bluuebunny/crossref_metadata_2025 huggingface dataset:
CCAR‐1 is a negative regulator of the heat‐shock response in Caenorhabditis elegans
Authors: Brunquell Jessica , Raynes Rachel , Bowers Philip , Morris Stephanie , Snyder Alana , Lugano Doreen , Deonarine Andrew , Westerheide Sandy D.
Published: July 2018

Defects in protein quality control during aging are central to many human diseases, and strategies are needed to better understand mechanisms of controlling the quality of the proteome. The heat‐shock response (HSR) is a conserved survival mechanism mediated by the transcription factor HSF1 which functions to maintain proteostasis. In mammalian cells, HSF1 is regulated by a variety of factors including the prolongevity factor SIRT1. SIRT1 promotes the DNA‐bound state of HSF1 through deacetylation of the DNA‐binding domain of HSF1, thereby enhancing the HSR. SIRT1 is also regulated by various factors, including negative regulation by the cell‐cycle and apoptosis regulator CCAR2. CCAR2 negatively regulates the HSR, possibly through its inhibitory interaction with SIRT1. We were interested in studying conservation of the SIRT1/CCAR2 regulatory interaction in Caenorhabditis elegans, and in utilizing this model organism to observe the effects of modulating sirtuin activity on the HSR, longevity, and proteostasis. The HSR is highly conserved in C. elegans and is mediated by the HSF1 homolog, HSF‐1. We have uncovered that negative regulation of the HSR by CCAR2 is conserved in C. elegans and is mediated by the CCAR2 ortholog, CCAR‐1. This negative regulation requires the SIRT1 homolog SIR‐2.1. In addition, knockdown of CCAR‐1 via ccar‐1 RNAi works through SIR‐2.1 to enhance stress resistance, motility, longevity, and proteostasis. This work therefore highlights the benefits of enhancing sirtuin activity to promote the HSR at the level of the whole organism.
Changes of the echocardiographic parameters in chronic heart failure patients with Ile337val, Glu23lys, and Ser1369ala polymorphisms of genes encoding the ATP‐sensitive potassium channels subunits in the Ukrainian population
Authors: Strutynskyi R. B. , Voronkov L. G. , Nagibin V. S. , Mazur I. D. , Stroy D. , Dosenko V. E.
Published: July 2018

Different allelic variants of genes that encode ATP‐sensitive potassium (KATP) channels’ subunits may contribute to the development of heart failure. The purpose of the work to investigate SNPs in genes that encode KATP channels in relation to echocardiographic parameters in chronic heart failure (CHF) patients. Ninety‐nine people with CHF of ischemic origin with left ventricular systolic dysfunction were examined. The control group is represented by 108 clinically healthy subjects. KCNJ11 polymorphisms Ile337Val and Glu23Lys, and ABCC8 polymorphism Ser1369Ala were genotyped using polymerase chain reaction. In CHF patients, the frequency of the Ile337Val genotype was: Ile/Ile, 40.4%; Ile/Val, 45.5%; and Val/Val, 14.1%. The patients with the Val/Val genotype had left ventricular (LV) mass that was 334.15 g, which was 27.3% (P < 0.05) lower versus Ile/Val patients (425.48 g). The index of this parameter was also significantly lower (28.4%, P < 0.05). In CHF patients, the frequency of Glu23Lys and Ser1369Ala was: Glu/Glu and Ser/Ser, 43.4%; heterozygote, 44.4%; Lys/Lys and Ala/Ala, 12.2%. The patients with the Lys/Lys and Ala/Ala genotypes had a significantly lower LV mass index and LV end‐diastolic volume (22.9% and 26.8%, P < 0.05) versus heterozygotes. Thus, the greatest LV mass and LV end‐diastolic volume values are associated with heterozygotes, while the smallest are associated with minor homozygotes.
Long‐term use of continuous subcutaneous hydrocortisone infusion therapy in patients with congenital adrenal hyperplasia
Authors: Mallappa Ashwini , Nella Aikaterini A. , Sinaii Ninet , Rao Hamsini , Gounden Verena , Perritt Ashley F. , Kumar Parag , Ling Alexander , Liu Chia‐Ying , Soldin Steven J. , Merke Deborah P.
Published: July 2018

Background

In a phase 2 short‐term (6 months) study of patients with congenital adrenal hyperplasia (CAH), continuous subcutaneous hydrocortisone infusion (CSHI) was found to be a safe, effective and well‐tolerated method of replacing cortisol with improved disease and patient‐related outcomes.

Objective

To evaluate the safety and efficacy of long‐term CSHI.

Design

Single‐centre, open‐label, phase 2 extension study.

Patients

Five adults with classic CAH.

Measurements

Biomarkers of disease control, metabolic indices and health‐related quality‐of‐life (HRQoL) estimates.

Results

Six of eight patients chose to continue on long‐term CSHI therapy. Compared to baseline, eighteen months of CSHI resulted in decreased (P = 0.043) 0700‐hour ACTH, 17‐hydroxyprogesterone, androstenedione and progesterone; increased whole‐body lean mass (P = 0.024); and improved HRQoL, especially symptoms of adrenal insufficiency (P = 0.003). Findings at six and eighteen months did not differ, and improvements achieved in androgen control, lean body mass and HRQoL after 6 months of CSHI were maintained at eighteen months. The hydrocortisone dose appeared to decrease with time [6 vs 18 months: 38.3 ± 8.8 vs 33.6 ± 12.2 mg/day (P = 0.062)], especially in women receiving oral contraceptives. Reduction of testicular adrenal rest and adrenal size observed at 6 months remained stable. In one patient, an adrenal adenoma continually decreased over time. Subjective improvement in hirsutism was reported.

