bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals with Acute Spinal Cord Injury: study protocol for a randomized controlled trial
Authors: DEMIREL Aynur , LI Jia , MORROW Casey , BARNES Stephen , JANSEN Jan , GOWER Barbara , KIRKSEY Keneshia , REDDEN David , Yarar-Fisher Ceren
Published: March 2020

Background: Therapies that significantly improve the neurological and functional recovery of individuals with spinal cord injury (SCI) are still urgently needed. The ketogenic diet (KD) has been shown to improve forelimb motor function in a SCI rat model, likely by reducing inflammation and cell death in the spinal cord. Furthermore, our recent pilot study in patients with SCI showed that, compared with a standard hospital diet (SD), 5 weeks of KD started during acute care, improved upper extremity motor function, and reduced serum levels of a neuroinflammatory blood protein. The primary goals of the current study are to: 1) show the safety and feasibility of administering a KD during acute care for SCI; 2) determine if consuming 5 weeks of a KD significantly improves motor and sensory functions, functional independence, and glycemic control; and 3) quantify serum biomarkers that are linked to improvements in neurological recovery and functional independence via targeted proteomics.
Methods/Design: In a single-masked, longitudinal, randomized parallel controlled study, a total of 60 eligible participants ranging in age from 18 to 60 years with acute traumatic SCI (cervical 5 – thoracic 12) American Spinal Injury Association impairment scale (AIS A-C): AIS-A, sensorimotor complete; AIS-B, sensory incomplete/motor complete; and AIS-C, non-functional motor incomplete, are being enrolled. Neurological and functional examinations, resting energy expenditure, blood, urine, and stool collections, and protein analyses related to neurological recovery will be performed within 72 h of injury (baseline measure) and repeated after 5 weeks of KD or SD (discharge measure). We anticipate a completion rate of 80% with a total of 48 participants.
Discussion: Intervention with a more neuroprotective diet during acute care of SCI can be implemented anywhere in the world at low cost and without major regulatory hurdles. Better functional recovery will lead to a better quality of life and long-term health outcomes in individuals with SCI. While this study targets SCI, if successful it has the potential to improve neurological outcomes for individuals with various traumatic injuries.
Trial registrations: ClinicalTrials.gov, NCT03509571. Registered in April 2018.
Therapeutic effect of TO901317 on 6-OHDA-induced Parkinson rats in vitro and in vivo
Authors: Li Miaomiao , Yang Junqing , Cheng Oumei , Peng Zhe , Luo Yin , Ran Dongzhi , Yang Yang , Xiang Pu , Huang Haifeng , Tan Xiaodan , Wang Hong
Published: March 2020

Background: Stem cells from different sources could differentiate into dopamine-producing cells and ameliorate behavioral deficits in Parkinsonian models. Especially, human bone marrow mesenchymal stem cells (hBMSCs) have many advantages without ethical dispute. Liver X receptor s (LXRs) are involved in the maintenance of the normal function of the central nervous system myelin. We have reported the induction of cocktail-induced da phenotypes from adult rat BMSCs by using sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF) and TO901317 (agonist of LXRs) with 87.42% of efficiency in 6 days of period of induction. But the previous work did not verify whether the induced cells had the corresponding neural function.
Methods: In this study, we demonstrated that TO901317 could promote the differentiation of hBMSCs into dopaminergic neurons. Neuronal markers (Tuj1, Neun and Nestin), dopamine neuron markers (tyrosine hydroxylase, TH), LXRa and LXRb were detected by immunofluorescence. RT-qPCR was used to measure the mRNA expressions of adenosine triphosphate-binding cassette transporter A1 (ABCA1). Western Blotting detected the changes of LXRa, LXRb and TH expression.
Results: TO901317 significantly enhanced the differentiation from hBMSCs to DA neurons. Only the LXR+GF group released dopamine by the result of enzyme linked immunosorbent assay (ELISA). Compared with the control group and GF group, the optimal time for differentiation of hBMSCs treated by 0.5mM TO901317 combined with GF was six days. And the maximum induction efficiency was 91.67%. After transplanting induced-cells into Parkinson's disease rats, the symptoms of Parkinson's rats decreased, and the number of dopamine neurons increased in the substantia nigra and striatum.
Conclusions: TO901317 promoted differentiation of hBMSCs into dopamine neurons may be related to activation of LXR-ABCA1 signaling pathway. These data suggest that TO901317 may serve as a potential therapeutic methods for Parkinson's disease.
Patient and befriender experiences of participating in a befriending programme for adults with psychosis: A qualitative study.
Authors: Burn Erin , Chevalier Agnes , Leverton Monica , Priebe Stefan
Published: March 2020

Background

Befriending is a popular form of volunteering in healthcare, and research suggests that it can be beneficial for people with mental illness. This study aimed to explore the experiences of a large sample of volunteer befrienders and patients who participated in the VOLUME trial, testing the efficacy of a structured befriending programme for individuals with psychosis. This is the first study to explore the specific challenges and benefits of befriending in both volunteers and patients in this population within the same programme.

