bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental Outcomes for Children at High Risk of Dyslexia and Children With Developmental Language Disorder
Authors: Snowling Margaret J. , Nash Hannah M. , Gooch Debbie C. , Hayiou‐Thomas Marianna E. , Hulme Charles ,   Wellcome Language and Reading Project Team
Published: January 2019

We followed children at family risk of dyslexia and children with preschool language difficulties from age 3½, comparing them with controls (N = 234). At age 8, children were classified as having dyslexia or Developmental Language Disorder (DLD) and compared at earlier time points with controls. Children with dyslexia have specific difficulties with phonology and emergent reading skills in the preschool period, whereas children with DLD, with or without dyslexia, show a wider range of impairments including significant problems with executive and motor tasks. For children with both dyslexia and DLD, difficulties with phonology are generally more severe than those observed in children with dyslexia or DLD alone. Findings confirm that poor phonology is the major cognitive risk factor for dyslexia.
Association between peripheral plasmablasts and postoperative exacerbation in patients with thymoma‐associated myasthenia gravis
Authors: Izaki Shoko , Tanaka Satoru , Oji Satoru , Kubota Akihiro , Fukaura Hikoaki , Nakayama Mitsuo , Nomura Kyoichi
Published: January 2019

Objective

Thymoma‐associated myasthenia gravis (TAMG) is a type of myasthenia gravis (MG) that has a higher likelihood of worsening in comparison with non‐TAMG, and MG symptoms often worsen after thymectomy. We measured peripheral T/B lymphocyte subsets before and after thymectomy in TAMG patients, and investigated the relationships with the occurrence of postoperative exacerbation of MG symptoms.

Methods

Participants were 10 TAMG patients, 40 healthy controls and five other surgical control patients. Peripheral lymphocyte subsets were measured using FACS‐Canto flow cytometry before, and 1, 7, and 28 days after thymectomy in the TAMG, and before and 7 days after thymectomy in the other surgical control patients.

Results

Natural killer cells modestly decreased, and plasmablasts increased significantly (P = 0.005) after 7 days postoperatively in comparison with preoperative values. Conversely, no obvious changes were observed in plasmablasts or natural killer cells in T/B lymphocyte subsets. From evaluation of postoperative clinical course and plasmablasts, exacerbation of MG symptoms was observed between 2 and 3 weeks after thymectomy in five of 10 patients (50%) of TAMG. In these five patients, plasmablasts markedly increased after thymectomy in three patients, among whom two patients had originally shown high plasmablast levels before thymectomy. There were also two patients who exacerbated without changes in plasmablast levels.

Conclusions

In patients with exacerbation of neurological symptoms after thymectomy for TAMG, the plasmablast levels were originally high and/or became high postoperatively. Thus, elevated plasmablast levels could potentially be predictive of postoperative exacerbation of MG.
Macrolide derivatives reduce proinflammatory macrophage activation and macrophage‐mediated neurotoxicity
Authors: Zhang Bei , Kopper Timothy J. , Liu Xiaodong , Cui Zheng , Van Lanen Steven G. , Gensel John C.
Published: January 2019

Introduction

Azithromycin (AZM) and other macrolide antibiotics are applied as immunomodulatory treatments for CNS disorders. The immunomodulatory and antibiotic properties of AZM are purportedly independent.

Aims

To improve the efficacy and reduce antibiotic resistance risk of AZM‐based therapies, we evaluated the immunomodulatory and neuroprotective properties of novel AZM derivatives. We semisynthetically prepared derivatives by altering sugar moieties established as important for inhibiting bacterial protein synthesis. Bone marrow‐derived macrophages (BMDMs) were stimulated in vitro with proinflammatory, M1, stimuli (LPS + INF‐gamma) with and without derivative costimulation. Pro‐ and anti‐inflammatory cytokine production, IL‐12 and IL‐10, respectively, was quantified using ELISA. Neuron culture treatment with BMDM supernatant was used to assess derivative neuroprotective potential.

Results

Azithromycin and some derivatives increased IL‐10 and reduced IL‐12 production of M1 macrophages. IL‐10/IL‐12 cytokine shifts closely correlated with the ability of AZM and derivatives to mitigate macrophage neurotoxicity.

Conclusions

Sugar moieties that bind bacterial ribosomal complexes can be modified in a manner that retains AZM immunomodulation and neuroprotection. Since the effects of BMDMs in vitro are predictive of CNS macrophage responses, our results open new therapeutic avenues for managing maladaptive CNS inflammation and support utilization of IL‐10/12 cytokine profiles as indicators of macrophage polarization and neurotoxicity.
Negative regulation of glial Tim‐3 inhibits the secretion of inflammatory factors and modulates microglia to antiinflammatory phenotype after experimental intracerebral hemorrhage in rats
Authors: Chen Zhou‐Qing , Yu Hao , Li Hai‐Ying , Shen Hai‐Tao , Li Xiang , Zhang Ju‐Yi , Zhang Zhu‐Wei , Wang Zhong , Chen Gang
Published: January 2019

Aims

To investigate the critical role of Tim‐3 in the polarization of microglia in intracerebral hemorrhage (ICH)‐induced secondary brain injury (SBI).

