bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing a community model of early pregnancy care
Authors: Cox Rebecca , Khalid Somia , Brierley Gemma , Forsyth Annie , McNamara Ruth , Heppell Victoria , Granne Ingrid
Published: December 2019

· Introduction
· In the UK Early Pregnancy Assessment Units (EPAUs) are usually situated alongside hospital maternity and gynaecology services. In June 2018, the Oxford EPAU relocated from the John Radcliffe Hospital to a community clinic. This is to our knowledge, the UK’s first community-based EPAU. This change was inspired by our patient feedback describing the co-location of the EPAU with maternity services as distressing.
· Methods
· Following the introduction of the community EPAU we developed a database to capture information on the patients seen in the clinic. This is a retrospective observational study of a single cohort of patients attending the clinic over an 8 month period. Data was collected from 1 st July 2018 to 28 th February 2019. This data included clinical, safety and patient experience outcomes.
· Results
· 2920 patient episodes were recorded, 1932 were new patients. 72.2% were diagnosed as viable pregnancies, 389 miscarriages were diagnosed, of which 84.1% were incomplete/missed and 15.9% were complete. Once miscarriage was confirmed 48.6% chose conservative management, 19.9% chose medical management, and 31.5% chose surgical management. 25 ambulance transfers occurred due to ruptured ectopic, suspected ectopic, heavy bleeding, collapse, or ectopic with no personal transport. 32 unplanned admissions from patients seen in EPAU accounted for 2.7% of all patients seen in EPAU. 58 patients had ultrasonographically confirmed or suspected ectopic pregnancies- 3% of patients seen in clinic. Patient feedback questionnaires have been consistently positive.
· Conclusion
· The development of a community EPAU has improved services to allow care closer to home in an environment separate from maternity care. Our data shows that a community EPAU is safe, can deliver good patient care and is a service valued by patients. Further research is indicated to evaluate the cost-effectiveness of community EPAUs and the long term safety and effectiveness of care.
Active Learning Through Discussion: ICAP Framework for Education in Health Professions
Authors: Lim Jaeseo , Ko Hyunwoong , Yang Jiwon , Kim Songeui , Lee Seunghee , Chun Myungsun , Ihm Jungjoon , Park Jooyong
Published: December 2019

Background The ICAP framework based on Cognitive Science posits four modes of cognitive engagement: Interactive, Constructive, Active, and Passive. Focusing on the wider applicability of discussion as interactive engagement in medical education, we investigated the effect of discussion when self-study preceded it and further investigated the effect of generating questions before discussions. Methods This study was conducted in the second semester of 2018, and 129 students majoring in health professions, including medicine, dentistry, veterinary medicine, and nursing, participated. The students were assigned into four different trial groups, who were asked to fill out a Subjective Mental Effort Questionnaire after completing each session. Their performance in post-test scores and their mental efforts were analyzed. Results These results indicated that the self-study and question group had the highest performance and that the lecture and summary group had the lowest performance when comparing the total score. Using the analysis of mental effort, it was confirmed that the participants who showed higher levels of mental effort also showed higher levels of studying and discussion. Conclusions Our findings support the ICAP framework and provide practical implications for medical education, representing the fact that students learn more when they are involved in active learning activities, such as self-study and question generation, prior to discussions.
Transcriptome sequencing of Saccharina japonica sporophytes during whole developmental periods reveals regulatory networks underlying alginate and mannitol biosynthesis
Authors: Shao Zhanru , Zhang Pengyan , Lu Chang , Li Shaoxuan , Chen Zhihang , Wang Xiuliang , Duan Delin
Published: December 2019

Background: Alginate is an important cell wall component and mannitol is a soluble storage carbon substance in the brown seaweed Saccharina japonica. Their contents vary with kelp developmental periods and harvesting time. Alginate and mannitol regulatory networks and molecular mechanisms are largely unknown. Results: With WGCNA and trend analysis of 20,940 known genes and 4,264 new genes produced from transcriptome sequencing of 30 kelp samples from different stages and tissues, we deduced that ribosomal proteins, light harvesting complex proteins and "imm upregulated 3"gene family are closely associated with the meristematic growth and kelp maturity. Moreover, 134 and 6 genes directly involved in the alginate and mannitol metabolism were identified, respectively. Mannose-6-phosphate isomerase (MPI2), phosphomannomutase (PMM1), GDP-mannose 6-dehydrogenase (GMD3) and mannuronate C5-epimerase (MC5E70 and MC5E122) are closely related with the high content of alginate in the distal blade. Mannitol accumulation in the basal blade might be ascribed to high expression of mannitol-1-phosphate dehydrogenase (M1PDH1) and mannitol-1-phosphatase (M1Pase) (in biosynthesis direction) and low expression of mannitol-2-dehydrogenase (M2DH) and Fructokinase (FK) (in degradation direction). Oxidative phosphorylation and photosynthesis provide ATP and NADH for mannitol metabolism whereas glycosylated cycle and tricarboxylic acid (TCA) cycle produce GTP for alginate biosynthesis. RNA/protein synthesis and transportation might affect alginate complex polymerization and secretion processes. Cryptochrome (CRY-DASH), xanthophyll cycle, photosynthesis and carbon fixation influence the production of intermediate metabolite of fructose-6-phosphate, contributing to high content of mannitol in the basal blade. Conclusions: The network of co-responsive DNA synthesis, repair and proteolysis are presumed to be involved in alginate polymerization and secretion, while upstream light-responsive reactions are important for mannitol accumulation in meristem of kelp. Our transcriptome analysis provides new insights into the transcriptional regulatory networks underlying the biosynthesis of alginate and mannitol during S. japonica developments. Keywords: Alginate, Mannitol, Transcriptome, Regulatory networks, Growth, Development, Saccharina japonica
Development & Validation of Attitude Toward Nutrition Counselling Questionnaire for use among Kuwaiti healthcare professionals
Authors: ALMughamis Nouf S , Alayoub Abdullah A. , Meraj Hafsa , Waqas Ahmed
Published: December 2019