Methods

A series of in-depth semi-structured interviews were conducted with 34 volunteer befrienders and 28 participating patients. All participants who had taken part in at least one befriending session were invited to be interviewed about their experiences with the aim of including a wide range of views, including those who were more or less engaged with the befriending programme. The data were analysed using Thematic Analysis.

Results

Four broad themes were developed from the analysis of the befriender and patient interviews which, although were largely discrete, captured the overall experiences of participating in the befriending programme: 1) Bridging the gap, 2) A genuine relationship that developed over time, 3) A big commitment, and 4) A flexible approach.

Conclusions

These results further support that, befriending programmes for individuals with psychosis can be a worthwhile experience for both befrienders and patients. However, participation also requires perseverance and flexibility from both sides. Different factors, such as incorporating participant preferences for frequency of meetings, have to be considered in the development and management of a befriending programme in order to provide effective support to both befrienders and patients.

Declaration of conflicting interests

None
SHED ameliorated concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis
Authors: Zhou Yikun , Yang Ruili , Zhu Lingsu , Huang Huaming , Cui Shengjie , Zhang Ting , Zhou Yanheng
Published: March 2020

Background：Autoimmune hepatitis (AIH) is serious autoimmune liver diseases that threaten people’s health worldwide, emphasizing the need to identify novel treatment. Stem cells from human exfoliated deciduous teeth (SHED), which is easy to obtain and non-invasive, showed pronounced proliferation and immunomodulation capacity. This study aims to investigate the effect of SHED on ConA-induced AIH and the potential underlying mechanisms.Methods: We used a concanavalin A (ConA) induced acute hepatitis mouse model and in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis and the underlying mechanisms.Results: SHED infusion could prevent aberrant histopathological architecture of liver with infiltration of abundant of CD3+, CD4+, TNF-α+ and IFN-γ+ inflammatory cells induced by ConA. The expression of ALT and AST which indicated the liver function significantly elevated in hepatitis mice. While SHED infusion could block the elevation of ALT and AST induced by ConA. Mechanistically, Con-A upregulated TNF-α and IFN-γ expression activated NF-κB pathways to induced hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from Con-A-induced apoptosis. Conclusions: These results demonstrated that SHED alleviated ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the NF-κB pathways. Our findings could provide a potential prevention and therapeutic strategy for hepatitis and acute hepatic injury.
Combined Beta Metric for Unsupervised Clustering of Microbiome Data
Authors: Shi Yushu , Zhang Liangliang , Peterson Christine , Do Kim-Anh , Jenq Robert
Published: March 2020

Background In Microbiome data analysis, unsupervised clustering is often used to identify naturally occurring clusters, which can then be assessed for associations with characteristics of interest. In this work, we systematically compared beta diversity and clustering methods commonly used in microbiome analyses. We applied these to four published datasets where highly distinct microbiome profiles could be seen between sample groups. Results Although no single method outperformed the others consistently, we did identify key scenarios where certain methods can underperform. Specifically, the Bray Curtis metric resulted in poor clustering in a dataset where high-abundance OTUs were relatively rare. In contrast, the unweighted UniFrac metric clustered poorly when used on a dataset with a high prevalence of low-abundance OTUs. To test our proposition, we systematically modified properties of the poorly performing datasets and found that this approach resulted in improved Bray Curtis and unweighted UniFrac performance. Conclusions Based on these observations, we rationally combined the Bray Curtis metric and the unweighted UniFrac metrics and found that this new beta diversity metric showed high performance across all datasets.
Fast recognition of Lecanicillium spp. and its virulence against Frankliniella occidentalis
Authors: zhou yeming , Zou Xiao , Zhi Junrui , Xie jiqin , Jiang Tao
Published: March 2020

Background: Frankliniella occidentalis (Thysanoptera: Thripidae) is a highly destructive sucking pest of numerous crops. The entomogenous fungi of Lecanicillium spp. are important pathogens of insect pests, and some have been developed as commercial biopesticides. In order to explore the wild resources of Lecanicillium spp. in the development of more effective F. occidentalis controls, efficient gene combinations for strain identification were screened from internal transcribed spacer (ITS) and the genes SSU, LSU, TEF, RPB1, and RPB2.Results: In this study, six genes were used to reconstruct the phylogeny of Lecanicillium genus respectively. Among these, only four events (ITS, TEF, RPB1, RPB2) were validated using the gold standard for identifying the strains. All the phylogenetic trees reconstruct by free combination of these four events exhibited the same topology. Bioassay studies of a purified conidial suspension further confirmed the infection of second-instar nymphs and adult female F. occidentalis by seven strains of Lecanicillium. L. attenuatum strains GZUIFR-lun1405 was the most virulent, approximately 8.33% of adult and 23.33% of nymphs F. occidentalis survived after a 7-d exposure. Two strains were selected to compare the effects on the amount of eggs laid by F. occidentalis. The number of nymphs of F. occidentalis significantly decreased when adult F. occidentalis were treated with L. cauligalbarum strain GZUIFR-ZHJ01 compared to the controls.Conclusions: We found that combination of ITS and TEF could be used for fast recognition of Lecanicillium spp. We demonstrated that L. attenuatum, L. cauligalbarum, L araneogenum, and L. aphanocladii had various efficacies against F. occidentalis which were the first to demonstrate efficient control of F. occidentalis. In addition, the L. cauligalbarum strain GZUIFR-ZHJ01 not only caused high mortality in F. occidentalis but also inhibited the fecundity of the pest.
The effectiveness and cost effectiveness of a hospital avoidance program in a residential aged care facility: a prospective cohort study and modelled decision analysis
Authors: Carter Hannah , Lee Xing J. , Dwyer Trudy , O’Neill Barbara , Jeffrey Dee , Doran Chris , Parkinson Lynne , Osborne Sonya , Reid-Searl Kerry , Graves Nicholas
Published: March 2020

