bluuebunny/crossref_metadata_2025 huggingface dataset:
Microglial Mincle receptor in the PVN contributes to sympathetic hyperactivity in acute myocardial infarction rat
Authors: Wang Yu , Yin Jie , Wang Cailing , Hu Hesheng , Li Xiaolu , Xue Mei , Liu Ju , Cheng Wenjuan , Wang Ye , Li Yan , Shi Yugen , Tan Jiayu , Li Xinran , Liu Fuhong , Liu Qiang , Yan Suhua
Published: October 2018

Malignant ventricular arrhythmias (VAs) following myocardial infarction (MI) is a lethal complication resulting from sympathetic nerve hyperactivity. Numerous evidence have shown that inflammation within the paraventricular nucleus (PVN) participates in sympathetic hyperactivity. Our aim was to explore the role of Macrophage‐inducible C‐type lectin (Mincle) within the PVN in augmenting sympathetic activity following MI,and whether NOD‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome/IL‐1β axis is involved in this activity. MI was induced by coronary artery ligation. Mincle expression localized in microglia within the PVN was markedly increased at 24 hours post‐MI together with sympathetic hyperactivity, as indicated by measurement of the renal sympathetic nerve activity (RSNA) and norepinephrine (NE) concentration. Mincle‐specific siRNA was administrated locally to the PVN, which consequently decreased microglial activation and sympathetic nerve activity. The MI rats exhibited a higher arrhythmia score after programmed electric stimulation than that treated with Mincle siRNA, suggesting that the inhibition of Mincle attenuated foetal ventricular arrhythmias post‐MI. The underlying mechanism of Mincle in sympathetic hyperactivity was investigated in lipopolysaccharide (LPS)‐primed naïve rats. Recombinant Sin3A‐associated protein 130kD (rSAP130), an endogenous ligand for Mincle, induced high levels of NLRP3 and mature IL‐1β protein. PVN‐targeted injection of NLRP3 siRNA or IL‐1β antagonist gevokizumab attenuated sympathetic hyperactivity. Together, the data indicated that the knockdown of Mincle in microglia within the PVN prevents VAs by attenuating sympathetic hyperactivity and ventricular susceptibility, in part by inhibiting its downstream NLRP3/IL‐1β axis following MI. Therapeutic interventions targeting Mincle signalling pathway could constitute a novel approach for preventing infarction injury.
CUDC‐907 blocks multiple pro‐survival signals and abrogates microenvironment protection in CLL
Authors: Chen Yixiang , Peubez Chloé , Smith Victoria , Xiong Shiqiu , Kocsis‐Fodor Gabriella , Kennedy Ben , Wagner Simon , Balotis Constantine , Jayne Sandrine , Dyer Martin J. S. , Macip Salvador
Published: October 2018

CUDC‐907, a dual PI3K/HDAC inhibitor, has been proposed to have therapeutic potential in hematopoietic malignancies. However, the molecular mechanisms of its effects in chronic lymphocytic leukaemia (CLL) remain elusive. We show that CLL cells are sensitive to CUDC‐907, even under conditions similar to the protective microenvironment of proliferation centres. CUDC‐907 inhibited PI3K/AKT and HDAC activity, as expected, but also suppressed RAF/MEK/ERK and STAT3 signalling and reduced the expression of anti‐apoptotic BCL‐2 family proteins BCL‐2, BCL‐xL, and MCL‐1. Moreover, CUDC‐907 downregulated cytokines BAFF and APRIL and their receptors BAFFR, TACI, and BCMA, thus blocking BAFF‐induced NF‐κB signalling. T cell chemokines CCL3/4/17/22 and phosphorylation of CXCR4 were also reduced by CUDC‐907. These data indicated that CUDC‐907 abrogates different protective signals and suggested that it might sensitize CLL cells to other drugs. Indeed, combinations of low concentrations of CUDC‐907 with inhibitors of BCL2, BTK, or the NF‐κB pathway showed a potent synergistic effect. Our data indicate that, apart from its known functions, CUDC‐907 blocks multiple pro‐survival pathways to overcome microenvironment protection in CLL cells. This provides a rationale to evaluate the clinical relevance of CUDC‐907 in combination therapies with other targeted inhibitors.
The effects of stenting on coronary endothelium from a molecular biological view: Time for improvement?
Authors: Cornelissen Anne , Vogt Felix Jan
Published: October 2018

Coronary artery stenting following balloon angioplasty represents the gold standard in revascularization of coronary artery stenoses. However, stent deployment as well as percutaneous transluminal coronary angioplasty (PTCA) alone causes severe injury of vascular endothelium. The damaged endothelium is intrinsically repaired by locally derived endothelial cells and by circulating endothelial progenitor cells from the blood, leading to re‐population of the denuded regions within several weeks to months. However, the process of re‐endothelialization is often incomplete or dysfunctional, promoting in‐stent thrombosis and restenosis. The molecular and biomechanical mechanisms that influence the process of re‐endothelialization in stented segments are incompletely understood. Once the endothelium is restored, endothelial function might still be impaired. Several strategies have been followed to improve endothelial function after coronary stenting. In this review, the effects of stenting on coronary endothelium are outlined and current and future strategies to improve endothelial function after stent deployment are discussed.
IL‐17A promotes cell migration and invasion of glioblastoma cells via activation of PI3K/AKT signalling pathway
Authors: Zheng Qianqian , Diao Shuo , Wang Qi , Zhu Chen , Sun Xun , Yin Bo , Zhang Xinwen , Meng Xin , Wang Biao
Published: October 2018