Objective This study aims to report the developmental processes and validation of Attitude Toward Nutrition Questionnaire in Arabic language. Results A total of 173 (response rate= 86.93%) participants responded to the survey. There was a total of 92 (53.2%) nutritionists and 81(46.8%) doctors/surgeons.The Attitude Toward Nutrition Counselling Questionnaire was found to have an acceptable validity and reliability. The first subscale named “Factual knowledge about nutrition” comprised of nine items. It yielded a Cronbach’s alpha value of 0.78. The second subscale “knowledge about nutrition in morbidities” comprised of seven items and yielded a Cronbach’s alpha value of 0.71. The third subscale “counselling of patients” comprised of 11 items and yielded a Cronbach’s alpha of 0.68. The fourth subscale comprising nine items yielded a Cronbach’s alpha value of 0.64 and was named, “Dietary programs and supplementation”.
Advanced Practice Nurses in Primary Care in Switzerland: An Analysis of Interprofessional Collaboration
Authors: Josi Renata , Bianchi Monica , Brandt Sophie
Published: December 2019

Background: The increase in the number of chronically ill patients due to ageing is calling existing models of primary care (PC) into question. New care models have recently been implemented in Swiss PC and involve interprofessional teams. This paper aimed to analyse the practice of interprofessional collaboration between advanced practice nurses, registered nurses, and medical practice assistants within new models of PC in Switzerland using the National Interprofessional Competency Framework. Methods: An ethnographic design comprising semi-structured interviews and non-participant observations was conducted. Sixteen interviews were conducted with care providers at their PC practice. Interviewees included four advanced practice nurses, two registered nurses, six medical practice assistants, and four general practitioners. Nine other health professionals were subsequently observed in their practice. Interviews and observations were conducted by the first author from February to April 2019. Results: Our analysis of interview and observational data confirmed that role clarification, team functioning, collaborative leadership, interprofessional conflict resolution, patient-centered care, and interprofessional communication have a significant influence on the interprofessional collaboration among health professionals in Swiss PC. Among these domains, role clarification and team functioning were the most frequently raised issues. Both were found to have the potential to negatively influence and, therefore, hinder efficient interprofessional collaboration within PC. Conclusion: From the analysis, it emerged that role clarification is crucial for effective interprofessional collaboration within new care delivery models in the Swiss PC context. Our study results may inform international health policymakers and practitioners about six important domains of interprofessional care when implementing new care models. Practical experience with new models of care involving advanced practice nurses and medical practice assistants may also influence the regulation of the scope of practice of these health professionals in Switzerland.
The Influence of dietary diversity on the nutritional status of children between 6 and 23 months of age in Tanzania
Authors: Khamis Ahmed Gharib , Mwanri Akwilina Wendelin , Ntwenya Julius Edward , Kreppel Katharina
Published: December 2019

Background: Undernutrition poses a serious health challenge in developing countries and Tanzania has the highest undernutrition burden of Eastern and Southern Africa. Here we examined to what extent dietary diversity is associated with undernutrition among children of 6 to 23 months in Tanzania.
Methods: Using existing data from the Tanzania Demographic and Health Survey of 2015-2016, we carried out secondary data analysis. Stunting, Wasting and Underweight of the surveyed children were calculated from Z-scores based on 2006 WHO standards. A composite dietary diversity score was created by summing the number of food groups reported for each child by the mother ranging from 0 to 7. Then, minimum dietary diversity (MDD) of 4 food groups out of seven was used to assess the diversity of the diet given to children. Bivariate and multivariate logistic regression techniques were used to assess the crude and adjusted odds ratios of undernutrition.
Results: A total of 2,960 children were enrolled in this study. The prevalence of stunting was 31%, wasting 6% and underweight 14%. Among all children, 51% were female and 49% male. The majority (74%) of children did not reach the MDD. The most commonly consumed types of foods were grains, roots and tubers (91%), and Vitamin A containing fruits and vegetables (65%). Consumption of a diverse diet was significantly associated with a reduction of stunting, wasting and being underweight in children. The likelihood of being stunted, wasted and underweight was found to decrease as the number of food groups consumed increased. Children who did not received the MDD had a significantly higher likelihood of being stunted (AOR=1.37, 95% CI; 1.13-1.65) and underweight (AOR=1.49, 95% CI; 1.15-1.92), but this was not the case for wasting. Consumption of animal-source foods has been found to be associated with reduced stunting among children.
Conclusion: Consumption of a diverse diet is associated with a reduction in undernutrition among children of 6 to 23 months in Tanzania. Measures to improve the type of complementary foods in order to meet the energy and nutritional demands of children should be considered in Tanzania.
TRA2A-induced upregulation of LINC00662 regulates blood-brain barrier permeability by affecting ELK4 mRNA stability in Alzheimer's microenvironment
Authors: Liu Qianshuo , Zhu Lu , Liu Xiaobai , Zheng Jian , Liu Yunhui , Ruan Xuelei , Cao Shuo , Cai Heng , Li Zhen , Xue Yixue
Published: December 2019