Conclusions

Long‐term use of CSHI is a safe and well‐tolerated treatment option in a select set of adults with classic CAH. Improvements observed short term in disease control and subjective health status continued long term.
Melatonin secretion following brain midline irradiation is diminished, but not correlated with subjective sleep disturbances
Authors: Rosenkranz Esther , Thissen Andrea , Siegel Sonja , Piroth Marc , Clusmann Hans , Gebauer Judith , Brabant Georg , Kreitschmann‐Andermahr Ilonka
Published: July 2018

Objective

Cranial irradiation for brain tumours or leukaemias has been related to cognitive, endocrine and psychosocial late effects as well as sleep disturbances and increased daytime sleepiness. Studies suggest that cranial irradiation might impact on pineal melatonin secretion. Melatonin is an important regulator in human circadian rhythms and the sleep‐wake cycle. The objective of this study was to investigate melatonin secretion, subjective sleep parameters and their interplay in a cohort of cranially irradiated head and brain tumour and leukaemia survivors at least 3 years after radiotherapy.

Design

Cross‐sectional study.

Patients

Thirty‐eight adults.

Measurements

Melatonin secretion was evaluated by measuring its metabolite 6‐sulphatoxymelatonin in collected overnight urine. Subjective sleep quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. The Beck Depression Inventory II was used to screen for depressive symptoms because of their impact on sleep.

Results

Patients irradiated in the brain midline had significantly lower melatonin secretion (P = 0.008). Subjects exhibited a high prevalence of sleeping difficulties, daytime sleepiness and depression, with females and overweight subjects particularly affected. Melatonin values and subjective sleep parameters did not correlate with each other or with treatment and most patient variables.

Conclusions

Our data suggest that radiation exposure to the pineal gland negatively affects melatonin secretion. This lack of pineal melatonin does not influence subjective sleep quality. As melatonin has important antioxidant and cancer‐protective effects, further research is necessary to elucidate whether these patients have an increased risk of developing secondary neoplasms and other radiation late effects.
β‐catenin regulates IRF3‐mediated innate immune signalling in colorectal cancer
Authors: Ding Chengming , He Jun , Zhao Jun , Li Junhua , Chen Jie , Liao Wenyan , Zeng Yi , Zhong Jing , Wei Chaoying , Zhang Liming , Zhou Mei , Jia Zeming , Zhang Yaoting , Li Hui , Zhou Yuzheng , Xiao Xiaolong , Han Dong , Li Chong , Zhu Zhu , Xia Zanxian , Peng Jian
Published: July 2018

Objective

β‐catenin is one of the most critical oncogenes associated with many kinds of human cancers, especially in the human CRC. Innate immunity recognizes tumour derived damage‐associated molecular patterns (DAMPs) and primes the anti‐tumour adaptive responses. While the function of β‐catenin in CRC tumourigenesis is well established, its impact on innate immune evasion is largely unknown. The aim of this study is to characterize the role of β‐catenin in inhibiting RIG‐I‐like receptor (RLR)‐mediated IFN‐β signalling in colorectal cancer.

Materials and Methods

Immunohistochemical staining and western blotting were conducted to study the expression of β‐catenin, IRF3 and phospho‐IRF3 (p‐IRF3) in CRC samples and cell lines. Plaque assay determining virus replication was performed to assess the regulation of β‐catenin on IFN‐β signalling. The inhibition of β‐catenin on RLR‐mediated IFN‐β signalling was further studied by real‐time analyses and reporter assays in the context of lentiviral‐mediated β‐catenin stably knocking down. Lastly, co‐immunoprecipitation and nuclear fractionation assay were conducted to monitor the interaction between β‐catenin and IRF3.

Results

We found that high expression of β‐catenin positively correlated with the expression of IRF3 in CRC cells. Overexpression of β‐catenin increased the viral replication. Conversely knocking down of β‐catenin inhibited viral replication. Furthermore, our data demonstrated that β‐catenin could inhibit the expression of IFN‐β and interferon‐stimulated gene 56 (ISG56). Mechanistically, we found that β‐catenin interacted with IRF3 and blocked its nuclear translocation.

Conclusion

Our study reveals an unprecedented role of β‐catenin in enabling innate immune evasion in CRC.
Effect of contrasting tillage and cropping systems on soil aggregation, carbon pools and aggregate‐associated carbon in rainfed Vertisols
Authors: Somasundaram J. , Chaudhary R. S. , Awanish Kumar D. , Biswas A. K. , Sinha N. K. , Mohanty M. , Hati K. M. , Jha P. , Sankar M. , Patra A. K. , Dalal R. , Chaudhari S. K.
Published: July 2018