Glioblastomas (GBMs) are the most common of both benign and malignant primary brain tumours, in which the inflammatory and immunologic abnormalities are involved. Interleukin‐17A (IL‐17A) plays an important role in various inflammatory diseases and cancers. Several recent studies revealed that the expression of IL‐17A was overexpressed in human GBMs tissue. However, the accurate role of IL‐17A in GBMs remains unclear. In this study, we aimed to explore the effect of IL‐17A on cell migration and invasion of GBMs and the mechanism by which the effects occurred. We found that exogenous IL‐17A promoted significantly cell migration and invasion abilities in two GBMs cell lines (U87MG and U251) in a time‐dependent manner. In addition, the protein expressions of PI3K, Akt and MMP‐2/9 were increased in the GBMs cells challenged by IL‐17A. Furthermore, a tight junction protein ZO‐1 was down‐regulated but Twist and Bmi1 were up‐regulated. Treatment with a PI3K inhibitor (LY294002) significantly reduced the abilities of both migration and invasion in U87MG and U251 cells. LY294002 treatment also attenuated the IL‐17A causing increases of protein levels of PI3K, AKT, MMP‐2/9, Twist and the decreases of protein level of ZO‐1 in the U87MG and U251 cells. Taken together, we concluded that IL‐17A promotes the GBM cells migration and invasion via PI3K/AKT signalling pathway. IL‐17A and its related signalling pathways may be potential therapeutic targets for GBM.
Revealing the Environmental Advantages of Industrial Symbiosis in Wood‐Based Bioeconomy Networks: An Assessment From a Life Cycle Perspective
Authors: Hildebrandt Jakob , O'Keeffe Sinéad , Bezama Alberto , Thrän Daniela
Published: October 2018

The German government has recently initiated funding schemes that incentivize strategies for wood‐based bioeconomy regions. Regional wood and chemical industries have been encouraged to act symbiotically, that is, share pilot plant facilities, couple processes where feasible, and cascade woody feedstock throughout their process networks. However, during the planning stages of these bioeconomy regions, options need to be assessed for sustainably integrating processes and energy integration between the various industries that produce bio‐based polymers and engineered wood products. The aim of this paper is to identify the environmental sustainability of industrial symbiosis for producing high‐value‐added, bio‐based products in the wood‐based bioeconomy region of Central Germany. An analysis was conducted of three possible future scenarios with varying degrees of symbiosis in the bioeconomy network. A life cycle assessment (LCA) approach was used to compare these three scenarios to a traditional fossil‐based production system. Eleven environmental impact categories were considered. The results show that, in most cases, the bioeconomy network outperformed the fossil‐based production system, mitigating environmental impacts by 25% to 130%.
Association between sexual behavior and suicidal ideation among South Korean middle school students
Authors: Song Seunghun , Lee Gyuyoung
Published: October 2018

Aim

To identify the association between sexual behavior and suicidal ideation among South Korean middle school students.

Methods

This study used raw data from the 2013 Korean Youth Risk Behavior Web‐Based Survey. Among the data from 72,435 students, the data from 36,530 individuals in middle school were analyzed. The prevalence of sexual behavior and suicidal ideation, according to the participants’ general characteristics, and suicidal ideation, according to sexual behaviors, were assessed by using a complex sample Chi‐squared test. A complex sample logistic regression was used to examine the association between sexual behavior and suicidal ideation.

Results

Overall, 3.8% of the students reported having had sexual intercourse and 17.6% of the students reported suicidal ideation during the past 12 months. Having had sexual intercourse was statistically significantly associated with suicidal ideation. The students who had had sexual intercourse usually used contraception and those who had contracted sexually transmitted diseases were more likely to report suicidal ideation in both the unadjusted and adjusted models.

Conclusion

This study illustrates the need to develop a prevention program that addresses the common factors between sexual behavior and suicidal ideation in order to effectively reduce both sexual behavior and suicidal ideation in middle school students.
Care Personnel's Attitudes and Fears Toward Care Robots in Elderly Care: A Comparison of Data from the Care Personnel in Finland and Japan
Authors: Coco Kirsi , Kangasniemi Mari , Rantanen Teemu
Published: October 2018

Purpose

The aim of the study was to analyze and compare elderly care personnel attitudes toward care robots in Finland and Japan.

Design

Cross‐sectional survey in Finland and Japan.

Methods

The Finnish sample was collected from care personnel in home care facilities in five municipalities in 2016. The Japanese sample was collected from personnel in two rehabilitative day centers and three residential care homes for the elderly in the north of Honshu Island in 2017. The data were analyzed using basic statistical methods and calculated descriptive statistics (frequencies). Differences between the Finnish and Japanese data have been analyzed using the Mann‐Whitney U test.

Findings

Overall, Japanese care personnel assessed the usefulness of robots more positively than did their Finnish counterparts. The data showed substantial national differences in the perceived importance of various potential tasks for care robots. The findings show that there are also certain fears related to the introduction of care robots, in particular among the Finnish care personnel.

Discussion

The data from the Japanese care personnel bring new perspectives to the concept of a close human–robot relationship. The differences seen in the results between Finland and Japan can be partly explained by cultural dissimilarity, but it is also known that Japan is a more developed country with regard to the use of robotics in nursing care. The research highlights the importance of cultural factors when examining the issue of care robotics. The factors affecting fear are a concern that care robots would be used to replace people, the dehumanization of treatment, and an increased loneliness in the elderly. Thus, further research is required to demonstrate the relationship between different cultural factors, and attitudes and conceptions toward care robots.