Background: Residential aged care facility residents experience high rates of hospital admissions which are stressful, costly and often preventable. The EDDIE program is a hospital avoidance initiative designed to enable nursing and care staff to detect, refer and quickly respond to early signals of a deteriorating resident. The program was implemented in a 96-bed residential aged care facility in regional Australia.Methods: A prospective pre-post cohort study design was used to collect data on costs of program delivery, hospital admission rates and length of stay for the 12 months prior to, and following, the intervention. A Markov decision model was developed to synthesize study data with published literature in order to estimate the cost-effectiveness of the program. Quality adjusted life years (QALYs) were adopted as the measure of effectiveness.Results: The EDDIE program was associated with a 19% reduction in annual hospital admissions and a 31% reduction in the average length of stay. The cost-effectiveness analysis found the program to be both more effective and less costly than usual care, with 0.06 QALYs gained and $249,000 health system costs saved in a modelled cohort of 96 residents. A probabilistic sensitivity analysis estimated that there was an 86% probability that the program was cost-effective after taking the uncertainty of the model inputs into account. Conclusions: This study provides promising evidence for the effectiveness and cost-effectiveness of a nurse led, early intervention program in preventing unnecessary hospital admissions within a residential aged care facility. Further research in multi-site randomised studies is needed to confirm these results.
Effects of intraoperative hypotension on postoperative renal function in arthroscopic shoulder surgery: a retrospective study
Authors: Lim Chaeseong , Lee Seounghun , Chung Woosuk , Kim Hoseop , Jeon Seungbin , Kim Yoon Hee
Published: March 2020

Background: Arthroscopic shoulder surgery tends to cause a drop in blood pressure due to the beach chair position used during the procedure, including activation of the Bezold-Jarisch reflex. We hypothesized that patients with low blood pressure undergoing arthroscopic shoulder surgery in the beach chair position would also have reduced renal function after surgery.Methods: The medical records of patients (N = 643) undergoing arthroscopic shoulder surgery in the beach chair position between July 2013 and May 2015 were examined. The vital signs were measured at 5-minute intervals, and the number of non-invasive blood pressure (NIBP) measurements in the upper arm dropping below a mean arterial pressure (MAP) of 50 mmHg (MAP50) or 60 mmHg (MAP60) were recorded. The primary outcome was change in creatinine immediately after surgery relative to the preoperative level (Cr post/pre). The factors affecting Cr post/pre were examined by correlation analysis.Results: A total of 597 patients were included in the analysis. Longer duration of hypotension during surgery (MAP50) was correlated with higher Cr post/pre (R = 0.107, P = 0.010). However, the correlation between MAP60 and Cr post/pre was not significant (R = 0.033, P = 0.431).Conclusions: It is necessary to ensure that the MAP does not fall below 50 mmHg to ensure sufficient renal function during general anesthesia for shoulder arthroscopy in a beach chair position.
Quantitative analysis of the global proteome in lung from mice with blast injury
Authors: Liu Ying , Liu Yunen , Tong Changci , Cong Peifang , Shi Xiuyun , Shi Lin , Hou Mingxiao , Jin Hongxu , Bao Yongli
Published: March 2020

Background The lung is very easily injured by primary shock wave in recent military conflicts. While it is not very clear for its mechanisms. Protein markers can provide new ideas for diagnosis and treatment. Methods A quantitative analysis of their global proteome was conducted in lung from mice with blast injury using LC-MS/MS. Protein annotation, unsupervised hierarchical clustering, functional classification, functional enrichment and cluster, and protein-protein interaction analyses were performed. Furthermore, western blotting was used to verify the differential protein. Results A total of 6498 proteins were identified, of which 5520 proteins were quantified. The fold-change cutoff was set at 1.2; 132 proteins were upregulated, and 104 proteins were downregulated. The bioinformatics analysis indicated that the differentially expressed proteins were involved in the cholesterol metabolism, asthma, non-alcoholic fatty liver disease and so on. Remarkably, the processe related to the change of oxidative phosphorylation including the NADH dehydrogenase, Cytochrome C reductase, Cytochrome C oxidase and F-type ATPase were significantly upregulated, which were further verified by western blotting. Conclusion These results confirmed that the oxidative phosphorylation is critical to blast-induced lung injury. LC/MS-based profiling presented candidate target/pathways that could be explored for future therapeutic development.
Obesity And Telomere Status In The Prognosis Of Colorectal Cancer Patients Submitted To Curative Intention Surgical Treatment
Authors: García-Martínez Sergio , González-Gamo Daniel , Fernández-Marcelo Tamara , Serna Sofía de la , Serrano Inmaculada , Cano-Valderrama Oscar , Barabash Ana , de Juan Carmen , Torres Antonio , Iniesta Pilar
Published: March 2020

