bluuebunny/crossref_metadata_2025 huggingface dataset:
The genomic pool of standing structural variation outnumbers single nucleotide polymorphism by threefold in the marine teleost Chrysophrys auratus
Authors: Catanach Andrew , Crowhurst Ross , Deng Cecilia , David Charles , Bernatchez Louis , Wellenreuther Maren
Published: February 2019

Recent studies have highlighted an important role of structural variation (SV) in ecological and evolutionary processes, but few have studied nonmodel species in the wild. As part of our long‐term research programme on the nonmodel teleost fish Australasian snapper (Chrysophrys auratus), we aim to build one of the first catalogues of genomic variants (SNPs and indels, and deletions, duplications and inversions) in fishes and evaluate overlap of genomic variants with regions under putative selection (Tajima's D and π), and coding sequences (genes). For this, we analysed six males and six females from three locations in New Zealand and generated a high‐resolution genomic variation catalogue. We characterized 20,385 SVs and found they intersected with almost a third of all annotated genes. Together with small indels, SVs account for three times more variation in the genome in terms of bases affected compared to SNPs. We found that a sizeable portion of detected SVs was in the upper and lower genomic regions of Tajima's D and π, indicating that some of these have an effect on the phenotype. Together, these results shed light on the often neglected genomic variation that is produced by SVs and highlights the need to go beyond the mere measure of SNPs when investigating evolutionary processes, such as species diversification and adaptation.
The fibroblast of radicular cyst facilitate osteoclastogenesis via the autocrine of Fibronectin containing extra domain A
Authors: Liu Chun‐yan , Wang Hai‐Cheng
Published: February 2019

Objective

To investigate the alternative spliced isoforms of Fibronectin (FN) in the stroma of radicular cysts and analyze the associations between these isoforms and the osteoclastogenic effects of fibroblasts.

Methods and materials

The specimens of radicular cysts were stained with immunohistochemistry, and the associations between each FN isoform and clinical parameters were assessed. The fibroblasts isolated from cysts or jaw bone were cultured to induce the Trap + MNCs. In the conditioned medium, the Fibronectin containing extra domain A (EDA + FN) was neutralized by antibody IST‐9, and the EDA exon of fibroblasts was knockout by CRISPR/Cas system, for assessing the osteoclastogenic effects. The mRNA level of FN isoforms and the osteoclastogenesis‐related genes were analyzed by quantitive PCR.

Results

EDA + FN staining was positively associated with the size of the lesions (p < 0.05). In contrast with the controls, the ratio of EDA + FN/total FN in the fibroblasts from radicular cysts was significantly higher (p < 0.05), and positively associate with Trap + MNCs counting, it was consistent with increased expression of COX‐2, IL‐6, IL‐17, and the RANKL/OPG (p < 0.05). The Trap + MNCs counting and osteoclastogenesis‐related genes were decreased by IST‐9 blocking and EDA exon knockout in fibroblasts, but the blockage of the interaction between EDA + FN and pre‐osteoclasts exhibited little effects on Trap + MNCs formation.

Conclusion

The microenvironment of the fibrous capsule of radicular cysts facilitates the splicing of EDA exon, it endues EDA + FN with autocrine effects on fibroblast itself, and it increases the expression of osteoclastogenesis‐related genes, by which the osteoclastogenesis in radicular cysts could be initiated.
Disruption of gene SPL35, encoding a novel CUE domain‐containing protein, leads to cell death and enhanced disease response in rice
Authors: Ma Jian , Wang Yongfei , Ma Xiaoding , Meng Lingzhi , Jing Ruonan , Wang Fan , Wang Shuai , Cheng Zhijun , Zhang Xin , Jiang Ling , Wang Jiulin , Wang Jie , Zhao Zhichao , Guo Xiuping , Lin Qibing , Wu Fuqing , Zhu Shanshan , Wu Chuanyin , Ren Yulong , Lei Cailin , Zhai Huqu , Wan Jianmin
Published: February 2019

Lesion mimic mutants that exhibit spontaneous hypersensitive response (HR)‐like necrotic lesions are ideal experimental systems for elucidating molecular mechanisms involved in plant cell death and defence responses. Here we report identification of a rice lesion mimic mutant, spotted leaf 35 (spl35), and cloning of the causal gene by TAIL‐PCR strategy. spl35 exhibited decreased chlorophyll content, higher accumulation of H2O2, up‐regulated expression of defence‐related marker genes, and enhanced resistance to both fungal and bacterial pathogens of rice. The SPL35 gene encodes a novel CUE (coupling of ubiquitin conjugation to ER degradation) domain‐containing protein that is predominantly localized in cytosol, ER and unknown punctate compartment(s). SPL35 is constitutively expressed in all organs, and both overexpression and knockdown of SPL35 cause the lesion mimic phenotype. SPL35 directly interacts with the E2 protein OsUBC5a and the coatomer subunit delta proteins Delta‐COP1 and Delta‐COP2 through the CUE domain, and down‐regulation of these interacting proteins also cause development of HR‐like lesions resembling those in spl35 and activation of defence responses, indicating that SPL35 may be involved in the ubiquitination and vesicular trafficking pathways. Our findings provide insight into a role of SPL35 in regulating cell death and defence response in plants.
Single kidney transplantation from donors with acute kidney injury: A single‐center experience
Authors: Jiang Yamei , Song Turun , Liu Jinpeng , Wang Zhiling , Wang Xianding , Huang Zhongli , Fan Yu , Lin Tao
Published: February 2019

Introduction

Despite a severe shortage of organ supply, patients are reluctant to accept organs from deceased donors with AKI, let alone from pediatric AKI donors.