Methods

An in vivo ICH model was established by autologous whole blood injection into the right basal ganglia in rats. The primary cultured microglia were treated with oxygen‐hemoglobin (OxyHb) to mimic ICH in vitro. In this experiment, specific siRNA for Tim‐3 and recombinant human TIM‐3 were exploited both in vivo and in vitro.

Results

Tim‐3 was increased in the brain after ICH, which mainly distributed in microglia, but not neurons and astrocytes. However, the blockade of Tim‐3 by siRNA markedly reduced secretion of inflammatory factors, neuronal degeneration, neuronal cell death, and brain edema. Meanwhile, downregulation of Tim‐3 promoted the transformation of microglia phenotype from M1 to M2 after ICH. Furthermore, upregulation of Tim‐3 can increase the interaction between Tim‐3 and Galectin‐9 (Gal‐9) and activate Toll‐like receptor 4 (TLR‐4) pathway after ICH. Increasing the expression of Tim‐3 may be related to the activation of HIF‐1α.

Conclusion

Tim‐3 may be an important link between neuroinflammation and microglia polarization through Tim‐3/Gal‐9 and TLR‐4 signaling pathways which induced SBI after ICH.
A review of evidence about use and performance of species distribution modelling ensembles like BIOMOD
Authors: Hao Tianxiao , Elith Jane , Guillera‐Arroita Gurutzeta , Lahoz‐Monfort José J.
Published: January 2019

Aim

The idea of combining predictions from different models into an ensemble has gained considerable popularity in species distribution modelling, partly due to free and comprehensive software such as the R package BIOMOD. However, despite proliferation of ensemble models, we lack oversight of how and where they are used for modelling distributions, and how well they perform. Here, we present such an overview.

Location

Global.

Methods

Since BIOMOD is freely available and widely used by ensemble species distribution modellers, we focused on articles that apply BIOMOD, filtering the initial 852 papers identified in our structured literature search to a relevant final subset of 224 eligible peer‐reviewed journal articles.

Results

BIOMOD‐based ensembles are used across many taxa and locations, with terrestrial plants being the most represented group of species (n = 72) and Europe being the most represented continent (n = 106). These studies often focus on forecasting distributions in the future (n = 109), and commonly use presence‐only species data (n = 139) and climatic environmental predictors (n = 219). An average of six models are used in ensembles, and approximately half of ensembles weight contributions of models by their cross‐validation performance. However, discussion about choices made in the modelling process and unambiguous information on the performance of ensemble models versus individual models are limited. The use of independent data to validate model performance is particularly uncommon.

Main conclusions

We document the breadth of ensemble applications, but could not draw strong quantitative conclusions about the predictive performance of ensemble models, due to lack of unambiguous information reported. Understanding how and where ensembles are best used when modelling species distributions is important for enabling best choices for different applications. To enable this objective to be achieved, we provide recommendations for thorough reporting practices in a BIOMOD‐based ensemble workflow.
Efficacy and safety of 0.6% sodium alginate solution in endoscopic submucosal dissection for esophageal and gastric neoplastic lesion: A randomized controlled study
Authors: Uemura Naomi , Oda Ichiro , Saito Yutaka , Ono Hiroyuki , Fujisaki Junko , Matsuhashi Nobuyuki , Ohata Ken , Yahagi Naohisa , Yada Tomoyuki , Satoh Masahiro , Tajiri Hisao , Inomata Masafumi , Kitano Seigo
Published: January 2019

Objectives

Sodium alginate (SA) solution has characteristic viscoelasticity. We aimed to determine efficacy and safety of 0.6% SA for submucosal injection during endoscopic submucosal dissection (ESD) in patients with localized neoplastic lesion in the esophageal and gastric mucosa.

Methods

We conducted a randomized controlled study at six major hospitals in Japan including 130 patients with endoscopically localized neoplastic lesion in the esophageal and gastric mucosa and eligible for ESD. Patients were randomly assigned to SA or 0.4% sodium hyaluronate (SH) group (control); ESD was performed using a submucosal injection of SA/SH. As a primary outcome measure, non‐inferiority of SA against SH was investigated using en bloc complete resection in ESD and formation and maintenance of mucosal elevation upon injection as an efficacy index. Adverse events during the study were evaluated as safety outcome measures. This study was registered with Pharmaceuticals and Medical Devices Agency (clinical trial no. 28‐277/2016‐18; clinical trial identification no. KP2013‐009_C001).

Results

Efficacy rate of submucosal injection during ESD was 91.7% (55/60) and 88.7% (55/62) in the SA and SH groups, respectively, demonstrating non‐inferiority of SA against SH. Adverse events for which a causal relationship with submucosal injection solution could not be eliminated were noted in 8.2% (5/61) and 4.7% (3/64) in the SA and SH groups, respectively, but symptoms disappeared without treatment/after drug administration in both groups.

Conclusions

In Japan, 0.4% SH is the only commercially approved formulation for submucosal injection during ESD. The study results may expand submucosal injection solution options in clinical practice.
Environmental influences on health and development: nutrition, substance exposure, and adverse childhood experiences
Authors: Gentner Maura B , Leppert Mary L O’Connor
Published: January 2019

Scientific advances over the last century have generated compelling evidence of the primary and secondary effects of gestational, infant, and childhood conditions. These early environmental influences have the potential not only to impact an individual's health outcomes, such as heart disease, type 2 diabetes, and cancer, but also to confer various protections and risks to that individual's descendants. The immediate and extended ramifications of early environmental exposure bring an understanding of epidemiological impact on disease states and a hope for prevention. This review highlights the contributions of several key population studies and briefly explores specific environmental influences, including nutritional deficiencies, exposure to substances and infections, and adverse childhood experiences. Mechanisms of these influences (e.g. stress and epigenetics) are discussed, as well as possible means of mitigating their negative consequences.

