypoxic CMECs was associated with the regulation of AMPK/mTOR/HIF‐1α pathway, and we speculated that QL also improved HIF‐1α stabilization through down‐regulating prolyl hydroxylases 3 (PHD3) expression.
Postprandial glucose‐lowering effect of premeal consumption of protein‐enriched, dietary fiber‐fortified bar in individuals with type 2 diabetes mellitus or normal glucose tolerance
Authors: Bae Jae Hyun , Kim Lee Kyung , Min Se Hee , Ahn Chang Ho , Cho Young Min
Published: March 2018

Aims/Introduction

Protein preload improves postprandial glycemia by stimulating secretion of insulin and incretin hormones. However, it requires a large dose of protein to produce a significant effect. The present study was carried out to investigate the postprandial glucose‐lowering effect of a premeal protein‐enriched, dietary fiber‐fortified bar (PFB), which contains moderate amounts of protein, in individuals with type 2 diabetes mellitus or normal glucose tolerance (NGT).

Materials and Methods

The participants (15 type 2 diabetes mellitus and 15 NGT) were randomly assigned to either a premeal or postmeal PFB group and underwent two mixed meal tolerance tests, 1 week apart in reverse order. Plasma levels of glucose, insulin, glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide were measured.

Results

During the mixed meal tolerance tests, the incremental area under the curve from 0 to 180 min of plasma glucose levels was lower with premeal PFB than with postmeal PFB in the type 2 diabetes mellitus (14,723 ± 1,310 mg min/dL vs 19,642 ± 1,367 mg min/dL; P = 0.0002) and NGT participants (3,943 ± 416 mg min/dL vs 4,827 ± 520 mg min/dL, P = 0.0296). In the type 2 diabetes mellitus participants, insulinogenic index and the incremental area under the curve from 0 to 180 min of plasma total glucagon‐like peptide‐1 levels were higher with premeal PFB than with postmeal PFB, but not in the NGT participants. There was no difference in postprandial glucose‐dependent insulinotropic polypeptide levels between premeal and postmeal PFB in both groups.

Conclusions

Acute administration of premeal PFB decreased postprandial glucose excursion in both type 2 diabetes mellitus and NGT participants. In the type 2 diabetes mellitus participants, premeal PFB augmented the early‐phase insulin secretion, possibly through enhancing glucagon‐like peptide‐1 secretion.
Study design and baseline characteristics of inpatients with diabetes mellitus in a tertiary hospital in China: A database study based on electronic medical records
Authors: Li Sheyu , Yu Chuan , Li Yun , Li Qianrui , Zhang Rui , Hou Qingtao , Zheng Tao , Ma Yi , Wang Miye , Su Na , Wu Ting , Liu Zhiwen , Sheng Xia , Li Nan , Liu Guanjian , Huang Yong , Xu Ting , Sun Xin , Tian Haoming
Published: March 2018

Aim

To describe the characteristics of inpatients with diabetes in a tertiary hospital in China using an electronic medical record (EMR)‐based database.

Methods

We identified the medical records of all patients with diabetes from nonpediatric departments of West China Hospital, Sichuan University (from February 2009 to December 2013), and extracted information on demographic, diagnosis, discharge outcome, department of discharge, laboratory test, and prescription from the EMR system. The quality of the database was assessed by analyzing missing data and extreme data and by reviewing the International Classification of Diseases 10th Revision (ICD‐10) coding.

Results

Among 683,267 discharged patients, 56,784 (8.3%) patients diagnosed with diabetes were identified from all departments. Among the patients with diabetes, the average age was 63.5 ± 13.1 years and the overall death in hospital was 2.2%. Laboratory test results were highly completed in our database with no extreme or discrepant value identified. Anthropometric parameters were of a relatively low quality as 62.2% body‐mass index data were missing. HbA1c levels at admission were available for 36.7% patients with diabetes. The ICD‐10 coding of the diagnosis of diabetes was accurate in 88.6% records reviewed. Dyslipidemia (76.5%), hypertension (51.3%), chronic kidney disease (22.1%), and hyperuricemia (16.2%) were the most commonly presented comorbidities among inpatients with diabetes.

Conclusions

Our study indicated a wide distribution of diabetes throughout the inpatients in a tertiary hospital in southwest China. This EMR‐based database of diabetes could be potentially useful in further investigations.
BEHAVIORAL ECONOMICS AND BEHAVIORAL FINANCE: A BIBLIOMETRIC ANALYSIS OF THE SCIENTIFIC FIELDS
Authors: Costa Daniel Fonseca , Carvalho Francisval de Melo , Moreira Bruno César de Melo
Published: March 2018