Methods

We assessed 70 patients who received kidneys from donors with AKI (10 with pediatric and 60 with adult donors) and 176 contemporaneous patients who received kidneys from non‐AKI donors (41 with pediatric and 135 with adult donors) between March 2012 and February 2017 for retrospectively evaluating the clinical outcomes.

Results

AKI was defined and staging by the RIFLE criteria and pediatric‐modified RIFLE criteria. Median age was 11.00 years IQR (4.50‐14.00 years), and median weight was 25.00 kg (IQR, 17.00‐45.00 kg) for all pediatric donors. Median follow‐up was 8 months (range, 1‐49 months). Adult AKI group had the highest incidence of DGF (35.0% vs 10%, 9.8%, and 19.3%, P = 0.011). There was a significant increase in DGF in higher AKI stages (Risk: 20.7%, Injury: 46.7%, Failure: 50.0%; P = 0.014) among patients with adult donors. No significant differences were noted in 1‐year (100.0%, 95.1%, 98.3%, and 97.8%; P = 0.751) and 3‐year (100.0%, 95.1%, 98.3%, and 97.8%; P = 0.751) patient survival, and 1‐year (90.0%, 97.6%, 98.3%, and 95.6%; P = 0.535) and 3‐year (90.0%, 97.6%, 98.3%, and 95.6%; P = 0.535) graft survival.

Conclusion

Transplants procured from donors with AKI, particularly pediatric ones, could achieve excellent intermediate‐term clinical outcomes and thus potentially expand the donor pool.
Holistic Conditionalization and Underminable Perceptual Learning
Authors: Miller Brian T.
Published: February 2019

Seeing a red hat can (i) increase my credence in the hat is red, and (ii) introduce a negative dependence between that proposition and potential undermining defeaters such as the light is red. The rigidity of Jeffrey Conditionalization makes this awkward, as rigidity preserves independence. The picture is less awkward given ‘Holistic Conditionalization’, or so it is claimed. I defend Jeffrey Conditionalization's consistency with underminable perceptual learning and its superiority to Holistic Conditionalization, arguing that the latter is merely a special case of the former, is itself rigid, and is committed to implausible accounts of perceptual confirmation and of undermining defeat.
Improvements cardiometabolic risk factors in Latin American Amerindians (the Mapuche) with concurrent training
Authors: Álvarez Cristian , Ramírez‐Vélez Robinson , Ramírez‐Campillo Rodrigo , Lucia Alejandro , Alonso‐Martinez Alicia M. , Faúndez Harry , Cadore Eduardo L. , Izquierdo Mikel
Published: February 2019

Our aim was to investigate the effects of 12 weeks of CT (ie, high‐intensity interval and resistance training) in Mapuche adults from Chile and in their peers of European descent. In total, 96 hyperglycemic adult women (mean age 46 years [95% confidence interval; 38, 53]) were divided in four groups: Mapuche CT (Map‐CT, n = 14) or control group (Map‐CG, n = 44), and European CT (Eur‐CT, n = 14) or control group (Eur‐CG, n = 23). The following endpoints were analyzed at baseline and after 12 weeks: anthropometric (body mass, body mass index, waist circumference), body composition (fat mass, muscle mass, lean mass), cardiovascular (systolic [SBP]/diastolic [DBP] blood pressure), metabolic (blood fasting glucose and total cholesterol), and muscle strength (handgrip of dominant/non‐dominant arm). There were significant positive changes in body mass, body fat, and muscle mass (P < 0.0001) in both Map‐CT and Eur‐CT groups, whereas waist circumference was decreased significantly only in the Eur‐CT group (P < 0.0001). Both Map‐CT and Eur‐CT groups showed decreased levels of fasting glucose (P < 0.05) and total cholesterol after the intervention (P < 0.0001). Also, both Map‐CT (P < 0.05) and Eur‐CT (P = 0.01) groups showed a lowered SBP. Finally, significant increases were observed after training in handgrip strength (dominant arm) in Map‐CT and Eur‐CT groups (both P < 0.0001). CT led to similar improvements in cardiometabolic risk factors for metabolic syndrome development in Mapuche and European participants, with additional improvements in other anthropometric, body composition, cardiovascular, metabolic, and muscle strength parameters related to the prevention of metabolic syndrome. These results suggest future more complex studies.
How Do Community Development Activities Affect the Construction of Rural Places? A Case Study from Finland
Authors: Kumpulainen Kaisu , Soini Katriina
Published: February 2019

Community‐based development practices have been seen as the prevailing paradigm for rural development. Rural community development practices are employed especially through local non‐governmental organisations, such as village associations, to ensure that rural communities are vital and attractive places to live. In this article, we explore how community development practices affect and shape rural places. The data were collected in three Finnish villages that each have an active village association and that have adopted community development practices as their method of keeping their village viable. According to the results of our study, the impacts of community practices on rural places can be classified in terms of three interconnected phenomena: the strengthening of entrepreneurial culture, the increase of networking and institutionalisation, which refers here to processes by which rural communities become incorporated in formal rural governance programmes. All of these phenomena indicate that community actions have become more goal‐oriented and emphasise the responsibility of community agency in developing rural areas.
The tissue viability imaging system—Suitable method for discovering minimal skin changes in occupational screenings? Results of a cross‐sectional field study
Authors: Weistenhöfer Wobbeke , Uter Wolfgang , Bernet Franziska , Drexler Hans
Published: February 2019

Background

For early detection of initial skin changes in occupational screenings, only few objective assessment systems are available.

