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Tendinopathy is a major complication of diet-induced obesity. However, the effects of a high-fat diet (HFD) on tendon have not been well characterised. We aimed to determine: [1] the impact of a HFD on tendon properties and gene expression; and [2] whether dietary transition to a control diet (CD) could restore normal tendon health.Sprague-Dawley rats were randomised into three groups from weaning and fed either a: CD, HFD or HFD for 12 weeks and then CD thereafter (HF-CD). Biomechanical, histological and structural evaluation of the Achilles tendon was performed at 17 and 27 weeks of age. Tail tenocytes were isolated with growth rate and collagen production determined. Tenocytes and activated THP-1 cells were exposed to conditioned media (CM) of visceral adipose tissue explants, and gene expression was analysed.There were no differences in the biomechanical, histological or structural tendon properties between groups. However, tenocyte growth and collagen production were increased in the HFD group at 27 weeks. There was lower SOX-9 expression in the HFD and HF-CD groups at 17 weeks and higher expression of collagen-Iα1 and matrix metalloproteinase-13 in the HFD group at 27 weeks. THP-1 cells exposed to adipose tissue CM from animals fed a HFD or HF-CD had lower expression of Il-10 and higher expression of Il-1β.In this rodent model, a HFD negatively altered tendon cell characteristics. Dietary intervention restored some gene expression changes; however, adipose tissue secretions from the HF-CD group promoted an increased inflammatory state in macrophages. These changes may predispose tendon to injury and adverse events later in life.

Nuclear receptor related 1 protein (Nurr1), a member of the nuclear receptor 4 family of orphan nuclear receptors, has been reported to display anti‑inflammatory properties. The present study investigated the alteration of Nurr1 immunoreactivity in the gerbil hippocampus proper following 5 min of transient global cerebral ischemia. In sham operated gerbils, Nurr1 immunoreactivity was observed in pyramidal neurons in all cornu ammonis 1‑3 (CA1‑3) subfields of the hippocampus proper. In ischemia‑operated gerbils, Nurr1 immunoreactivity was altered in the CA1 subfield. Nurr1 immunoreactivity in CA1 pyramidal neurons gradually decreased until 2 days post‑ischemia, and, at 4 days post‑ischemia, Nurr1 immunoreactivity was concentrated in CA1 pyramidal neurons. Additionally, Nurr1 immunoreactivity was newly expressed in microglia in the CA1 subfield at 4 days post‑ischemia. Conversely, in the CA2/3 subfield, time‑dependent alteration of Nurr1 immunoreactivity was not identified at any time following ischemia. These results indicated that the alteration of Nurr1 expression in the CA1 subfield in the hippocampus may be associated with the death of CA1 pyramidal neurons.

Bisphosphonates are used in treating patients with breast cancer. In vitro studies have shown that bisphosphonates act directly on tumour cells, inhibiting cell proliferation and inducing apoptosis. In most such studies, drugs were added to culture media exposing cells to high bisphosphonate concentrations in solution. However, since bisphosphonates bind to bone hydroxyapatite with high affinity and remain bound for very long periods of time, these experimental systems are not an optimal model for the action of the drugs in vivo. The aim of this study was to determine whether bone-bound zoledronate has direct effects on adjacent breast cancer cells. Bone slices were pre-incubated with bisphosphonate solutions, washed, and seeded with cells of the breast cancer cell lines, MCF7 or MDA-MB-231. Proliferation was assessed by cell counts and thymidine incorporation for up to 72 h. Inhibition of the mevalonate pathway was tested by measuring the levels of unprenylated Rap1A, and apoptosis was examined by the presence of cleaved caspase-8 on western blots. The proliferation rate of breast cancer cells on zoledronate-treated bone was significantly lower compared to cells on control bone. Other bisphosphonates showed a similar inhibitory effect, with an order of potency similar to their clinical potencies. Unprenylated Rap1A accumulated in MCF7 cells on zoledronate-treated bone, suggesting zoledronate acted through the inhibition of the mevalonate pathway. Accumulation of cleaved caspase-8 in MDA-MB-231 cells on bisphosphonate-treated bone indicated increased apoptosis in the cells. In conclusion, bone-bound zoledronate inhibits breast cancer cell proliferation, an activity that may contribute to its clinical anti-tumour effects.