The aim of the study is to conduct a bibliometric analysis of the scientific field of Behavioral Economics and Behavioral Finance. The research was conducted using the Web of Science database, which returned 2617 articles, revealing that the amount of research within these fields has grown over time. Furthermore, the results also prove the relevance of the works of Daniel Kahneman and Amos Tversky for the field of Behavioral Economics and Finance, and Steven Hursh to Behavioral Economics. It is still possible to note that the field of Behavioral Economics encompasses subjects that connect human behavior with demand, consumption and price, with investments and with managerial decisions, as well as with the role played by heuristics and cognitive biases in decision‐making processes. In turn, the field of Behavioral Finance is more focused on the study of errors of judgment and of decision‐making characteristics in financial investments. Additionally, it is inferred that the field of Behavioral Economics is more wide‐ranging than the field of Behavioral Finance, as the latter is a byproduct of Behavioral Economics. Finally, a conclusion is then reached, demonstrating that the fields of Behavioral Economics and Finance have turned into an important field of study.
Impact of stent deformity induced by the kissing balloon technique for bifurcating lesions on in‐stent restenosis after coronary intervention
Authors: Gamou Tadatsugu , Sakata Kenji , Terai Hidenobu , Horita Yuki , Ikeda Masatoshi , Namura Masanobu , Yamagishi Masakazu , Kawashiri Masa‐aki
Published: March 2018

Objectives

To investigate the impact of stent deformity induced by final kissing balloon technique (KBT) for coronary bifurcation lesions on in‐stent restenosis (ISR).

Background

In experimental models, the detrimental effects of KBT have been clearly demonstrated, but few data exists regarding the impact of proximal stent deformity induced by KBT on clinical outcomes.

Methods

We examined 370 coronary lesions where intravascular ultrasound (IVUS)‐guided second‐generation drug‐eluting stent (DES) implantation for coronary bifurcation lesions was performed. Based on IVUS analysis, the stent symmetry index (minimum/maximum stent diameter) and stent overstretch index (the mean of stent diameter/the mean of reference diameter) were calculated in the proximal main vessel.

Results

The stent symmetry index was significantly lower (0.75 ± 0.07 vs 0.88 ± 0.06, P < 0.0001) and the stent overstretch index was significantly higher (1.04 ± 0.08 vs 1.01 ± 0.06, P = 0.0007) in lesions with KBT (n = 174) compared to those without KBT (n = 196). The number of two‐stent technique in lesions with KBT was 31 (18%). In multivariate analysis, the degree of stent deformity indices was not associated with ISR in lesions with KBT; however, two‐stent technique use was the only independent predictor of ISR at 8 months (hazard ratio: 3.96, 95% confidence interval: 1.25‐12.5, P = 0.01).

Conclusions

Second‐generation DES deformity induced by KBT was not associated with mid‐term ISR.
Being perceived as a knowledge sender or knowledge receiver: A multistudy investigation of the effect of age on knowledge transfer
Authors: Burmeister Anne , Fasbender Ulrike , Deller Jürgen
Published: March 2018

As a result of demographic changes, workforces are becoming older and more age diverse. While interactions between workers from different age groups can provide opportunities for mutual learning through bidirectional knowledge transfer, research has yet to investigate how age influences knowledge transfer between age‐diverse colleagues. Building on the organizational theory of age effects, we conducted two studies to examine how age influenced the roles assigned to individuals in knowledge transfer processes, that is, whether they were perceived as knowledge senders or knowledge recipients. In Study 1, we used an experimental vignette design with 450 employees to assess how age affected perceived ability and motivation to share and receive knowledge. Further, we tested the extent to which trustworthiness moderated these relationships. In Study 2, we extended these findings using a dyadic research design with data from 53 age‐diverse knowledge transfer dyads. We examined through which mechanisms the age of one's colleague affected one's knowledge transfer behaviour. We found that the age of one's colleague had a positive effect on one's knowledge receiving behaviour and a negative effect on one's knowledge sharing behaviour. Further, perceived ability to receive knowledge and perceived motivation to share knowledge mediated these effects.
An impact of Deoxynivalenol produced by Fusarium graminearum on broiler chickens
Authors: Yu Y.‐H. , Hsiao F. S.‐H. , Proskura W. S. , Dybus A. , Siao Y.‐H. , Cheng Y.‐H.
Published: March 2018

Deoxynivalenol (DON) is a major mycotoxin from the trichothecene family of mycotoxins produced by Fusarium fungi that cause disease in grains. Food and feed contaminated with DON cause a variety of adverse health effects in humans and farm animals. However, the fermentation conditions of DON for toxicological study remain to be optimised. Deoxynivalenol levels were increased in a constant temperature of 20°C after fermentation for 7 and 14 days compared with cycling temperatures between 10–20°C and 15–20°C. We have established that optimum conditions for DON production on rice‐based medium is constant temperature at 20°C. In feeding experiments, the villus height and the ratio of villus height and crypt depth were reduced in the duodenum of DON‐fed broiler chickens, whereas a mycotoxin degradation agent efficiently reversed the abnormal morphology of the small intestine in the DON‐fed broilers. The expression of pro‐inflammatory gene, COX‐2, was induced in the spleen and bursa of Fabricius of DON‐fed broilers. This effect was alleviated in the presence of mycotoxin degradation agent. DON produced in solid‐state fermentation is able to cause toxic effects in broilers and induce an abnormal morphology of the small intestine, particularly the duodenum.
Age‐dependent leaf physiology and consequences for crown‐scale carbon uptake during the dry season in an Amazon evergreen forest
Authors: Albert Loren P. , Wu Jin , Prohaska Neill , de Camargo Plinio Barbosa , Huxman Travis E. , Tribuzy Edgard S. , Ivanov Valeriy Y. , Oliveira Rafael S. , Garcia Sabrina , Smith Marielle N. , Oliveira Junior Raimundo Cosme , Restrepo‐Coupe Natalia , da Silva Rodrigo , Stark Scott C. , Martins Giordane A. , Penha Deliane V. , Saleska Scott R.
Published: March 2018

Satellite and tower‐based metrics of forest‐scale photosynthesis generally increase with dry season progression across central Amazônia, but the underlying mechanisms lack consensus.