Background The risk of colorectal cancer (CRC) development has been related to telomere dysfunction and obesity. However, prognosis of patients affected by CRC has not clearly established considering both telomere attrition and obesity status. Previous published data highlights the importance of studying how obesity influences telomere function and its potential role as a predictor of prognosis in CRC. The aim of this study was to evaluate the impact of obesity and telomere status in the prognosis of patients affected by CRC and submitted to curative surgical treatment. Methods We performed a prospective study including 162 CRC patients submitted to curative surgical treatment. Samples were obtained from tumor and non-tumor tissues. Subjects were classified according to their Body Mass Index (BMI). Telomere status was established through telomere length and telomerase evaluation. Statistical analyses were performed using the SPSS software package version 22. Differences in two or more groups of study were calculated by parametric or non-parametric tests, depending on normality and homoscedasticity conditions of the variables. Prognosis was analyzed using the Kaplan-Meier method. The potential prognostic impact of the variables considered in this work jointly, was evaluated by Cox multivariate regression analyses. Results Patients with shorter telomeres, both in the tumor (median telomere length < 6.5 kb) and their non-tumor paired tissues (median telomere length < 7.1 kb), had the best clinical evolution, independently of the Dukes' stage of cancers (P = 0.025, for tumor samples; P = 0.003, for non-tumor samples). Telomere shortening was inversely associated with BMI in CRC patients. Also, subjects with a BMI > 31.85kg/m 2 showed the worse clinical outcomes. Of interest, the impact of BMI showed gender dependence, since only the group of men showed significant differences in CRC prognosis in relation to obesity status (P = 0.037). Conclusions Telomere length constitutes a useful biomarker to predict prognosis in CRC. Independently of BMI values, the better clinical evolution was associated with shorter telomeres. Obesity seems to have an impact on the clinical outcomes of CRC; however, the impact of BMI seems to be related to other factors such as gender.
WRKY40, WRKY70, and Downy Mildew Resistant 6 (DMR6)-Like Oxygenase 1 are universal marker genes for the salicylic acid pathway in bananas
Authors: Tzean Yuh , Hou Bo-Han , Tsao Shu-Ming , Chen Ho-Ming , Cheng An-Po , Chen Elena Gamboa , Chou Wei-Yi , Chao Chih-Ping , Shen Wei-Chiang , Yeh Hsin-Hung
Published: March 2020

Background: Banana, an important cash and staple crop worldwide, suffers from various biotrophic and hemi-biotrophic pathogens. In plants’ defense against these pathogens, the phytohormone salicylic acid (SA) plays a key role in the regulation of immune response. Using a specific set of SA-responsive genes as markers is frequently adopted to monitor the onset of SA-mediated immune response. However, reliable SA-responsive genes marker genes have not been well established in bananas. Results: From the transcriptome analysis of SA-treated ‘Pei-Chiao’ banana roots, we identified 19 up-regulated and 3 down-regulated genes. Four of the up-regulated genes previously reported to play crucial roles in SA-mediated immunity in other species were further analyzed for their applicability in different tissues and cultivars of bananas using real-time quantitative reverse-transcription PCR. The analysis showed that WRKY40, WRKY70, and Downy Mildew Resistant 6 (DMR6)-Like Oxygenase 1 (DLO1) were significantly induced upon SA treatment in both the leaves and roots of ‘Pei-Chiao’ (AAA genome), ‘Pisang Awak’ (ABB genome), and ‘Lady Finger’ (AA genome) bananas.Conclusions: The uncovering of common marker genes WRKY40, WRKY70, and DLO1 for SA response in different banana genome types provides the stepping stone for studies towards understanding of SA-mediated immune response in bananas.
Bio-organic fertilizers stimulate indigenous soil Pseudomonas populations to enhance plant disease suppression
Authors: Tao Chengyuan , Li Rong , Xiong Wu , Shen Zongzhuan , Liu Shanshan , Wang Beibei , Ruan Yunze , Geisen Stefan , Shen Qirong , Kowalchuk George A.
Published: March 2020