What this paper adds

Substance exposures in utero are associated with epigenetic changes and negative outcomes.

Adverse childhood experiences in early childhood can induce HPA and epigenetic changes.
Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease
Authors: Charytan David M. , Solomon Scott D. , Ivanovich Peter , Remuzzi Giuseppe , Cooper Mark E. , McGill Janet B. , Parving Hans‐Henrik , Parfrey Patrick , Singh Ajay K. , Burdmann Emmanuel A. , Levey Andrew S. , Eckardt Kai‐Uwe , McMurray John J.V. , Weinrauch Larry A. , Liu Jiankang , Claggett Brian , Lewis Eldrin F. , Pfeffer Marc A.
Published: January 2019

Aims

Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis.

Materials and methods

All‐cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non‐users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin‐alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non‐users and in multivariable proportional hazards models.

Results

There were 591 individuals who used metformin at baseline and 3447 non‐users. Among propensity‐matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non‐users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all‐cause mortality (HR, 0.49; 95% CI, 0.36‐0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32‐0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51‐0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61‐0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65‐1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed.

Conclusions

Metformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD.
Evaluation of left ventricular diastolic function based on flow energetic parameters in chronic kidney disease with diastolic dysfunction
Authors: Wang Wei , Wang Yueheng , Chen Xiaoxue , Yuan Lijun , Bai Hui
Published: January 2019

Background

Intra‐ventricular blood flow dynamics is considered as an important component of left ventricular (LV) function assessment. The purpose of this study was to evaluate the LV diastolic function in chronic kidney disease (CKD) with different degrees of LV diastolic dysfunction (LVDD) by using flow energetic parameters.

Methods

In this study, a total of 96 cases were recruited, including 58 CKD patients and 38 healthy controls. CKD patients were divided into 2 groups according to LVDD severity, named as DD1 and DD2. Vector flow‐mapping (VFM) analysis was executed to calculate left ventricle average energy loss (EL) during early filling phase (E‐EL_ave), atrial filling phase (A‐EL_ave), diastole phase (D‐EL_ave), and ejection phase (S‐EL_ave). Moreover, the average vortex circulation during early filling phase (E‐cir_ave) and atrial filling phase (A‐cir_ave) was also assessed in the apical three‐chamber view. The rate of average EL during early filling and atrial filling was expressed as E/A‐EL.

Result

Compared to the control group, A‐EL_ave, S‐EL_ave, and A‐cir_ave in the DD1 group were higher (P < 0.05), and all parameters were obviously higher in the DD2 group (P < 0.05). In the control group and the DD2 subgroup, the E‐EL_ave value was significantly higher than A‐EL_ave value, which was opposite to the DD1 group. As diastolic dysfunction worsened, E‐EL_ave and D‐EL_ave risen gradually (P < 0.05), and A‐EL_ave and S‐EL_ave were slightly elevated with no significance. There were significant correlations between LV diastolic function and flow energetic parameters. Stepwise multiple regression analysis revealed that various LV function parameters could be regarded as independent predictors of average diastolic EL (all P < 0.01).

Conclusions

For CKD patient with LVDD and LVEF > 50%, effective LV filling and systolic ejection with optimized energy consumption have been impaired. As a new flow‐derived index, EL can quantitatively evaluate LV diastolic function in terms of blood fluid dynamics in CKD with various LVDD.
Moving on from early intervention for psychosis services: Service user perspectives on the facilitators and barriers of transition
Authors: Loughlin Matthew , Berry Katherine , Brooks Joanna , Bucci Sandra
Published: January 2019

Aim

Early intervention for psychosis services (EIS) has been established worldwide and is offered to individuals experiencing a first episode of psychosis. Engagement with EIS typically lasts for 3 years, after which point, service users are either transferred to primary care or community mental health teams, according to perceived needs. Although UK National Institute for Clinical Excellence (NICE) guidelines recommend transfer of care should be arranged in conjunction with the receiving service, there exists little, if any, practical guidance as to how this should actually be managed. This study aims to investigate the barriers and facilitators of transition from EIS to both primary and secondary care services in the United Kingdom from the perspectives of service users.

Methods

Fifteen EIS service users who had either been discharged to primary or secondary services were interviewed about their experience of discharge. Data were analysed using interpretive thematic analysis, adopting a critical realist stance.

Results

Four themes were identified: feeling ready for discharge; relationships and trust; planning for discharge; life after EIS.