The blood-brain barrier (BBB) plays a pivotal role in maintenance and regulation of the neural microenvironment. The occurrence of BBB disruption is the pathological change of early Alzheimer’s disease (AD). RNA-binding proteins and long non-coding RNAs are involved in the regulation of BBB permeability. Our study was performed to demonstrate TRA2A/LINC00662/ELK4 axis in regulating BBB permeability in AD microenvironment. In Aβ1-42-incubated microvascular endothelial cells (ECs) of BBB model in vitro, TRA2A and LINC00662 were enriched. TRA2A increased the stability of LINC00662 by binding with it. The knockdown of either TRA2A or LINC00662 decreased the BBB permeability via upregulating the expressions of tight junction-related proteins. ELK4 was lower expressed in BBB model in vitro in AD microenvironment. LINC00662 mediated the degradation of ELK4 mRNA by SMD pathway. The downregulated ELK4 increased the permeability of BTB by increasing the tight junction-related proteins expressions. TRA2A/LINC00662/ELK4 axis plays a crucial role in the regulation of BBB permeability in AD microenvironment, which may provide a novel target for the therapy of AD.
Factors associated with risk of developmental delay in preschool children in a setting with high rates of malnutrition: a cross-sectional analysis of data from the IHOPE study, Madagascar
Authors: Miller Ann , Garchitorena Andres , Rabemananjara Faramalala , Cordier Laura , Randriamanambintsoa Marius , Rabeza Victor , Razanadrakoto Hery-Tiana Rahaniraka , Ramakasoa Ranaivozafindary Rakoto , Ratsimbazafy Baolova Nathaline , Ouenzar Mohammed Ali , Bonds Matthew H. , Ratsifandrihamanana Lisy
Published: December 2019

Background: 50% of Malagasy children have moderate to severe stunting. In 2016, a new 10 year National Nutrition Action Plan (PNAN III) was initiated to help address stunting and developmental delay. We report factors associated with risk of developmental delay in 3 and 4 year olds in the rural district of Ifanadiana in southeastern Madagascar in 2016. Methods: The data are from a cross-sectional analysis of the 2016 wave of IHOPE panel data (a population-representative cohort study begun in 2014). We interviewed women ages 15-49 using the MICS Early Child Development Indicator (ECDI) module, which includes questions for physical, socio-emotional, learning and literacy/numeracy domains. We analyzed ECDI data using standardized z scores for relative relationships for 2 outcomes: at-risk-for-delay vs. an international standard, and lower-development-than-peers if ECDI z scores were >1 standard deviation below study mean. Covariates included demographics, adult involvement, household environment, and selected child health factors. Variables significant at alpha of 0.1 were included a multivariable model; final models used backward stepwise regression, clustered at the sampling level. Results: Of 432 children ages 3 and 4 years, 173 (40%)were at risk for delay compared to international norms and 68 children (16.0%) had lower-development than peers. This was driven mostly by the literacy/numeracy domain, with only 7% of children considered developmentally on track in that domain. 50.5% of children had moderate to severe stunting. 76 (17.6%) had >=4 stimulation activities in past 3 days. Greater paternal engagement (OR 1.59(1.13, 2.21)) was associated with increased delay vs. international norms. Adolescent motherhood (OR3.89 (1.32, 11.48)) decreased children’s development vs. peers. Engagement from a non-parental adult reduced odds of delay for both outcomes (OR(95%CI =0.76 (0.61, 0.93) & 0.28(0.16, 0.50) respectively). Stunting was not associated with delay risk (1.33 (0.83, 2.14) or low development (0.91(0.47, 1.74)) when controlling for other factors. Conclusions: In this setting of high child malnutrition, stunting is not independently associated with developmental risk. A low proportion of children receive developmentally supportive stimulation from adults, but non-parent adults provide more stimulation in general than either mother or father. Stimulation from non-parent adults is associated with lower odds of delay
The difficulties experienced during the preparation and administration of oral drugs by parents at home: a cross-sectional study from Palestine
Authors: Ali Ra'fat , Shadeed Abdullah , Fitian Hasan , Zyoud Sa'ed
Published: December 2019

