bluuebunny/crossref_metadata_2025 huggingface dataset:
Think-aloud usability testing of an app to increase physical activity
Authors: Fischer Tillmann , Reinhardt Gesine , Stumpf Paul , Schwarz Peter E.H. , Harst Lorenz
Published: December 2019

Background Insufficient physical activity is one of the most important risk factors for non-communicable diseases and should therefore be intensively prevented in all age groups. According to several trials, activity can be effectively increased by smartphone-based interventions. However, the use of digital applications depends on many factors such as user acceptance and intuitive operability. Therefore, usability testing has proven to be important for the successful development of digital interventions. Thus, the German app “VIDEA bewegt” was tested for its usability in order to assess strengths and weaknesses and to improve the app. Methods In April 2019, ten interviews were conducted using the think-aloud method and following a standardised protocol. The adult participants were confronted with “VIDEA bewegt” for the first time and had to perform pre-defined tasks covering the main features of the app. Demographics of the participants and their expectations towards the app were collected. The interviews were recorded and transcribed. The analysis of the transcripts was performed independently by two team members following the deductive qualitative content analysis according to Mayring. Results The app was rated positively in terms of design, basic registration process and the largely self-explanatory navigation. Users missed an explanation of the basic structure and included components of the programme. Several usability problems were described, including technical errors and problems with understanding individual control elements. Four of ten participants could imagine using the app in the future. Conclusions All test participants were able to use the app independently to a large extent and most of the a priori defined goals were achieved successfully. With certain minor changes, the usability can therefore be assessed as good. Trial registration The performed usability test is the basis of a study named “Evaluation of an app-based activity intervention for statutory health insured people” which is registered in the German Clinical Trials Register (DRKS). DRKS-ID: DRKS00017392 (14 June 2019)
Enhanced antitumor efficacy on colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perﬂuorocarbon
Authors: Wu pingping , Zhou Qing , Zhu Huayun , Zhuang Yan , Bao Jun
Published: December 2019

Background: Recurrence and metastasis are the shortcomings of the clinical treatment of colon cancer. Finding an efficacy strategy for the treatment of colon cancer is important. In recent years, poly lactic-co-glycolic acid (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. This study aimed to design a dual-loaded nanoparticles drug delivery system to overcome the limitations of chemotherapeutic drugs in colon cancer therapy. Methods: We developed epidermal growth factor (EGF) functionalized poly PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perﬂuorocarbon (PFC) (EGF-PLGA@5Fu/PFC NPs) for target therapy of colon cancer. EGF-PLGA@5Fu /PFC NPs were estimated by morphology, size distribution, in vitro stability and release profile. CCK-8, Hoechst33342 staining and flow cytometry assays were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Results: We found that EGF-PLGA@5Fu/PFC NPs had an average size of 200 nm with a 5Fu-loading efficiency of 7.29%. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs in colon cancer cells. EGF-PLGA@5Fu/PFC NPs were found to have the best efficiency on cell viability suppression and apoptosis induction in SW620 colon cancer cells. In xenograft mice, EGF-PLGA@5Fu/PFC NPs had the best suppressive effects on tumor growth compared with 5Fu, PLGA@5Fu and PLGA@5Fu/PFC NPs. The results of histopathological analysis further indicated that EGF-targeted NPs were the most efficient on tumor growth inhibition. Mechanically, the data demonstrated the improved therapeutic outcomes were owing to the fact that PFC relieved tumor hypoxia via transporting oxygen to the tumor. Conclusions: We creatively constructed a biocompatible nanodrug delivery system and functionalized nanoparticles might provide new potential for selective delivery of chemotherapy drugs to cancers.
Cell-division pattern and phylogenetic position of a new ciliate genus Parasincirra n. g. (Protista, Ciliophora, Hypotrichia), with report of a new soil species, P. sinica n. sp. found from northwest China
Authors: Ma Jiyang , Zhao Yan , Zhang Tengyue , Shao Chen , Al-Rasheid Khaled A.S. , Song Weibo
Published: December 2019