Conclusions

This is the first in‐depth exploration of a sample of largely male service users' views on transition from EIS to primary and/or secondary care services. We highlight several practical steps that EIS and receiving services can take to facilitate a more optimal discharge and transition experience for EIS service users. Taking into account service pressures, the discharge process should be one that is gradual, allowing time for the service user to both process the news and gradually sever ties with keyworkers.
Circularized and solubility‐enhancedMSPs facilitate simple and high‐yield production of stable nanodiscs for studies of membrane proteins in solution
Authors: Johansen Nicolai Tidemand , Tidemand Frederik Grønbæk , Nguyen Tam T. T. N. , Rand Kasper Dyrberg , Pedersen Martin Cramer , Arleth Lise
Published: January 2019

Recently, an enzymatic reaction was utilized to covalently link the N and C termini of membrane scaffold proteins to produce circularized nanodiscs that were more homogeneous and stable than standard nanodiscs. We continue this development and aim for obtaining high yields of stable and monodisperse nanodiscs for structural studies of membrane proteins by solution small‐angle scattering techniques. Based on the templateMSP1E3D1, we designed an optimized membrane scaffold protein (His‐lsMSP1E3D1) with a sortase recognition motif and high abundance of solubility‐enhancing negative charges. With these modifications, we show that high protein expression is maintained and that the circularization reaction is efficient, such that we obtain a high yield of circularized membrane scaffold protein (csMSP1E3D1) and downstream circularized nanodiscs. We characterize the circularized protein and corresponding nanodiscs biophysically by small‐angle X‐ray scattering, size‐exclusion chromatography, circular dichroism spectroscopy, and light scattering and compare to noncircularized samples. First, we show that circularized and noncircularized (lsMSP1E3D1) nanodiscs are structurally similar and have the expected nanodisc structure. Second, we show that lsMSP1E3D1 nanodiscs are more stable compared to the templateMSP1E3D1 nanodiscs as an effect of the extra negative charges and that csMSP1E3D1 nanodiscs have further improved stability as an effect of circularization. Finally, we show that a membrane protein can be efficiently incorporated in csMSP1E3D1 nanodiscs. Large‐scale production methods for circularized nanodiscs with improved thermal and temporal stability will facilitate better access to the nanodisc technology and enable applications at physiologically relevant temperatures.
More‐than‐human emotions: Multispecies emotional labour in the tourism industry
Authors: Dashper Katherine
Published: January 2019

The concept of emotional labour has been subject to critique, evaluation, development and extension over the last 35 years, but it remains firmly anthropocentric. This article begins to address this shortcoming by illustrating some of the productive potential of extending the concept of emotional labour to include more‐than‐human and multispecies perspectives. Organizations are not solely human phenomena, but research usually fails to consider the role of non‐humans in work in contemporary capitalism. Using the example of trail horses in tourism, I argue that some non‐human animals should be considered workers, and that they do perform emotional labour in service to commercial organizations. More‐than‐human and multispecies perspectives capture some of the complexities of everyday organizational practices, and can inform feminist research attuned to the experiences of marginalized others, human and non‐human.
Cost‐effectiveness analysis of screen‐and‐treat strategy in asymptomatic Chinese for preventing Helicobacter pylori‐associated diseases
Authors: Chen Qi , Liang Xiao , Long Xiaohua , Yu Lou , Liu Wenzhong , Lu Hong
Published: January 2019

Background

The high prevalence of Helicobacter pylori (H pylori) infection in China results in a substantial public health burden. Medical experts have not agreed on the best solution of population intervention for this problem. We presented a health economic evaluation of a population‐based H pylori screen‐and‐treat strategy for preventing gastric cancer, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD).

Materials and Methods

Decision trees and Markov models were developed to evaluate the cost‐effectiveness of H pylori screening followed by eradication treatment in asymptomatic Chinese. The modeled screen‐and‐treat strategy reduced the risk of gastric cancer, PUD, and NUD. The main outcomes were the costs, effectiveness, and the incremental cost‐effectiveness ratio. Uncertainty was explored by one‐way and probabilistic sensitivity analyses.

Results

For preventing gastric cancer, PUD, and NUD together in a cohort of 10 million asymptomatic Chinese at the age of 20 years, the H pylori screen‐and‐treat strategy saved 288.1 million dollars, 28 989 life years, and 111 663 quality‐adjusted life years, and prevented 11 611 gastric cancers, 5422 deaths from gastric cancer, and 1854 deaths from PUD during life expectancy. Uncertainty of screening age from 20 to 60 did not affect the superiority of the screen‐and‐treat strategy over the no‐screen strategy. The one‐way and probabilistic sensitivity analyses confirmed the robustness of our study's results.

Conclusions

Compared with the no‐screen strategy, population‐based screen‐and‐treat strategy for H pylori infection proved cheaper and more effective for preventing gastric cancer, PUD, and NUD in Chinese asymptomatic general population.
The top 50 most‐cited articles published in the International Endodontic Journal
Authors: Ahmad P. , Dummer P. M. H. , Noorani T. Y. , Asif J. A.
Published: January 2019

Aim

To analyse the main characteristics of the top 50 most‐cited articles published in the International Endodontic Journal from 1967 to 2018.

Methodology

The Clarivate Analytics’ Web of Science ‘All Databases’, Elsevier's Scopus, Google Scholar and PubMed Central were searched to retrieve the 50 most‐cited articles in the IEJ published from April 1967 to December 2018. The articles were analysed and information including number of citations, year of publication, contributing authors, institutions and countries, study design, study topic, impact factor and keywords was extracted.