Worldwide, conservation agriculture practices involving minimal soil disturbances and retention of crop residue (>30%) have been practised increasingly and recognized to enhance soil health by optimizing key soil attributes. However, little information is available on the short‐term effects of conservation agriculture practices on soil properties under rainfed Vertisols of Central India. Thus, our aim was to study the short‐term effects of contrasting tillage treatments and cropping systems on soil aggregation, aggregate‐associated carbon (C), carbon pools and crop productivity. This study comprised three tillage systems (TS), reduced tillage (RT), no tillage (NT) with retention of crop residue and conventional tillage (CT), together with four cropping systems (CS), namely soya bean (Glycine max L.) + pigeon pea (Cajanus cajan L.) (2:1), soya bean–wheat (Titricum durum L.), maize (Zea mays L.) + pigeon pea (1:1), and maize–chickpea Cicer arietinum L.). The experiment was laid out in a split‐plot design with three replicates. Soil samples were collected at four depths: 0–5, 5–15, 15–30 and 30–45 cm from the experimental field after completion of four crop cycles. Results indicated that at depths 0–5 and 5–15 cm, tillage and cropping system had a significant effect on aggregate mean weight diameter (MWD). The MWDs of 0.97 and 0.94 mm were larger for NT than CT (0.77 and 0.83 mm) at 0–5‐ and 5–15‐cm depths, respectively. Water‐stable aggregates (WSAs) were also larger for NT (70.74%) and RT (70.09%) than CT (59.50%) at 0–5 cm. Tillage practice, cropping system and their interaction had a greater effect (P < 0.05) on the content of aggregate‐associated C for large macroaggregates (LM). There was more aggregate‐associated C for NT and RT at 0–5‐cm depth than for CT. Cropping system also had a significant effect (P < 0.05) on aggregate‐associated C at 0–5‐cm depth. Soil organic C (%) fractions were in the order of non‐labile >very labile >less labile >labile for 0–5‐ and 5–15‐cm depths after four crop cycles. Less labile and non‐labile C fractions contributed >50% of TOC, indicating a more recalcitrant form of carbon present in the soil. Tillage had no significant effect (P > 0.05) on crop yields after four crop cycles. Conservation agriculture can have a positive effect on aggregate stability, aggregate‐associated C and different carbon pools in a Vertisol.

Highlights

Does conservation agriculture affect soil aggregation, aggregate stability and carbon pools more than conventional tillage?

The SOC concentration increases with aggregate size and provides physical protection and stabilization of carbon (C).

Aggregate‐associated C content was significantly affected by tillage practices and cropping system.

Less labile and non‐labile C fractions contribute >50% TOC in the rainfed Vertisols of central India.
Biodiversity monitoring, earth observations and the ecology of scale
Authors: Anderson Christopher B.
Published: July 2018

Human activity and land‐use change are dramatically altering the sizes, geographical distributions and functioning of biological populations worldwide, with tremendous consequences for human well‐being. Yet our ability to measure, monitor and forecast biodiversity change – crucial to addressing it – remains limited. Biodiversity monitoring systems are being developed to improve this capacity by deriving metrics of change from an array of in situ data (e.g. field plots or species occurrence records) and Earth observations (EO; e.g. satellite or airborne imagery). However, there are few ecologically based frameworks for integrating these data into meaningful metrics of biodiversity change. Here, I describe how concepts of pattern and scale in ecology could be used to design such a framework. I review three core topics: the role of scale in measuring and modelling biodiversity patterns with EO, scale‐dependent challenges linking in situ and EO data and opportunities to apply concepts of pattern and scale to EO to improve biodiversity mapping. From this analysis emerges an actionable approach for measuring, monitoring and forecasting biodiversity change, highlighting key opportunities to establish EO as the backbone of global‐scale, science‐driven conservation.
An operational risk assessment framework for a plant health diagnostic laboratory
Authors: Murugan S. , Kumarasinghe L.
Published: July 2018

The establishment of an operational risk assessment framework (ORAF) for effective management of risks is vital to any organization. An ORAF at the Ministry for Primary Industries (MPI) Plant Health and Environment Laboratory (PHEL), Auckland, New Zealand has identified the key risks in the laboratory operations and methods for mitigating and managing these risks. Ultimately, clear accountabilities have been set for risk management so that PHEL can maximize its ability to meet its strategic objectives and the wider goals of MPI. In addition, this framework provides an opportunity to affirm the effectiveness of the existing business process and continuously builds upon it to address gaps and also centralizes risk management information for staff. This study presents the steps that PHEL has undertaken to develop, implement and enhance its ORAF. The potential risks faced by plant diagnostic laboratories, planning of staff resources and development of the tools required to undertake risk assessment activities are included. This study also explains how the laboratory implements treatment plans, mitigates risk events and monitors and maintains the framework. Finally, this study explains some of the challenges faced by PHEL during the establishment of the ORAF.
Rapid shifts in distribution and high‐latitude persistence of oceanographic habitat revealed using citizen science data from a climate change hotspot
Authors: Champion Curtis , Hobday Alistair J. , Tracey Sean R. , Pecl Gretta T.
Published: July 2018

The environmental effects of climate change are predicted to cause distribution shifts in many marine taxa, yet data are often difficult to collect. Quantifying and monitoring species’ suitable environmental habitats is a pragmatic approach for assessing changes in species distributions but is underdeveloped for quantifying climate change induced range shifts in marine systems. Specifically, habitat predictions present opportunities for quantifying spatiotemporal distribution changes while accounting for sources of natural climate variation. Here we demonstrate the utility of a marine‐based habitat model parameterized using citizen science data and remotely sensed environmental covariates for quantifying shifts in oceanographic habitat suitability over 22 years for a coastal‐pelagic fish species in a climate change hotspot. Our analyses account for the effects of natural intra‐ and interannual climate variability to reveal rapid poleward shifts in core (94.4 km/decade) and poleward edge (108.8 km/decade) oceanographic habitats. Temporal persistence of suitable oceanographic habitat at high latitudes also increased by approximately 3 months over the study period. Our approach demonstrates how marine citizen science data can be used to quantify range shifts, but necessitates shifting focus from species distributions directly, to the distribution of species’ environmental habitat preferences.
Validation of the Haemophilia & Exercise Project‐Test‐Questionnaire (HEP‐Test‐Q)—An instrument for the assessment of subjective physical functioning in children with haemophilia
Authors: von Mackensen S. , Hilberg T. , Valentino L. A. , Kurnik K. , Khair K.
Published: July 2018

Introduction

Contemporary haemophilia management recommends sport and physical activity in children with haemophilia. Assessment of subjective physical functioning requires standardized and validated instruments.