Spinal cord ischemia can result from cardiac arrest. It is an important cause of severe spinal cord injury that can lead to serious spinal cord disorders such as paraplegia. Hypothermia is widely acknowledged as an effective neuroprotective intervention following cardiac arrest injury. However, studies on effects of hypothermia on spinal cord injury following asphyxial cardiac arrest and cardiopulmonary resuscitation (CA/CPR) are insufficient. The objective of this study was to examine effects of hypothermia on motor deficit of hind limbs of rats and vulnerability of their spinal cords following asphyxial CA/CPR. Experimental groups included a sham group, a group subjected to CA/CPR, and a therapeutic hypothermia group. Severe motor deficit of hind limbs was observed in the control group at 1 day after asphyxial CA/CPR. In the hypothermia group, motor deficit of hind limbs was significantly attenuated compared to that in the control group. Damage/death of motor neurons in the lumbar spinal cord was detected in the ventral horn at 1 day after asphyxial CA/CPR. Neuronal damage was significantly attenuated in the hypothermia group compared to that in the control group. These results indicated that therapeutic hypothermia after asphyxial CA/CPR significantly reduced hind limb motor dysfunction and motoneuronal damage/death in the ventral horn of the lumbar spinal cord following asphyxial CA/CPR. Thus, hypothermia might be a therapeutic strategy to decrease motor dysfunction by attenuating damage/death of spinal motor neurons following asphyxial CA/CPR.

This study examines how frequently committed ethical misconduct regarding values closely aligned to an organizational mission affects stakeholders’ pro-organizational responses to an offending nonprofit. Using a 2 × 2 experimental survey, findings showed that ethical misconduct in primary values resulted in significantly decreased positive attitudes toward and donation intentions to the organization. Also, the patterns of unethical behaviors significantly increased stakeholders’ negative attitudes toward the organization and willingness to assign the organization responsibility for unethical behavior. Perceived organizational responsibility for ethical misconduct and deteriorating organization–public relationships (OPRs) were significant mediators for the effects of primary ethical violations.

PurposeThe purpose of this paper is to demonstrate whether or not public relations efforts in corporate social responsibility (CSR) influence the news media in corporate crisis situations.Design/methodology/approachThe study conducted a content analysis of press releases and news media based on traditional human-coded cross-lag analyses and a machine learning technique, a novel method of big data analysis to test hypotheses.FindingsResults indicate that CSR press releases indeed influenced the news media. During the crisis point, however, agenda-building was not observed.Practical implicationsCorporations need to continue CSR activities and provide public relations materials consistently even after a crisis, as an agenda-building role could be recovered.Originality/valueThe study examines the relationship between CSR and crisis situations in an agenda-building theoretical framework. The authors introduce agenda-building in the corporate sector with machine learning techniques.

Solanum chacoense is a wild tuber-bearing species belonging to Solanaceae family. The chloroplast genome of the species was completed by de novo assembly using a small amount of whole genome sequencing data. The genome is the circular DNA molecule with a length of 155,532 bp containing 159 predicted genes totally, including 105 protein-coding, 45 tRNA and eight rRNA genes. Maximum-likelihood phylogenetic analysis with 26 species in Solanaceae revealed that S. chacoense is the most closely grouped with S. commersonii.

Erigeron annuus (L.) PERS. (EALP) and Clematis mandshurica RUPR. (CMR) have been used in traditional remedies due to their medicinal effects. Recently, we reported that pretreatment with 200 mg/kg of YES-10® (a combination of extracts from leaves of EALP and CMR) displayed neuroprotective effects against brain ischemia and reperfusion injury. The present study analyzed the major ingredients of YES-10® and investigated whether neuroprotection from YES-10® was dependent upon antioxidant effects in the cornu ammonis 1 (CA1) field in the gerbil hippocampus, after transient forebrain ischemia for 5 min. YES-10® was demonstrated to predominantly contain scutellarin and chlorogenic acid. Pretreatment with YES-10® significantly increased protein levels and the immunoreactivity of copper/zinc-superoxide dismutase (SOD1) and manganese-superoxide dismutase (SOD2) was in the pyramidal neurons of the hippocampal CA1 field when these were examined prior to transient ischemia induction. The increased SODs in CA1 pyramidal neurons following YES-10® treatment were maintained after ischemic injury. In this case, the CA1 pyramidal neurons were protected from ischemia-reperfusion injury. Oxidative stress was significantly attenuated in the CA1 pyramidal neurons, and this was determined by 4-hydroxy-2-nonenal immunohistochemistry and dihydroethidium histofluorescence staining. Taken together, the results indicated that YES-10® significantly attenuated transient ischemia-induced oxidative stress and may be utilized for developing a protective agent against ischemic insults.