Clinical Relevance

Management plays a key role when implementing robotics. It is important to help care personnel accept care robots, and to diminish any fears that their introduction would make the treatment of elderly people inhumane or in some way add to their loneliness. As such, education is crucial in changing attitudes and making care personnel understand that care robots can perform routine tasks, allowing care personnel to focus on providing improved care and nursing.
Nursing knowledge of essential maternal and newborn care in a high‐mortality urban African setting: A cross‐sectional study
Authors: Murphy Georgina A. V. , Gathara David , Mwaniki Ann , Nabea Grace , Mwachiro Jacintah , Abuya Nancy , English Mike
Published: October 2018

Aims

To assess the knowledge of nurses of national guidelines for emergency maternity, routine newborn and small and sick newborn care in Nairobi County, Kenya.

Background

The vast majority of women deliver in a health facility in Nairobi. Yet, maternal and neonatal mortality remain high. Ensuring competency of health workers, in providing essential maternal and newborn interventions in health facilities will be key if further progress is to be made in reducing maternal and neonatal mortality in low‐resource settings.

Design

Cross‐sectional survey.

Methods

Questionnaires comprised of clinical vignettes and direct questions and were administered in 2015–2016 to nurses (n = 125 in 31 facilities) on duty in maternity and newborn units in public and private facilities providing 24/7 inpatient neonatal services. Composite knowledge scores were calculated and presented as weighted means. Associations were explored using regression. STROBE guidelines were followed.

Results

Nurses scored best for knowledge on active management of the mother after birth and immediate routine newborn care. Performance was worst for questions on infant resuscitation, checking signs and symptoms of sick newborns, and managing hypertension in pregnancy. Overall knowledge of care for sick newborns was particularly low (score 0.62 of 1). Across all areas assessed, nurses who had received training since qualifying performed better than those who had not. Poorly resourced and low case‐load facilities had lower average knowledge scores compared with better‐resourced and busier facilities.

Conclusion

Overall, we estimate that 31% of maternity patients, 3% of newborns and 39% of small and sick newborns are being cared for in an environment where nursing knowledge is very low (score <0.6).

Relevance to clinical practice

Focus on periodic training, ensuring retention of knowledge and skills among health workers in low‐case load setting, and bridging the know‐do gap may help to improve the quality of care delivered to mothers and newborns in Kenya.
Communication training and its effects on carer and care‐receiver outcomes in dementia settings: A systematic review
Authors: Nguyen Hoang , Terry Daniel , Phan Hoang , Vickers James , McInerney Fran
Published: October 2018

Aims and objectives

To review communication interventions that aim to improve regular care interactions between people with dementia and their carers in various settings; and to examine the impact of such interventions on both carer and care‐receiver outcomes.

Background

Effective communication is imperative to ensure quality of care for people living with dementia. Due to neurodegenerative changes, people with dementia encounter ongoing and progressive difficulties in both understanding and expressing themselves. This in turn creates challenges for carers, which highlights the need for equipping them with necessary communication skills to respond to the specific communication needs of people with dementia.

Design

Systematic review and meta‐analysis.

Method

Medline, Embase, CINAHL, ProQuest and PsycINFO databases were searched for eligible interventions with any date of the publication. Hand searching was also conducted through reviewing the reference lists of relevant articles. The screening and selection of studies were based on the inclusion/exclusion criteria for eligibility and the methodological quality assessment checklist. Random‐effects meta‐analyses were conducted on comparable quantitative data. The review is reported following the PRISMA reporting guidelines.

Results

Seventeen studies were included in the final review, including 12 randomised controlled trials (RCTs), three nonrandomised controlled trials (NRCTs) and two controlled before–after interventions. The intervention designs, settings and outcome measures were varied. The findings suggest that the communication training had a positive impact on both carer and care‐receiver outcomes, albeit to different degrees. The intervention effects were found to be strongest on carer communication skills and knowledge.

Conclusion

There is solid evidence for the positive impact of communication training on the skills and knowledge of carers. More research is needed regarding the effects of such educational interventions on carer physio‐psychological outcomes and care‐receiver neuropsychiatric symptoms. It is important to establish best practices in training design, develop validated outcome measures and adopt consistent reporting approaches.

Relevance to clinical practice

The increasing global prevalence of people with dementia manifests across clinical and community contexts. The profound impact of dementia on communication and associated care raises the imperative for enhanced health worker and carer communication skills to meet the needs of this particular client group. The findings of this review indicate that educational interventions incorporating face‐to‐face and diverse instructional delivery methods in dementia communication showed positive outcomes for communication skills in all carer groups and warrant inclusion as strategies in dementia training.
Breast cancer survivors' experiences of dealing with information during and after adjuvant treatment: A qualitative study
Authors: Aunan Siv Tove , Wallgren Gry Ciekals , Sætre Hansen Britt
Published: October 2018

Aims and objectives

To describe breast cancer (BC) survivors' experiences of participating in a 2‐day educational programme (Breast Cancer School, BCS) and their critical reflection on information received during and after adjuvant treatment. The following research questions guided the study. How do BC survivors experience their participation in an educational programme? How do BC survivors experience the information trajectory during and after adjuvant treatment?