We conducted demographic surveys of leaf age composition, and measured the age dependence of leaf physiology in broadleaf canopy trees of abundant species at a central eastern Amazon site. Using a novel leaf‐to‐branch scaling approach, we used these data to independently test the much‐debated hypothesis – arising from satellite and tower‐based observations – that leaf phenology could explain the forest‐scale pattern of dry season photosynthesis.

Stomatal conductance and biochemical parameters of photosynthesis were higher for recently mature leaves than for old leaves. Most branches had multiple leaf age categories simultaneously present, and the number of recently mature leaves increased as the dry season progressed because old leaves were exchanged for new leaves.

These findings provide the first direct field evidence that branch‐scale photosynthetic capacity increases during the dry season, with a magnitude consistent with increases in ecosystem‐scale photosynthetic capacity derived from flux towers. Interactions between leaf age‐dependent physiology and shifting leaf age‐demographic composition are sufficient to explain the dry season photosynthetic capacity pattern at this site, and should be considered in vegetation models of tropical evergreen forests.
Dense infraspecific sampling reveals rapid and independent trajectories of plastome degradation in a heterotrophic orchid complex
Authors: Barrett Craig F. , Wicke Susann , Sass Chodon
Published: March 2018

Heterotrophic plants provide excellent opportunities to study the effects of altered selective regimes on genome evolution. Plastid genome (plastome) studies in heterotrophic plants are often based on one or a few highly divergent species or sequences as representatives of an entire lineage, thus missing important evolutionary‐transitory events.

Here, we present the first infraspecific analysis of plastome evolution in any heterotrophic plant. By combining genome skimming and targeted sequence capture, we address hypotheses on the degree and rate of plastome degradation in a complex of leafless orchids (Corallorhiza striata) across its geographic range.

Plastomes provide strong support for relationships and evidence of reciprocal monophyly betweenC. involutaand the endangeredC. bentleyi. Plastome degradation is extensive, occurring rapidly over a few million years, with evidence of differing rates of genomic change among the two principal clades of the complex. Genome skimming and targeted sequence capture differ widely in coverage depth overall, with depth in targeted sequence capture datasets varying immensely across the plastome as a function of GC content.

These findings will help to fill a knowledge gap in models of heterotrophic plastid genome evolution, and have implications for future studies in heterotrophs.
The democratizing impact of governance networks: From pluralization, via democratic anchorage, to interactive political leadership
Authors: Sørensen Eva , Torfing Jacob
Published: March 2018

Initially, governance networks were intended as tools for making public governance more effective. Yet, scholars have argued that governance networks also have the potential to democratize public governance. This article provides an overview of theoretical arguments pertaining to the democratizing impact of governance networks. It claims that the initial celebration of the pluralization of public governance and the subsequent call for a democratic anchorage of governance networks should give way to a new concern for how governance networks can strengthen and democratize political leadership. Tying political leadership to networked processes of collaborative governance fosters ‘interactive political leadership’. The article presents theoretical arguments in support of interactive political leadership, and provides an illustrative case study of a recent attempt to strengthen political leadership through the systematic involvement of elected politicians in local governance networks. The article concludes by reflecting on how interactive political leadership could transform our thinking about democracy.
Efficacy and safety of phosphodiesterase 4 inhibitors in patients with asthma: A systematic review and meta‐analysis
Authors: Luo Jian , Yang Ling , Yang Jing , Yang Dan , Liu Bi‐Cui , Liu Dan , Liang Bin‐Miao , Liu Chun‐Tao
Published: March 2018

Phosphodiesterase 4 (PDE4) inhibitors are a novel medication approved for airway inflammatory diseases including chronic obstructive pulmonary disease. Their role and application in asthma are controversial and not defined.

A comprehensive search was performed in major databases (1946–2016) using the keywords: ‘phosphodiesterase 4 inhibitor’ or ‘roflumilast’ and ‘asthma’. Placebo‐controlled trials reporting lung function, airway hyperresponsiveness by direct challenge, asthma control and exacerbations, and adverse events were included. Random or fixed‐effects models were used to calculate odds ratios (OR) and mean differences between the two treatment groups. Statistical analyses were conducted using Mann–Whitney U‐tests and Cochrane systematic review software, Review Manager.