Objectives

With the aim of assessing an objective measurement method for hand eczema, we trialed the application of the tissue viability imaging (TiVi) system, quantifying erythema non‐invasively by polarized light spectroscopy.

Materials and Methods

In a field study with 625 employees of a semiconductor production company, 411 were exposed to prolonged wearing of occlusive gloves in the clean room. TiVi system and Hand Eczema Score for Occupational Screenings (HEROS), a quantitative skin score for the hands, were used, supplemented by a standardized personal interview.

Results

TiVi values of 65 up to 246 for each hand (palm or back), for each participant summed to overall 289 up to 848 (median 389), were measured. Higher TiVi values were noted for men, smokers, and with increasing age. Correlation between TiVi and HEROS was only weak. Several factors like skin pigmentation, thickness of the skin, or tattoos seem to influence TiVi results.

Conclusions

The practical relevance of one‐time measurements with the TiVi system in occupational screenings seems to be limited. Specifically, the TiVi system cannot replace dermatological examinations at the workplace. Notwithstanding, the application for other scientific purposes might be useful.
Confocal Raman Spectroscopy as a tool to measure the prevention of skin penetration by a specifically designed topical medical device
Authors: Laing Sabrina , Bielfeldt Stephan , Wilhelm Klaus‐Peter , Obst Joachim
Published: February 2019

Background/Aim

The scope of this study was to utilize confocal Raman spectroscopy in the evaluation of the degree of non‐penetration into the viable skin layers of a paraffin and petrolatum‐based product for use in the intimate areas of the skin. The formulation was purposely designed with properties to prevent undesirable skin penetration.

Methods

Product—The test product was a proprietary topical medical device comprising paraffinum liquidum, petrolatum, paraffin, and tocopheryl acetate.

Volunteers—A total of 20 healthy volunteers were recruited onto the study—17 females and three males.

Product Testing—Raman spectra were obtained at Baseline and 90 minutes after product application.

Product Penetration—Skin penetration was calculated from Raman spectra taken at skin depths of −5, 0, 5, 10, 15, and 20 μm.

Results

Raman spectra of the investigated product could be clearly differentiated from the skin spectrum. The minimum measurable concentration of the test product was determined at a detection level of 0.5%. In this study, the test product did not penetrate down to skin depths of 10 to 20 μm.

Conclusions

Within the precision range of the test method, the investigated product did not penetrate into the compact part of the stratum corneum. The study revealed Raman spectroscopy to be suitable to detect not only penetration but also non‐penetration of substances into human skin.
Interventions for the control of Aedes aegypti in Latin America and the Caribbean: systematic review and meta‐analysis
Authors: Bardach Ariel Esteban , García‐Perdomo Herney Andrés , Alcaraz Andrea , Tapia López Elena , Gándara Ruth Amanda Ruano , Ruvinsky Silvina , Ciapponi Agustín
Published: February 2019

Objective

To determine the effectiveness and degree of implementation of interventions for the control of Aedes aegypti in Latin America and the Caribbean (LAC) as reported in scientific literature.

Methods

We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, and LILACS, for experimental and observational studies, economic assessments and qualitative experiences carried out in LAC from 2000 to 2016. We assessed incidence and morbimortality of Aedes aegypti‐related diseases and entomological indices: Breteau (containers), House, and Pupae per Person. We used GRADE methodology for assessing quality of evidence.

Results

Of 1826 records retrieved, 75 were included and 9 cluster randomised clinical trials could be meta‐analysed. We did not identify any intervention supported by a high certainty of evidence. In consistency with qualitative evidence, health education and community engagement probably reduces the entomological indices, as do the use of insecticide‐treated materials, indoor residual spraying and the management of containers. There is low certainty of evidence supporting the use of ovitraps or larvitraps, and the integrated epidemiological surveillance strategy to improve indices and reduce the incidence of dengue. The reported degree of implementation of these vector control interventions was variable and most did not extend to whole cities and were not sustained beyond 2 years.

Conclusions

We found a general lack of evidence on effectiveness of vector control in the region, despite a few interventions that showed moderate to low certainty of evidence. It is important to engage and educate the community, apart from achieving the implementation of integrated actions between the health and other sectors at national and regional level.
A Nck‐associated protein 1‐like protein affects drought sensitivity by its involvement in leaf epidermal development and stomatal closure in rice
Authors: Huang Lichao , Chen Long , Wang Lan , Yang Yaolong , Rao Yuchun , Ren Deyong , Dai Liping , Gao Yihong , Zou Weiwei , Lu Xueli , Zhang Guangheng , Zhu Li , Hu Jiang , Chen Guang , Shen Lan , Dong Guojun , Gao Zhenyu , Guo Longbiao , Qian Qian , Zeng Dali
Published: February 2019

Water deficit is a major environmental threat affecting crop yields worldwide. In this study, a drought stress‐sensitive mutant drought sensitive 8 (ds8) was identified in rice (Oryza sativa L.). The DS8 gene was cloned using a map‐based approach. Further analysis revealed that DS8 encoded a Nck‐associated protein 1 (NAP1)‐like protein, a component of the SCAR/WAVE complex, which played a vital role in actin filament nucleation activity. The mutant exhibited changes in leaf cuticle development. Functional analysis revealed that the mutation of DS8 increased stomatal density and impaired stomatal closure activity. The distorted actin filaments in the mutant led to a defect in abscisic acid (ABA)‐mediated stomatal closure and increased ABA accumulation. All these resulted in excessive water loss in ds8 leaves. Notably, antisense transgenic lines also exhibited increased drought sensitivity, along with impaired stomatal closure and elevated ABA levels. These findings suggest that DS8 affects drought sensitivity by influencing actin filament activity.
Carbohydrate antigen expression and anti‐pig antibodies in New World capuchin monkeys: Relevance to studies of xenotransplantation
Authors: Li Qi , Shaikh Sahar , Iwase Hayato , Long Cassandra , Lee Whayoung , Zhang Zhongqiang , Wang Yi , Ayares David , Cooper David K.C. , Hara Hidetaka
Published: February 2019

Background

Old World non‐human primates (OWNHPs) are used for preclinical pig‐to‐NHP studies. However, like pigs, OWNHPs express Neu5Gc, and therefore do not develop natural anti‐Neu5Gc antibodies. New World NHPs (NWNHPs) have been reported not to express Neu5Gc. We investigated the potential of NWNHPs in xenotransplantation research.