Background

BC is the most prevalent cancer among women in Norway. BC survivors have a substantial need for information about the disease, treatment and recovery. During the past few years, BC treatment in Norway has changed from inpatient‐ to outpatient‐based treatment. Oncology nurses and oncologists are obliged to provide patients and their families with information, which has necessitated reorganisation of the procedures for providing information. New arenas such as the Breast Cancer School (BCS) offer the opportunity to learn from experts and fellow patients.

Design

Qualitative, descriptive design.

Methods

Focus groups with 20 BC survivors after having participated in the BCS were used to enable critical reflection. The COREQ checklist was followed to ensure rigour in the study.

Results

Two themes emerged from qualitative analysis: Balancing between the need for and the fear of information and Moving from a safe structure to lonely recovery. We identified differences between BC survivors in diversity, uniqueness and need for information. Continuity and expert knowledge provided by a primary oncology nurse and oncologists were highlighted as important.

Conclusion

The study reveals the need for information tailored to each BC survivor's unique needs. The BC survivors expressed both the need for and the fear of information. BCS takes both a systematic and individual approach to provide expert information, dialog and the opportunity to meet with fellow patients. The transition from the structure of the treatment to lonely recovery after the most intensive treatment was perceived as unsafe and challenging. BC patients' experiences must be continuously valued and used to improve educational programmes, care and treatment. Oncology nurses play an important part in the information chain and continuity.

Relevance to clinical practice

This study highlights the importance of including BC survivors in the design and evaluation of educational programmes. The provision of information and supportive care with continuity between oncology nurses and oncologists through the trajectory of treatment and care is crucial.
A qualitative analysis of eating behaviour change for patients with diabetes and non‐dialysis dependent chronic kidney disease stages 4–5
Authors: Notaras Stephanie , Conti Janet
Published: October 2018

Background

Dietary changes recommended for chronic kidney disease (CKD) stages 4–5 and concurrent diabetes are difficult to follow given the multitude of food and fluid restrictions aimed at reducing the rate of CKD progression. Reduced adherence is commonplace and there is limited literature on patients’ experiences with dietary changes and potential strategies to overcome this.

Objectives

Examine patients’ experiences when adopting dietary changes recommended for CKD Stages 4–5 (pre‐dialysis) and diabetes, and their perceptions of dietetic services and how they can be improved to assist them with dietary change.

Methods

An exploratory qualitative study was undertaken using a purposive sampling method from a dietetic pre‐dialysis clinic. Participants were interviewed using a semi‐structured interview style. Data were analysed using an inductive thematic analysis from a constructivist perspective.

Results

Three themes were identified: (1) Negative motivation to change eating behaviour to avoid dialysis; (2) sustaining motivation for change is challenging due to a sense of loss and confusion to incorporate the dietary changes recommended and (3) support is needed for eating behaviour change.

Conclusion

These findings have implications for dietitians to enhance their understanding of the patient experience and improve their skills in motivational counselling. Development of dietitian‐specific communication and nutrition counselling programmes are recommended to equip dietitians with skills to better support patients. CKD Stage 3 nutrition education programmes could be beneficial to promote earlier access to dietetic services and dietary recommendations.
Leaving behind pegylated interferon‐based regimens to eliminate hepatitis C as a public health threat by 2030 as set out by WHO
Authors: Lazarus Jeffrey V. , Pericàs Juan M. , Elsharkawy Ahmed M.
Published: October 2018

See Article on Page 1911
Petrography and geochemistry of lunar meteorites Dhofar 1673, 1983, and 1984
Authors: Hill Patrick J. A. , Osinski Gordon R. , Banerjee Neil R. , Korotev Randy L. , Nasir Sobhi J. , Herd Christopher D. K.
Published: October 2018

The Dhofar 1673, Dhofar 1983, and Dhofar 1984 meteorites are three lunar regolith breccias classified based on their petrography, mineralogy, oxygen isotopes, and bulk chemistry. All three meteorites are dominated by feldspathic lithic clasts; however, impact melt rock clasts and spherules are also found in each meteorite. The bulk chemistry of these samples is similar to other feldspathic highland meteorites with the Al2O3 content only slightly lower than average. Within the lithic clasts, the Mg # of mafic phases versus the anorthite content of feldspars is similar to other highland meteorites and is found to plot intermediate of the ferroan‐anorthositic suite and magnesian suite. The samples lack any KREEPy signature and have only minor indications of a mare basalt component, suggesting that the source region of all three meteorites would have been distal from the Procellarum KREEP Terrane and could have possibly been the Feldspathic Highland Terrane. All three meteorites were found within 500 m of each other in the Dhofar region of Oman. This, together with their similar petrography, stable isotope chemistry, and geochemistry indicates the possibility of a pairing.
Untangling the knots: Co‐infection and diversity of Bartonella from wild gerbils and their associated fleas
Authors: Gutiérrez Ricardo , Cohen Carmit , Flatau Ron , Marcos‐Hadad Evgeniya , Garrido Mario , Halle Snir , Nachum‐Biala Yaarit , Covo Shay , Hawlena Hadas , Harrus Shimon
Published: October 2018