Results

The number of citations of the 50 selected papers varied from 575 to 130 (Web of Science), 656 to164 (Elsevier's Scopus), 1354 to 199 (Google Scholar) and 123 to 3 (PubMed). The majority of papers were published in the year 2001 (n = 7). Amongst 102 authors, the greatest contribution was made by four contributors that included Gulabivala K (n = 4), Ng YL (n = 4), Pitt Ford TR (n = 4) and Wesselink PR (n = 4). The majority of papers originated from the United Kingdom (n = 8) with most contributions from King's College London Dental Institute (UK) and Eastman Dental Hospital, London. Reviews were the most common study design (n = 19) followed by Clinical Research (n = 16) and Basic Research (n = 15). The majority of topics covered by the most‐cited articles were Outcome Studies (n = 9), Intracanal medicaments (n = 8), Endodontic microbiology (n = 7) and Canal instrumentation (n = 7). Amongst 76 unique keywords, Endodontics (n = 7), Mineral Trioxide Aggregate (MTA) (n = 7) and Root Canal Treatment (n = 7) were the most frequently used.

Conclusion

This is the first study to identify and analyse the top 50 most‐cited articles in a specific professional journal within Dentistry. The analysis has revealed information regarding the development of the IEJ over time as well as scientific progress in the field of Endodontology.
Patient-reported barriers to medication adherence in heart failure in Scotland
Authors: Forsyth Paul , Richardson Janice , Lowrie Richard
Published: January 2019

Objectives

Medication adherence is the end result of a complex set of interwoven factors. Non-adherence with medication in heart failure patients is associated with excess mortality and morbidity. Studies describing interventions to improve adherence in heart failure are limited by a lack of robust methods and inconsistent outcomes. The aim of this evaluation was to explore the barriers to medication adherence in Scottish heart failure patients in order to inform the development of complex interventions.

Methods

Qualitative patient interviews. Participants were aged ≥18 years with current or previous signs or symptoms of clinical heart failure, reduced left ventricular ejection fraction ≤45% and confirmed adherence of <80% in tablet counts of heart failure therapy. Thematic analysis was employed.

Key findings

Eleven patients were recruited. The median age was 79 years old, and participants were typically from socially deprived communities. Participants were prescribed a mean 9.9 different medications per day. Seven distinct themes emerged around barriers to medication adherence: co-morbidity; treatment burden; health literacy; trust in NHS; socioeconomic factors; autonomy and health expectations.

Conclusions

The factors affecting medication adherence in heart failure are multi-factorial and are unlikely to be improved by one single-faceted intervention. Future interventions need to treat patients holistically, build their trust as partners, simplify complex treatment regimens where possible and involve educational and social elements. The skill set and opportunities afforded to pharmacists may be well placed to deliver many of these aspects but this would need tested in the context of the development of complex interventions.
Consumer recommendations for enhancing the Safewards model and interventions
Authors: Kennedy Hamilton , Roper Cath , Randall Rory , Pintado Daniel , Buchanan‐Hagen Sally , Fletcher Justine , Hamilton Bridget
Published: January 2019

This paper critiques the Safewards model through the lens of lived experiences of psychiatric hospitalization, diagnosis of mental illness, and distress. Special focus is given to the model's tested 10 interventions and to five lesser known interventions, identifying the impact they can have on hospitalized consumers. We highlight the role and prevalence of trauma, as well as the need to prevent harm in hospital settings. We draw upon notions of hospital as a sanctuary for people and the importance of providing a safe ward. ‘Sanctuary harm’ and ‘Sanctuary trauma’ are thus defined, with emphasis placed on the Safewards interventions as means by which sanctuary can be achieved. Finally, the consumer‐perspective authors propose expansions to the model, critiquing the defining literature and moving towards a consumer experience of safety that is beyond the model’s original intention: to reduce seclusion and restraint practices. Throughout the paper, the term ‘consumer’ is used in this context to mean people who have experienced or are experiencing psychiatric inpatient care.
The prevalence, incidence, and associated factors of pressure injuries among immobile inpatients: A multicentre, cross‐sectional, exploratory descriptive study in China
Authors: Liu Ying , Wu Xinjuan , Ma Yufen , Li Zhen , Cao Jing , Jiao Jing , Liu Ge , Li Fangfang , Song Baoyun , Jin Jingfen , Liu Yilan , Wen Xianxiu , Cheng Shouzhen , Lin Frances
Published: January 2019

The aim of this study was to assess the prevalence, incidence, and the associated factors of pressure injuries (PIs) among immobile hospitalised patients in China. Being immobile during hospitalisation put these patients at a higher risk of PIs. There is little literature about pressure injury (PI) prevalence or PI incidence in immobile hospitalised patients in hospitals in China. This was a multicentre, cross‐sectional, exploratory descriptive study. A total of 23 985 immobile patients were recruited from 25 general hospitals in six provinces of China from November 1, 2015 to March 18, 2016. Information was collected on demographic characteristics, physical assessment information, and treatment and nursing care measures. The PI period prevalence was 3.38%, and the PI cumulative incidence was 1.23%. Most PIs (84.03%) were Stage 1 or Stage 2. A total of 48.22% of PIs occurred in the sacrum or heel region. In the multivariate analysis, the following factors were associated with higher PI prevalence: age, gender, length of immobility, type of hospital, modified Braden Scale score, urinary incontinence, faecal incontinence, low serum albumin, the usage of fixation or restraint devices, and patient's discharge diagnosis (lower limb fracture, malnutrition, and spinal cord injury). PI prevalence for immobile hospitalised patients in the study was lower than those reported in literature. However, because of the large population in China, the number of patients who suffer with PIs can be very high. The relating factors of higher PI prevalence identified in this study were consistent with current literature. Patients with a higher number of these associated factors should be monitored more closely, and preventative measures should be taken to prevent PI occurrence in high‐risk populations.
A change in the prevalence and the etiological factors of chronic wounds in Helsinki metropolitan area during 2008‐2016
Authors: Ahmajärvi Kirsti M. , Isoherranen Kirsi M. , Mäkelä Anita , Venermo Maarit
Published: January 2019