Along with the occurrence of the big data era, digital transformation has had a transformative effect on modern education tremendously in higher education. It transforms an institutional core value of education to better meet students' needs by leveraging big data and digital technology. Based on this background, this study attempts to catch the principal trends, or new directions, paradigms as predictors with an association of each topic by discovering the up-to-date research trends on teaching and learning in higher education via text mining technique. For this, 285 research articles in the area of teaching and learning in higher education were collected from several big databases (distinguishable publishers' web platforms) through search engines for two years in 2018 ~ 2019. Then it was analyzed using a semantic network analysis that processes natural human language. In consequence, research results show a relatively high connection with 'student' or 'student-centered/led' rather than 'teacher-led.' Moreover, it exhibits that the practice and assessment in learning can be attained via diverse learning activities, containing community or outreach activities. Besides, research in academic contexts, experience-based classes, the effect of group activities, how students' feelings or perceptions, and relationships affect learning outcomes were addressed as the main topics through topic modeling of LDA, a machine learning algorithm. This study proposes that educators, researchers, and even academic leaders can exert the extraordinary power to reshape educational quality programs for future education and in a timely manner with recognizable trends or agendas in teaching and learning of higher education.

Digital transformation in higher education has had a transformative effect on modern education. It means transforming an institutional core value of education to better meet students’ needs by leveraging digital technology and big data. Accordingly, this study aims to catch the principal directions, trends, or new paradigms as predictors with a linkage of each topic by identifying the latest research agendas of teaching and learning in higher education through semantic network analysis. For this, 285 research articles from four international ‘top-tier’ journals ranked as ISI/SCOPUS Q1 were gathered in the area of teaching and learning in higher education for two years in 2018 ~ 2019, and then it was analyzed using a text mining technique that processes natural language. Consequently, the study of researches on teaching and learning shows a relatively high connection with ‘student’ or ‘student-centered/led’ rather than ‘teacher-led’. Moreover, it is observed that the practice and assessment of learning can be achieved through various activities including community activities. Besides that, experience-based classes, research in academic contexts, the effect of group activities, how students’ perceptions or feelings and relationships affect learning outcomes were mentioned as the main topics through topic modeling of LDA, a machine learning algorithm. This study proposes that educators, researchers, and academic leaders can exert the remarkable power to reshape the educational programs for future quality education properly and a timely fashion based on recognizable trends or topics in teaching and learning of higher education.

The use of peptide hydrogels is of growing interest in bone regeneration. Self-assembling peptides form hydrogels and can be used as injectable drug delivery matrices. Injected into the defect site, they can gel in situ, and release factors that aid bone growth. We report on the design, synthesis and characterization of three β-hairpin peptide hydrogels, and on their osteoblast cytocompatibility as well as delivery of the lactoferrin glycoprotein, a bone anabolic factor. Osteoblasts cultured in hydrogels of the peptide with sequence NH2-Leu-His-Leu-His-Leu-Lys-Leu-Lys-Val-DPro-Pro-Thr-Lys-Leu-Lys-Leu-His-Leu-His-Leu-Arg-Gly-Asp-Ser-CONH2 (H4LMAX-RGDS) increased the osteoblast cell number and the cells appeared healthy after seven days. Furthermore, we showed that H4LMAX-RGDS was capable of releasing up to 60% of lactoferrin (pre-encapsulated in the gel) over five days while retaining the rest of the glycoprotein. Thus, H4LMAX-RGDS hydrogels are cytocompatible with primary osteoblasts and capable of delivering bio-active lactoferrin that increases osteoblast cell number.