Methods

We investigated expression of Gal, Neu5Gc, and Sda antigens on RBCs and PBMCs from humans, selected OWNHPs, and capuchin monkeys (a NWNHP). Serum anti‐Gal and anti‐Neu5Gc IgM and IgG levels were measured by ELISA. Binding of primate serum IgM and IgG to pig RBCs was measured by flow cytometry.

Results

(a) Neither humans, OWNHPs, or capuchin monkeys expressed Gal on their RBCs, but capuchins expressed Gal on PBMCs. Humans and capuchins did not express Neu5Gc on either RBCs or PBMCs, but OWNHPs expressed Neu5Gc on both cells. Sda was not expressed on any RBCs or PBMCs. (b) By ELISA, human and OWNHP, but not capuchin, sera showed IgM and IgG binding to Gal. Human and capuchin, but not OWNHP, sera demonstrated some binding to Neu5Gc. (c) Anti‐Sda IgM/IgG antibodies were detected in OWNHP sera. Knockout of Sda on pig RBCs did not significantly reduce human and capuchin antibody binding.

Conclusion

Capuchin monkeys could be surrogates for humans in experiments using RBCs, islets, neuronal cells, etc, from triple‐knockout pigs (but may be too small to be used as recipients of pig organ grafts).
Potential pathological role of pro‐inflammatory cytokines (IL‐6, TNF‐α, and IL‐17) in xenotransplantation
Authors: Zhao Yanli , Cooper David K. C. , Wang Huiyun , Chen Pengfei , He Chen , Cai Zhiming , Mou Lisha , Luan Shaodong , Gao Hanchao
Published: February 2019

The major limitation of organ transplantation is the shortage of available organs from deceased human donors which leads to the deaths of thousands of patients each year. Xenotransplantation is considered to be an effective way to resolve the problem. Immune rejection and coagulation dysfunction are two major hurdles for the successful survival of pig xenografts in primate recipients. Pro‐inflammatory cytokines, such as IL‐6, TNF‐α, and IL‐17, play important roles in many diseases and in allotransplantation. However, the pathological roles of these pro‐inflammatory cytokines in xenotransplantation remain unclear. Here, we briefly review the signaling transduction and expression regulation of IL‐6, TNF‐α, and IL‐17 and evaluate their potential pathological roles in in vitro and in vivo models of xenotransplantation. We found that IL‐6, TNF‐α, and IL‐17 were induced in most in vitro or in vivo xenotransplantation model. Blockade of these cytokines using gene modification, antibody, or inhibitor had different effects in xenotransplantation. Inhibition of IL‐6 signaling with tocilizumab decreased CRP but did not increase xenograft survival. The one possible reason is that tocilizumab can not suppress IL‐6 signaling in porcine cells or organs. Other drugs which inhibit IL‐6 signaling need to be investigated in xenotransplantation model. Inhibition of TNF‐α was beneficial for the survival of xenografts in pig‐to‐mouse, rat, or NHP models. Blockade of IL‐17 using a neutralizing antibody also increased xenograft survival in several animal models. However, the role of IL‐17 in the pig‐to‐NHP xenotransplantation model remains unclear and needs to be further investigated. Moreover, blockade of TNF‐α and IL‐6 together has got a better effect in pig‐to‐baboon kidney xenotransplantation. Blockade two or even more cytokines together might get better effect in suppressing xenograft rejection. Better understanding the role of these cytokines in xenotransplantation will be beneficial for choosing better immunosuppressive strategy or producing genetic modification pig.
Structural assessments in decellularized extracellular matrix of porcine semilunar heart valves: Evaluation of cell niches
Authors: Roderjan João Gabriel , de Noronha Lúcia , Stimamiglio Marco Augusto , Correa Alejandro , Leitolis Amanda , Bueno Ronaldo Rocha Loures , da Costa Francisco Diniz Affonso
Published: February 2019