Aims

To adapt and psychometrically test the adult Haemophilia & Exercise Project‐Test‐Questionnaire (HEP‐Test‐Q) for children (aged 6‐17 years).

Methods

In discussion rounds with children, single items of the adult HEP‐Test‐Q were reformulated to make them understandable without changing the item concept. The validation of the child‐adapted version in children with haemophilia (n = 228) included pre‐testing with feasibility testing, cognitive interviewing (n = 34), pilot‐testing of the revised version in the EIS Study (n = 67) and field‐testing in the SO‐FIT Study (n = 127).

Results

Pre‐testing revealed a completion time of 8.2 ± 4.1 minutes and children liked the instrument. Cognitive interviews demonstrated that most items were easy to understand; 9 items were reformulated. Pilot‐testing demonstrated good psychometric characteristics in terms of reliability (α = .94 Total Score) and validity. Convergent validity testing showed moderate correlations with the Haemo‐QoL (r = −.491), but low correlations with the Petrini Score (r = −.293). Known groups’ validity revealed significant differences in clinical subgroups; chronic pain (P < .002) and target joints (P < .021). Field‐testing confirmed psychometric characteristics; Cronbach's alpha ranged from α = .80 (“endurance”) to α = .94 (Total Score). The child‐adapted HEP‐Test‐Q showed moderate correlations with the PedHAL (r = .634, P < .0001) and the Haemo‐QoL SF (r = −.575, P < .0001). Known groups’ validity testing proved that the HEP‐Test‐Q could discriminate between clinical subgroups.

Conclusion

The child‐adapted HEP‐Test‐Q is a short, practical and acceptable instrument for the assessment of subjective physical functioning. Outcomes can be compared to adults because item concepts are identical to the adult version.
Emotional distress in haemophilia: Factors associated with the presence of anxiety and depression symptoms among adults
Authors: Pinto P. R. , Paredes A. C. , Moreira P. , Fernandes S. , Lopes M. , Carvalho M. , Almeida A.
Published: July 2018

Introduction

Haemophilia is related to several clinical and psychosocial challenges that have been associated with increased emotional distress. These may impact on disease adjustment and health outcomes, reinforcing the attention given to psychosocial health of people with haemophilia (PWH), in the scope of optimal comprehensive care.

Aim

To identify potentially modifiable factors associated with the presence of anxiety and depression symptoms among adult PWH.

Methods

This was a cross‐sectional observational study examining socio‐demographic, clinical and psychosocial variables among 102 patients with haemophilia A or B who participated on a mail survey of haemophilia in Portugal.

Results

People with haemophilia revealing higher anxiety and depression symptoms were more likely to have had, in the previous year, more urgent hospital visits due to haemophilia, more bleeding episodes, more affected joints and pain, as well as worst levels of perceived functionality and quality of life. After controlling for demographic (age and education) and clinical (haemophilia severity and joint deterioration) variables in multivariate hierarchical logistic regression analyses, professional status (OR = 4.646, P = .004; OR = 3.333, P = .029) and pain interference (OR = 1.397, P = .011; OR = .1.347, P = .037) were significantly associated with both anxiety and depression symptoms. Additionally, physical activity (OR = 0.302, P = .024) and the perception of consequences underlying haemophilia (OR = 1.600, P = .012) also emerged as key factors significantly associated with depression symptoms.

Conclusion

Current findings increased knowledge on factors associated with anxiety and depression among PWH. These highlight potential intervention targets, which are amenable to change through evidence‐based tailored interventions aiming to decrease emotional distress, promote well‐being and improving haemophilia‐related health outcomes among these patients.
Clinical and radiologic results after open‐wedge high tibial osteotomy in haemophilic knee arthropathy with varus deformity
Authors: Cho Y. J. , Song S. J. , Rhyu K. H. , Jang T. S. , Park C. H.
Published: July 2018

Introduction

The previous studies have described only closed‐wedge high tibial osteotomy (HTO) in haemophilic arthropathy (HA).

Aim

The purpose of this study was to evaluate clinical and radiographic results after open‐wedge HTO in HA with varus knee deformity.

Methods

We included 13 open‐wedge HTOs in HA performed between 2005 and 2016. The mean age of patients was 28.9 years. Visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC), and range of motion (ROM) indices were assessed. Any complications or requirements for total knee arthroplasty (TKA) were investigated. Mechanical axis (MA), minimal joint space width (mJSW) and Pettersson score were measured. Bone union rates at 3 and 6 months postoperative were evaluated.

Results

VAS improved from 5.1 to 2.4 (P < .001). WOMAC was 66.5 preoperatively, and 26.6 postoperatively (P < .001). Pre‐ and postoperative ROM did not differ significantly. There were no cases of HTO converted to TKA, but one case of HTO required TKA 152 months postoperative. No complications were observed. The MA was corrected from varus 5.1° to valgus 1.2° (P < .001). Pre‐ and postoperative mJSW did not significantly differ. Pettersson score improved from 3.84 to 2.47 (P < .001). The bone union rates at the osteotomy gap were 45.2% and 67.8% at 3 and 6 months postoperative.