Ciliated species, unicellular eukaryotes, are extremely diverse and occupy a very broad spectrum of ecological niches. Even though there is a growing recognition that enormous ciliates associates with key ecosystem processes in different niches, their diversity is not well understood. One reason is that ciliates are very tiny and may often be overlooked in routine biodiversity survey. Furthermore, the morphological and genetic diversity of ciliates per se is vast and dwarfs that among other multicellular eukaryotes. Here, we present the study of a new stichotrichid ciliate, Parasincirra sinica n. g., n. sp. based on classical living morphology, infraciliature, ontogenesis analyses and a comprehensive phylogenetic study, and enhance understanding of ciliates diversity in sludge soil.
This new, monotypic genus is defined by having a bipartite adoral zone of membranelles, three frontal cirri, an amphisiellid median cirral row about as long as, or slightly longer than, the adoral zone, one short frontoventral cirral row, cirrus III/2 and transverse cirri present, buccal cirrus and caudal cirri absent, three dorsal kineties. The main morphogenetic features are: (1) five frontoventral-transverse cirral anlagen (excluding undulating membranes anlage) are formed in primary mode; (2) the amphisiellid median cirral row is formed by anlagen V and VI, while the frontoventral row is generated from anlage IV; (3) cirral streaks IV to VI generate one transverse cirrus each; (4) frontoventral-transverse cirral anlage II generates one or two cirri, while the posterior one will be absorbed in late stages, that is, no buccal cirrus is formed; (5) the posterior part of the parental adoral zone of membranelles is renewed; (6) dorsal morphogenesis follows a typical Gonostomum -pattern. Based on the SSU rDNA information, analyses of the phylogenetic relationship inferred from Bayesian inference and maximum likelihood analyses were unable to outline the exact position of this new form among some other species of related genera which are generally assigned in the family Amphisiellida . The morphological/ morphogenetical differences between the new genus/species and Uroleptoides / Parabistichella , as well as other amphisiellids, clearly support the validity of the establishment of this new genus Parasincirra .
P2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis
Authors: Wen Ruoxue , Shen Hui , Huang Shuxian , Wang Liping , Li Zongwei , Peng Peng , Mamtilahun Muyassar , Tang Yaohui , Shen Fanxia , Tian Heng-Li , Yang Guo-Yuan , Zhang Zhijun
Published: December 2019

The authors have withdrawn this preprint from Research Square
Incidence and predictive factors of diaphragmatic dysfunction in acute stroke.
Authors: Catalá-Ripoll Jose Vicente , Monsalve-Naharro Jose Ángel , Hernández-Fernández Francisco
Published: December 2019

The authors have withdrawn this preprint from Research Square
Comprehensive utilization of Aspergillus niger mycelium waste from citric acid fermentation on the basis of steam explosion and ionic liquid pretreatment
Authors: Ma Qinyuan , Gao Xiuzhen , Bi Xinyu , Xia Menglei , Han Qi , Peng Mingmeng , Tu Linna , Yang Yupeng , Shen Yanbing , wang min
Published: December 2019

Background Aspergillus niger mycelium waste, a by-product from citric acid fermentation is considered a good raw material to produce fungal chitosan and glucosamine (GlcN). However, its successful application has always been a challenge.Results In this work, the effects of combined pretreatment involving steam explosion and ionic liquid (IL) on mycelium waste were investigated. Results show that pretreatment of mycelium waste at 2.5 MPa for 1 min improved the GlcN hydrochloride yield by 65.49%, the release of soluble sugar reached 0.46 g/g of sample, and the deacelation degree of fungal chitosan by hydrolysis of chitin deacetylase from Rhodococcus equi CGMCC14861 (ReCDA) was from scratch and a 1.3-fold increase by combined with IL pretreatment. In addition, a recycling strategy for by-products, which promoted the fermentation of ReCDA used for fungal chitosan, was efficiently developed.Conclusion This is the first report of comprehensive utilization of Aspergillus niger mycelium waste from citric acid fermentation on the basis of steam explosion and ionic liquid pretreatment. This study demonstrates a green-like technology for the comprehensive utilization of A. niger mycelium waste from citric acid fermentation.
Blood pressure and risk of cognitive impairment. The role of vascular disease in neurodegeneration.
Authors: Carmona-Abellan Mar , Trzeciak Malwina , Recio-Fernandez Miriam , Echeveste Beatriz , Imaz Laura , Luquin-Piudo Rosario , Riverol Mario
Published: December 2019

Background: Both cerebral vascular disorders and cognitive decline increase in incidence with age. The role of cerebral vascular disease and hemodynamic changes in the development of cognitive deficits is controversial. The objective of this study was to assess cardiovascular response during cardiac stress testing in neurologically asymptomatic individuals who developed cognitive impairment several years after the cardiac stress testing.Methods: This is a retrospective cohort study of patients who underwent cardiac stress testing between January 2001 and December 2010. Patients were followed up until May 2015 and we selected those who developed cognitive dysfunction including dementia, mild cognitive impairment and subjective cognitive decline, after the stress test. Heart rate and blood pressure both at rest and at peak exercise and the mean R-R interval at rest were recorded. For each patient who developed cognitive impairment, we selected one matched control who did not show cognitive decline by the end of the follow-up period.Results: From this cohort of 7224 patients, 371 developed cognitive impairment; of these, 186 (124 men) met the inclusion criteria and 186 of the other patients were selected as matched controls. During follow-up, cognitive impairment appeared 6.2 ± 4.7 years after the cardiac stress test. These patients who subsequently developed cognitive impairment had significantly lower at-rest systolic, diastolic and mean blood pressure than controls (p<0.05). Further, compared with controls, their maximum heart rate was significantly higher at peak exercise and both systolic and diastolic blood pressures increased significantly more during exercise. Conclusion: The results from this study suggest that differences in cardiovascular response to stress are present in the preclinical phase of cognitive decline, serving as a potential risk factor for cognitive impairment. These findings challenge the potential use of blood pressure and heart rate variability at rest and during cardiac stress assessment as a risk factor for cognitive impairment.
Extended spectrum β-lactamase (ESBL)-producing Escherichia coli inactivation by UVA-LED irradiation system in a Japanese hospital
Authors: Ulfa Maria , Azuma Momoyo , Sato Masami , Shimohata Takaaki , Fukushima Shiho , Kido Junko , Nakamoto Mariko , Uebanso Takashi , Mawatari Kazuaki , Emoto Takahiro , Akutagawa Masatake , Kinouchi Yohsuke , Takahashi Akira
Published: December 2019