Background: Plant diseases caused by fungal pathogen result in a substantial economic impact on the global food and fruit industry. Application of organic fertilizers supplemented with biocontrol microorganisms (i.e. bioorganic fertilizers) has been shown to improve resistance against plant pathogens at least in part due to impacts on the structure and function of the resident soil microbiome. However, it remains unclear whether such improvements are driven by the specific action of microbial inoculants, microbial populations naturally resident to the organic fertilizer or the physical-chemical properties of the compost substrate. The aim of this study was to seek the ecological mechanisms involved in the disease suppressive activity of bio-organic fertilizers.Results: To disentangle the mechanism of bio-organic fertilizer action, we conducted an experiment tracking Fusarium wilt disease of banana and changes in soil microbial communities over three growth seasons in response to the following four treatments: bio-organic fertilizer (containing Bacillus amyloliquefaciens W19), organic fertilizer, sterilized organic fertilizer and sterilized organic fertilizer supplemented with B. amyloliquefaciens W19. We found that sterilized bioorganic fertilizer to which Bacillus was re-inoculated provided a similar degree of disease suppression as the non-sterilized bioorganic fertilizer. We further observed that disease suppression in these treatments could be linked to impacts on the resident soil microbial communities, with noted increases in specific Pseudomonas spp.. The link between Bacillus amendment and indigenous Pseudomonas spp. was further examined using pot experiments and biofilm assays. Conclusion: Together we demonstrate that the action of bioorganic fertilizer is a product of the biocontrol inoculum within the organic amendment and its impact on the resident soil microbiome. This knowledge should help in the design of more efficient biofertilizers designed to promote soil function.
Proteomic analysis of Rickettsia akari proposes a 44 kDa-OMP as a novel biomarker for Rickettsialpox diagnosis
Authors: Csicsay František , Flores-Ramirez Gabriela , Zuñiga-Navarrete Fernando , Bartošová Mária , Fučíková Alena , Pajer Petr , Dresler Jiří , Škultéty Ľudovít , Quevedo-Diaz Marco Antonio
Published: March 2020

Background: Rickettsialpox is a febrile illness caused by the mite-borne pathogen Rickettsia akari. Several cases of this disease are reported worldwide. Nevertheless, the relationship between the immunogenicity of R. akari and the disease development remains poorly understood. Therefore, misdiagnosis is frequent. Our study is aimed to identify immunogenic proteins that may improve disease recognition and enhance subsequent treatment. To achieve this goal, two proteomics methodologies were applied, followed by immunoblot confirmation. Results: Three hundred and sixteen unique proteins were identified in the whole-cell extract of R. akari. The most represented protein groups were found to be those involved in translation, post-translational modifications, energy production, and cell wall development. A significant number of proteins belonged to amino acid transport and intracellular trafficking. Also, some proteins affecting the virulence were detected. In silico analysis of membrane enriched proteins revealed 25 putative outer membrane proteins containing beta-barrel structure and 11 proteins having a secretion signal peptide sequence. Using rabbit and patient sera, various immunoreactive proteins were identified from which the 44 kDa uncharacterized protein (A8GP63) has demonstrated a unique detection capability. It positively distinguished the sera of patients with Rickettsialpox from other rickettsia positive patient sera. Conclusion: Our proteomic analysis certainly contributed to the knowledge of the pathogenesis of R. akari. The result obtained may also serve as a guideline for a more accurate diagnosis of rickettsial diseases. Identified R. akari antigenic protein can be design as a unique marker of rickettsialpox and used as a target for the development of more effective treatment.
Magnitude of metabolic syndrome and its components among adult residents of Mekelle city, Northern Ethiopia, community-based cross-sectional study.
Authors: Gebrehiwot Gebremedhin Gebreegziabiher , Belachew Tefera , Mehari Kibrti , Tamiru Dessalegn
Published: March 2020

Background: Metabolic Syndrome is becoming a big public health problem in developing countries like Ethiopia. The risk of dying from NCDs in low and lower-middle-income countries is almost two times that in high-income countries. NCDs account for 42% of deaths in Ethiopia. The trend of deaths due to NCD is increasing over time in Ethiopia. The objective of this study was to assess the magnitude of metabolic syndrome and its components among adult residents of Mekelle city.Method: a community-based cross-sectional study was conducted from July to September 2019 among adults aged 20 years and above in Mekelle city. Around 266 study participants were selected using a simple random sampling technique. Sociodemographic, lifestyle, anthropometric measurements, and blood biochemical tests were performed using WHO stepwise technique. Blood glucose and lipid profiles were determined after overnight fasting. The classification of metabolic syndrome was based on the international diabetic federation criteria. Descriptive statistics and logistic regression analysis were done using SPSS version 24.Result: the prevalence of Metabolic syndrome was 21.8%. Elevated waist circumference was the most prevalent metabolic syndrome component followed by hypertriglyceridemia, with a prevalence of 41.7% and 38.0% respectively. The prevalence of the remaining three components of MetS were also 33.8%, 32.7%, 21.4%, and 14.3% for systolic blood pressure, diastolic blood pressure, fasting blood glucose, and lower high-density lipoprotein cholesterol respectively. Age of 40 years and above, the highest rank of monthly income, blood cholesterol greater than 200mg/dl, waist to height ratio greater than 0.55, and walking at least 10 minutes daily were identified as significant predictors of metabolic syndrome.Conclusion : Adult residents of Mekelle city have a high magnitude of Metabolic syndrome and its components which may aggravate the risk of developing cardiovascular disease. This result emphasizes an urgent need for a public health strategy for preventive, early detection, and management of metabolic syndrome, and its individual components.
Improvement of therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet
Authors: Lee Yu Na , Yi Hye-Jin , Seo Eun Hye , Oh Jooyun , Lee Song , Ferber Sarah , Okano Teruo , Shim Inkyong , Kim Song Cheol
Published: March 2020