The prevalence of chronic wounds in the Helsinki metropolitan area in 2008 was investigated. Thereafter, a specialised wound care team was founded as part of the City of Helsinki Health Services, aiming for early diagnoses of chronic wounds. In the current study, we have repeated the prevalence study to analyse the changes in the prevalence of chronic wounds. A questionnaire on wound patients was sent to all units of social and health care in the Helsinki metropolitan area. We asked about the number of patients with wounds treated during a 24‐hour period, as well the aetiology and location of the wounds. A total of 911 patients had, altogether, 1021 wounds. Thus, prevalence was 0.08%. Pressure and multifactorial ulcers were the most common aetiological groups, whereas wound without defined aetiology had diminished greatly (61%) The prevalence of chronic wound decreased when compared with 2008 (0.08% vs 0.1%). The number of elderly people aged over 65 years had increased 35%, and the age‐adjusted prevalence had decreased. Wounds are treated mostly in primary care units and as outpatients. Therefore, the following conclusion may be reached: diagnostic process and implementation of treatment paths are strengthened within primary care units, yet prevalence of wounds has decreased.
Liberalism's Religion and Laborde's Integrity
Authors: Seglow Jonathan
Published: January 2019

This response to Cecile Laborde's Liberalism's Religion explores her use of integrity in defence of legal accommodation for religious groups, noting some problems and issues raised by her account. It goes on to examine her novel category of Integrity Protecting Commitments, and then her views on reasonable disagreement. Integrity too, I suggest, may be the object of reasonable disagreement. Finally, it considers the two more general accounts of exemptions Laborde offers (into which the notion of integrity is inserted), disproportionate burden and majority bias.
Relict populations and Central European glacial refugia: The case of Rhododendron ferrugineum (Ericaceae)
Authors: Suchan Tomasz , Malicki Marek , Ronikier Michał
Published: January 2019

Aim

To assess the origin and genetic relationship of the northernmost population of Rhododendron ferrugineum in the Karkonosze Mts. (the Sudetes), located 350 km north of the previously acknowledged species limit, in the context of the whole species range; to discuss, based on this case study, the glacial history of the Central European mountain flora and importance of rare, relict populations for biogeographical inference and diversity conservation.

Location

European mountains: Sudetes, Alps, Pyrenees.

Methods

We sampled 90 individuals from 26 R. ferrugineum populations spanning the whole species’ range. To infer genetic structure, diversity and relationships among populations and isolated parts of the geographical range, we applied genome‐wide amplified fragment length polymorphism (AFLP) genotyping and sequencing of four cpDNA fragments and nrDNA ITS region.

Results

Our AFLP analysis revealed four distinct genetic groups in R. ferrugineum, one formed by the northernmost population from (a) the Karkonosze Mts. (the Sudetes) and the other three comprising populations from the (b) Western Alps and Pyrenees, (c) South‐Westernmost Alps and (d) Eastern Alps. Genetic isolation of the Karkonosze population was further corroborated by a repetitive pattern differentiation in plastid DNA sequences, otherwise almost monomorphic across the range. Population from the Karkonosze was most closely related to those from the Western Alps and not from the geographically closest Eastern Alps.

Main conclusions

We show that the population of R. ferrugineum in the Karkonosze Mts. is a glacial relict and not a recently established or introduced population. Its distinctiveness and high genetic diversity show that it represents a northern, previously undetected, genetic lineage of the species in Europe, which persisted through climatic changes in a small but stable microrefugium. Our case study highlights the importance of an adequate coverage of a species’ range in phylogeographical studies and the significance of peripheral parts of the range to reveal biogeographical history of lineages. It also supports the Karkonosze Mountains as an important refugium for the Central European mountain flora.
O‐GlcNAc transferase activates stem‐like cell potential in hepatocarcinoma through O‐GlcNAcylation of eukaryotic initiation factor 4E
Authors: Cao Benjin , Duan Meng , Xing Yang , Liu Chanjuan , Yang Fan , Li Yinan , Yang Tianxiao , Wei Yuanyan , Gao Qiang , Jiang Jianhai
Published: January 2019