Based on molecular data, previous studies have suggested a high overall diversity and co‐infection rates of Bartonella bacteria in wild rodents and their fleas. However, partial genetic characterization of uncultured co‐infecting bacteria limited sound conclusions concerning intra‐ and inter‐specific diversity of the circulating Bartonella. To overcome this limitation, Bartonella infections of wild populations of two sympatric gerbil species and their fleas were explored by multiple isolations of Bartonella organisms. Accordingly, 448 pure Bartonella isolates, obtained from 20 rodent blood and 39 flea samples, were genetically characterized to the genotype and species levels. Results revealed a remarkable diversity and co‐infection rates of Bartonella among these sympatric rodents and their associated fleas. Specifically, 38 genotypes, classified into four main Bartonella species, were identified. Co‐infection was confirmed in 56% of the samples, which contained two to four Bartonella genotypes per sample, belonging to up to three different species. Recombination within and between these species was demonstrated, serving as a direct evidence of the frequent bacteria–bacteria interactions. Moreover, despite the noticeable interchange of common Bartonella genotypes between rodents and fleas, the co‐occurrence of genotypes was not random and differences in the overall diversity, and the ecological and phylogenetic similarities of the infection compositions were significantly associated with the carrier type (rodent vs. flea) and the rodent species. Thus, comprehensive identification of the co‐infecting organisms enabled the elucidation of ecological factors affecting the Bartonella distribution among reservoirs and vectors. This study may serve as a model for the investigation of other vector‐borne organisms and their relationships with Bartonella.
Classical Planning Model‐Based Approach to Automating Construction Planning on Earthwork Projects
Authors: Li Duanshun , Lu Ming
Published: October 2018

Extensive research in automated operation planning has led to significant advances in the area of robotics. Theories and methods resulting from robotics have yet to be adapted to enable automated project planning in construction engineering. Aiming to demonstrate the potential of implementing automated planning theory and methods in construction project planning, we developed an automated earthwork planner prototype following the principles and framework of classical planning model in computer science. As time is not explicitly represented, implementing classical planning model to perform optimization and planning simultaneously results in potential temporal–spatial conflicts (TSCs). The present research develops a two‐step approach to separate operations optimization and earthwork planning in typical rough grading projects. As such, TSCs encountered in existing mathematical programming based earthwork planning methods are resolved. To enable fully integrated and automated earthwork planning, the prototype system has been seamlessly integrated with project scheduling and operations simulation software for higher level analyses. To demonstrate advantages of the automated planning methodology, construction plans were independently produced by 14 graduate student teams on the same “testbed” project; results were evaluated and compared with the plan generated by the proposed system.
High‐dose linaclotide is effective and safe in patients with chronic constipation: A phase III randomized, double‐blind, placebo‐controlled study with a long‐term open‐label extension study in Japan
Authors: Fukudo Shin , Miwa Hiroto , Nakajima Atsushi , Kinoshita Yoshikazu , Kosako Masanori , Hayashi Kenta , Akiho Hiraku , Kuroishi Kentaro , Johnston Jeffrey M , Currie Mark , Ohkusa Toshifumi
Published: October 2018

Background

A previous phase II dose‐ranging study of linaclotide in a Japanese chronic constipation (CC) population showed that 0.5 mg was the most effective dose. This study aimed to verify the hypothesis that 0.5 mg of linaclotide is effective and safe in Japanese CC patients.

Methods

This was a Japanese phase III randomized, double‐blind, placebo‐controlled (part 1), and long‐term, open‐label extension (part 2) study of linaclotide. CC patients (n = 186) diagnosed using the Rome III criteria were randomly assigned to linaclotide 0.5 mg (n = 95) or placebo (n = 91) for a 4‐week double‐blind treatment period in part 1, followed by an additional 52 weeks of open‐label treatment with linaclotide in part 2. The primary efficacy endpoint was the change from baseline in weekly spontaneous bowel movement (SBM) frequency at the first week. Secondary endpoints included responder rate for complete SBM (CSBM), changes in stool consistency, and severity of straining.

Key Results

Part 1: Change in weekly mean SBM frequency in the first week of treatment with linaclotide (4.02) was significantly greater than that with placebo (1.48, P < 0.001). Linaclotide produced a higher CSBM responder rate (52.7%) compared to placebo (26.1%, P < 0.001). Part 2: Patients continued to show improved SBM frequency with linaclotide. Through parts 1 and 2, the most common drug‐related adverse event was mild and occasionally moderate diarrhea.

Conclusions and Inferences

The results of this study indicate that a linaclotide dose of 0.5 mg/day is effective and safe in Japanese CC patients.
Linaclotide increases cecal pH, accelerates colonic transit, and increases colonic motility in irritable bowel syndrome with constipation
Authors: Farmer Adam D. , Ruffle James K. , Hobson Anthony R.
Published: October 2018

Background

Linaclotide is efficacious in the management of irritable bowel syndrome with constipation (IBS‐C), yet relatively little is known regarding its effect on human gastrointestinal physiology. The primary aim of the study was to examine the effect of linaclotide on change in pH across the ileocecal junction (ICJ), a proposed measure of cecal fermentation, and its relationship to symptoms and quality of life (QoL) in IBS‐C.

Methods

A total of 13 participants with Rome III IBS‐C underwent a standardized wireless motility capsule (WMC). Stool consistency was measured using the Bristol stool form scale (BSFS) and frequency with spontaneous bowel movements (SBM). Gastrointestinal symptoms and QoL were assessed using validated questionnaires. The WMC and questionnaires were repeated after 28 days of linaclotide 290 g po od.