Tissue‐engineered heart valves aim to reproduce the biological properties of natural valves with anatomically correct structure and physiological performance. The closest alternative to creating an ideal heart valve substitute is to use decellularized porcine heart valves, due to their anatomy and availability. However, the immunological barrier and the structural maintenance limit the long‐term physiological performance of decellularized porcine heart valves. This study investigated the extracellular matrix (ECM) structure of aortic and pulmonary porcine valves decellularized by a low concentration sodium dodecyl sulfate (SDS)‐based method in order to determine theECMscaffold (ECMS) conditions related to remodeling potential. To assess the structures of the leaflets and conduits of the heart valves,ECMcomponents and their organization were evaluated by histology, biochemical analysis (BC), scanning electron microscopy, multiphoton microscopy, tensile test, immunofluorescence labeling (IF), and Raman microspectroscopy used to draw a profile of the cell niches. Histology and multiphoton imaging of decellularized aortic and pulmonary leaflets and conduits revealed a collagen and elastin histoarchitecture with rearrangement, loosening fibers, and glycosaminoglycan depletion confirmed by biochemistry quantification. The potential cytotoxicity ofSDSresidues was eliminated after 10 wash cycles. The mechanical properties of the structure of the valve indicated a functional resistance of decellularizedECM. TheIFdemonstrated the presence of basement membrane, suggesting a potential structure for host cell attachment. TheRManalysis showed evidence of molecular interactions, suggesting conservation of the chemical composition, particularly among the protein molecular structures. The structural analyses performed in the semilunar porcine heart valves demonstrate that decellularizedECMShas structural properties that support physiological performance and potential host tissue integration. In fact, decellularized leaflet scaffolds were prone to cell interaction after human adipose‐derived stromal cell seeding and culturing. Further analysis of biocompatibility, particularly theECM‐cell interaction, can elucidate the remodeling process, in preserved decellularized heart valve scaffold.
Validity and reliability of lower‐limb pulse‐wave velocity assessments using an oscillometric technique
Authors: Stone Keeron , Fryer Simon , Kelsch Elizabeth , Burnet Kathryn , Zieff Gabriel , Faulkner James , Credeur Daniel , Lambrick Danielle , Hanson Erik D. , Stoner Lee
Published: February 2019

New Findings

What is the central question of this study?

There is growing interest in the effects of sedentarism on central and peripheral cardiovascular health. To permit further investigation, including larger epidemiological studies, there is a need to identify arterial health assessment tools that are valid (accurate) and reliable (precise), yet practical.

What is the main finding and its importance?

Lower‐limb vascular health (femoral–ankle pulse‐wave velocity) can be determined in a supine position with accuracy and precision using an oscillometrically based device. This technology might help to improve our understanding of the pathological mechanisms linking cardiovascular disease to sedentarism, including the interaction between peripheral and central vasculature.

There is a growing interest in the deleterious effects of sedentary behaviour on lower‐limb arterial health. To permit further investigation, including larger epidemiological studies, there is a need to identify lower‐limb arterial health assessment tools that are valid and reliable, yet simple to administer. In this study, we sought to determine the validity and between‐day reliability of femoral–ankle pulse‐wave velocity (faPWV) measures obtained using an oscillometrically based device (SphygmocCor XCEL) in supine and seated positions. Doppler ultrasound was used as the criterion. A total of 47 healthy adults were recruited for validity (n = 32) and reliability (n = 15) analyses. Validity was determined by measuring faPWV in seated and supine positions using the XCEL and Doppler ultrasound devices, in a randomized order. Between‐day reliability was determined by measuring seated and supine faPWV using the XCEL on three different mornings, separated by a maximum of 7 days. The validity criterion [absolute standard error of estimate (aSEE) < 1.0 m s−1] was met in the supine [aSEE = 0.8 m s−1, 95% confidence interval (CI) 0.4–1.0], but not in the seated (aSEE = 1.2 m s−1, 95% CI 1.1–1.2) position. Intraclass correlation coefficient (ICC) estimates revealed that the XCEL demonstrated good reliability in the supine position (ICC = 0.83, 95% CI 0.65–0.93), but poor reliability in the seated position (ICC = 0.29, 95% CI 0.23–0.63). The oscillometric XCEL device can be used to determine lower‐limb pulse‐wave velocity with acceptable validity and reliability in the conventionally recommended supine position, but not in the seated position.
The actin ‘A‐triad's’ role in contractile regulation in health and disease
Authors: Schmidt William , Cammarato Anthony
Published: February 2019

Striated muscle contraction is regulated by Ca2+‐dependent modulation of myosin cross‐bridge binding to F‐actin by the thin filament troponin (Tn)‐tropomyosin (Tm) complex. In the absence of Ca2+, Tn binds to actin and constrains Tm to an azimuthal location where it sterically occludes myosin binding sites along the thin filament surface. This limits force production and promotes muscle relaxation. In addition to Tn‐actin interactions, inhibitory Tm positioning requires associations between other thin filament constituents. For example, the actin ‘A‐triad’, composed of residues K326, K328 and R147, forms numerous, highly favourable electrostatic contacts with Tm that are critical for establishing its inhibitory azimuthal binding position. Here, we review recent findings, including the identification and interrogation of modifications within and proximal to the A‐triad that are associated with disease and/or altered muscle behaviour, which highlight the surface feature's role in F‐actin‐Tm interactions and contractile regulation.

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CaMKII does not control mitochondrial Ca2+ uptake in cardiac myocytes
Authors: Nickel Alexander G. , Kohlhaas Michael , Bertero Edoardo , Wilhelm Daniel , Wagner Michael , Sequeira Vasco , Kreusser Michael M. , Dewenter Matthias , Kappl Reinhard , Hoth Markus , Dudek Jan , Backs Johannes , Maack Christoph
Published: February 2019

Key points

Mitochondrial Ca2+ uptake stimulates the Krebs cycle to regenerate the reduced forms of pyridine nucleotides (NADH, NADPH and FADH2) required for ATP production and reactive oxygen species (ROS) elimination.

Ca2+/calmodulin‐dependent protein kinase II (CaMKII) has been proposed to regulate mitochondrial Ca2+ uptake via mitochondrial Ca2+ uniporter phosphorylation.

We used two mouse models with either global deletion of CaMKIIδ (CaMKIIδ knockout) or cardiomyocyte‐specific deletion of CaMKIIδ and γ (CaMKIIδ/γ double knockout) to interrogate whether CaMKII controls mitochondrial Ca2+ uptake in isolated mitochondria and during β‐adrenergic stimulation in cardiac myocytes.