Seventeen studies were included in the systematic review, of which 14 studies were included in the meta‐analysis. Except for significant statistical heterogeneity in pre‐ and post‐challenge predicted percentage of forced expiratory volume in 1 s (FEV1%; I2 = 72%, χ2 = 3.35, P = 0.06), there was no heterogeneity in outcome measures. Roflumilast (500 μg) significantly improved FEV1 (mean difference: 0.05, 95% CI: 0.01–0.09, Z = 2.50, P = 0.01), peak expiratory flow, asthma control and exacerbations, but showed variable effects on airway responsiveness to methacholine and a 20% fall in FEV1.Of note, PDE4 inhibitors were accompanied with significantly higher adverse events such as headache (OR: 3.99, 95% CI: 1.65–9.66, Z = 3.07, P = 0.002) and nausea (OR: 5.53, 95% CI: 1.38–22.17, Z = 2.41, P = 0.02).

In patients with mild asthma, oral PDE4 inhibitors can be considered as an alternative treatment to regular bronchodilators and inhaled controllers.
Bronchiectasis in indigenous and non‐indigenous residents of Australia and New Zealand
Authors: Blackall Sean R. , Hong Jae B. , King Paul , Wong Conroy , Einsiedel Lloyd , Rémond Marc G.W. , Woods Cindy , Maguire Graeme P.
Published: March 2018

Background and objective

Bronchiectasis not associated with cystic fibrosis is an increasingly recognized chronic lung disease. In Oceania, indigenous populations experience a disproportionately high burden of disease. We aimed to describe the natural history of bronchiectasis and identify risk factors associated with premature mortality within a cohort of Aboriginal Australians, New Zealand Māori and Pacific Islanders, and non‐indigenous Australians and New Zealanders.

Methods

This was a retrospective cohort study of bronchiectasis patients aged >15 years at three hospitals: Alice Springs Hospital and Monash Medical Centre in Australia, and Middlemore Hospital in New Zealand. Data included demographics, ethnicity, sputum microbiology, radiology, spirometry, hospitalization and survival over 5 years of follow‐up.

Results

Aboriginal Australians were significantly younger and died at a significantly younger age than other groups. Age‐ and sex‐adjusted all‐cause mortality was higher for Aboriginal Australians (hazard ratio (HR): 3.9), and respiratory‐related mortality was higher for both Aboriginal Australians (HR: 4.3) and Māori and Pacific Islander people (HR: 1.7). Hospitalization was common: Aboriginal Australians had 2.9 admissions/person‐year and 16.9 days in hospital/person‐year. Despite Aboriginal Australians having poorer prognosis, calculation of the FACED score suggested milder disease in this group. Sputum microbiology varied with Aspergillus fumigatus more often isolated from non‐indigenous patients. Airflow obstruction was common (66.9%) but not invariable.

Conclusions

Bronchiectasis is not one disease. It has a significant impact on healthcare utilization and survival. Differences between populations are likely to relate to differing aetiologies and understanding the drivers of bronchiectasis in disadvantaged populations will be key.
How Many People Are Exposed to Suicide? Not Six
Authors: Cerel Julie , Brown Margaret M. , Maple Myfanwy , Singleton Michael , van de Venne Judy , Moore Melinda , Flaherty Chris
Published: March 2018

It has long been stated that six people are left behind following every suicide. Despite a lack of empirical evidence, this has been extensively cited for over 30 years. Using data from a random‐digit dial survey, a more accurate number of people exposed to each suicide is calculated. A sample of 1,736 adults included 812 lifetime suicide‐exposed respondents who reported age and number of exposures. Each suicide resulted in 135 people exposed (knew the person). Each suicide affects a large circle of people, who may be in need of clinician services or support following exposure.
Perceived Burdensomeness Predicts Outcomes of Short‐Term Psychological Treatment of Young People at Risk of Suicide
Authors: Hains Alex , Janackovski Atanas , Deane Frank P. , Rankin Kathryn
Published: March 2018

The interpersonal‐psychological theory of suicide (IPTS; Joiner, ) provides a model for understanding the mechanisms underlying suicide risk, but there is limited research measuring change in the constructs over the course of treatment. This study aimed to test whether changes in perceived burdensomeness (PB) and thwarted belongingness (TB) mediated the effects of changes in depression and hopelessness on suicide risk. The sample comprised 226 Australian young people (aged 12–24; 67.7% female; 5.7% Aboriginal and Torres Strait Islander) receiving short‐term psychological treatment for suicide‐related behaviors. Change scores over the course of therapy were generated using admission and discharge measures of PB, TB, depression, hopelessness, and suicide risk. Results revealed partial support for the theory. The relationship between changes in depression and hopelessness on suicide risk was fully mediated by changes in PB. However, changes in TB did not mediate these relationships. This study offers encouragement for the potential use of the IPTS in the context of psychological treatment of young people. Assessment of the IPTS constructs may be helpful in assessing change in suicide risk and further assist in treatment.
Extending shelf life of dithiothreitol‐treated panel RBCs to 28 days
Authors: Sigle J.‐P. , Mihm B. , Suna R. , Bargetzi M.
Published: March 2018

Background

Daratumumab (DARA) causes non‐specific results in indirect agglutination testing (IAT). Dithiothreitol (DTT) treatment of panel red blood cells (RBCs) abolishes DARA interference. The objective of our study was to extend stability of DTT‐treated panel RBCs to 28 days through application of a commercially available panel RBC stabilizer.