Key Results

Linaclotide reduced the change in pH across the ICJ (−2.4 ± 0.2 vs −2.1 ± 0.4, P = 0.01) as a function of a relative alkalinization of the cecum (5.2 ± 0.2 vs 5.5 ± 0.3, P = 0.02). Linaclotide accelerated colonic transit time (2650 minutes (2171‐4038) vs. 1757 (112‐3011), P = 0.02), increased colonic log motility index (15 ± 1.8 vs. 16.5 ± 1.8, P = 0.004) but had no effect of gastric emptying or small bowel transit. Change in pH across the ICJ correlated with improvement in symptom intensity, unpleasantness, and visceral sensitivity index (r = 0.62, P = 0.03, r = 0.63, P = 0.02, r = 0.62, P = 0.02) and with increases in BSFS type and SBM (r = 0.9, P < 0.0001, r = 0.6, P = 0.02).

Conclusions & Inferences

Linaclotide's effects are confined to the colon where it increases cecal pH, potentially representing a reduction in cecal fermentation and accelerates colonic motility.
Parent–child relationships and Chinese children's social adaptations: Gender difference in parent–child dyads
Authors: Xu Liangyuan , Liu Lisha , Li Yanfang , Liu Lijun , Huntsinger Carol S.
Published: October 2018

Based on data from 1,366 Chinese preschoolers aged 31–77 months from 62 preschools, this study compared differences among four parent–child dyads in parent–child relationships and the associations between parent–child relationships and children's social adaptations. According to the results, the same‐sex dyad and opposite‐sex dyad patterns were tested. The results showed the same‐sex dyad and opposite‐sex dyad patterns in parent–child closeness. Mother–daughter dyads had more closeness than mother–son dyads; father–daughter dyads had more closeness than father–son dyads. The results were more supportive of the same‐sex dyad pattern in the associations between parent–child relationships and social adaptations. Mother–child closeness predicted girls' greater social skills and fewer problem behaviors; father–child conflict predicted boys' worse social skills and greater problem behaviors.
The cancellability test for conversational implicatures
Authors: Zakkou Julia
Published: October 2018

Many people follow Grice in thinking that all conversational implicatures are cancellable. And often enough, they use this insight as a test for conversational implicatures. If you want to find out whether something is a conversational implicature, the test has it, you should ask yourself whether the thing in question is cancellable; if you find that it is not cancellable, you can infer that it is not a conversational implicature. If you find that it is cancellable, you can infer that it might well be a conversational implicature and that you should now do further testing. Various philosophers and linguists have questioned the test however. Some have held that Grice's cancellability claim is subject to counterexamples and that the test is not reliable. Others have argued that even though Grice's claim can be defended against the examples in question, the test is not as informative as people have hoped. This article provides an overview of the recent discussion on the cancellability test and suggests a way forward.
Impact of donor and recipient cytomegalovirus serology on long‐term survival of heart transplant recipients
Authors: Mabilangan Curtis , Preiksaitis Jutta K. , Cervera Carlos ,   University of Alberta Cardiothoracic Transplant Group
Published: October 2018

Background

Some studies have shown that pre‐transplant cytomegalovirus (CMV) serostatus is associated with heart transplant patient survival while others have not. We analyzed the relationship between pre‐transplant donor/recipient CMV serostatus and long‐term mortality in a retrospective cohort of heart transplant recipients at our center.

Methods

Adult (Age >17 years) heart recipients transplanted between July 1985‐December 2015 were analyzed. Variables included age, sex, pre‐transplant donor (D)/recipient (R) serostatus [D−/R−, D−/R+, D+/R+, D+/R−], CMV infection within 2 years of transplant and transplant eras divided by changes in CMV prevention strategies: Era 1 (Pre‐ganciclovir, July 1985‐April 1998), Era 2 (Oral ganciclovir, May 1998‐December 2004), Era 3 (Valganciclovir, January 2005‐December 2015). Survival analysis and Cox regression were performed at 10 years.

Results

A total of 620 heart transplants were included in our analysis; 20% were CMV mismatched pre‐transplant. Thirty‐eight percent of patients were infected with CMV within the first two post‐transplant years. Survival analysis showed D/R CMV serostatus did not significantly impact survival of heart recipients at 10 years (P = 0.11). Survival was significantly different across eras for D−/R+, D+/R+, and D+/R+ (P = 0.043) but not D−/R− patients (P = 0.8). Cox regression revealed that patients transplanted in the valganciclovir era have an estimated 29% reduced risk of death (P = 0.047) compared to patients transplanted in the pre‐ganciclovir era after controlling for age at transplantation, D/R CMV serostatus and CMV infection.

Conclusion

Our review of the impact of CMV managed differently across eras suggests in heart transplantation there is no influence of D/R CMV serostatus on 10 year survival.
Endo‐lysosomal sorting of G‐protein‐coupled receptors by ubiquitin: Diverse pathways for G‐protein‐coupled receptor destruction and beyond
Authors: Dores Michael R. , Trejo JoAnn
Published: October 2018

Ubiquitin is covalently attached to substrate proteins in the form of a single ubiquitin moiety or polyubiquitin chains and has been generally linked to protein degradation, however, distinct types of ubiquitin linkages are also used to control other critical cellular processes like cell signaling. Over forty mammalian G protein‐coupled receptors (GPCRs) have been reported to be ubiquitinated, but despite the diverse and rich complexity of GPCR signaling, ubiquitin has been largely ascribed to receptor degradation. Indeed, GPCR ubiquitination targets the receptors for degradation by lysosome, which is mediated by the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery, and the proteasome. This has led to the view that ubiquitin and ESCRTs primarily function as the signal to target GPCRs for destruction. Contrary to this conventional view, studies indicate that ubiquitination of certain GPCRs and canonical ubiquitin‐binding ESCRTs are not required for receptor degradation and revealed that diverse and complex pathways exist to regulate endo‐lysosomal sorting of GPCRs. In other studies, GPCR ubiquitination has been shown to drive signaling and not receptor degradation and further revealed novel insight into the mechanisms by which GPCRs trigger the activity of the ubiquitination machinery. Here, we discuss the diverse pathways by which ubiquitin controls GPCR endo‐lysosomal sorting and beyond.
Inefficient Signalling, Education Arms Race and Education Inflation in China
Authors: Liu Weiguang
Published: October 2018