O‐GlcNAcylation catalysed by O‐GlcNAc transferase (OGT) is a reversible post‐translational modification. O‐GlcNAcylation participates in transcription, epigenetic regulation, and intracellular signalling. Dysregulation of O‐GlcNAcylation in response to high glucose or OGT expression has been implicated in metabolic diseases and cancer. However, the underlying mechanisms by which OGT regulates hepatoma development remain largely unknown. Here, we employed the lentiviral shRNA‐based system to knockdown OGT to analyse the contribution of OGT in hepatoma cell proliferation and stem‐like cell potential. The sphere‐forming assay and western blot analysis of stem‐related gene expression were used to evaluate stem‐like cell potential of hepatoma cell. We found that the level of total O‐GlcNAcylation or OGT protein was increased in hepatocellular carcinoma. OGT activated stem‐like cell potential in hepatoma through eukaryotic initiation factor 4E (eIF4E) which bound to stem‐related gene Sox2 5'‐untranslated region. O‐GlcNAcylation of eIF4E at threonine 168 and threonine 177 protected it from degradation through proteasome pathway. Expression of eIF4E in hepatoma was determined by immunostaining in 232 HCC patients, and Kaplan‐Meier survival analysis was used to determine the correlation of eIF4E expression with prognosis. High glucose promoted stem‐like cell potential of hepatoma cell through OGT‐eIF4E axis. Collectively, our findings indicate that OGT promotes the stem‐like cell potential of hepatoma cell through O‐GlcNAcylation of eIF4E. These results provide a mechanism of HCC development and a cue between the pathogenesis of HCC and high glucose condition.
Deficiency of apoptosis‐stimulating protein two of p53 ameliorates acute kidney injury induced by ischemia reperfusion in mice through upregulation of autophagy
Authors: Ji Jing , Zhou Xiaoshuang , Xu Ping , Li Yafeng , Shi Honglin , Chen Dexi , Li Rongshan , Shi Hongbo
Published: January 2019

Acute kidney injury (AKI) has become a common disorder with a high risk of morbidity and mortality, which remains major medical problem without reliable and effective therapeutic intervention. Apoptosis‐stimulating protein two of p53 (ASPP2) is a proapoptotic member that belongs to p53 binding protein family, which plays a key role in regulating apoptosis and cell growth. However, the role of ASPP2 in AKI has not been reported. To explore the role of ASPP2 in the progression of AKI, we prepared an AKI mouse model induced by ischaemia reperfusion (I/R) in wild‐type (ASPP2+/+) mice and ASPP2 haploinsufficient (ASPP2+/−) mice. The expression profile of ASPP2 were examined in wild‐type mice. The renal injury, inflammation response, cellular apoptosis and autophagic pathway was assessed in ASPP2+/+ and ASPP2+/− mice. The renal injury, inflammation response and cellular apoptosis was analysed in ASPP2+/+ and ASPP2+/− mice treated with 3‐methyladenine or vehicle. The expression profile of ASPP2 showed an increase at the early stage while a decrease at the late stage during renal injury. Compared with ASPP2+/+ mice, ASPP2 deficiency protected mice against renal injury induced by I/R, which mainly exhibited in slighter histologic changes, lower levels of blood urea nitrogen and serum creatinine, and less apoptosis as well as inflammatory response. Furthermore, ASPP2 deficiency enhanced autophagic activity reflecting in the light chain 3‐II conversion and p62 degradation, while the inhibition of autophagy reversed the protective effect of ASPP2 deficiency on AKI. These data suggest that downregulation of ASPP2 can ameliorate AKI induced by I/R through activating autophagy, which may provide a novel therapeutic strage for AKI.
JS‐K induces reactive oxygen species‐dependent anti‐cancer effects by targeting mitochondria respiratory chain complexes in gastric cancer
Authors: Zhao Xudong , Cai Aizhen , Peng Zheng , Liang Wenquan , Xi Hongqing , Li Peiyu , Chen Guozhu , Yu Jiyun , Chen Lin
Published: January 2019

As a nitric oxide (NO) donor prodrug, JS‐K inhibits cancer cell proliferation, induces the differentiation of human leukaemia cells, and triggers apoptotic cell death in various cancer models. However, the anti‐cancer effect of JS‐K in gastric cancer has not been reported. In this study, we found that JS‐K inhibited the proliferation of gastric cancer cells in vitro and in vivo and triggered mitochondrial apoptosis. Moreover, JS‐K induced a significant accumulation of reactive oxygen species (ROS), and the clearance of ROS by antioxidant reagents reversed JS‐K‐induced toxicity in gastric cancer cells and subcutaneous xenografts. Although JS‐K triggered significant NO release, NO scavenging had no effect on JS‐K‐induced toxicity in vivo and in vitro. Therefore, ROS, but not NO, mediated the anti‐cancer effects of JS‐K in gastric cancer. We also explored the potential mechanism of JS‐K‐induced ROS accumulation and found that JS‐K significantly down‐regulated the core proteins of mitochondria respiratory chain (MRC) complex I and IV, resulting in the reduction of MRC complex I and IV activity and the subsequent ROS production. Moreover, JS‐K inhibited the expression of antioxidant enzymes, including copper‐zinc‐containing superoxide dismutase (SOD1) and catalase, which contributed to the decrease of antioxidant enzymes activity and the subsequent inhibition of ROS clearance. Therefore, JS‐K may target MRC complex I and IV and antioxidant enzymes to exert ROS‐dependent anti‐cancer function, leading to the potential usage of JS‐K in the prevention and treatment of gastric cancer.
Regulation of CXCL1 chemokine and CSF3 cytokine levels in myometrial cells by the MAFF transcription factor
Authors: Saliba James , Coutaud Baptiste , Solovieva Vera , Lu Fangshi , Blank Volker
Published: January 2019