Background: Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheets formation could improve differentiation efficiency and graft survival.Methods: Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1 and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency were confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPCs suspension was injected by portal vein (PV), and IPCs sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation and hepatotoxicity with IPCs injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging.Results: Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. One and two weeks following IPC sheet transplantation, immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin.Conclusions: In conclusion, cell sheet formation enhanced the differentiation function and maturation of IPCs in vitro. Additionally, parameters for clinical application such as distribution, therapeutic efficacy, and toxicity were favorable. The cell sheet technique may be used with IPCs derived from various cell sources in clinical applications.
The Effect of a Telerehabilitation Virtual Reality Intervention on Functional Upper Limb Activities in People with Multiple Sclerosis: A Study Protocol for the TEAMS Pilot Randomized Controlled Trial
Authors: Kalron Alon , Achiron Anat , Pau Massimiliano , Cocco Eleonora
Published: March 2020

Background: Approximately 60% of people with multiple sclerosis (PwMS) suffer from upper limb dysfunction. Our primary goal is to implement a single-blind, randomized control trial (RCT) designed to compare the effectiveness of an 8-week home-based telerehab virtual reality (VR) program with conventional therapy in PwMS with manual dexterity difficulties. Secondary aims include: a) evaluating the impact of the programs on quality of life after the intervention and a follow up 1 month later; and b) evaluating the impact of the programs on adherence and satisfaction. Methods: Twenty-four PwMS will be recruited to the study which will be conducted at two established MS centers: (1) The Regional Center for Diagnosis and Treatment of Multiple Sclerosis, Binaghi Hospital, Cagliari, Italy; (2) The Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Israel. Participants will complete a total of three assessments focusing on upper limb functions. Both groups will receive 16 training sessions focusing on functional upper limb activities. The home-based telerehab VR intervention will comprise a custom-made software program running on a private computer or laptop. PwMS will perform several ADL functions associated with self-care, dressing and meal preparation. Conventional therapy will focus on task-related upper-limb treatments while in a sitting or prone position, indicative of the standard care in MS. Following 8-weeks of training, participants will complete a further outcome assessment. The same tests will be conducted 1 month (as a follow-up) after completion of the intervention. Discussion: The outcomes of this study have tremendous potential to improve the quality of evidence and informed decisions of functional upper limb activities in PwMS. If comparable results are found between the treatments in improving upper limb outcomes, this would suggest that PwMS can choose the program that best meets their personal needs, e.g., financial concerns, transportation or accessibility issues. Secondly, this information can be used by healthcare providers and medical professionals in developing upper limb exercise programs that will most likely succeed in PwMS.Trial registration: ClinicalTrials.gov NCT04032431. Registered on 19 July 2019.
A clinical randomized trial comparing T-tube drainage versus choledochojejunostomy in hepatolithiasis patients with sphincter of Oddi laxity: a study protocol (NCT04218669)
Authors: Chen Jiangming , Yan Xiyang , Zhu Tao , Chen Zixiang , Zhao Yijun , Xie Kun , Liu Fubao , Geng Xiaoping
Published: March 2020

Background: Residual and recurrent stones remain one of the most important challenges of hepatolithiasis and is reported in 20% to 50% of patients treated for this condition. To date, the two most common surgical procedures performed for hepatolithiasis are choledochojejunostomy and T-tube drainage for biliary drainage. The goal of the present study was to evaluate the therapeutic safety and perioperative and long-term outcomes of choledochojejunostomy versus T-tube drainage for hepatolithiasis patients with sphincter of Oddi laxity (SOL).Methods/Design: In total, 210 patients who met the following eligibility criteria were included and were randomized to the choledochojejunostomy arm or T-tube drainage arm in a 1:1 ratio: (1) diagnosed with hepatolithiasis with SOL during surgery, (2) underwent foci removal, stone extraction and stricture correction during the operation, (3) provided written informed consent, (4) was willing to complete a 3-year follow-up, and (5) aged between 18 and 70 years. The primary efficacy endpoint of the trial will be the incidence of biliary complications (stone recurrence; biliary stricture; cholangitis) during the 3 years after surgery. The secondary outcomes will be the surgical, perioperative and long-term follow-up outcomes.Discussion: This is a prospective, single-centre and randomized controlled two-group parallel trial designed to demonstrate which drainage method (Roux-en-Y hepaticojejunostomy or T-tube drainage) can better reduce biliary complications (stone recurrence; biliary stricture; cholangitis) in hepatolithiasis patients with SOL.Trial Registration: Clinical Trials.gov: NCT04218669; Registered January 6, 2020, https://clinicaltrials.gov/ct2/show/NCT04218669.
Peer Support During In Vivo Exposure Homework to Reverse Attrition from Prolonged Exposure Therapy for PTSD: Description of a Randomized Controlled Trial
Authors: Hernandez-Tejada Melba , Muzzy Wendy , Price Matthew , Hamski Stephanie , Hart Stephanie , Foa Edna , Acierno Ron
Published: March 2020