Oxcarbazepine (OXC), a voltage-gated sodium channel blocker, is an antiepileptic medication and used for the bipolar disorders treatment. Some voltage-gated sodium channel blockers have been demonstrated to display strong neuroprotective properties in models of cerebral ischemia. However, neuroprotective effects and mechanisms of OXC have not yet been reported. Here, we investigated the protective effect of OXC and its mechanisms in the cornu ammonis 1 subfield (CA1) of gerbils subjected to 5 min of transient global cerebral ischemia (tGCI). tGCI led to death of most pyramidal neurons in CA1 at 5 days after ischemia. OXC (100 and 200 mg/kg) was intraperitoneally administered once at 30 min after tGCI. Treatment with 200 mg/kg, not 100 mg/kg OXC, significantly protected CA1 pyramidal neurons from tGCI-induced injury. OXC treatment significantly decreased superoxide anion production, 4-hydroxy-2-nonenal and 8-hydroxyguanine levels in ischemic CA1 pyramidal neurons. In addition, the treatment restored levels of superoxide dismutases, catalase, and glutathione peroxidase. Furthermore, the treatment distinctly inhibited tGCI-induced microglia activation and significantly reduced levels of pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). In particular, OXC treatment significantly enhanced expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream protein heme oxygenase-1 in ischemic CA1. The neuroprotective effects of OXC were abolished by brusatol (an inhibitor of Nrf2). Taken together, these results indicate that post-treatment of OXC can display neuroprotection against brain injuries following ischemic insults. This neuroprotection may be displayed by attenuation of oxidative stress and neuroinflammation, which can be mediated by activation of Nrf2 pathway.

The degree of transient ischemic damage in the cerebral hemisphere is different according to duration of transient ischemia and cerebral regions. Mongolian gerbils show various lesions in the hemisphere after transient unilateral occlusion of the common carotid artery (UOCCA) because they have different types of patterns of anterior and posterior communicating arteries. We examined differential regional damage in the ipsilateral hemisphere of the gerbil after 30 min of UOCCA by using 2,3,5-triphenyltetrazolium chloride (TTC) staining, cresyl violet (CV) Nissl staining, Fluoro-Jade B (F-J B) fluorescence staining, and NeuN immunohistochemistry 5 days after UOCCA. In addition, regional differences in reactions of astrocytes and microglia were examined using GFAP and Iba-1 immunohistochemistry. After right UOCCA, neurological signs were assessed to define ischemic symptomatic animals. Moderate symptomatic gerbils showed several infarcts, while mild symptomatic gerbils showed selective neuronal death/loss in the primary motor and sensory cortex, striatum, thalamus, and hippocampus 5 days after UOCCA. In the areas, morphologically changed GFAP immunoreactive astrocytes and Iba-1 immunoreactive microglia were found, and their numbers were increased or decreased according to the damaged areas. In brief, our results demonstrate that 30 min of UOCCA in gerbils produced infarcts or selective neuronal death depending on ischemic severity in the ipsilateral cerebral cortex, striatum, thalamus and hippocampus, showing that astrocytes and microglia were differently reacted 5 days after UOCCA. Taken together, a gerbil model of 30 min of UOCCA can be used to study mechanisms of infarction and/or regional selective neuronal death/loss as well as neurological dysfunction following UOCCA.

BACKGROUND/AIMS The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSION CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.

Applying the expectancy violation theory, the study examines how a company’s commitment to corporate social responsibility (CSR) interacts with the timing of receiving inconsistency message cues (i...

Subject area The case could be used in many courses in the field of business and management, for example, environmental management, strategic management, corporate strategy, green or sustainable marketing and international business. Study level/applicability The case has a difficulty level of being appropriate for undergraduate and postgraduate students. However, in utilizing this case as a required component of business courses at various levels, the authors have discovered a different approaching between undergraduate students and postgraduate students in answering those discussion questions. Undergraduate students have tended to focus on the more conceptual and basic approaching based on understanding the main concepts of environmental upgrading. Postgraduate students have a better application and critical thinking based on a better understanding of the fundamental knowledge and concepts. Accordingly, the case has been developed in a manner that will allow students to realize the importance of environmental issues and analyze the company’s main issues as detailed in the case and then suggest opinions and any ideas for the strategy the company should consider and pursue in future. Furthermore, students should identify several points on the company’s chosen strategies and actions for environmental upgrading. Case overview This case is written in the form of an interview with the Chairman and chief executive officer of VIYELLATEX Group, one of the leading firms which embarked upon environmental upgrading in the apparel industry of Bangladesh and in the world. This is an analytical case and not a decision-making one. The main theme of the case revolves around analyzing what drove VIYELLATEX Group to upgrade environmentally, how the group upgraded, the challenges that VIYELLATEX Group has faced and outcomes of environmental upgrading. Environmental upgrading implies an improvement in environmental performance through changes in technological, social and organizational processes and avoiding or reducing the environmental impacts of businesses. In summary, the VIYELLATEX case is an investigation of a leading company in Bangladesh to implement environmental standards and management practices being part of the apparel global apparel industry governed by global retailers and brand marketers. Expected learning outcomes The learning outcomes are understanding of “corporate sustainability” as a corporate social responsibility of business philosophy, understanding of key features of the apparel industry in Bangladesh, understanding of the main issues and challenges faced by the apparel firms (suppliers) involved in international business regarding environmental upgrading, understanding of the relationship with primary stakeholders, in particular buyers of apparel firm (defining stakeholders and how to cooperate with stakeholders) and understanding of the environmental upgrading in terms of its drivers, processes and outcomes. Supplementary materials Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes. Subject code: CSS 4 Environmental Management.