Background: The prevalence of extended spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing rapidlyand spreading worldwide, particularly in Asia compared to other regions. In the last 10 years, in our hospital, in particular, there has been <30% increase. To prevent the spread of ESBL in hospitals and in the community, the ultraviolet (UV) A-light-emitting diode (LED) irradiation device was used to inactivate ESBL- E. coli in human livestock and the environment . Methods: ESBL- E. coli and E. coli bacterial samples were collected from patients at Tokushima University Hospital (Tokushima City, Japan). The UVA-LED irradiation system had 365 nm single wavelength, and the current of the circuit was set to 0.23 or 0.50 A consistently. Results: Results demonstrated that UVA-LED was useful for the inactivation of ESBL- E. coli and E. coli . The minimum energy dosage required to inactivate ESBL- E. coli and E. coli was 40.75 J/cm 2 (45 min) in the first type of UVA-LED and 38.85 J/cm 2 (5 min) in the second type. There were no significant differences between ESBL- E. coli and E. coli . The inactivation of ESBL- E. coli was dependent on energy. Conclusions: These findings suggest that UVA-LED with 365 nm single wavelength could be useful for surface decontamination in healthcare facilities.
Wealth and unintended pregnancy in Ghana: Analysis of 2014 Ghana Demographic and Health Survey
Authors: Paintsil Jones Arkoh , Ameyaw Edward Kwabena
Published: December 2019

Background: Pregnancy intention is a critical factor for both short and long term maternal and 27 child health outcomes. Some evidence show that wealth status has varying implications on 28 unintended pregnancy. In this study, we investigated wealth and unintended pregnancy among 29 women of reproductive age in Ghana. 30Methods: Our descriptive analysis comprised calculation of wealth status and unintended 31 pregnancy. The same calculation was done for socio-demographic characteristics and 32 unintended pregnancy. Due to the binary nature of the outcome variable (unintended 33 pregnancy), Binary Logistic Model was used for the inferential analysis. The first model 34 (Model I), constituted wealth quintile and unintended pregnancy. The second model (Model II) 35 was developed by adjusting for five key socio-demographic variables. 36Results: Women in the richest wealth quintile had less likelihood of experiencing unintended 37 pregnancy (OR=0.740, CI=0.42-1.28). Considering women aged 15-19 as the reference 38 category, women in all other age categories had less likelihood of unintended pregnancy 39 especially those aged 45-49 (AOR=0.26, CI=0.04-1.58). The findings revealed that those who 40 listened to radio at least once a week (AOR=0.56, CI=0.36-0.89) were less probable to report 41 unintended pregnancy, having those not listening to radio at all as the reference category. 42 Women in urban settings were less likely to have unintended pregnancies (AOR=0.74, 43 CI=0.46-1.19). 44Conclusions: This study has indicated that unintended pregnancy to larger extent is poverty 45 driven. The study suggests that the mass media, particularly radio, is valuable in 46 communicating birth control measures and messages on unintended pregnancies. Efforts to 47 halt unintended pregnancies must target poor women, especially those in the rural locations.
The efficiency and safety of recombinant factor VIIa for bleeding in patients without haemophilia: a meta-analysis of 12 randomized controlled trials
Authors: Zhang Ying , Wang Yuting , Zhou Youfa , Li Jian , Zhou Haiyan
Published: December 2019

Background: Recombinant factor VIIa (rFVIIa) is widely used for off-label indications to control bleeding and reduce blood transfusion. However, the efficacy and safety of rFVIIa for bleeding in patients without haemophilia are uncertain and worthy of further study. This meta-analysis has been updated to incorporate recent trial data.Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, EMBASE and other medical databases up to 20 July 2019. The results of this work are synthetized and reported in accordance with the PRISMA statement.Results: Twelve trials met our inclusion criteria. High dose rFVIIa reduced the requirements of red cell transfusion (mean difference [MD], -232.34; 95% confidence interval [CI]; -448.33 to 234.89). rFVIIa did not significantly affect mortality (relative risk[RR], 1.00;95%CI, 0.82–1.21), total thromboembolic events (RR, 1.13; 95%CI, 0.94–1.36), myocardial infarction (RR, 1.37; 95%CI, 0.92–2.05), deep vein thrombosis (RR, 0.83; 95%CI, 0.52–1.33), ICU-stay (RR, 0.40; 95%CI, -1.28 to 2.07) and numbers of patients for red cell transfusion (RR, 0.94; 95%CI, 0.83-1.08). However, it may increase the incidence of arterial events (RR, 1.38; 95%CI, 1.08–1.77).Conclusion: High dose rFVIIa is effective to reduce the need of red cell transfusion for bleeding in patients without haemophilia. However, it may increase the risk of arterial events.
Effects of Ultrasound-Guided Paravertebral Block on MMP-9 and Postoperative Pain in Patients Undergoing VATS Lobectomy: A Randomized, Controlled Clinical Trial
Authors: Chu Haichen , Dong He , Wang Yongjie , Niu Zejun
Published: December 2019