CaMKIIδ/γ did not control Ca2+ uptake, respiration or ROS emission in isolated cardiac mitochondria, nor in isolated cardiac myocytes, during β‐adrenergic stimulation and pacing.

The results of the present study do not support a relevant role of CaMKII for mitochondrial Ca2+ uptake in cardiac myocytes under physiological conditions.

Mitochondria are the main source of ATP and reactive oxygen species (ROS) in cardiac myocytes. Furthermore, activation of the mitochondrial permeability transition pore (mPTP) induces programmed cell death. These processes are essentially controlled by Ca2+, which is taken up into mitochondria via the mitochondrial Ca2+ uniporter (MCU). It was recently proposed that Ca2+/calmodulin‐dependent protein kinase II (CaMKII) regulates Ca2+ uptake by interacting with the MCU, thereby affecting mPTP activation and programmed cell death. In the present study, we investigated the role of CaMKII under physiological conditions in which mitochondrial Ca2+ uptake matches energy supply to the demand of cardiac myocytes. Accordingly, we measured mitochondrial Ca2+ uptake in isolated mitochondria and cardiac myocytes harvested from cardiomyocyte‐specific CaMKII δ and γ double knockout (KO) (CaMKIIδ/γ DKO) and global CaMKIIδ KO mice. To simulate a physiological workload increase, cardiac myocytes were subjected to β‐adrenergic stimulation (by isoproterenol superfusion) and an increase in stimulation frequency (from 0.5 to 5 Hz). No differences in mitochondrial Ca2+ accumulation were detected in isolated mitochondria or cardiac myocytes from both CaMKII KO models compared to wild‐type littermates. Mitochondrial redox state and ROS production were unchanged in CaMKIIδ/γ DKO, whereas we observed a mild oxidation of mitochondrial redox state and an increase in H2O2 emission from CaMKIIδ KO cardiac myocytes exposed to an increase in workload. In conclusion, the results obtained in the present study do not support the regulation of mitochondrial Ca2+ uptake via the MCU or mPTP activation by CaMKII in cardiac myocytes under physiological conditions.
Parametric Study of the Design Variables of an Arborizing Catheter on Dispersal Volume Using a Biphasic Computational Model
Authors: Elenes Egleide Y. , Rausch Manuel K. , Rylander Christopher G.
Published: February 2019

Convection-enhanced delivery (CED) is an investigational therapy developed to circumvent the limitations of drug delivery to the brain. Catheters are used in CED to locally infuse therapeutic agents into brain tissue. CED has demonstrated clinical utility for treatment of malignant brain tumors; however, CED has been limited by lack of CED-specific catheters. Therefore, we developed a multiport, arborizing catheter to maximize drug distribution for CED. Using a multiphasic finite element (FE) framework, we parametrically determined the influence of design variables of the catheter on the dispersal volume of the infusion. We predicted dispersal volume of a solute infused in a permeable hyperelastic solid matrix, as a function of separation distance (ranging from 0.5 to 2.0 cm) of imbedded infusion cavities that represented individual ports in a multiport catheter. To validate the model, we compared FE solutions of pressure-controlled infusions to experimental data of indigo carmine dye infused in agarose tissue phantoms. The Tc50, defined as the infusion time required for the normalized solute concentration between two sources to equal 50% of the prescribed concentration, was determined for simulations with infusion pressures ranging from 1 to 4 kPa. In our validated model, we demonstrate that multiple ports increase dispersal volume with increasing port distance but are associated with a significant increase in infusion time. Tc50 increases approximately tenfold when doubling the port distance. Increasing the infusion flow rate (from 0.7 μL/min to 8.48 μL/min) can mitigate the increased infusion time. In conclusion, a compromise of port distance and flow rate could improve infusion duration and dispersal volume.
Extraordinary tensile strength and ductility of scalable nanoporous graphene
Authors: Kashani Hamzeh , Ito Yoshikazu , Han Jiuhui , Liu Pan , Chen Mingwei
Published: February 2019

Excellent tensile strength and ductility of porous graphene can be realized by 3D bicontinuous nanoarchitecture.
High-tide flooding disrupts local economic activity
Authors: Hino Miyuki , Belanger Samanthe Tiver , Field Christopher B. , Davies Alexander R. , Mach Katharine J.
Published: February 2019

High-tide flooding reduces customer access to businesses, and impacts are projected to increase sharply with sea level rise.
STEM faculty who believe ability is fixed have larger racial achievement gaps and inspire less student motivation in their classes
Authors: Canning Elizabeth A. , Muenks Katherine , Green Dorainne J. , Murphy Mary C.
Published: February 2019

Racial achievement gaps are twice as large, and all students are less motivated, when STEM faculty believe ability is fixed.
In-memory computing on a photonic platform
Authors: Ríos Carlos , Youngblood Nathan , Cheng Zengguang , Le Gallo Manuel , Pernice Wolfram H. P. , Wright C. David , Sebastian Abu , Bhaskaran Harish
Published: February 2019

Nonvolatile multilevel phase-change memories on integrated photonic devices enable all-optical direct in-memory multiplications.
Theoretical guidelines to create and tune electric skyrmion bubbles
Authors: Pereira Gonçalves M. A. , Escorihuela-Sayalero Carlos , Garca-Fernández Pablo , Junquera Javier , Íñiguez Jorge
Published: February 2019

Our second-principles results illustrate a strategy for obtaining topological electric textures akin to magnetic skyrmions.
Power flow–conformal metamirrors for engineering wave reflections
Authors: Díaz-Rubio Ana , Li Junfei , Shen Chen , Cummer Steven A. , Tretyakov Sergei A.
Published: February 2019