Background: Failure to properly administer drugs to children at home may cause adverse events and may be fatal, which makes it a challenging job for parents or caregivers. The main goal of this study was to investigate the problems and difficulties that parents or caregivers faced when administering oral drugs to their children at home. Methods: A cross-sectional study was conducted using a questionnaire consisting of ‘yes/no’ and multiple-response questions to assess parents' experiences and problems with administering medication to their children at home. Data was collected from parents who visited primary health care centres in Nablus. Descriptive analysis was conducted to describe the characteristics of the sample. Results: We interviewed 420 participants. 91.9% of the participants used drugs without prescription from a doctor, and the most commonly used non-prescription medicines were antipyretics (n=386, 100%), influenza drugs (n=142, 36.8%), cough drugs (n=109, 28.2%) and antibiotics (n= 102, 26.4%). The study showed that 83.6% of parents use a syringe, 21.7% use a teaspoon, 9.3% use the cup attached with the drug and 7.1% use a tablespoon in administering oral liquid medications to their children. 36.8% of the parents who mentioned that their children did not like taking tablets persuaded their children to drink more water, 31.1% requested another form of drug and 30.2% crushed a capsule. When the children did not like taking liquid medications, almost two-thirds of the participants (65.7%) insisted their children take them, 25.5% persuaded them to drink it with more water and 21.5% mixed it with juice. Conclusions: This study has shown that there is a proportion of caregivers or parents who administer oral drugs to their children wrongly, which may involve giving them at the wrong intervals or doses, using incorrect instruments, using non-prescription drugs or mixing them with food, juice or milk. The development of educational programs that will provide parents with education about medication administration is therefore recommended.
EphB4/ TNFR2/Erk/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation
Authors: Zhang Yu , Yang Chengzhe , Ge Shaohua , Wang Limei , Zhang Jin , Yang Pishan
Published: December 2019

Low concentrations of tumor necrosis factor-alpha and its receptor TNFR2 are both reported to promote osteogenic differentiation of osteoblast precursor cells. Moreover, low concentrations of TNF-α up-regulate the expression of EphB4. However, the molecular mechanisms underlying TNF-α-induced osteogenic differentiation and the roles of TNFR2 and EphB4 have not been fully elucidated. This study showed that with increase in ALP activity, mRNA and protein expression of Runx2, BSP and EphB4, TNFR2 expression was significantly promoted under 0.5 ng/ml TNF-α stimulation in osteoblast precursor cells MC3T3-E1. After TNFR2 was inhibited by gene knockdown with lentivirus-mediated shRNA interference or by a neutralizing antibody against TNFR2, the pro-osteogenic effect of TNF-α was partly reversed, but up-regulation of EphB4 by TNF-α kept unchanged. With EphB4 forward signaling suppressed by a potent inhibitor of EphB4 auto-phosphorylation, NVP-BHG712, TNF-α-enhanced expressions of TNFR2, BSP and Runx2 were significantly decreased. Further investigation into the signaling pathways revealed that TNF-α significantly augmented expression of p-JNK, p-Erk and p-p38, however, only p-Erk expression was significantly inhibited in TNFR2-knockdown cells. In addition, the Erk pathway inhibitor, U0126 (10μM), significantly inhibited the protein levels of Runx2 and BSP when compared with cells treated with TNF-α only. In conclusion, the EphB4, TNFR2 and Erk/MAPK signaling pathway comprise a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation.
Lysyl oxidase 473G/A (rs1800449) polymorphism influences the risk of cancer progression: a meta-analysis
Authors: Mongkolrob Rungrawee , Tharabenjasin Phuntila , Bualuang Aporn , Pabalan Noel
Published: December 2019

The genetics of cancer progression is important for devising optimal therapeutic strategies. Lysyl oxidase (LOX) is a cancer progression gene that has been studied enough to warrant synthesis of its primary data from association studies. However, reported associations between the LOX G473A (rs1800449) gene polymorphisms and cancer have been inconsistent prompting a meta-analysis so that we could obtain more precise estimates. Databases searches of the published literature yielded seven case-control studies. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using four genetic models, homozygous (H), recessive (R), dominant (D) and codominant (C). Subgroup analysis was based on ethnicity and cancer type. Outlier analysis was used to examine sources of heterogeneity. Strength of evidence was based on high associative significance (expressed in terms of the Bayes Factor), consistency and magnitude of effects, homogeneity and robustness. H/R outcomes exerted more associative effects than D/C results. Two reasons for these are: (i) H/R analyses precluded outlier treatment; (ii) magnitude of H/R (ORs of > 2.0) was twice that of D/C (ORs > 1.0). All else being equal, significant pooled ORs in all genetic models had high significance (Pa < 10-5). Strong evidence for associations were found in the outcomes for Asian and digestive cancers. In summary, the LOX rs1800449 polymorphism confers significant overall susceptibility, particularly in digestive cancers and places Asians at risk.
Carbon Nanoparticles Enhance Potassium Uptake via Upregulating Potassium Channel Expression and Imitating Biological Ion Channels in BY-2 Cells
Authors: Chen Lijuan , Yang Jinchu , Li Xiang , Liang Taibo , Nie Cong , Xie Fuwei , Liu Kejian , Peng Xiaojun , Xie Jianping
Published: December 2019