Since the higher education expansion and education marketization from 1998, China’s education inflation has become increasingly serious. And correspondingly, the income of graduates remains in a low level. This paper built a model and explained two important reasons. First, the quality of Chinese high education is relatively low, which means the signal effect of education will be less efficient. Second, every individual has an incentive to occupy higher status in the education hierarchy, which means there is a zero-sum education arms race game. I try to build a simple but powerful model in this essay to explain how thses two factors contribute to Chinese education inflation and how they intertwine with each other.
Desempeño económico de la mayor empresa de servicios educativos del mundo: un estudio de Kroton Educativa con base en sus segmentos operativos
Authors: Alves e Souza Júlia , Mendonça Douglas José , Carmo da Silva Beatriz , Carvalho de Benedicto Gideon
Published: October 2018

A Kroton Educacional é uma empresa brasileira que se destaca como a líder mundial no mercado de serviços educacionais. Este artigo tem por objetivo efetuar uma análise do desempenho econômico da Kroton Educacional no período de 2011 a 2016, tendo por base as informações por segmentos operacionais referentes a essa empresa. A coleta de dados foi efetuada a partir das demonstrações contábeis da companhia e identificaram-se as informações por segmentos divulgadas conforme o pronunciamento CPC 22: Informações por Segmento. A partir do cálculo dos indicadores de lucratividade e de rentabilidade, observa-se que o segmento de ensino superior à distância (EAD) foi o que mais contribuiu para a lucratividade da empresa. Já o segmento de ensino superior presencial, embora tenha sido responsável pela maior parte das receitas, não se destacou em termos de lucratividade ou de rentabilidade. Nota-se que o segmento de educação básica foi o que teve maior rentabilidade para a empresa. A companhia tem investido em estratégias de expansão e diversificação, incrementando sua lucratividade e rentabilidade. A análise efetuada auxilia para que o desempenho econômico da empresa seja compreendido com maior nível de detalhamento. Assim, destaca-se a contribuição do artigo ao propor análises econômicas baseadas nos indicadores por segmentos operacionais das empresas.
Satisfação em aprender: identificando a percepção dos estudantes sobre o uso de tecnologias da educação
Authors: Costa Quintana Alexandre , Afonso Luís Eduardo
Published: October 2018

Este trabalho tem dois objetivos. O primeiro é analisar o reflexo do uso de chats e fóruns de discussão no processo de aprendizagem, sob a perspectiva do nível de satisfação e de eficácia de aprendizagem. O segundo é verificar a percepção do estudante sobre o uso destas tecnologias. A combinação de tecnologias da educação com o processo de ensino, por meio de alternativas complementares pode gerar reflexos no aprendizado, em ambientes nos que o estudante tem mais facilidades e habilidades. Com isso, envolve-se o professor em um processo de ajuste na sua forma de atuar para atingir o objetivo de levar o conhecimento e a informação ao estudante. O estudo consistiu na realização de um experimento em que foram constituídos um grupo de tratamento e um grupo de controle. O primeiro, além das atividades normais da disciplina, experimentou as interações tecnológicas no primeiro bimestre. No segundo bimestre, os grupos foram invertidos, com o grupo de controle passando a ser o de tratamento e vice-versa. Os resultados mostram que o uso das tecnologias não interferiu na satisfação e eficácia de aprendizagem. Em relação à percepção, observou-se que 80% dos estudantes entendem que o efeito da tecnologia no processo de aprendizagem pode ser positivo.
In situ identification of Gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid A
Authors: Akram Ahsan R. , Chankeshwara Sunay V. , Scholefield Emma , Aslam Tashfeen , McDonald Neil , Megia-Fernandez Alicia , Marshall Adam , Mills Bethany , Avlonitis Nicolaos , Craven Thomas H. , Smyth Annya M. , Collie David S. , Gray Calum , Hirani Nik , Hill Adam T. , Govan John R. , Walsh Timothy , Haslett Christopher , Bradley Mark , Dhaliwal Kevin
Published: October 2018

A topically administered fluorescently labeled peptide targeting lipid A permits rapid, real-time visualization of bacteria in the distal human lung.
Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis
Authors: Scott Nicholas A. , Andrusaite Anna , Andersen Peter , Lawson Melissa , Alcon-Giner Cristina , Leclaire Charlotte , Caim Shabhonam , Le Gall Gwenaelle , Shaw Tovah , Connolly James P. R. , Roe Andrew J. , Wessel Hannah , Bravo-Blas Alberto , Thomson Carolyn A. , Kästele Verena , Wang Ping , Peterson Daniel A. , Bancroft Allison , Li Xuhang , Grencis Richard , Mowat Allan McI , Hall Lindsay J. , Travis Mark A. , Milling Simon W. F. , Mann Elizabeth R.
Published: October 2018