INTRODUCTION Congenital myopathies are muscle diseases characterized by specific histopathologic features, generalized hypotonia from birth, and perinatal complications, although some cases develop during childhood or, rarely, in adulthood. We undertook this study to characterize congenital myopathies among patients registered at our institution. METHODS Clinical, histopathologic, and genetic features were evaluated in 34 patients recruited for this study. RESULTS The majority of patients experienced a childhood onset, and no disease-related mortality was recorded during follow-up. Functional outcomes were no better for those with late-onset disease, indicating later disease progression can be significant. Nemaline myopathy was the most frequent pathology, followed by central core disease and centronuclear myopathy. Among the 18 (54.5%) genetically confirmed patients, NEB and RYR1 mutations were the most common, followed by DNM2 mutations. DISCUSSION This study shows features not previously reported and suggests that congenital myopathy should be considered an important issue among adult patients. Muscle Nerve 58: 235-244, 2018.

Purpose - This study involves the following questions: “Does internalization theory fully explain reality?” and “Which additional factors may add...

Nemaline myopathy (NM), the most common of the congenital myopathies, is caused by various genetic mutations. In this study, we attempted to identify the causative mutations of NM and to reveal any specific genotype-phenotype relationship in Korean patients with this disease. We investigated the clinical features and genotypes in 15 pathologically diagnosed NM patients, using whole exome sequencing (WES) combined with targeted sequencing and array-based comparative genomic hybridization. This strategy revealed pathogenic causative mutations in seven patients (46.7%), among whom mutations in the nebulin gene (NEB) were the most frequent (5 patients, 33.3%). Copy number variation (CNV) abnormality in NEB was not observed in any of our patients. In those with NEB-associated NM, the clinical spectrum was highly variable regardless of the mutation type. However, the majority of patients showing anterior lower leg weakness were associated with mutations located between NEB exons 166 and 177. We concluded that the combination of WES and targeted Sanger sequencing is an effective strategy for analyzing genotypes in patients with NM, and that CNV in NEB may not be a frequent cause of this disease among Koreans.

Trichomes are specialized epidermal structures that protect plants from abiotic and biotic stresses. Cultivated potato (Solanum tuberosum) is known to have both glandular and non-glandular trichomes. However, the criteria for trichome type classification have not been studied in detail. In addition, there is a poor understanding of the types of trichomes that exist in wild potato species. Here, the morphology and density of trichomes were compared between a representative cultivated potato variety and 17 wild potato species using Cryo Scanning Electron Microscopy (CryoSEM). Based on trichome morphology, the cultivated variety and each of the wild species were seen to have two glandular and two non-glandular trichome types. We classified the eighteen potato species into four groups using trichome type and density criteria. Groups I and II represented species with a higher density of glandular or non-glandular trichomes, respectively, on both abaxial and adaxial leaf surfaces. Group III represented species with a higher density of non-glandular trichomes on abaxial leaf surfaces alone. Group IV represented species with an overall lower trichome density on both abaxial and adaxial leaf surfaces, but which was formed of both glandular and non-glandular types. Honey dew spots were quantified following infestation with the aphid Macrosiphum euphorbiae to test whether trichome composition is associated with resistance to aphid feeding. Fewer honey dew spots were observed in the Group I representative species S. berthaultii and S. hougasii compared to that in species from other groups. Furthermore, correlation coefficient analysis showed that honey dew spot number was negatively associated with glandular trichome density. These results imply that glandular trichomes play an important role in aphid resistance and thus can be used for developing insect-resistant potato.