Background: Carbon nanoparticles (CNPs) have been reported to boost plant growth, while CNPs enhancing potassium uptake for plant growth have not been reported so far.Results: In this study, the function of CNPs promoting potassium uptake in BY-2 cells was established and the potassium accumulation in cells has a significant correlation relationship with BY-2 cell fresh biomass. The K + accumulation in cells increased with the increasing concentration of CNPs. The K + influx reached high level after treatment with CNPs and exhibited significantly higher than the control group and the negative group treated with K + channels blocker, tetraethylammonium chloride (TEA + ). The K + accumulation was not reduced in the presence of CNPs inhibitors. In presence of the potassium channel blocker TEA + and the CNPs inhibitors, NKT1 expression was downregulated. The CNPs were found to preferentially transport K + than other cations determined by rectification of ion current assay (RIC) in a conical nanocapillary.Conclusions: These results indicated that CNPs upregulated potassium gene expression to enhance K + accumulation in BY-2 cells. Moreover, it was speculated that the CNPs simulated protein ion channels via bulk of carboxyl for K + permeating. These findings will provide support for improving plant growth by carbon nanoparticles.
Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery
Authors: Zhang Shubiao , Zhao Yinan , Du Yanyan , Cao Yingnan , Xuan Yang , Chen Huiying , Zhi Defu , Guo Shutao
Published: December 2019

Background: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency.Results: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp(-0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in Hela cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplexes was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid.Conclusions: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.
The exopolysaccharide–eDNA interaction modulates 3D architecture of Bacillus subtilis biofilm
Authors: Peng Na , Cai Peng , Mortimer Monika , Wu Yichao , Gao Chunhui , Huang Qiaoyun
Published: December 2019

Background Bacterial biofilms are a surface-adherent microbial community in which individual cells are surrounded by a self-produced extracellular matrix of polysaccharides, extracellular DNA (eDNA) and proteins. Interactions among matrix components within the biofilms are responsible for creating an adaptable structure during biofilm development. However, it is unclear how the interaction among matrix components contributes to the construction of the three-dimensional (3D) biofilm architecture.Results DNase I treatment could significantly inhibit B. subtilis biofilm formation in early phases. Confocal laser scanning microscopy (CLSM) and image analysis revealed that eDNA was cooperative with EPS in early stages of B. subtilis biofilm development, while EPS played a major structural role in the later stages. In addition, deletion of EPS production gene epsG in B. subtilis SBE1 resulted in loss of the interaction between EPS and eDNA, and reduction of biofilm biomass in pellicles at air-liquid interface. The physical interaction between these two essential biofilm matrix components was confirmed by isothermal titration calorimetry (ITC).Conclusions The biofilm 3D structures become interconnected through surrounding eDNA and EPS. eDNA interacts with EPS in the early phases of biofilm development, while EPS mainly participates in the maturation of biofilm. The findings of this study provide better understanding of the role of interaction between eDNA and EPS in shaping the biofilm 3D matrix structure and biofilm formation.
Jejunal inflammatory cytokines, barrier proteins and microbiome-metabolome responses to early supplementary feeding of Bamei suckling piglets
Authors: Jipeng Jin , Zhang Liping , Jia Jianlei , Chen Qian , Zhang Xiaoyan , Sun Weibo , Ma Cunming , Xu Fafang , Zhan Shoujun , Ma Limin , Zhou Guihua , Chen Qiaoxi
Published: December 2019

Background: Dietary intervention has been reported to improve intestinal health. The intestinal microbiota of newborn animals plays a fundamental role in the development of intestinal function and the innate immune system. However, little is currently known about dietary interventions in the gut microbiota and barrier function of livestock, especially suckling Bamei piglets. To this end, we studied the effect of early dietary supplementation on intestinal bacterial communities and intestinal barrier function in piglets.Results: 10 purebred Bamei sows were randomly allocated into two groups. In one group, the piglets received a supplementary milk replacer on day 7 of age, whereas the other was allowed sow’s milk alone. At 21 days, piglets of average weight in each group were randomly selected and sacrificed. Tissue and digesta samples were collected from the jejunum to compare the differences in the microbiome-metabolome and the mRNA expression of inflammatory cytokines (TLR4, TNFα and IL-8) and barrier proteins (ZO-1, Occludin and Claudin-1)) between the two groups. Sequencing of 16S rRNA revealed that early supplementary feeding significantly improved the gut microbiome composition in Bamei suckling piglets. In addition, metabolomics analysis shows simuitaneous affect, and mang gut microflora–related metabolites also being affected. Meanwhile, early supplementary feeding of Bamei suckling piglets altered the expression of inflammatory cytokine and barrier protein genes in the jejunum.Conclusions: In summary, these results provide important insights into the relationship between the jejunal microbiota and related metabolites, and jejunal barrier function during early life of Bamei suckling piglets.
Milk exosome-derived miRNAs from water buffalo are implicated in immune response and metabolism process
Authors: Chen Zujing , Xie Yueqin , Luo Junyi , Chen Ting , Xi Qianyun , Zhang Yongliang , SUN JIAJIE
Published: December 2019