BackgroundEffective treatments for posttraumatic stress disorder (PTSD) (e.g., Prolonged Exposure (PE); Cognitive Processing Therapy (CPT)) exist and are widely adopted by the Departments of Veterans Affairs (VA) and Defense (DoD). Unfortunately, dropout from these treatments regularly exceeds 30%. However, in a recent survey of patients who dropped out of PE, approximately half indicated a greater likelihood of completion if a peer who had completed treatment were available to help with the in vivo exposure homework.MethodsWe will use a between-groups randomized controlled design with repeated assessment at baseline, post treatment, and 3- and 6-month follow-up across measures of PTSD, depression, and functioning with 150 veterans who have indicated they intend to drop out of treatment. Participants will be randomly assigned to one of two PE + peer support conditions: (1) a peer will offer support directly during in vivo exposure homework for 3-4 weeks; vs (2) a peer will call weekly for 3-4 weeks to offer general support and to check in on treatment progress.DiscussionThe present study was designed to test the hypothesis that dropout from exposure-based PTSD treatment may be mitigated by using peers as support agents directly during PE's in vivo homework experiences. Specifically, we intend to determine: whether patients who have dropped out of PE and are offered the ‘in vivo peer’ adjunctive component to PE therapy will a) return and complete treatment and b) evince reduced PTSD symptomatology, compared to the same PE treatment, but with general peer support more reflective of current VA practices.Trial registrationThis study protocol is approved and information is available on ClinicalTrials.gov under the number NCT03485391. Registered on April 2, 2018.
An antibiotic stewardship programme to reduce inappropriate antibiotic prescribing for acute respiratory infections in rural Chinese primary care facilities: study protocol for a clustered randomised controlled trial
Authors: Zhuo Chao , Wei Xiaolin , Zhang Zhitong , Hicks Joseph Paul , Zheng Jinkun , Chen Zhixu , Haldane Victoria , Walley John , Guan Yubao , Xu Hongyan , Zhong Nanshan
Published: March 2020

Background: Inappropriate prescribing of antibiotics for acute respiratory infections at primary care level represents the major source of antibiotic misuse in healthcare, and is a major driver for antimicrobial resistance worldwide. In this study we will develop, pilot and evaluate the effectiveness of a comprehensive antibiotic stewardship programme in China’s primary care hospitals to reduce inappropriate prescribing of antibiotics for acute respiratory infections among all ages.Methods: We will use a parallel-group, cluster-randomised, controlled, superiority trial with blinded outcome evaluation but unblinded treatment (providers and patients). We will randomise 34 primary care hospitals from two counties within Guangdong province into the intervention and control arm (1:1 overall ratio) stratified by county (8:9 within-county ratio). In the control arm, antibiotic prescribing and management will continue through usual care. In the intervention arm, we will implement an antibiotic stewardship programme targeting family physicians and patients/caregivers. The family physician components include: 1) training using new operational guidelines, 2) improved management and peer-review of antibiotic prescribing, 3) improved electronic medical records and smart phone app facilitation. The patient/caregiver component involves patient education via family physicians, leaflets and videos. The primary outcome is the proportion of prescriptions for acute respiratory infections (excluding pneumonia) that contain any antibiotic(s). Secondary outcomes will address how frequently specific classes of antibiotics are prescribed, how frequently key non-antibiotic alternatives are prescribed and the costs of consultations. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and a long-term benefit evaluation. The duration of the intervention will be 12 months, with another 24 months post-trial long-term follow-up.Discussion: Our study is one of the first trials to evaluate the effect of an antibiotic stewardship programme in primary care settings in a low- or middle-income country (LMIC). All intervention activities will be designed to be embedded into routine primary care with strong local ownership. Through the trial we intend to impact on clinical practice and national policy in antibiotic prescription for primary care facilities in rural China and other LMICs.Trial registration: ISRCTN, ISRCTN96892547. Registered 18 August 2019, http://www.isrctn.com/ISRCTN96892547
Elevated neurofilament light chain in plasma is associated with reduced right hippocampal and amygdala volume in Alzheimer's patients
Authors: Li Wei , Yue Ling , Wu Ye , Sun Lin , Xiao Shifu
Published: March 2020

Background

Plasma neurofilament light (NfL) levels have been considered as an especially promising biomarker for dementia, however, the mechanism of NfL regulating cognition is not very clear.

Methods

43 amnesic mild cognitive impairment(aMCI), 35 Alzheimer’s disease (AD) and 30 cognitively normal subjects were recruited. Plasma NfL levels were examined by the Single Molecule array (Simoa) technique; the volumes of the hippocampus and amygdala were calculated and compared by T1-weighted MRI; and cognitive function was assessed by the Beijing version of the Montreal Cognitive Assessment (MoCA)

Results

Our results showed significantly increased plasma NfL levels in AD group (29.42 pg/ml) compared to aMCI(15.92 pg/ml) group and normal (12.85 pg/ml) group (both p < 0.001), while there was no statistical difference (p>0.05) between aMCI group and normal group. And the results of partial correlation analysis showed that plasma NfL levels were negatively correlated (p<0.05)with MoCA total score (r=-0.415, p=0.013), right hippocampal volume(r=-0.335,p=0.036) and right amygdala volume(r=-0.337, p=0.048).