Conclusions

Open‐wedge HTO should be considered in cases of HA with varus deformity in young haemophilic patients, even though inflammatory arthritis is not an optimal indication for this procedure. It can be an appropriate treatment with respect to the choice to postpone TKA.
Effect of peroxyl radicals on the structure and gel properties of isolated rabbit meat myofibrillar proteins
Authors: Wang Zhaoming , He Zhifei , Gan Xiao , Li Hongjun
Published: July 2018

We investigated the effect of peroxyl radicals (ROO·), which are products of lipid peroxidation, on the structure and gel properties of myofibrillar proteins (MPs) isolated from rabbit meat. 2,2′‐Azobis(2‐amidinopropane) dihydrochloride (AAPH) was heated to stably derive ROO·. As the AAPH concentration increased, the protein carbonyl compounds significantly accumulated (P < 0.05), and the total sulfhydryl content was significantly lost (P < 0.05). Circular dichroism spectra, UV absorption spectra, intrinsic fluorescence spectra and surface hydrophobicity revealed that ROO· caused protein unfolding and conformational changes in MPs. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) analysis indicated that moderate (0–3 mm) and relatively high (5 and 10 mm) AAPH concentrations could lead to protein crosslinking and protein aggregation, respectively. These changes in protein structure could influence the gelling properties of MPs. Low‐level protein oxidation could increase gel strength and water holding capacity, whereas high‐level protein oxidation could reduce gel properties.
Membrane vesicles from Pseudomonas aeruginosa activate the noncanonical inflammasome through caspase‐5 in human monocytes
Authors: Bitto Natalie J , Baker Paul J , Dowling Jennifer K , Wray‐McCann Georgie , De Paoli Amanda , Tran Le Son , Leung Pak Ling , Stacey Katryn J , Mansell Ashley , Masters Seth L , Ferrero Richard L
Published: July 2018

Outer membrane vesicles (OMVs) are constitutively produced by Gram‐negative bacteria both in vivo and in vitro. These lipid‐bound structures carry a range of immunogenic components derived from the parent cell, which are transported into host target cells and activate the innate immune system. Recent advances in the field have shed light on some of the multifaceted roles of OMVs in host–pathogen interactions. In this study, we investigated the ability of OMVs from two clinically important pathogens, Pseudomonas aeruginosa and Helicobacter pylori, to activate canonical and noncanonical inflammasomes. P. aeruginosa OMVs induced inflammasome activation in mouse macrophages, as evidenced by “speck” formation, as well as the cleavage and secretion of interleukin‐1β and caspase‐1. These responses were independent of AIM2 and NLRC4 canonical inflammasomes, but dependent on the noncanonical caspase‐11 pathway. Moreover, P. aeruginosa OMVs alone were able to activate the inflammasome in a TLR‐dependent manner, without requiring an exogenous priming signal. In contrast, H. pylori OMVs were not able to induce inflammasome activation in macrophages. Using CRISPR/Cas9 knockout THP‐1 cells lacking the human caspase‐11 homologs, caspase‐4 and ‐5,we demonstrated that caspase‐5 but not caspase‐4 is required for inflammasome activation by P. aeruginosa OMVs in human monocytes. In contrast, free P. aeruginosa lipopolysaccharide (LPS) transfected into cells induced inflammasome responses via caspase‐4. This suggests that caspase‐4 and caspase‐5 differentially recognize LPS depending on its physical form or route of delivery into the cell. These findings have relevance to Gram‐negative infections in humans and the use of OMVs as novel vaccines.
Grain yield of wheat (Triticum aestivum L.) under long‐term heat stress is sink‐limited with stronger inhibition of kernel setting than grain filling
Authors: Hütsch Birgit W. , Jahn Dana , Schubert Sven
Published: July 2018

The aim of the study was to investigate source‐sink relations of wheat under continuous heat stress and to identify bottle necks of yield formation. A pot experiment was conducted in two climatic chambers exposing wheat plants (Triticum aestivum L. cv. Thasos) either to day/night temperatures of 20/20°C (control conditions) or of 30/25°C (heat stress) during the whole vegetation period in the absence of plant water deficit. Plants were harvested at four phenological stages: three‐node stage (DC 33), start of flowering (DC 61), grain filling (DC 75) and maturity (DC 94). Heat stress shortened the development phases of the plants and caused a significant decrease in total above‐ground biomass between 19% and 41%. At grain filling and at maturity, the reductions in total shoot biomass mainly resulted from grain yield depressions by 77% and 58%, respectively. The ear number per plant was significantly higher under heat stress in comparison with the control, at maturity it was more than doubled. On the contrary, under heat stress, the kernel number per ear was strongly decreased by 83% and 75% during grain filling and at maturity, respectively. The decrease in individual kernel weight was 23% at maturity. Thus, the heat‐stressed plants were able to strongly increase the number of ear‐bearing tillers which were able to set only a small number of kernels, yet these kernels showed good grain filling. The harvest index (HI) of heat‐stressed plants was significantly reduced by 36% (control: HI = 50.1% ± 0.4, heat: HI = 32.2% ± 0.9***). The plants in the stress treatment adapted to the adverse conditions by less biomass production which presumably allowed a higher transpiration without an increase in total water consumption. Nevertheless, under heat stress, the water use efficiency (WUEgrain) was strongly decreased by 62% as a result of a small grain yield. In ears and grains, the sucrose, glucose and fructose concentrations were not significantly different between control and heat stress at start of flowering and during grain filling. Thus, the supply of assimilates was not restricted (no source limitation). Sink capacity was reduced by heat stress, as lesser and smaller kernels were produced than in the control. Concerning sink activity, the sink‐limiting step during kernel set is probably the active transport of hexoses across the plasma membrane into the developing kernels, which could also affect grain filling. This needs to be investigated in more detail in further studies.
Ambulatory blood pressure monitoring in the 21st century
Authors: O'Brien Eoin , White William B. , Parati Gianfranco , Dolan Eamon
Published: July 2018