Buffalo milk represents an indispensable source of nourishment, and recently receives increasing research interest and investment in various countries due to its high nutrient content compared with non-buffalo milks. Exosomes are membranous vesicles of endocytic origin that are found in various breast milks, and those can mediate intercellular communication with exosomal miRNAs. In comparison with non-buffalo milks, we therefore hypothesized that buffalo milk exosomes provided novel information on miRNA composition, and highlighted the unrealized physiological importance of exosomes on drinking behaviour. Here, we isolated exosomes from buffalo and cow milk samples that were obtained at mid-lactation period, and the exosomal miRNA profiles were then generated using RNA-seq. As control, miRNA sequencing data of pig, human and panda milk exosomes were downloaded from GEO database. Finally, a total of 27 milk exosomal miRNA profiles that included 4 buffalo, 4 cow, 8 pig, 4 human and 7 panda were analyzed using the miRDeep2 program. For these datasets there were 558 unique miRNA candidates existed across all species, and the top 10 highly expressed miRNA were evolutionarily conserved across multiple species. Functional analysis revealed that these milk enriched miRNAs targeted 400 putative sites to modulate disease resistance, immune responsiveness and basic metabolism events. In addition, a total of 32 miRNAs in buffalo milk were significantly up-regulated compared with non-buffalo milks, while 16 were significantly down-regulated. Of interest, functional analysis showed that up-regulated miRNAs were mainly related to host metabolism processes, while the predicted functions of down-regulated miRNAs were enriched in immune response. In this study, we explored the exosomal miRNAome differences between milks of different animals, expanding the theoretical basis for potential applications of the miRNA-containing vesicles.
Model Construction of Medical Endoscope Service Evaluation System-Based on the Analysis of Delphi Method
Authors: Zheng Jun , Lou Ligang , Xie Ying , Chen Siyao , Li Jun , Wei Jingming , Feng Jingyi
Published: December 2019

Background: Medical endoscope is widely used in clinical practice for the purpose of diagnosis and treatment,occupying around 5% of the medical device market. Evaluating the true service level of medical endoscope is essential and necessary to improve overall performance of medical diagnosis and treatment, and to maintain competitiveness of endoscope manufacturers, however, such a tool is not available in the market. This study develops an Evaluation Index System (EIS) to assess service level of medical endoscope, and to provide suggestions for improving the service level through the Delphi method. Methods: Firstly, the possible factors influencing the service level were identified from literature review. In parallel, the Delphi expert method questionnaire was designed and 25 experts were invited to conduct three rounds of questionnaire, to evaluate and rate the possible factors. Finally, we determined the weights associated with the factors, using the analytic hierarchy process (AHP) and percentage method, and developed theservice level EIS. Results: The EIS consists of 3 first-level indicators, 24 second-level indicators and 68 third-level indicators. According to the weights computed using AHP, first-level indicators are ranked as post-sale (0.62), in-sale (0.25) and pre-sale (0.13). Through case verification, the medical endoscope brand Olympus had a total score of 4.17, Shanghai Aohua had a total score of 3.71, and Shanghai Chengyun had a total score of 3.28, which matches its market popularity and ranking in terms of market share. The results obtained from the EIS are consistent with the reality. Conclusions: The EIS established in this study is comprehensive, reliable and reasonable with strong practicality. The EIS can act as a tool for the endoscope users to evaluate potential products and make informed choices. It also provides a measurable basis for endoscope manufacturers and service providers to improve service quality.
Improving Injection Safety Practices of Cambodian Healthcare Workers through Training
Authors: Kanagasabai Udhayashankar , Singh Adarshpal , Shiraishi Ray W. , Ly Vanthy , Hy Chhaily , Sanith Sou , S Sok , Sansam Sim , Liu Yuliang , Jones Gerald , Ijeoma Ugonna C. , Bock Naomi , Benech Irene , Selenic Dejana , Drammah Bakary , Gadde Renuka , Mili Fatima D.
Published: December 2019

Background This study evaluated the impact of a safe injection safety training on healthcare worker (HCW) practice and knowledge following an HIV outbreak in Roka commune, Cambodia. Methods Surveys were conducted at baseline (September 2016) and seven months after a training intervention (March 2018) using the World Health Organization standardized injection practices assessment tool. HCWs were sampled at 15 purposively government health facilities in two provinces. HCWs were observed during injection practices and interviewed by trained experts from Becton-Dickinson and the Ministry of Health Cambodia. The Rao-Scott chi square test was used test for differences between baseline and follow-up. Results We completed 115 observations of practice at baseline and 206 at post-training follow-up. The proportion of patients whose identification was confirmed by HCWs prior to procedure being performed increased from 40.4% to 98% (p = 0.0000). The proportion of HCWs who practiced correct hand hygiene increased from 22.0% to 80.6% (p = 0.056) [therapeutic observations] and 17.2% to 63.4% (p = 0.0012) [diagnostic observations]. Immediate disposal of sharps by HCWs decreased from 96.5% to 92.5% (p = 0.0030). Conclusions We found significant improvements in the practice of patient identity confirmation and hand hygiene but not in the immediate disposal of sharps in the post-training intervention. However, findings are not representative of all HCWs in the country. Further pre-service and in-service training and monitoring are necessary to ensure sustained behavior change.
Genome sequencing and transcriptome analysis of Geotrichum citri-aurantii on citrus reveal the potential pathogenic- and guazatine resistance-related genes
Authors: Zhao Juan , Zhang DeYao , Wang Zhe , Tian Zhonghuan , Yang Fan , Lu XinJun , Long Chao-an
Published: December 2019