Power flow–conformal metasurfaces allow perfect manipulations of reflected waves without excitation of auxiliary fields.
Lithiophilicity chemistry of heteroatom-doped carbon to guide uniform lithium nucleation in lithium metal anodes
Authors: Chen Xiang , Chen Xiao-Ru , Hou Ting-Zheng , Li Bo-Quan , Cheng Xin-Bing , Zhang Rui , Zhang Qiang
Published: February 2019

The lithiophilicity of carbon materials is explained by the electronegativity, local dipole, charge transfer, and Li bond theory.
Sculpting stable structures in pure liquids
Authors: Emeršič Tadej , Zhang Rui , Kos Žiga , Čopar Simon , Osterman Natan , de Pablo Juan J. , Tkalec Uroš
Published: February 2019

Orientational phase domains in nonequilibrium nematic fluids are sculpted by microfluidic flows and laser pulses.
The early proximal αβ TCR signalosome specifies thymic selection outcome through a quantitative protein interaction network
Authors: Neier Steven C. , Ferrer Alejandro , Wilton Katelynn M. , Smith Stephen E. P. , Kelcher April M. H. , Pavelko Kevin D. , Canfield Jenna M. , Davis Tessa R. , Stiles Robert J. , Chen Zhenjun , McCluskey James , Burrows Scott R. , Rossjohn Jamie , Hebrink Deanne M. , Carmona Eva M. , Limper Andrew H. , Kappes Dietmar J. , Wettstein Peter J. , Johnson Aaron J. , Pease Larry R. , Daniels Mark A. , Neuhauser Claudia , Gil Diana , Schrum Adam G.
Published: February 2019

Quantitative activity through the TCR-proximal protein network specifies thymic positive versus negative selection.
Spinal epidural lipomatosis following bilateral spinal decompression surgery
Authors: Greenish Davyd , Watura Karen , Harding Ian
Published: February 2019

A 73-year-old man underwent bilateral spinal decompression of L4/5 for severe spinal canal stenosis, requiring minimal analgesia and providing immediate relief. Two days post-operatively, he presented with new onset bilateral leg pain and difficulty mobilising. MRI demonstrated spinal epidural lipomatosis (SEL), which was not present pre-operatively, at L5/S1. Further surgery was performed with decompression of L5/S1 through removal of epidural fat. At both 3 weeks and 5 months follow-up clinics, the patient was asymptomatic. To our knowledge, this is the first case of acute spinal epidural lipomatosis directly following spinal surgery. It is important to recognise SEL as a complication following spinal surgical intervention, due to the potential development of significant neurological consequences.
Validity of ICD-10-CM codes for determination of diabetes type for persons with youth-onset type 1 and type 2 diabetes
Authors: Chi Gloria C , Li Xia , Tartof Sara Y , Slezak Jeff M , Koebnick Corinna , Lawrence Jean M.
Published: February 2019

Objective

Diagnosis codes might be used for diabetes surveillance if they accurately distinguish diabetes type. We assessed the validity ofInternational Classification of Disease, 10th Revision, Clinical Modification(ICD-10-CM) codes to discriminate between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) among health plan members with youth-onset (diagnosis age <20 years) diabetes.

Research design and methods

. Diabetes case identification and abstraction of diabetes type was done as part of the SEARCH for Diabetes in Youth Study. The gold standard for diabetes type is the physician-assigned diabetes type documented in patients’ medical records. Using all healthcare encounters with ICD-10-CM codes for diabetes, we summarized codes within each encounter and determined diabetes type using percent of encounters classified as T2DM. We chose 50% as the threshold from a receiver operating characteristic curve because this threshold yielded the largest Youden’s index. Persons with ≥50% T2DM-coded encounters were classified as having T2DM. Otherwise, persons were classified as having T1DM. We calculated sensitivity, specificity, positive and negative predictive values, and accuracy overall and by demographic characteristics.

Results

According to the gold standard, 1911 persons had T1DM and 652 persons had T2DM (mean age (SD): 19.1 (6.5) years). We obtained 90.6% (95% CI 88.4% to 92.9%) sensitivity, 96.3% (95% CI 95.4% to 97.1%) specificity, 89.3% (95% CI 86.9% to 91.6%) positive predictive value, 96.8% (95% CI 96.0% to 97.6%) negative predictive value, and 94.8% (95% CI 94.0% to 95.7%) accuracy for discriminating T2DM from T1DM.

Conclusions

ICD-10-CM codes can accurately classify diabetes type for persons with youth-onset diabetes, showing promise for rapid, cost-efficient diabetes surveillance.
Body image dissatisfaction in patients with inflammatory bowel disease: a systematic review
Authors: Beese Sophie Elizabeth , Harris Isobel Marion , Dretzke Janine , Moore David
Published: February 2019

Background and aims

Little is known about the relationship between inflammatory bowel disease (IBD) and body image. The aim of this systematic review was to summarise the evidence on body image dissatisfaction in patients with IBD across four areas: (1) body image tools, (2) prevalence, (3) factors associated with body image dissatisfaction in IBD and (4) association between IBD and quality of life.

Methods

Two reviewers screened, selected, quality assessed and extracted data from studies in duplicate. EMBASE, MEDLINE, PsycINFO and Cochrane CENTRAL were searched to April 2018. Study design–specific critical appraisal tools were used to assess risk of bias. Narrative analysis was undertaken due to heterogeneity.

Results

Fifty-seven studies using a body image tool were included; 31 for prevalence and 16 and 8 for associated factors and association with quality of life, respectively. Studies reported mainly mean or median scores. Evidence suggested female gender, age, fatigue, disease activity and steroid use were associated with increased body image dissatisfaction, which was also associated with decreased quality of life.