In clinical practice, ambulatory blood pressure monitoring (ABPM) tends to be used solely for diagnosing hypertension, especially to identify white‐coat and masked hypertension. However, ABPM can provide additional information to guide the management and drug treatment of hypertension. In this brief review, the general principles governing the use of ABPM in clinical practice, such as the devices and software, recording requirements, the thresholds for the day, night and 24‐hour periods and how often to repeat ABPM are summarized. The use of ABPM for diagnosing, determining the efficacy of treatment, and assessing the long‐term control of hypertension are discussed.
Office blood pressure measurement in the 21st century
Authors: Myers Martin G. , Asmar Roland , Staessen Jan A.
Published: July 2018

Measurement of blood pressure (BP) using the auscultatory method must follow specific rules and conditions to be reliable. Nonetheless, these requirements are often not followed in clinical practice, resulting in inaccurate BP readings. Simply replacing manual sphygmomanometers with an oscillometric device may still produce readings that are associated with a white coat effect. These limitations can be overcome by using an oscillometric sphygmomanometer that automatically records multiple readings with the patient resting quietly and alone, called automated office (AO)BP. AOBP produces office readings with a reduced white coat effect, which are also similar to the awake ambulatory BP. There is also evidence that AOBP is a better predictor of target organ damage than attended office BP. Furthermore, clinical outcome data support AOBP as having both a similar diagnostic threshold as awake ambulatory BP and a lower treatment target. Using AOBP in clinical practice simplifies recording office BP by not requiring an additional period of rest before activation of the device and by not having staff present during the actual measurements. Recent studies have reported that automatic BP measurements taken by staff in research studies with close adherence to guidelines using AOBP devices may produce similar readings to AOBP. Further research is needed to determine the best method for recording BP at systolic targets < 130 mm Hg and the relationship of office BP to ambulatory BP and home BP.
Patterns of ambulatory blood pressure: clinical relevance and application
Authors: O'Brien Eoin , Kario Kazuomi , Staessen Jan A. , de la Sierra Alejandro , Ohkubo Takayoshi
Published: July 2018

Ambulatory blood pressure measurement (ABPM) is now recommended in all patients suspected of having hypertension. However, in practice, the mean daytime pressures are often used to make diagnostic and therapeutic decisions, and the information from abnormal patterns of blood pressure behavior is often overlooked. This paper presents daytime patterns (eg, white coat hypertension and siesta dipping), nocturnal patterns (eg, dipping, non‐dipping, reverse dipping, and the morning surge), and discusses ambulatory hypotension, and abnormal patterns and indices of related hemodynamic parameters (eg, heart rate, pulse pressure, and blood pressure variability).
Guidelines for blood pressure measurement: development over 30 years
Authors: Stergiou George S. , Parati Gianfranco , McManus Richard J. , Head Geoffrey A. , Myers Martin G. , Whelton Paul K.
Published: July 2018

In the last 2 decades, several scientific societies have published specific guidelines for blood pressure (BP) measurement, providing detailed recommendations for office, home, and ambulatory BP monitoring. These documents typically provided strong support for using out‐of‐office BP monitoring (ambulatory and home). More recently, several organizations recommended out‐of‐office BP evaluation as a primary method for diagnosing hypertension and for treatment titration, with office BP regarded as a screening method. Efforts should now be directed towards making ambulatory and home BP monitoring readily available in primary care and ensuring that such measurements are obtained by following current guidelines. Moreover, it should be mandatory for all published clinical research papers on hypertension to provide details on the methodology of the BP measurement.
Blood pressure variability: clinical relevance and application
Authors: Parati Gianfranco , Stergiou George S. , Dolan Eamon , Bilo Grzegorz
Published: July 2018

Blood pressure variability is an entity that characterizes the continuous and dynamic fluctuations that occur in blood pressure levels throughout a lifetime. This phenomenon has a complex and yet not fully understood physiological background and can be evaluated over time spans ranging from seconds to years. The present paper provides a short overview of methodological aspects, clinical relevance, and potential therapeutic interventions related to the management of blood pressure variability.
Development, characterization and virus susceptibility of a continuous cell line from the caudal fin of marbled eel (Anguilla marmorata)
Authors: Pao H Y , Wu C Y , Huang C H , Wen C M
Published: July 2018

A continuous cell line consisting mostly of epithelioid cells was established from the caudal fin of marbled eels (Anguilla marmorata) and designated as marbled eel caudal fin (MECF)‐1. The cells multiplied well in Leibovitz's L‐15 medium containing 2% to 15% foetal bovine serum at temperatures of 20°C to 35°C and were subcultured for >90 passages during a 5‐year period from 2012 to 2017. Transcripts of ictacalcin, keratin 13, cd146, nestin, ncam1 and myod1 were demonstrated in the cells using reverse transcription polymerase chain reaction. The results indicated that MECF‐1 was composed of epidermal and mesenchyme stem and progenitor cells including myoblasts. MECF‐1 was susceptible to Japanese eel herpesvirus HVA980811, marbled eel polyoma‐like virus (MEPyV), aquabirnavirus MEIPNV1310 and aquareovirus CSV. By contrast, MECF‐1 was noted refractory to megalocytiviruses RSIV‐Ku and GSIV‐K1 infection. Moreover, the cells were resistant to betanodavirus infection. In conclusion, MECF‐1 derived from marbled eel is suitable for studies on anguillid viruses and interaction with host cells.
Railroad development, temporal‐spatial externalities, and growth spillover: Theory and empirical evidence
Authors: Chen Yun , Wei Lijia
Published: July 2018