Background: Local anesthesia can reduce the response to surgical stress and decrease the consumption of opioids, which may reduce immunosuppression and potentially delay postoperative tumor recurrence. We compared paravertebral block(PVB) combined with general anesthesia(GA) and general anesthesia regarding their effects on matrix metalloproteinase-9 (MMP-9) and postoperative pain after video-assisted thoracoscopic surgery(VATS) lobectomy.Methods: 54 patients undergoing elective VATS lobectomy at a single tertiary care, teaching hospital located in Qingdao between May 2 2018 and Sep 28 2018 were randomised by computer to either paravertebral block combined with general anesthesia or general anesthesia. The primary outcome was pain scores during postoperative 48h. The secondary outcome were plasma concentrations of MMP-9, complications, and duration of postoperative hospital stay. Results: 75 were enrolled to the study, of whom 21 were excluded before surgery. We analyzed lobectomy patients undergoing paravertebral block combined with general anesthesia (n=25) or general anesthesia (n=24). Both groups were similar regarding baseline characteristics. Pain scores were lower at 4h and 24h in PVB/GA group, compared with GA group (2.53±0.83 vs 3.4±0.91; 2.2±0.94 vs 3.0±0.93, respectively, P<0.05). There were no difference at 1h and 48h between groups. Patients in the PVB/GA group showed a greater decrease in plasma MMP-9 level at T1 and T2 after VATS lobectomy (P<0.05). Postoperative complications and length of stay did not differ by anesthetic technique.Conclusions: The paravertebral block/general anesthesia can provide statistically better pain relief and attenuate MMP-9 response to surgery and after VATS lobectomy. This technique may be beneficial for patients to recover rapidly after lung surgery and reduce postoperative tumor recurrence.
Impact of embryo biopsy stage on implantation potential in thalassemias: a propensity score matching study
Authors: Wang Yizi , Ding Chenhui , Lu Baomin , Zeng Yanhong , Liu Xinyan , Zhou Canquan , Xu Yanwen
Published: December 2019

Objective: To investigate the impact of biopsy stage on implantation potential of frozen-warmed blastocysts in pre-implantation genetic testing (PGT) cycles for those with thalassemias.Design: Retrospective paired cohort study using propensity score matching (PSM). A time-to-event analysis of Fine-Gray’s analysis was used to compare cumulative live birth rate (CLBR).Setting: Single university-affiliated center .Patient(s): A total of 439 PGT couples were included who underwent PGT for thalassemias between 2015 and 2017.Intervention(s): Two biopsy strategies were evaluated; cleavage-stage biopsy (CB) and blastocyst-stage biopsy (BB).Main Outcome Measure(s): Implantation rate and CLBR.Result(s): A total of 202 ovum pick-up (OPU) cycles from Group CB and 237 OPU cycles from Group BB were included. PSM was conducted for two groups covering characteristics on the OPU cycle and the first frozen-warmed blastocyst transfer (FWBT) cycle , resulting in 140 matched pairs. The implantation rate was significantly lower in the CB group (41.0%, 30.3%, 20.4% in 1st, 2nd and 3rd FWBT cycle respectively, weighted mean 34.2%) than those in the BB group (51.8%, 43.5%, and 40.5% (weighted mean 48.1%), respectively; at P = 0.044, 0.047, 0.039). This was a 28.9% relative reduction ( P = 0.002). The CLBR across three FWBT cycles was significantly higher in the BB group compared with the CB group (80.0% vs. 62.1%, P = 0.032), while the likelihood of LBR was 1.21-fold higher after regression adjustment. Conclusion(s): Cleavage-stage biopsy may partially affect the implantation potential and CLBRs of frozen-warmed blastocysts, compared with blastocyst stage biopsy.
Comparative genomic analysis reveals metabolic mechanisms for Kluyveromyces marxianus’ fast growth during evolution
Authors: Mo Wenjuan , Ren Haiyan , Yang Xianmei , Luo Tongyu , Lu Wanlin , Zhou Jungang , Yu Yao , Qi Ji , Lv Hong
Published: December 2019