Materials and Methods

Serological antigen typing and IAT using DARA sera and DARA plasma spiked with weakly reacting alloantibodies was performed up to 28 days after DTT treatment and stabilization.

Results

DTT treatment resulted in loss of Fy‐antigen expression on some panel RBCs. Antigen profiles of stabilized, DTT‐treated panel RBCs remained stable. Alloantibodies in DARA sera and DARA plasma were reliably detected.

Conclusions

Application of a commercially available RBC stabilizer extends shelf life of DTT‐treated panel RBCs to 28 days.
Dynamic simulation and steady-state computation of 3D physiologically structured population models
Authors: Van Dyck Michiel , Woot De Trixhe Xavier , Vanroose Wim
Published: March 2018

The PSP modelling approach allows you to model biological/pharmaceutical behaviour by combining micro-scale ordinary differential equation (ODE) models with macro-scale ODE models and their bi-directional interaction. E.g.: based on the model of a single cell, billions of cells can be simulated to get the response of an entire organ (also incorporating the organ to cell reaction). The PSP approach allows to simulate this in a mathematically efficient way by characterising different cells by a set of physiologically relevant quantities [2], [3]. Our framework is capable of taking into account up to 3 physiological parameters resulting in a 3D structure for which a partial differential equation (PDE) should be solved. We achieve considerable speed-up by using a semi-Lagrangian PDE solver that allows big stable time stepping. Combining this with a low level C-language implementation, we achieve exceptional efficient usage of the computing processing unit (CPU). Furthermore we accelerate the computation of the steady-state by using a Newton-Krylov method. For ease of use, a PSP description language is constructed to allow straightforward input of different models. The simulator should empower future computational/mathematical biologists to create and evaluate more detailed models than currently is common practice.
But Then There Were also Such Bulgarians: A Bibliography for the Teacher, Enlightener and Statesman Nestor Markov
Authors: Pancheva Tsvetanka H.
Published: March 2018

This is a review article on the book [1]. The original text is published in Bulgarian in [2].В [1]В В Mladenova, Maria. Nestor Markov 1836-1916. Biobibliography, Pleven, 2016 В (in Bulgarian).[2]В Pancheva, Tsvetanka. But then there were also such Bulgarians: A Bibliography for the Teacher, Enlightener and Statesman Nestor Markov. В In: Blagoeva, D. (Ed.), Nestor Markov and his contribution to the lexicography and education, Proceedings of the Jubilee Science Session dedicated to the 180th anniversary of the birth of Nestor Markov, Sofia, 2016 (in Bulgarian).
Complete Genome Sequence of an Enterovirus A71 Strain Isolated in 2006 from a Patient in Shenzhen, Southern China, with a Lethal Case of Enterovirus Infection
Authors: Yao Xiang-Jie , Chen Long , Yang Hong , Meng Jun , Zhang Hai-Long , Jiang Min , Zhang Hong-Yu , He Ya-Qing , Wu Chun-Li , Zhang Ren-Li
Published: March 2018

The whole-genome sequence of an enterovirus A71 strain (EV71/SHENZHEN001/2006) isolated in 2006 from a patient with a fatal case of enterovirus infection was determined. Phylogenetic analysis based on the complete VP1 gene classified this strain as subgenotype C4a.
Complete Genome Sequence of a Zika Virus Strain Isolated from the Serum of an Infected Patient in Thailand in 2006
Authors: Nitatpattana Narong , Chaiyo Kumchol , Rajakam Supoth , Poolam Kanya , Chansiprasert Kusuma , Pesirikan Norapath , Buree Supanat , Rodpai Ekkarat , Yoksan Sutee
Published: March 2018

The complete genome of Zika virus (ZIKV) strain CVD_06-274 was isolated from the serum of an infected patient in Thailand in 2006. Phylogenetic analysis showed that this strain belongs to the Asian lineage and also high titers in Vero cells (RCB 10-87). It has potential for development as an inactivated ZIKV vaccine.
Draft Genome Sequences of Four Parasaccharibacter apium Strains Isolated from Honey Bees
Authors: Corby-Harris Vanessa , Anderson Kirk E.
Published: March 2018

Parasaccharibacter apium
displays multiple ecological strategies in its honey bee host. We sequenced the genomes of four strains found in larvae and the adult gut in order to better understand its ecology and relationship to other
Acetobacteraceae
. The
P. apium
genome consists of 2,009,892 bp and 1,830 protein-coding genes.
Virulence-Related Genes Identified from the Genome Sequence of the Non-O1/Non-O139 Vibrio cholerae Strain VcN1, Isolated from Dhaka, Bangladesh
Authors: Hossain Maqsud , Alam Munirul , Khaleque Abdul , Islam Sohidul , Sadique Abdus , Khan Nayeim , Halim Zahra , Sarker Mrinmoy , El-Sayed Najib M. , Huq Anwar , Ahsan Gias Uddin , Colwell Rita R.
Published: March 2018