Conclusion

This is the first systematic review on body image in patients with IBD. The evidence suggests that body image dissatisfaction can negatively impact patients, and certain factors are associated with increased body image dissatisfaction. Greater body image dissatisfaction was also associated with poorer quality of life. However, the methodological and reporting quality of studies was in some cases poor with considerable heterogeneity. Future IBD research should incorporate measurement of body image dissatisfaction using validated tools.
Analytical accuracy of the handheld PICO monitoring device during emergencies
Authors: Renier Walter Sylvain , Erard Koen , Sabbe Marc , Hubloue Ives , Verbakel Jan Y , Aertgeerts Bert , Buntinx Frank
Published: February 2019

Introduction

General practitioners (GP) use few technical devices during emergency situations. They have to recognise which patients have a life-threatening disease in order to treat or refer them appropriately. Monitoring by a wearable device could help GPs while waiting for the emergency physician to arrive. The PICO monitor is a handheld monitoring device, capable of registering five routine parameters and small enough to be carried in the GP’s bag. We aim to determine the analytical accuracy of the PICO monitor in adults, comparing the recorded vital signs and ECGs of the PICO with those of a standard emergency department (ED) monitor.

Methods

Adult (≥18 years) patients, admitted on two inpatient university EDs in Belgium, were recruited. We recorded the SpO2, heart rate (HR), respiration rate (RR), temperature (T°) and 5-lead ECGs. We analysed the correlation and agreement between the continuous and dichotomous variables of the PICO and the ED monitors.

Results

We included 226 patients (84% of 268 approached), mean age 66 years, 61% were men. The Bland and Altman analysis confirmed the good accuracy, giving a nearly perfect agreement for SpO2(difference —0.9%), for HR (−1.5 beats), for RR between the monitors (0.1 breaths), for RR between the manually counted and the PICO or the monitor (respectively 0.2 and 0.0 breaths), also confirmed by the regression analysis (Passing-Bablok). Analysis of 219 ECG records provided a near perfect agreement between the devices (kappa respectively 0.61–0.80 and 0.81–1.00) for the most important ECG abnormalities. In none of the comparisons, differences were clinically relevant.

Conclusion

We were able to confirm the analytical accuracy of the PICO monitor in comparison with the ED monitors. The PICO monitor can be considered a reliable device for monitoring patients during emergencies by GPs and even in ambulances or EDs as a mobile alternative.
Telephone announcements encouraging common cold self-management reduce demand for general practice appointments
Authors: Kerr Robin , Grainger Alan , Messer Carol , Kerr Hamish
Published: February 2019

Background

Patients consulting with the common cold contribute to seasonal demand for general practice appointments. Seeing a community pharmacist or using self-management may have been more appropriate options. The study aimed to measure if the use of telephone announcements signposting appropriate patients with the common cold in the direction of community pharmacy or self-management reduced demand for general practice consultations.

Methods

Patients telephoning a UK general practice to request an appointment between December 2017 and March 2018 heard announcements regarding management of the common cold. The percentage of callers choosing to continue to speak to a receptionist was compared with baseline data prior to the intervention. The mean waiting time to the third available routine general practice appointment during the intervention was compared with the previous year.

Results

Routine calls continuing to reception reduced by 5.5 % (p<0.001) when the incidence of the common cold is at its highest and by 3.9% (p<0.001) throughout the intervention. The mean waiting time to the third available routine appointment reduced by 21%.

Conclusion

This study has demonstrated that the use of telephone announcements signposting appropriate patients with the common cold in the direction of community pharmacy or self-management reduces calls to reception. This strongly infers that the telephone announcements reduce demand for general practice appointments and is supported by the reduced mean waiting time to the third available routine appointment. Implementation of this intervention could help general practitioners reduce seasonal demand in their own practices.
Does sector matter for the quality of care services? A secondary analysis of social care services regulated by the Care Inspectorate in Scotland
Authors: Bach-Mortensen Anders Malthe , Montgomery Paul
Published: February 2019

Objectives

Social services are increasingly commissioned to third and for-profit sector providers, but little is known about whether and how these changes influence quality indicators. We assessed quality-related outcomes across for-profit, public and third sector organisations delivering social care services.

Design

A secondary analysis was conducted on publically available data collected by the independent regulator of social care organisations in Scotland. All outcomes are reported as predicted probabilities derived from multivariate logistic regression coefficients. Generalised ordered logit models are utilised for the quality domains and the risk assessment score and logistic regression for whether complaints or requirements were issued to organisations.

Setting

Organisations inspected by the Care Inspectorate in Scotland.

Population

13 310 social care organisations (eg, nursing homes and day care organisations).

Primary outcomes

The quality and risk domains collected by the Care Inspectorate and complaints and requirements issued to organisations within the last 3 years.

Results

Controlling for multiple factors, we find that public and third sector providers performed consistently and statistically significantly better than for-profit organisations on most outcomes. For example, for-profit services were the most likely to be rated as high and medium risk (6.9% and 13.2%, respectively), and the least likely to be classified as low risk (79.9%). Public providers had the highest probability of being categorised as low risk (91.1%), and the lowest probability of having their services classified as medium (6.9%) and high risk (2%), followed by third sector providers (86%, 8.5% and 4.5%, respectively). Public providers performed better than third sector providers in some outcomes, but differences were relatively low and inconsistent.

Conclusion

Public and third sector providers were rated considerably higher than their for-profit counterparts on most observed outcomes. Regulators might use this information to consider how social care providers across sector are incentivised to manage their resources.