Background Using yeast fermentation to produce bioethanol, is an economic and renewable way to tackle the rapid increase in fuel consumption. Faster cell growth rate guarantees the superior result of fermentation course. The “non-conventional” yeast Kluyveromyces marxianus is the known fastest-growing eukaryote on the earth. Although its wide application in industry, the molecular mechanisms for its fast growth have seldom been discovered.Results We first carried out a comparative genome content analysis for K. marxianus evolution in Saccharomycetaceae and identified the gain/lost genes as well as highly copied genes during K. marxianus speciation. Then RNA-seq analyses for K. marxianus and S. cerevisiae at different time points along cultivation were performed, to infer the function of K. marxianus-specific genes and to find out the difference in homologous gene expression patterns between the two species. RNA-seq results were further validated with RT-qPCR analysis. Genome content analysis shows the highly intense events of genes’ gain/loss happened at the occurrence of Saccharomycetaceae and Kluyveromyces, and K. marxianus has particularly high copy numbers of genes participating in iron transport and biotin biosynthesis. The RNA-seq analysis reveals 40% of K. marxianus-specific genes were up-regulated and may participate in glucose transport and mitochondrial function. Furthermore, compared to S. cerevisiae, K. marxianus has developed two features in homologous gene expressions to ensure its fast growth: (1) enhanced fundamental expressions of TCA cycle and respiratory chain genes at the beginning of cultivation; (2) tightly co-up-regulated expressions of respiratory chain, F0F1 ATPase, and glucose transporter genes at its fastest growth phase. Those co-expressions are mainly ascribed to the higher number of significant motifs in the upstream sequences of involved genes in K. marxianus than in S. cerevisiae, indicating the importance of transcriptional network remodelling during evolution.Conclusions This study gives insights into the possible mechanisms of K. marxianus’ fast growth trait, via efficiently supplying sufficient energy for cell growth, meanwhile reinforcing glucose transport to guarantee the competition for environmental resources. Our findings present a theoretical support for K. marxianus’ prospective application in industry, and give clues for further rational construction of fast-growing yeast strains.
NLRP3 maintains healthy pericytes in the brain
Authors: Quan Wenqiang , Luo Qinghua , Tang Qiqiang , Furihata Tomomi , Li Dong , Fassbender Klaus , Liu Yang
Published: December 2019

Background Pericytes regulate structure and function of cerebral capillaries. Growing evidence shows that pericytes are damaged in the brain of Alzheimer’s disease (AD), which potentially contributes to AD pathogenesis. NLRP3-contained inflammasome is activated in AD brain and considered as a promising target for therapy. However, how NLRP3 affects brain pericytes is unclear. In our study, we investigated physiological function of NLRP3 in pericytes. Methods Immunohistological methods and Western blot were used to investigate pericytes and vasculature in the brains of 9-month-old NLRP3-deficient and wild-type littermate mice. Pericytes were also cultured and treated with NLRP3 inhibitor, recombinant IL-1β and AKT inhibitor. Then, proliferation, apoptosis and expression of PDGFRβ and CD13 in pericytes were analysed with biochemical methods. To investigate underlying molecular mechanisms, phosphorylation of protein kinases such as AKT, ERK and NF- k B were quantified. Results We observed that NLRP3 deficiency reduced the coverage of PDGFRβ-positive pericytes and collagen type IV-immunereactive vasculature in the brain. NLRP3 deficiency was also shown to decrease PDGFRβ and CD13 proteins in isolated cerebral microvessels. In cultured pericytes, inhibition of NLRP3 with MCC950 attenuated cell proliferation but did not induce apoptosis. NLRP3 inhibition also decreased protein levels of PDGFRβ and CD13. On the contrary, treatments with IL-1β increased protein levels of PDGFRβ and CD13 in pericytes. The alteration of PDGFRβ and CD13 protein levels was correlated with phosphorylation of AKT. Inhibition of AKT reduced PDGFRβ and CD13 in cultured pericytes. Conclusions NLRP3 might be essential to maintain healthy pericytes in the brain through activating AKT. Adverse effects on brain pericytes should be considered in the possible clinical therapies with NLRP3 inhibitors.
Sevoflurane preconditioning reduces brain inflammation after experimental stroke by enhancing glycogen synthesis kinase-3 β/ nuclear factor erythroid 2-related factor - dependent microglial M2 polarization
Authors: Cai Min , Sun Sisi , Wang Shiquan , Dong Beibei , Tian Li , Dong Hailong , Hou Wugang
Published: December 2019

Background: Sevoflurane preconditioning (SPC) results in cerebral ischemic tolerance; however, the mechanism remains unclear. In current study, we aimed to assess the M1/M2 shift in the brain induced by SPC and whether glycogen synthesis kinase-3β (GSK-3β)-regulated nuclear factor erythroid 2-related factor (Nrf2) activation was involved in the M2 polarization mediated by SPC. Methods: Mouse primary microglia with SPC were challenged by oxygen-glucose deprivation (OGD) or lipopolysaccharide (LPS), and mice with SPC were subjected to middle cerebral artery occlusion (MCAO). Then, the mRNA and protein levels of proinflammatory/anti-inflammatory factors were analysed. GSK-3β phosphorylation and Nrf2 nuclear translocation were measured. The mRNA and protein expression of proinflammatory/anti-inflammatory factors, neurological scores, infarct volume, cellular apoptosis, the proportion of M1/M2-positive cells, and the generation of super-oxidants were examined after SPC or GSK-3β inhibitor TDZD treatment with or without Nrf2 deficiency. Results: SPC promoted M2 phenotype polarization both in vitro and in vivo . GSK-3β phosphorylation at Ser9 was increased after SPC. Both SPC and TDZD administration enhanced Nrf2 nuclear translocation, promoted M2 phenotype polarization and elicited a neuroprotective effect. Nrf2 deficiency abolished the promoted M2 polarization and ischemic tolerance induced by TDZD treatment. The reduced percentage of M1-positive cells and super-oxidants generation induced by SFC or TDZD was also reversed by Nrf2 knockdown. Conclusions: Our results indicated that SPC exerts brain ischemic tolerance and enhances M2 polarization by GSK-3β-dependent Nrf2 activation, which provides a novel mechanism for SPC-induced neuroprotection.
Complications rate and risk factors in unplanned reoperation of degenerative lumbar spondylolisthesis in geriatric patients: a retrospective single-center cohort study of 33 patients
Authors: Zhong Weiyang , Liang Xinjie , Luo Xiaoji , Huang Tianji , Quan Zhengxue
Published: December 2019