We report here the first draft genome sequence of the non-O1/non-O139
Vibrio cholerae
strain VcN1, isolated from Dhaka, Bangladesh. The data submitted to GenBank for this strain will contribute to advancing our understanding of this environmentally disseminated bacterium, including its virulence and its evolution as an important pathogen.
Electroacupuncture Mitigates Endothelial Dysfunction via Effects on the Pi3K/Akt Signalling Pathway in High Fat Diet-Induced Insulin-Resistant Rats
Authors: Lan Danchun , Xu Nenggui , Sun Jian , Li Zhixing , Liao Rongzhen , Zhang Hongtao , Liang Xiaoli , Yi Wei
Published: March 2018

Objective

To investigate the effect of electroacupuncture (EA) on endothelial dysfunction related to high fat diet (HFD)-induced insulin resistance through the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway.

Methods

Twenty-four male Sprague-Dawley rats were fed a regular diet (Control group, n=8) or a HFD (n=16) for 12 weeks to induce an insulin resistance model. HFD-fed rats were divided into two groups that remained untreated (HFD group, n=8) or received electroacupuncture (HFD+EA group, n=8). EA was applied at PC6, ST36, SP6 and BL23. At the end of the experiment, fasting blood glucose (FBG), serum insulin (FINS), serum C-peptide (C-P) and homeostatic model assessment of insulin resistance (HOMA-IR) indices were determined. Pancreatic islet samples were subjected to histopathological examination. The thoracic aorta was immunostained with anti-rat insulin receptor substrate (IRS)-1, Akt and endothelial nitric oxide synthase (eNOS) antibodies. mRNA and protein expression of IRS-1, PI3K, Akt2 and eNOS in the vascular endothelium were determined by real-time PCR and Western blot analysis, respectively.

Results

The bodyweight increase of the HFD+EA group was smaller than that of the untreated HFD group. Compared with the HFD group, the levels of FBG, FINS, C-P and HOMA-IR in the HFD+EA group decreased significantly (P<0.01). Histopathological evaluation indicated that EA improved pancreatic islet inflammation. The expression of endothelial markers, such as IRS-1, PI3K, Akt2 and eNOS, decreased in the HFD group, while EA treatment appeared to ameliorate the negative impact of diet.

Conclusion

EA may improve insulin resistance and attenuate endothelial dysfunction, and therefore could play a potential role in the prevention or treatment of diabetic complications and cardiovascular disease through the PI3K/Akt signalling pathway.
Development and validation of a prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults
Authors: Mathioudakis Nestoras Nicolas , Everett Estelle , Routh Shuvodra , Pronovost Peter J , Yeh Hsin-Chieh , Golden Sherita Hill , Saria Suchi
Published: March 2018

Objective

To develop and validate a multivariable prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults.

Research design and methods

We collected pharmacologic, demographic, laboratory, and diagnostic data from 128 657 inpatient days in which at least 1 unit of subcutaneous insulin was administered in the absence of intravenous insulin, total parenteral nutrition, or insulin pump use (index days). These data were used to develop multivariable prediction models for biochemical and clinically significant hypoglycemia (blood glucose (BG) of ≤70 mg/dL and <54 mg/dL, respectively) occurring within 24 hours of the index day. Split-sample internal validation was performed, with 70% and 30% of index days used for model development and validation, respectively.

Results

Using predictors of age, weight, admitting service, insulin doses, mean BG, nadir BG, BG coefficient of variation (CVBG), diet status, type 1 diabetes, type 2 diabetes, acute kidney injury, chronic kidney disease (CKD), liver disease, and digestive disease, our model achieved a c-statistic of 0.77 (95% CI 0.75 to 0.78), positive likelihood ratio (+LR) of 3.5 (95% CI 3.4 to 3.6) and negative likelihood ratio (−LR) of 0.32 (95% CI 0.30 to 0.35) for prediction of biochemical hypoglycemia. Using predictors of sex, weight, insulin doses, mean BG, nadir BG, CVBG, diet status, type 1 diabetes, type 2 diabetes, CKD stage, and steroid use, our model achieved a c-statistic of 0.80 (95% CI 0.78 to 0.82), +LR of 3.8 (95% CI 3.7 to 4.0) and −LR of 0.2 (95% CI 0.2 to 0.3) for prediction of clinically significant hypoglycemia.