This paper develops an extended Solow model by considering the time‐variant spillover effect of interregional economies. Instead of using fixed spatial distances among regions, the regions' temporal‐spatial distances are measured by constructing a database of train types and calculating the fastest region‐to‐region routes. We collect provincial economic data and railroads data over the period 2003–2012 in China to establish a dynamic temporal‐spatial panel model. The estimation results indicate significant temporal‐spatial externalities. Compared with classical spatial models, the temporal‐spatial model not only has a much better goodness‐of‐fit but also has consistent total effects, direct effects and indirect effects.
Single and multiple dose pharmacokinetics of a novel mirtazapine transdermal ointment in cats
Authors: Buhles William , Quimby Jessica M. , Labelle Daizie , Williams Valentine S.
Published: July 2018

Single and multiple dose pharmacokinetics (PK) of mirtazapine transdermal ointment applied to the inner ear pinna of cats were assessed. Study 1 was a randomized, cross‐over single dose study (n = 8). Cats were treated once with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner ear pinna (treatment) or administered orally (control) and then crossed over after washout. Plasma was collected predose and at specified intervals over 96 hr following dosing. Study 2 was a multiple dose study (n = 8). Cats were treated daily for 14 days with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner pinna. Plasma was collected on Day 13 predose and at specified intervals over 96 hr following the final dose. In Study 1, single transdermal administration of mirtazapine resulted in mean Tmax = 15.9 hr, Cmax = 21.5 ng/mL, AUC0‐24 = 100 ng*hr/mL, AUC0‐∞ = 260 ng*hr/mL and calculated half‐life = 26.8 hr. Single oral administration of mirtazapine resulted in mean Tmax = 1.1 hr, Cmax = 83.1 ng/mL, AUC0‐24 = 377 ng*hr/mL, AUC0‐∞ = 434 ng*hr/mL and calculated half‐life = 10.1 hr. Mean relative bioavailability (F) of transdermal to oral dosing was 64.9%. In Study 2, daily application of mirtazapine for 14 days resulted in mean Tmax = 2.1 hr, Cmax = 39.6 ng/mL, AUC0‐24 = 400 ng*hr/mL, AUC0‐∞ = 647 ng*hr/mL and calculated half‐life = 20.7 hr. Single and repeat topical doses of a novel mirtazapine transdermal ointment achieve measurable plasma concentrations in cats.
Hookworms Make Us Human: The Microbiome, Eco‐immunology, and a Probiotic Turn in Western Health Care
Authors: Lorimer Jamie
Published: July 2018

Historians of science have identified an ecological turn underway in immunology, driven by the mapping of the human microbiome and wider environmentalist anxieties. A figure is emerging of the human as a holobiont, composed of microbes and threatened by both microbial excess and microbial absence. Antimicrobial approaches to germ warfare are being supplemented by probiotic approaches to restoring microbial life. This article examines the political ecology of this probiotic turn in Western health care. It focuses onNecator americanus—a species of human hookworm—and its relations with immunologists. The analysis moves from a history of human disentanglement from hookworm, to contemporary anxieties about their absence. It examines the reintroduction of worms for helminthic therapy and explores emerging trajectories for probiotic health care involving the synthesis, modification, and/or restoration of worms and their salutary ecologies. The conclusion differentiates these trajectories and identifies an emerging model of “post‐paleo” microbiopolitics.
The impact of transposable elements in adaptive evolution
Authors: Schrader Lukas , Schmitz Jürgen
Published: July 2018

The growing knowledge about the influence of transposable elements (TEs) on (a) long‐term genome and transcriptome evolution; (b) genomic, transcriptomic and epigenetic variation within populations; and (c) patterns of somatic genetic differences in individuals continues to spur the interest of evolutionary biologists in the role ofTEs in adaptive evolution. AsTEs can trigger a broad range of molecular variation in a population with potentially severe fitness and phenotypic consequences for individuals, different mechanisms evolved to keepTEactivity in check, allowing for a dynamic interplay between the host, itsTEs and the environment in evolution. Here, we review evidence for adaptive phenotypic changes associated withTEs and the basic molecular mechanisms by which the underlying genetic changes arise: (a) domestication, (b) exaptation, (c) host gene regulation, (d)TE‐mediated formation of intronless gene copies—so‐called retrogenes and (e) overall increased genome plasticity. Furthermore, we review and discuss how the stress‐dependent incapacitation of defence mechanisms against the activity ofTEs might facilitate adaptive responses to environmental challenges and how such mechanisms might be particularly relevant in species frequently facing novel environments, such as invasive, pathogenic or parasitic species.
Work of breathing for cuffed and uncuffed pediatric endotracheal tubes in an in vitro lung model setting
Authors: Thomas Jörg , Weiss Markus , Cannizzaro Vincenzo , Both Christian Peter , Schmidt Alexander Robert
Published: July 2018

Background

Over the last decade, cuffed endotracheal tubes are increasingly used in pediatric anesthesia and also in pediatric intensive care. However, the smaller inner diameter of cuffed endotracheal tubes and, implicitly, the increased endotracheal tube resistance is still a matter of debate.