Background: The study aimed to investigate the complications rate and risk factors in unplanned reoperation among geriatric patients who underwent posterior lumbar fusion(PLF) for degenerative lumbar spondylolisthesis(DLS).Methods: 1100 DLS patients who were older than 60 years were reviewed from January 2006 to December 2016 and 33 patients underwent unplanned reoperations who were analyzed and divided to two groups(Group A: posteriolateral fusion, Group B: intervertebral fusion). Gender, body mass index (BMI), radiographic data and clinical outcomes data were analyzed to evaluate complications rate and the risk factors for unplanned reoperations.Results: 33 patients were performed by the unplanned reoperations(3%).The patients were followed up for an average of 4.20±2.25 years (Group A)and 4.32±2.54 years(Group B)without significant difference. The significant difference was found in mean age, levels involved levels, hospital stay, surgery time, blood loss between the groups. The causes of unplanned operation were: wound infection, screw misplacement, neurological deficit, nonunion, screw fracture which were significant except the wound infection between the groups. Higher BMI (obesity), diabetes mellitus(DM), more bleeding and gender(female) were the risk factors of the complications. The cases of the screw misplacement, neurological deficit, nonunion and screw fracture in group A were more significantly than in group B.Conclusion: The patients of higher BMI, DM, age, posteriolateral fusion, female predicted higher incidence of unplanned reoperations. The spine surgeons maybe need to pay more attention in their preoperative training and in improving surgical technique which could reduce the reoperation rate.
Value of digital mammography in predicting lymphovascular invasion of breast cancer
Authors: Liu Zhuangsheng , Li Xiaoping , Liang Keming , Chen Junhao , Chen Xiangmeng , Li Ruqiong , Li Ronggang , Zhang Xin , Yi Lilei , Long Wansheng
Published: December 2019

Background: To use digital mammography, a more popular imaging tool, for predicting lymphovascular invasion(LVI) in breast cancer patients preoperatively.Methods: 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018 were collected, which were divided into positive group (n=42) and negative group (n=80) according to the presence or absence of LVI.Results: The differences of these variables(childbearing history, miscarriage history, other breast diseases history, nipple discharge, breast cancer marker CA153, age, ER, PR, HER-2, E-CAD, P53, Ki-67) between LVI positive group and the LVI negative group were not statistically significant, except that of Ki-67 (P=0.012). For the image features of digital mammography, the differences of interstitial edema (P=0.013) and skin thickening (P=0.000) between LVI positive group and negative groups were statistically significant. The differences of other imaging patterns, that is, fibroglandular tissue density, size , solitary/multiple, mass shape, mass margin , subcutaneous fat, axillary adenopathy and so on, between the two groups were not statistically significant. Multiple factor analysis shows that, there are three independent risk factors for predicting LVI occurrence: interstitial edema (OR = 12.610, 95% confidence interval CI: 1.061, 149.922, P=0.045), subcutaneous fat (OR=0.081, 95% confidence interval CI: 0.012, 0.645, P =0.017) and skin thickening (OR=9.041, 95% confidence interval CI: 2.553, 32.022, P=0.001).Conclusion: Interstitial edema, blurring of subcutaneous fat layer, and skin thickening were independent risk factors for predicting LVI occurrence. When applying these three imaging patterns together, the specificity of LVI prediction was as high as 98.8%.
Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules
Authors: Pinton Laura , Magri Sara , Masetto Elena , Vettore Marina , Schibuola Ilaria , Ingangi Vincenzo , Marigo Ilaria , Matha Kevin , Benoit Jean-Pierre , Puppa Alessandro Della , Bronte Vincenzo , Lollo Giovanna , Mandruzzato Susanna
Published: December 2019

BackgroundMyeloid Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attractive therapeutic strategy to relieve immunosuppression and, in this frame, we previously demonstrated that lipid nanocapsules (LNCs) loaded with lauroyl-modified gemcitabine efficiently target monocytic MDSCs in melanoma patients. In this study, we investigated the impact of the physico-chemical characteristics of LNCs, namely size and surface potential, towards immunosuppressive cell targeting. We exploited myeloid cells isolated from glioblastoma patients, which play a relevant role in the immunosuppression, to demonstrate that tailored nanosystems can target not only tumor cells but also tumor-promoting cells, thus constituting an efficient system that could be used to inhibit their function.ResultsThe incorporation of different LNC formulations with a size of 100 nm, carrying overall positive, neutral or negative charge, was evaluated on leukocytes and tumor-infiltrating cells freshly isolated from glioblastoma patients. We observed that the maximum LNC uptake was obtained in monocytes with neutral 100 nm LNCs, while positively charged 100 nm LNCs were more effective on macrophages and tumor cells, maintaining at low level the incorporation by T cells. The mechanism of uptake was elucidated, demonstrating that LNCs are incorporated mainly by caveolae-mediated endocytosis. ConclusionsWe demonstrated that LNCs can be directed towards immunosuppressive cells by simply modulating their size and charge and provided a novel approach to exploit nanosystems for anticancer treatment in the frame of immunotherapy.
Meta-regression analysis of the effect of lifestyle interventions on mediators of inflammation in postmenopausal breast cancer women with cardiovascular risk factors
Authors: Milambo Jean Paul Muambngu , Kotze Maritha , Rajiv Erasmus , Akudugu John , Jacques Tamuzi Lukenze
Published: December 2019