Conclusions

Hospitalized patients at risk of insulin-associated hypoglycemia can be identified using validated prediction models, which may support the development of real-time preventive interventions.
Adequacy of clinical trial evidence of metformin fixed-dose combinations for the treatment of type 2 diabetes mellitus in India
Authors: Evans Valerie , Roderick Peter , Pollock Allyson M
Published: March 2018

There is growing national and international concern about the drug regulatory system in India. Parliamentary reports have highlighted the presence of high numbers of unapproved medicines and irrational combinations of both approved and unapproved drugs in the Indian market-place. Fixed-dose combinations (FDCs) are a peculiar feature of the Indian pharmaceutical landscape. Although metformin is a first-line treatment, FDCs for diabetes in India account for two-thirds of all diabetes medicine sales, and some have not been approved by the Central Drugs Standard Control Organization (CDSCO). This study examines the basis of efficacy and safety of top-selling metformin FDCs in India against four WHO criteria from clinical trials guidelines for the approval of FDCs. Data from a commercial drug sales database (PharmaTrac) were combined with searches through published literature, clinical trial registries, and published and unpublished trial websites of metformin FDCs in adults with type 2 diabetes mellitus. Five metformin FDCs in India from November 2011 to October 2012 accounted for 80% of all metformin FDC sales by value and volume. Although all five had obtained CDSCO approval, three had been sold and marketed prior to receiving this approval. Evaluation of published and unpublished clinical trials of these five FDCs found none provided robust evidence of safety and efficacy for the treatment of type 2 diabetes. Recommendations are made for publishing evidence that underpins drug approvals, marketing bans, greater transparency through updated clinical trials databases and legislative reform in order to prevent irrational FDCs from entering the market.
Epidemiology of antibiotic-resistant wound infections from six countries in Africa
Authors: Lai Peggy S , Bebell Lisa M , Meney Carron , Valeri Linda , White Michelle C
Published: March 2018

Introduction

Little is known about the antimicrobial susceptibility of common bacteria responsible for wound infections from many countries in sub-Saharan Africa.

Methods

We performed a retrospective review of microbial isolates collected based on clinical suspicion of wound infection between 2004 and 2016 from Mercy Ships, a non-governmental organisation operating a single mobile surgical unit in Benin, Congo, Liberia, Madagascar, Sierra Leone and Togo. Antimicrobial resistant organisms of interest were defined as methicillin-resistantStaphylococcus aureus(MRSA) orEnterobacteriaceaeresistant to third-generation cephalosporins. Generalised mixed-effects models accounting for repeated isolates in a patient, potential clustering by case mix for each field service, age, gender and country were used to test the hypothesis that rates of antimicrobial resistance differed between countries.

Results

3145 isolates from repeated field services in six countries were reviewed. In univariate analyses, the highest proportion of MRSA was found in Benin (34.6%) and Congo (31.9%), while the lowest proportion was found in Togo (14.3%) and Madagascar (14.5%); country remained a significant predictor in multivariate analyses (P=0.002). In univariate analyses, the highest proportion of third-generation cephalosporin-resistantEnterobacteriaceaewas found in Benin (35.8%) and lowest in Togo (14.3%) and Madagascar (16.3%). Country remained a significant predictor for antimicrobial-resistant isolates in multivariate analyses (P=0.009).

Conclusion

A significant proportion of isolates from wound cultures were resistant to first-line antimicrobials in each country. Though antimicrobial resistance isolates were not verified in a reference laboratory and these data may not be representative of all regions of the countries studied, differences in the proportion of antimicrobial-resistant isolates and resistance profiles between countries suggest site-specific surveillance should be a priority and local antimicrobial resistance profiles should be used to guide empiric antibiotic selection.
Using domiciliary non-invasive ventilator data downloads to inform clinical decision-making to optimise ventilation delivery and patient compliance
Authors: Mansell Stephanie K , Cutts Steven , Hackney Isobel , Wood Martin J , Hawksworth Kevin , Creer Dean D , Kilbride Cherry , Mandal Swapna
Published: March 2018

Introduction

Ventilation parameter data from patients receiving home mechanical ventilation can be collected via secure data cards and modem technology. This can then be reviewed by clinicians and ventilator prescriptions adjusted. Typically available measures include tidal volume (VT), leak, respiratory rate, minute ventilation, patient triggered breaths, achieved pressures and patient compliance. This study aimed to assess the potential impact of ventilator data downloads on management of patients requiring home non-invasive ventilation (NIV).

Methods

A longitudinal within-group design with repeated measurements was used. Baseline ventilator data were downloaded, reviewed and adjustments made to optimise ventilation. Leak, VTand compliance data were collected for comparison at the first review and 3–7 weeks later. Ventilator data were monitored and amended remotely via a modem by a consultant physiotherapist between the first review and second appointment.

Results

Analysis of data from 52 patients showed increased patient compliance (% days used >4 hours) from 90% to 96% (p=0.007), increased usage from 6.53 to 6.94 hours (p=0.211) and a change in VT(9.4 vs 8.7 mL/kg/ideal body weight, p=0.022). There was no change in leak following review of NIV prescriptions (mean (SD): 43 (23.4) L/min vs 45 (19.9)L/min, p=0.272).

Conclusion

Ventilator data downloads, via early remote assessment, can help optimise patient ventilation through identification of modifiable factors, in particular interface leak and ventilator prescriptions. However, a prospective study is required to assess whether using ventilator data downloads provides value in terms of patient outcomes and cost-effectiveness. The presented data will help to inform the design of such a study.
Has the UK Healthy Start voucher scheme been associated with an increased fruit and vegetable intake among target families? Analysis of Health Survey for England data, 2001–2014
Authors: Scantlebury Rachel Jane , Moody Alison , Oyebode Oyinlola , Mindell Jennifer Susan
Published: March 2018

Background

Healthy Start (HS) is a UK government programme, introduced in 2006, providing vouchers to pregnant women or families with children aged <4 who are in receipt of certain benefits. Vouchers can be exchanged for fruit and vegetables (F&V), milk or infant formula. We sought to identify any association between HS and F&V intake.