Background: Citrus grow in more than 100 countries and is one of the most produced fruit genus. Sour rot, caused by Geotrichum citri-aurantii , is a major postharvest disease of citrus，and it causes economic losses. In recent years, the disease had a rising trend year by year. In this study, the genome sequence of G. citri-aurantii and transcriptome sequence of pathogenic- and guazatine resistance were sequenced with a view to explore the potential pathogenic mechanism and drug resistance mechanism of G. citri-aurantii on citrus. Results: We sequenced a high-quality genome sequence of G. citri-aurantii by SMRT. This sequence encodes 6,783 predicted genes of the 28.1-Mb G. citri-aurantii genome. Approximately 5.43 Gb of clean data were obtained after Hi-C sequencing, and a 27.94-Mb genomic sequence was positioned to the 10 chromosome groups after Hi-C assembly , accounting for 99.43% of the previously measured G. citri-aurantii genome. In the process of studying pathogenic mechanisms, the content of polygalacturonase (PG) and polymethylgalacturonase (PMG) was considerably increased in the Newhall navel orange infected by G. citri-aurantii. Then, three polygalacturonase (PG) genes (EVM0005942, EVM0004416, EVM0002276) related to pathogenicity were identified and the expression level was significantly increased during the infection by quantitative RT-PCR. Additionally, G. citri-aurantii is only sensitive to the chemical fungicide guazatine. Massive guazatine use has led to evolution of the wild G. citri-aurantii in citrus-producing areas. Owing to its uniqueness, RNA sequencing analysis of guazatine-resistance showed that the guazatine-resistance of G. citri-aurantii is may related to two ABC transporter family genes, six MFS transporter family genes and two MATE transporter family genes. Conclusions: We found three polygalacturonase (PG) genes related to pathogenicity and ten genes related to guazatine-resistance from molecular level. Our research may provide novel insights into the effective control of this pathogen. Keywords: Geotrichum citri-aurantii , citrus, genome, pathogenicity, guazatine, drug resistance
Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells
Authors: Helgeland Hanna , Gabrielsen Ingvild , Akselsen Helle , Sundaram Arvind Y.M. , Flåm Siri Tennebø , Lie Benedicte Alexandra
Published: December 2019

Background: The thymus is a highly specialized organ of the immune system where T cell precursors develop and differentiate into self-tolerant CD4+ or CD8+ T cells. No studies to date have investigated how the human transcriptome profiles differ, between T cells still residing in the thymus and T cells in the periphery.Results: We have performed high-throughput RNA sequencing to characterize the transcriptomes of primary single positive (SP) CD4+ and CD8+ T cells from infant thymic tissue, as well as primary CD4+ and CD8+ T cells from infant and adult peripheral blood, to enable the comparisons across tissues and ages. In addition, we have assessed the expression of candidate genes related to autoimmune diseases in thymic CD4+ and CD8+ T cells. Thymic SP T cells displayed a broader transcriptome than peripheral T cells, indicated by a higher number of uniquely expressed genes. Comparing T cells of thymic and blood origin, revealed more differentially expressed genes, than between infant and adult blood. Functional enrichment analysis revealed an over-representation of genes involved in cell cycle and replication in thymic T cells, whereas infant blood T cells were dominated by immune related terms. Comparing adult and infant blood T cells, the former was enriched for inflammatory response, cytokine production and biological adhesion, while upregulated genes in infant blood T cells were associated with cell cycle, cell death and gene expression.Conclusion: This study provides valuable insight into the transcriptomes of the human primary SP T cells still residing within the thymus, and offers a unique comparison to the more frequently studied primary blood derived T cells. We discovered that genes involved in migration, homing and recirculation, between peripheral blood and lymphatic tissue, were particularly active in infant blood T cells, suggesting active migration and recirculation in young children.
TRPP2 and STIM1 form a microdomain to regulate store-operated Ca2+ entry and blood vessel tone
Authors: Guo Jizheng , Zhao Ren , Zhou Muyao , Li Jie , Yao Xiaoqiang , Du Juan , Chen Jiexia , Shen Bing
Published: December 2019