Background: Chronic inflammation is associated with obesity, dyslipidemia, and different types of malignancies that may play a complex role in the risk of breast cancer (BC) recurrence and therapy related side effects. The purpose of this review was to determine the effects of lifestyle interventions on mediators of inflammation (C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α)) and other therapy related adverse events in postmenopausal BCS with cardiovascular related risk factors. Methods: A systematic search for relevant articles was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis criteria using available databases (PubMed, Scopus, The Cochrane Library, OpenGrey, Google Scholar and CENTRAL). Results: Twelve eligible randomized controlled trials (RCT) met the inclusion criteria. The mean ages of postmenopausal BC women ranged from 49 to 56 years. The meta-regression revealed that there was moderate evidence that MSE decreased the mean difference (MD) of inflammatory markers in BCS, with CVD risk factors (MD: 0.31; 95% CI: 0.05 to 0.57, P=0.02; heterogeneity: Tau² = 0. 12; Chi² = 106.30, df = 19, I² = 0. 50.4%). Conclusion: There is a moderate level of evidence on the effects of MSE on mediators of inflammation in postmenopausal BCS with cardiovascular risk factors. A number of shared risk factors between postmenopausal status and CVD should be considered, while treating postmenopausal BCS.
Strengthening the quality of paediatric primary care: A process evaluation of a complex health systems intervention in South Africa
Authors: Curran Robyn Leigh , Murdoch Jamie , Cornick Ruth Vania , Picken Sandra , Bachmann Max , Bateman Eric , Simelane Makhosazana Lungile , Fairall Lara Rosemary
Published: December 2019

BACKGROUND: Innovative strategies like WHO’s Integrated Management of Childhood Illness (IMCI) have resulted in progress in addressing infant and child mortality. However, the needs of children continue to present a burden upon primary healthcare services. The capacity of services and quality of care offered require greater support to address these needs and extend integrated curative and preventive care, specifically, for the well child, the child with a long-term health condition and the child older than 5 years, not included in IMCI. In response to these needs, the PACK Child intervention was developed, based on a similar successful approach in adults, that expands the scope and reach of integrated management and training programmes for paediatric primary care. We report findings from the process evaluation of the integration of PACK Child intervention within the existing primary health care system. METHODS: A mixed methods process evaluation was completed in ten primary health care facilities in the Western Cape province in South Africa, where clinicians were trained to integrate PACK Child into routine practice. Qualitative data included interviews with managers, clinicians, caregivers and policymakers; observations of training, consultations and clinic flow. Quantitative data included training logs and clinicians’ questionnaires. RESULTS: Impact of PACK Child on clinical practice: Longer consultations, improved clinical knowledge and practice, better teamwork, strengthening of appropriate referrals and inclusion of psychosocial risk screening. Implementation fidelity of PACK Child was hindered by over-reliance on documentation and embedded checklist approach to consultations limited to acute episodic illnesses. PACK Child increased caregiver participation during consultations. CONCLUSIONS: The PACK Child intervention has strengthened primary care for children despite institutionalised care provided by a limited number of clinicians focusing on acute illness with little participation of the caregiver. With refinement of the programme, there is potential for PACK Child to strengthen paediatric care in low-resource settings.
Iron Overload contributes to General Anesthesia-induced Neurotoxicity and Cognitive Deficits
Authors: Wu Jing , Yang Shuofei , Cao Yan , Li Huihui , Zhao Hongting , Yang Jian-Jun , Li Kuanyu
Published: December 2019

Background Increasing evidence suggests that exposure to general anesthesia (GA) could be detrimental to cognitive development in young subjects, and might also contribute to accelerated neurodegeneration in the elderly. Iron is essential for normal neuronal function and excess iron in brain is a hallmark of neuroinflammation and is implicated in several neurodegenerative diseases. However, the role of iron in GA-induced neurotoxicity and cognitive deficits has not been studied.Methods We used the primary hippocampal neurons and rodents including young rats and aged mice to examine whether GA impacts iron metabolism and whether the impact contributed to neuronal outcomes. In addition, a pharmacological suppression of iron metabolism was performed to explore the molecular mechanism underlying GAs-mediated iron overload in the brain.Results Our results demonstrated that GA, induced by intravenous ketamine or inhalational sevoflurane, disturbed iron homeostasis and caused iron overload in both in vitro hippocampal neuron culture and in vivo hippocampus. Interestingly, ketamine or sevoflurane-induced cognitive deficits, very likely, result from a novel regulated iron-dependent cell death, ferroptosis. Notably, iron chelator deferiprone attenuated the GA-induced mitochondrial dysfunctions, ferroptosis, and further cognitive deficits. Moreover, we found that GA-induced iron overload was activated by NMDAR-RASD1 signalling via DMT1 action in the brain.Conclusion We conclude that disturbed iron metabolism may be involved in the pathogenesis of GA-induced neurotoxicity and cognitive deficits. Our study provides new insights into a potential novel therapy for prevention in GA-associated neurological disorders.
Cytokine levels and fatigue in patients with depression: A case-control study
Authors: Petrozzi Bruno Pedraz , Neumann Elena , Sammer Gebhard
Published: December 2019