Cytokines play key roles in a variety of reproductive processes including normal parturition as well as preterm birth. Our previous data have shown that MAFF, a member of the MAF family of bZIP transcription factors, is rapidly induced by pro‐inflammatory cytokines in PHM1‐31 myometrial cells. We performed loss‐of‐function studies in PHM1‐31 cells to identify MAFF dependent genes. We showed that knockdown of MAFF significantly decreased CXCL1 chemokine and CSF3 cytokine transcript and protein levels. Using chromatin immunoprecipitation analyzes, we confirmed CXCL1 and CSF3 genes as direct MAFF targets. We also demonstrated that MAFF function in PHM1‐31 myometrial cells is able to control cytokine and matrix metalloproteinase gene expression in THP‐1 monocytic cells in a paracrine fashion. Our studies provide valuable insights into the MAFF dependent transcriptional network governing myometrial cell function. The data suggest a role of MAFF in parturition and/or infection‐induced preterm labour through modulation of inflammatory processes in the microenvironment.
Barrier membranes: More than the barrier effect?
Authors: Omar Omar , Elgali Ibrahim , Dahlin Christer , Thomsen Peter
Published: January 2019

Aim

To review the knowledge on the mechanisms controlling membrane–host interactions in guided bone regeneration (GBR) and investigate the possible role ofGBRmembranes as bioactive compartments in addition to their established role as barriers.

Materials and Methods

A narrative review was utilized based onin vitro,in vivoand available clinical studies on the cellular and molecular mechanisms underlyingGBRand the possible bioactive role of membranes.

Results

Emerging data demonstrate that the membrane contributes bioactively to the regeneration of underlying defects. The cellular and molecular activities in the membrane are intimately linked to the promoted bone regeneration in the underlying defect. Along with the native bioactivity ofGBRmembranes, incorporating growth factors and cells in membranes or with graft materials may augment the regenerative processes in underlying defects.

Conclusion

In parallel with its barrier function, the membrane plays an active role in hosting and modulating the molecular activities of the membrane‐associated cells duringGBR. The biological events in the membrane are linked to the bone regenerative and remodelling processes in the underlying defect. Furthermore, the bone‐promoting environments in the two compartments can likely be boosted by strategies targeting both material aspects of the membrane and host tissue responses.
Distribution of heating surface areas in sugar juice evaporation process for maximum energy efficiency
Authors: Chantasiriwan Somchart
Published: January 2019

The conversion of diluted sugar juice into raw sugar and molasses requires thermal energy for evaporating the water content in sugar juice. The supply of thermal energy is saturated steam at around 200 kPa. The efficiency of energy use by the process is determined from the amount of saturated steam to process a given amount of sugar juice. It depends on heating surfaces of the juice heater and the evaporator. This article investigates the improvement in energy efficiency of the sugar juice evaporation process that has five evaporator effects by distributing fixed heating surface areas of the evaporator and the juice heater optimally. It is shown that there exists the optimum distribution of heating surfaces that results in the maximum energy efficiency for a specified sugar juice flow rate.

Practical applications

A mathematical model of quintuple‐effect evaporator in sugar juice evaporation process is presented in this paper. The proposed model should be useful for the design and analysis of the process. The article also presents an example of the application of the proposed model in determining the optimum distribution of fixed total heating surface areas that results in the maximum energy efficiency. The method presented in this article can be used by a process designer to determine the optimum distributions of evaporator and juice heater surface areas when total heating surface areas and sugar juice flow rate are given.
The Effect of a Comprehensive Dementia Care Management Program on End‐of‐Life Care
Authors: Jennings Lee A. , Turner Maurice , Keebler Chandra , Burton Carl H. , Romero Tahmineh , Wenger Neil S. , Reuben David B.
Published: January 2019

BACKGROUND/OBJECTIVES

Although Alzheimer disease and other dementias are life limiting, only a minority of these patients or their proxy decision makers participate in advance care planning. We describe end‐of‐life care preferences and acute care and hospice use in the last 6 months of life for persons enrolled in a comprehensive dementia care management program.

DESIGN

Observational, retrospective cohort.

SETTING

Urban, academic medical center.

PARTICIPANTS

A total of 322 persons enrolled in dementia care management after July 1, 2012, who died before July 1, 2016.

INTERVENTION

Dementia care comanagement model using nurse practitioners partnered with primary care providers and community organizations to provide comprehensive dementia care, including advance care planning.

MEASUREMENTS

Advance care preferences, use of Physician Orders for Life Sustaining Treatment (POLST), hospice enrollment, and hospitalizations and emergency department (ED) visits in the last 6 months of life obtained from electronic health record data.

RESULTS

Nearly all decedents (99.7%, N = 321) had a goals‐of‐care conversation documented (median = 3 conversations; interquartile range = 2‐4 conversations), and 64% had advance care preferences recorded. Among those with recorded preferences, 88% indicated do not resuscitate, 48% limited medical interventions, and 35% chose comfort‐focused care. Most patients (89%) specified limited artificial nutrition, including withholding feeding tubes. Over half (54%) had no hospitalizations or ED visits in the last 6 months of life, and intensive care unit stays were rare (5% of decedents). Overall, 69% died on hospice. Decedents who had completed a POLST were more likely to die in hospice care (74% vs 62%; P = .03) and die at home (70% vs 59%; P = .04).

CONCLUSIONS

Enrollees in a comprehensive dementia care comanagement program had high engagement in advance care planning, high rates of hospice use, and low acute care utilization near the end of life. Wider implementation of such programs may improve end‐of‐life care for persons with dementia. J Am Geriatr Soc 67:443–448, 2019.