Conclusions

NfL in plasma of AD patients is significantly increased, and the protein is related to atrophy of right hippocampus and right amygdala.
Cancer-associated fibroblasts-derived exosomes suppresses immune cell function in breast cancer via miR-92/PD-L1 pathway
Authors: Dou Dongwei , Ren Xiaoyang , Han Mingli , Xu Xiaodong , Ge Xin , Gu Yuanting , Wang Xingxing
Published: March 2020

Background Cancer associated fibroblasts (CAF) are important component in tumor microenvironment and has been reported contributes to tumor progression through many mechanisms, however, the detailed mechanism underling immune-suppression effect are not clearly defined. Methods In this study, human breast cancer-derived cancer associated fibroblasts was cultured, and CAF-derived exosomes in culture medium was isolated. Cancer cell migration was evaluated by transwell and wound healing assay, miR-92 binding to the LATS2 3’ untranslated region was validated by luciferase report assay, and underlying mechanism was investigated by chromatin immunoprecipitation and Immunoprecipitation. Results After treatment by CAF-derived exosomes, breast cancer cells express higher PD-L1, accompanied with increased miR-92 expression. Increased PD-L1 expression which induced by CAF- derived exosomes significantly promotes apoptosis and impaired proliferation of T cell. proliferation and migration of breast cancer cells was increased after transfection of miR-92, LATS2 was recognized as target gene of miR-92, which was proved by luciferase assay. Immunoprecipitation (IP) shown that LATS2 can interact with YAP1, after nuclear translocation, YAP1 could binds to enhancer region of PD-L1 to promotes transcription activity, which was confirmed by chromatin immunoprecipitation (ChIP). Furthermore, animal study confirmed that cancer associated fibroblasts significantly promotes tumor progression and impaired function of tumor infiltrated immune cells in vivo. Conclusion Our data revealed a novel mechanism which can induce immune suppression in tumor microenvironment.
Psychological status of health care workers during the outbreak of Coronavirus disease in China: a cross-sectional study
Authors: Song Xiangrui , Ni Chunyan , Cai Wenpeng , Hou Tianya , Lian Bin , Chen Aibin , Yin Qianlan , Deng Guanghui , Li Huifen
Published: March 2020

Background: Following the outbreak of Coronavirus disease (COVID-19) in Wuhan, China, thousands of health care workers (HCWs) joined in the battle to prevent epidemic. The purposes of this study were to assess the psychological status of health care workers fighting against COVID-19 and compared their status with non-health care workers.Methods: 1521 participants were invited to complete a cross-sectional survey which consisted of a demographic questionnaire, the symptom checklist-90 (SCL-90), the Connor-Davidson Resilience scale (CD-RISC) and Chinese-Version Social support revalued scale (SSRS). SCL-90 was used as a measure of psychological status, CD-RISC was used as a measure of resilience and SSRS was used as a measure of social support. All analyses were completed by SPSS21.0 and two-tailed with significance defined as p <0.05.Results: HCWs showed higher level of obsessive-compulsive symptoms ( p = 0.002), depression ( p =0.011), anxiety ( p = 0.037) and had lower level of subjective support ( p <0.001) as well as strength ( p =0.012). Compared with those who working in other hospital departments, HＣＷｓ working in internal medicine department had high level of obsessive-compulsive, anxiety and interpersonal sensitivity, they also had low level of social support and resilience.Conclusions: HCWs were vulnerable to mental disorders, and health organizations and government should initiate psychological assistant program to keep them immune to mental disorders. HCWs who working in internal medicine department (IMD) were supposed to rebuild their resilience, social support systems, confidence and job satisfaction under the guidance of psychologists.
A comparison between body mass index and waist circumference for identifying continuous metabolic syndrome risk score components in school-aged children using a structural equation modeling approach: the CASPIAN-V study
Authors: Ejtahed Hanieh-Sadat , Mahmoodi Zohre , qorbani mostafa , Angoorani Pooneh , Motlagh Mohammad Esmaeil , Hasani-Ranjbar Shirin , Endocrinologist Hasan Ziaodini , Taheri Majzoubeh , Heshmat Ramin , Kelishadi Roya
Published: March 2020

Background The purpose of this study was to investigate the association of anthropometric measures with continuous metabolic syndrome (cMetS) risk score components in a large population-based sample of children and adolescents using a path analysis. Methods This multi-centric study was performed on 3843 students aged 7-18 years who were selected by multistage, stratified cluster sampling method from 30 provinces of Iran. Demographic, anthropometric and biochemical factors were obtained and standardized residuals ( z -scores) were calculated for MetS components. A structural equation modeling approach was applied to evaluate the relationships among the study variables and to implement the subsequent structural modeling. Results The mean age of participants (52.3% boys) was 12.4±3.05 years. Standardized scores of body mass index (ZBMI) and waist circumference (ZWC) had a direct effect on standardized scores of mean arterial pressure (ZMAP) (0.23 and 0.24 in boys and 0.22 and 0.23 in girls; respectively) and triglyceride (ZTG) (0.07 and 0.04 in boys and 0.02 and 0.06 in girls; respectively), but the effect of ZWC was stronger than ZBMI on these variables. Age, socioeconomic status and sedentary behaviors showed a positive direct effect on ZWC (0.01, 0.05 and 0.07 in boys and 0.05, 0.08 and 0.002 in girls; respectively). These variables induced indirect effects on cMets risk score components through ZWC. Conclusions The magnitude of association between WC and continuous metabolic syndrome risk score components was higher compared with BMI in school-aged children, emphasizing on paying more attention to central obesity in childhood.