1. AbstractBackground: Depression represents a highly disabling disease. A relationship between augmented cytokine concentrations and depression has been suggested. Fatigue, frequently being part of depressive symptoms and being associated with infectious diseases and autoimmune diseases, could constitute a link between inflammation mechanisms and depression. The aim of this work was to show the pattern of relationships between depression, fatigue, and inflammation. Methods: A case-control study with 27 patients and 33 matched controls was conducted. IL-6, IL-1β, TNF-α, IFN-γ and CRP were assessed in venous blood samples. Fatigue was assessed behaviorally with a sustained attention task (SAT) and subjectively with a questionnaire (FIS-D). Depression scores were assessed using a questionnaire (BDI-FS). Results: IL-6 was higher in the patient group (U test = 304.00; p = 0.045). For the whole sample size, IL-1β concentration differences were found between BDI-FS categories (H (3) = 11.34, p = 0.01). In patients, correlations were found between BDI-FS categories and IL-1β (ρ = 0.409, p = 0.038), psychosocial fatigue and IL-6 (ρ = 0.437, p = 0.029), and somatic fatigue and TNF-α (ρ = 0.390, p = 0.049). However, correlations failed p = 0.05 threshold for controls. Finally, the total number of omitted responses in the SAT and TNF-α were positively correlated in the patient group (ρ = 0.488, p = 0.011) as well as in the control group (ρ = 0.454, p = 0.008). Conclusions: The results suggest the presence of inflammation in both depression and fatigue. However, each correlates with different pro-inflammatory parameters, indicating potential biological heterogeneity.
Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information
Authors: Hugenschmidt Harald , Labori Knut Jørgen , Brunborg Cathrine , Verbeke Caroline Sophie , Seeberg Lars Thomas , Schirmer Cecilie Bendigtsen , Renolen Anne , Borgen Elin , Naume Bjørn , Wiedswang Gro
Published: December 2019

Background: Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow are associated with impaired prognosis in a variety of epithelial cancers. For a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC). Methods: Preoperative bone marrow samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis. Results: Successful resection of malignant tumours was performed in 179 (74.0%) of the cases, 30 patients resected (12.4%) had benign pancreatic disease based on postoperative histology, and 33 (13.6%) were deemed inoperable during laparotomy due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The frequency of CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the whole cohort nor in the subgroup previously tested negative for circulating tumour cells in blood. Conclusions: The results indicate that CK-positive cells may be present in patients with both malignant and benign diseases of the pancreas. CK-positive cell presence was not associated with differences in prognosis for any patient group. Trial registration: clinicaltrials.gov (NCT01919151)
Analgesic effect of preoperative intravenous administration of paracetamol on post-cesarean pain: A randomized clinical trial
Authors: Moghadam Seyyed Hamid Pakzad , Pourparizi Masoud , Goujani Reza , Khalilabadi Tayyebeh Mirzaei , Ravari Ali , Askari Shayesteh , Khalilabadi Sakineh Mirzaei
Published: December 2019

Background Pain control after every surgery, especially cesarean is highly important, and physicians are striving to discover pain control methods using the least amount of opioid and Paracetamol is a non-opioid analgesic with few complications. The present study was aimed to investigate the analgesic effect of preoperative intravenous administration of paracetamol on post-cesarean pain.Methods This randomized double-blind clinical trial was conducted on 240 pregnant women under spinal anesthesia who were candidate for elective cesarean. The patients’ weight, height, age and body mass index (BMI) were recorded, and patients were randomly divided into two equal groups (n=120). In the first group, 10 mg/kg paracetamol in 100cc normal saline (paracetamol group) and in the second group 100cc normal saline (control group) administered 15 minutes before surgery intravenously. Blood pressure, pulse rate, chills and nausea were recorded during and 1 hour after surgery, and pain visual analogue scale (VAS) and need for additional analgesic were recorded 1, 2, 4, 6, 12 and 24 hours after surgery.Results No significant difference was found between the two groups in frequency of chills and nausea (p>0.05). Mean pethidine consumed was lower in paracetamol group than control group but not significantly. Systolic blood pressure of both groups during surgery and one hour after surgery did not show a significant difference, but diastolic blood pressure was significantly lower in paracetamol group 15 minutes (p=0.046) and 60 minutes after surgery (p=0.042) than control group. The mean scores of pain were significantly lower in paracetamol group than control group 6 hours (0.008) and 24 hours (p=0.038) after surgery.Conclusions Within the limitations of the current study, preoperative intravenous administration of paracetamol significantly reduced post-cesarean pain within 24 hours.