A prevalent view of visual working memory (VWM) is that visual information is actively maintained in the form of perceptually integrated objects. Such reliance on object-based representations would predict that after an object is fully encoded into VWM, all features of that object would need to be maintained as a coherent unit. Here, we evaluated this idea by testing whether memory resources can be redeployed to a specific feature of an object already stored in VWM. We found that observers can utilize a retrospective cue presented during the maintenance period to attenuate both the gradual deterioration and complete loss of memory for a cued feature over time, but at the cost of accelerated loss of information regarding the uncued feature. Our findings demonstrate that object representations held within VWM can be decomposed into individual features and that having to retain additional features imposes greater demands on active maintenance processes.

Lipophilic bioactive compounds and hydrophilic primary metabolites from potato (solanum tubersum L.) tubers with different-colored flesh (white-, yellow-, red-, and purple) were characterized. The carotenoid content was relatively higher in red-colored potatoes, in which lutein was most plentiful. Among the other lipophilic compounds analyzed, including policosanols, tocopherols, and phytosterols, octacosanol was measured in the largest amount, followed by β-sitosterol, irrespective of color variations. Forty-three hydrophilics consisting of amino acids, organic acids, sugars, and sugar alcohols and 18 lipophilics were subjected to data-mining processes. The results of multivariate statistical analyses clearly distincted the different varieties and separated red-fleshed potatoes from other color-fleshed potatoes according to abundance of amino acids, sugars, and carotenoids. This study confirmed the metabolic association-related biochemical pathway between metabolite characteristic and color differences in potato tubers. These results can facilitate understanding the metabolic differences among diverse colored potatoes and provide fruitful information for genetic engineering of potato cultivars.

Introduction Several clinical studies using tacrolimus revealed reasonable therapeutic mechanisms and efficacy in patients with myasthenia gravis (MG). However, long-period studies in a large number of patients with MG are limited; therefore, the aim of this study was to investigate the therapeutic efficacies and safety of tacrolimus in patients with MG during a 12-month follow-up period. Methods Tacrolimus was administered to 150 patients with MG who were recruited based on the inclusion criteria. Fifteen medical centers in Korea participated in this study. The efficacy of tacrolimus was assessed using MG composite scales (MGCS) and the prednisolone-sparing effect. And the adverse drug reactions (ADRs) of tacrolimus were monitored in each patient from the beginning of tacrolimus treatment to the end of the follow-up period. Results After starting tacrolimus, the 32 patients were affected by ADRs, and consequentially 134 patients of the enrolled patients were followed up for 12 months. They showed that the mean prednisolone dosage significantly decreased (6.1 ± 7.6 mg/day), compared to that in the baseline (11.3 ± 9.5 mg/day), and MGCS significantly improved after 12 months of tacrolimus treatment, compared to that at the baseline. Conclusions Our study showed that tacrolimus would be an effective immunosuppressant as an initial therapeutic agent in patients with MG; in addition, it showed tolerable safety profiles during the 12-month follow-up evaluation.

Cell-cell communication plays a crucial role in bone development and maintenance, in health and disease. Our knowledge of the signalling pathways that regulate the communication of osteoblasts, osteoclasts and osteocytes is improving with time, giving us a better understanding of the regulation of the bone remodelling process. Bone cell communication has wider significance than the local tissue environment, however, with bone derived factors playing a role in whole-body homeostasis, including energy metabolism and kidney function. Similarly, there are a range of systemic conditions which affect the maintenance of bone mass. Understanding these complex interactions, the autocrine, paracrine and endocrine signalling involved in the regulation of bone health is paramount to a better understanding of bone disease, and ultimately developing targets for pharmaceutical intervention.

Existing relationship research has interpreted low trust as being equivalent to high distrust and high trust as the evidence of low distrust, which has failed to capture the full scope of the functions of trust and distrust in organization–public relationships. Recent research in this area suggests that trust and distrust might simultaneously exist during relational interactions and might play uniquely positive and negative functions in certain social contexts. The main purpose of this study was to offer a new insight in trust–distrust research by providing distinctions in conceptualization and operationalization between trust and distrust. This study also empirically tested the functions of four pairings of trust and distrust on two core public relations concepts (i.e., symmetrical communication and public engagement). The results from the surveys (N = 704; in 20 companies) of US consumers showed sound discriminant validity of trust and distrust. Further, the statistical results revealed that sym...