BackgroundTRPP2 (Polycystin-2) is a Ca2+ permeable nonselective cationic channel essential for maintaining physiological function in live cells. Stromal interaction molecule 1 (STIM1) is an important Ca2+ sensor in store-operated Ca2+ entry (SOCE). Both TRPP2 and STIM1 are expressed in endoplasmic reticular membrane and participate in Ca2+ signaling, suggesting a physical interaction and functional synergism.MethodsWe performed co-localization, co-immunoprecipitation, and fluorescence resonance energy transfer assay to identify the interactions of TRPP2 and STIM1 in transfected HEK293 cells and native vascular smooth muscle cells (VSMCs). The function of the TRPP2-STIM1 complex in TG or ATP-induced SOCE was explored using specific siRNA. Further, we created TRPP2 CKO mouse to investigate the functional role of TRPP2 in agonist-induced vessel contraction.ResultsTRPP2 and STIM1 form a complex in transfected HEK293 cells and native VSMCs. Genetic manipulations with TRPP2 siRNA, dominant negative TRPP2 or STIM1 siRNA significantly suppressed adenosine triphosphate (ATP) and thapsigargin (TG)-induced intracellular Ca2+ release and SOCE in HEK293 cells. Inositol triphosphate receptor inhibitor 2-aminoethyl diphenylborinate (2APB) abolished ATP-induced Ca2+ release and SOCE in HEK293 cells. In addition, TRPP2 and STIM1 knockdown significantly inhibited ATP- and TG-induced STIM1 puncta formation and SOCE in VSMCs. Importantly, knockdown of TRPP2 and STIM1 or conditional knockout TRPP2 markedly suppressed agonist-induced mouse aorta contraction.Conclusions Our data indicate that TRPP2 and STIM1 are physically associated and form a functional complex to regulate agonist-induced intracellular Ca2+ mobilization, SOCE and blood vessel tone.
Loss-of-function mutations in KEAP1 drive lung squamous cell carcinoma progression via KEAP1/NRF2 pathway activation
Authors: Meiling Gong , Li Yan , Ye Xiao-Ping , Zhang Linlin , Wang Zhifang , Xu Xiaowen , Shen Yejing , Zheng Cui-Xia
Published: December 2019

Background and Purpose Targeted therapy has led to dramatic change in the treatment of lung adenocarcinoma, but lung squamous cell carcinoma(LSCC) lacks targeted therapy options. High-frequency somatic mutations in KEAP1/NRF2 (27.9%) have been identified in LSCC. In this study, we explored the role of KEAP1 somatic mutations in the development of LSCC and whether a nuclear factor erythroid 2-related factor 2(NRF2) inhibitor be potential to target lung cancer carrying KEAP1/NRF2 mutations.Methods Lung cancer cell lines A549 and H460 with loss-of-function mutations in KEAP1 stably transfected with wild-type (WT) KEAP1 or somatic mutations in KEAP1 were used to investigate the functions of somatic mutations in KEAP1 .Flow cytometry,plate clone formation experiments,and scratch tests were used to examine reactive oxygen species, proliferation, and migration of these cell lines.Results The expression of NRF2 and its target genes increased, and tumor cell proliferation, migration, and tumor growth were accelerated in A549 and H460 cells stably transfected with KEAP1 mutants compared to control cells with a loss-of-function KEAP1 mutation and stably transfected with WT KEAP1 in both in vitro and in vivo studies. Inhibited proliferation was more apparent in the A549 cell line trasfected with the R320Q KEAP1 mutant than the A549 cell line trasfected with WT KEAP1 after treatment with NRF2 inhibitor ML385.Conclusion Somatic mutations in KEAP1 identified from patients with lung carcinoma likely promote tumorigenesis mediated by activation of the KEAP1/NRF2 antioxidant stress response pathway. NRF2 inhibition with ML385 could inhibit the proliferation of tumor cells with KEAP1 mutation.
Associations of the intestinal microbiome with the complement system in age-related macular degeneration
Authors: Zysset-Burri Denise Corinne , Keller Irene , Berger Lieselotte E. , Largiadèr Carlo R. , Wittwer Matthias , Wolf Sebastian , Zinkernagel Martin S.
Published: December 2019

Background: Age-related macular degeneration (AMD) is a leading cause of severe vision loss in the aged population. The etiology of AMD is multifactorial and includes nutritional factors, genetic variants mainly in the complement pathway, environmental risk factors and alterations in the intestinal microbiome. However, it remains largely unexplored whether there is an interdependency of these factors leading to the development of AMD. To investigate this issue, a comprehensive shotgun metagenomics analysis of 57 AMD and 58 healthy controls as well as of 16 complement C3 deficient mice and 16 wildtypes was performed. Single nucleotide polymorphisms (SNPs) in the complement factors were assessed with pre-designed TaqMan® SNP genotyping assays. Results: The composition of the intestinal microbiome differed significantly between AMD patients and controls. Whereas the class Negativicutes was more abundant in patients, the genus Oscillibacter and Bacteroides species had a significantly higher prevalence in persons without AMD. While SNPs within the complement factor B gene were more abundant in controls, SNPs within the high temperature requirement A serine peptidase 1 and complement factor H (CFH) genes were associated with AMD. Using a classification model, Negativicutes was identified as a potential biomarker for AMD and furthermore, it positively correlated with CFH. In addition, similar taxonomic features were identified that distinguished wildtype mice from C3 deficient mice. Conclusion: The composition of the intestinal microbiome differs between AMD patients and controls as well as between C3 deficient mice and wildtype mice. Moreover, since the phylum Firmicutes has been identified as potential biomarker for AMD and positively correlates with the genetic risk factor CFH, the study suggests an association between the intestinal microbiome and the complement system in AMD.