Methods

We analysed repeated cross-sectional data from the Health Survey for England. Study participants were classified into one of four groups: one HS-eligible group and three control groups, meeting only the income or demographic or no eligibility criterion. Outcome measures were mean F&V intake and the proportions of participants consuming ≥3 and ≥1 portion/day. Outcomes were compared across the four groups over four time periods: 2001–2003, 2004–2006, 2007–2009 and 2010–2014. Regression analyses examined whether F&V intake among HS-eligible participants had a significantly different rate of change from those in the control groups.

Results

The change in mean F&V consumption over time was similar in HS-eligible adults and children to that of the control groups. Likewise, the change in odds of consuming ≥3 or ≥1 portion of F&V/day over time was similar among HS-eligible participants and control groups.

Conclusion

This study found that during the period 2001–2003 to 2010–2014, F&V consumption among adults and children in households deemed eligible for HS changed similarly to that of other adults and children. Potential explanations include that vouchers may have been spent on milk or infant formula, or that vouchers helped protect F&V consumption in low-income households.
Secular change in the association between urbanisation and abdominal adiposity in China (1993–2011)
Authors: Inoue Yosuke , Howard Annie Green , Thompson Amanda L , Gordon-Larsen Penny
Published: March 2018

Background

Little attention has been paid to how the association between urbanisation and abdominal adiposity changes over the course of economic development in low-income and middle-income countries.

Methods

Data came from the China Health and Nutrition Survey waves 1993–2011 (seven waves). A mixed linear model was used to investigate the association between community-level urbanisation with waist-to-height ratio (WHtR; an indicator of abdominal adiposity). We incorporated interaction terms between urbanisation and study waves to understand how the association changed over time. The analyses were stratified by age (children vs adults).

Results

Adult WHtR was positively associated with urbanisation in earlier waves but became inversely associated over time. More specifically, a 1 SD increase in the urbanisation index was associated with higher WHtR by 0.002 and 0.005 in waves 1993 and 1997, while it was associated with lower WHtR by 0.001 in 2011. Among child participants, the increase in WHtR over time was predominantly observed in more urbanised communities.

Conclusion

Our study suggests a shift in adult abdominal adiposity from more urbanised communities to less urbanised communities over a time of rapid economic development in China. Children living in more urbanised communities had higher increase in abdominal obesity with urbanisation over time relative to children living in less urbanised communities.
Dual Effects for Lovastatin in Anaplastic Thyroid Cancer: The Pivotal Effect of Transketolase (Tkt) on Lovastatin and Tumor Proliferation
Authors: Wang Chih-Yuan , Shui Hao-Ai , Chang Tien-Chun
Published: March 2018

This study tested the hypothesis that the effects of lovastatin on anaplastic thyroid cancer cell growth are mediated by upregulation of transketolase (TKT) expression. The effects of lovastatin on TKT protein levels in ARO cells were determined using western blot and proteomic analyses. After treatment with lovastatin and oxythiamine, the in vitro and in vivo growth of ARO cells was determined using 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assays and tumor xenografts in nude mice. TKT protein expression in the ARO tumors was assessed using immunohistochemistry analysis. Proteomic analysis revealed that 25 µM lovastatin upregulated TKT expression. Co-treatment of ARO cells with 1 µM lovastatin + 1 µM oxythiamine increased TKT protein expression compared with control levels; however, no differences were observed with 10 µM lovastatin + 1 µM oxythiamine. Furthermore, treatment with either oxythiamine or lovastatin alone reduced ARO tumor expression of TKT, as well as decreased ARO cell proliferation in vitro and tumor growth in vivo. However, mice treated with both lovastatin and oxythiamine at the same time had tumor volumes similar to that of the untreated control group. We conclude that either lovastatin or oxythiamine reduced ARO cell growth; however, the combination of these drugs resulted in antagonism of ARO tumor growth.
Making sense of place-based clinical leadership: is England catching up?
Authors: Adams Ted , Ryan Danny , Taunt Richard
Published: March 2018

Introduction

Successful health care organisations have understood the need to engage with clinicians, with a resulting desire for clinical leaders to emerge and be trained.

Sustainability and transformation plans (STPs)

The development of sustainability and transformation plans has highlighted the need for clinical leaders to be engaged at every level of each regional plan. The plans are based around a geographical area rather than being focussed on pre-existing organisations, so-called place-based plans. Health care place-based plans need place-based clincal leaders.

Examples of clincial place-based leadership

Clinical leaders have existed across boundaries before STPs were developed, for example in Canterbury District Health Board in New Zealand or closer to home in Wales.

Conclusion

We discuss the benefits that removing organisation boundaries could have on clinical care, believing that as patients cross organisational boundaries so should their health care and so should clinical leaders.