Antibiotics disrupt intestinal immunity in mice.
Gut Microbial Divergence between Two Populations of the Hadal Amphipod Hirondellea gigas
Authors: Zhang Weipeng , Watanabe Hiromi Kayama , Ding Wei , Lan Yi , Tian Ren-Mao , Sun Jin , Chen Chong , Cai Lin , Li Yongxin , Oguri Kazumasa , Toyofuku Takashi , Kitazato Hiroshi , Drazen Jeffrey C. , Bartlett Douglas , Qian Pei-Yuan
Published: October 2018

The taxonomic composition and functional potential of animal gut microbiota in deep-sea environments remain largely unknown. Here, by performing comparative metagenomics, we suggest that the gut microbial compositions of two
Hirondellea gigas
populations from the Mariana Trench and the Japan Trench have undergone significant divergence. Through analyses of functional potentials and microbe-microbe correlations, our findings shed light on the contributions of animal gut microbiota to host adaptation to hadal environments.
Longitudinal Clinical Performance of the RNA-Based Aptima Human Papillomavirus (AHPV) Assay in Comparison to the DNA-Based Hybrid Capture 2 HPV Test in Two Consecutive Screening Rounds with a 6-Year Interval in Germany
Authors: Iftner Thomas , Neis Klaus-Joachim , Castanon Alejandra , Landy Rebecca , Holz Barbara , Woll-Herrmann Astrid , Iftner Angelika , Staebler Annette , Wallwiener Diethelm , Hann von Weyhern Claus , Neis Felix , Haedicke-Jarboui Juliane , Martus Peter , Brucker Sara , Henes Melanie , Sasieni Peter
Published: October 2018

Longitudinal data on the E6/E7 mRNA-based Aptima human papillomavirus (AHPV) assay exceeding three years in comparison to the gold standard Digene Hybrid Capture 2 (HC2) test are not available. We previously reported the cross-sectional data of the German AHPV Screening Trial (GAST) in which 10,040 women were recruited and tested by liquid-based cytology, the HC2 assay, and the AHPV assay.
Eurasian Avian-Like Swine Influenza A Viruses Escape Human MxA Restriction through Distinct Mutations in Their Nucleoprotein
Authors: Dornfeld Dominik , Petric Philipp P. , Hassan Ebrahim , Zell Roland , Schwemmle Martin
Published: October 2018

The human MxA protein efficiently blocks the replication of IAV from nonhuman species. In rare cases, however, these IAV overcome the species barrier and become pandemic. All known pandemic viruses have acquired and maintained MxA escape mutations in the viral NP and thus are not efficiently controlled by MxA. Intriguingly, partial MxA resistance can also be acquired in other hosts that express antivirally active Mx proteins, such as swine. To perform a risk assessment of IAV circulating in the European swine population, we analyzed the degree of MxA resistance of Eurasian avian-like swine IAV. Our data demonstrate that these viruses carry formerly undescribed Mx resistance mutations in the NP that mediate efficient escape from human MxA. We conclude that Eurasian avian-like swine IAV possess substantial zoonotic potential.
BCL6 Inhibitor-Mediated Downregulation of Phosphorylated SAMHD1 and T Cell Activation Are Associated with Decreased HIV Infection and Reactivation
Authors: Cai Yanhui , Abdel-Mohsen Mohamed , Tomescu Costin , Xue Fengtian , Wu Guoxin , Howell Bonnie J. , Ai Yong , Sun Jie , Azzoni Livio , Le Coz Carole , Romberg Neil , Montaner Luis J.
Published: October 2018

The expansion and accumulation of HIV-infected BCL6
+
Tfh CD4
+
T cells are thought to contribute to the persistence of viral reservoirs in infected subjects undergoing ART. Two mechanisms have been raised for the preferential retention of HIV within Tfh CD4
+
T cells: (i) antiretroviral drugs have limited tissue distribution, resulting in insufficient tissue concentration and lower efficacy in controlling HIV replication in lymphoid tissues, and (ii) cytotoxic CD8
+
T cells within lymphoid tissues express low levels of chemokine receptor (CXCR5), thus limiting their ability to enter the GCs to control/eliminate HIV-infected Tfh cells. Our results indicate that the BCL6 inhibitor FX1 can not only repress HIV infection of tonsillar Tfh
ex vivo
but also suppress HIV infection and reactivation in primary, non-Tfh CD4
+
T cells. Our study provides a rationale for targeting BCL6 protein to extend ART-mediated reduction of persistent HIV and/or support strategies toward HIV remission beyond ART cessation.
A MicroRNA Derived from Adenovirus Virus-Associated RNAII Promotes Virus Infection via Posttranscriptional Gene Silencing
Authors: Wakabayashi K. , Machitani M. , Tachibana M. , Sakurai F. , Mizuguchi H.
Published: October 2018

Several types of viruses encode viral miRNAs which regulate host and/or viral gene expression via posttranscriptional gene silencing, leading to efficient viral infection. Adenovirus (Ad) expresses miRNAs derived from VA-RNAs (mivaRNAI and -II); however, recent studies have revealed that processing of VA-RNAI into mivaRNAI inhibits Ad replication. Conversely, we demonstrate here that mivaRNAII significantly promotes Ad replication and that mivaRNAII-mediated suppression of CUL4A expression via posttranscriptional gene silencing induces accumulation of c-Jun, leading to promotion of Ad infection. These results exhibited the significance of VA-RNAII for supporting Ad infection through a mechanism complementary to that of VA-RNAI. These observations could provide important clues toward a new perspective on host-virus interaction. Moreover, Ad is widely used as a basic framework for viral vectors and oncolytic viruses. Our findings will help to regulate Ad infection and will promote the development of novel Ad vectors and oncolytic Ad.