Aims

This in vitro study investigated work of breathing and inspiratory airway pressures in cuffed and uncuffed endotracheal tubes and the impact of pressure support ventilation and automatic tube compensation.

Methods

In 5 simulated neonatal and pediatric lung models, the Active Servo Lung 5000 and an intensive care ventilator were used to quantify the differences in work of breathing under spontaneous breathing (with and without pressure support ventilation and automatic tube compensation) between cuffed and uncuffed endotracheal tubes. Additionally, differences in inspiratory airway pressures, measured either proximal or distal of the endotracheal tube, between cuffed and uncuffed endotracheal tubes under mechanical ventilation were investigated.

Results

Work of breathing was overall 10.27% [95% confidence interval 9.01‐11.94] higher with cuffed than with uncuffed endotracheal tubes and was dramatically reduced by 34.19% [95% confidence interval 31.61‐35.25] with the application of pressure support. Automatic tube compensation almost diminished work of breathing differences between the 2 endotracheal tube types in nearly all pediatric lung models. Peak inspiratory and mean airway pressures measured at the proximal endotracheal tube end revealed significantly higher values in cuffed than in uncuffed endotracheal tubes. However, these differences measured at the distal end of the endotracheal tube became minimal.

Conclusion

This in vitro study confirmed significant differences in work of breathing and inspiratory pressures between cuffed and uncuffed endotracheal tubes. Work of breathing, however, is almost neutralized by pressure support ventilation with automatic tube compensation and distal inspiratory airway pressures that, from a clinical perspective, are not significantly increased.
Estimated glomerular filtration rate after nephrectomy for Wilms tumor
Authors: Kazama Takuro , Nio Masaki , Sasaki Hideyuki , Fukuzawa Taichi , Sato Tomoyuki
Published: July 2018

Background

The aim of this study was to assess long‐term residual kidney function after unilateral nephrectomy for non‐syndromic Wilms tumor (NSWT).

Methods

Of the patients who underwent one‐sided NSWT at Tohoku University Hospital between 1977 and 2003, nine were followed up until age ≥18 years. For these nine patients, we retrospectively evaluated estimated glomerular filtration rate (eGFR) in childhood (3–10 years old), adolescence (11–17 years old) and adulthood (≥18 years).

Results

Mean age at the last follow up was 23.0 years. Tumor classification was as follows: stage I tumor, n = 6; stage II tumor, n = 3; mixed‐type nephroblastoma, n = 8; and congenital mesoblastic nephroma, n = 1. Mean eGFR was 101.3 ± 21.2 mL/min/1.73 m2 in childhood, 106.0 ± 32.1 mL/min/1.73 m2 in adolescence and 100.5 ± 20.7 mL/min/1.73 m2 in adulthood. Therefore, no significant change in eGFR was observed over the three life stages evaluated. Further, none of the patients met the diagnostic criteria for chronic kidney disease by early adulthood.

Conclusions

eGFR after unilateral nephrectomy in patients with NSWT remained ≥60 mL/min/1.73 m2 during the transition from childhood to early adulthood, with no development of chronic kidney disease or end‐stage kidney failure.
Investigating spatial variations in access to childcare provision using network‐based Geographic Information System models
Authors: Langford Mitchel , Higgs Gary , Dallimore David J.
Published: July 2018

A “flagship” policy outlined in the current Welsh Government's 2016 Programme for Government aims to provide 30 hours of free early education and childcare per week to the working parents of three‐ and four‐year‐olds. However, in common with many other countries, there is currently a lack of detail regarding existing levels of childcare provision that can act as a benchmark with which to examine the impacts of this policy. This article addresses an urgent need to understand current levels of provision at detailed geographical scales so as to provide an accurate picture of early childhood education and care across Wales. By drawing on Geographic Information System network models we compare the spatial distribution of providers with that of potential demand arising from those population groups targeted in the childcare offer. These provide a simple to understand supply‐to‐demand ratio that overcome the limitations of ratios derived for arbitrary administrative boundaries. The types of map‐based outputs that emanate from such an approach are demonstrated to provide more insights into spatial patterns of accessibility to current levels of childcare provision. These have guided the choice of pilot studies that will inform the roll out of the full childcare offer by the Welsh Government in 2020.
Social policies and solidarity during the Greek Crisis
Authors: Kourachanis Nikos , Lalioti Varvara , Venieris Dimitris
Published: July 2018

This article provides a succinct overview of the phenomenon of solidarization in crisis‐ridden Greece. Brief accounts of the pre‐ and post‐crisis situation in four core social policy areas (health, employment, housing, education) are combined with the presentation of four illustrative case studies, one for each of the aforementioned areas. Drawing on a broad range of primary and secondary data, including 20 in‐depth interviews with key stakeholders and end‐users of the actions examined, we argue that while the crisis provoked a further “residualization” of the institutionalized solidarity system, it also triggered the development of new solidarity ventures, both by state and non‐state actors, often even including partnerships between them. These ventures reflect the building of a bridge between institutionalized and informal solidarity in Greece and the shift towards a new type of mixed, although fragmented, mode of solidarity.
A parametric study of DIC measurement uncertainties on cracked metals
Authors: Wigger Tim , Lupton Colin , Tong Jie
Published: July 2018

Displacements and strains in the presence of a crack in welded steels have been studied using digital image correlation (DIC) under zero load and selected loading conditions. A parametric study has been carried out to assess the effects of some of the key parameters, including subset size, step size, and the size of the measurement window, on the measurement uncertainties for systematic and random errors. The assessments were carried out a region around the crack tip, where high strain gradients and inhomogeneous deformation present significant challenges for DIC measurements.