bluuebunny/crossref_metadata_2025 huggingface dataset:
Bach1 Inhibitors Reduce Stasis in Townes Sickle Cell Mouse Model
Authors: Belcher John D , Biddle Margaret , Stickens Domi , Olson Lyndsay , Bell Eric , Chen Chunsheng , Abdulla Fuad , Nguyen Julia , Kiser Zachary Monroe , Lloyd Jacob , Vercellotti Gregory M
Published: February 2020

In sickle cell disease (SCD) excessive release of Hb and heme into the vasculature can activate innate immune toll-like receptor 4 (TLR4) signaling in the vasculature leading to inflammation and vaso-occlusion. Heme-mediated TLR4 signaling can be interrupted by inducing heme oxygenase 1 (HO-1) to degrade heme or ferritin heavy chain (FTH1) to sequester iron. Globin synthesis, HO-1 expression, heme/iron homeostasis, and antioxidant levels are regulated in part by antioxidant response genes, which is a set of hundreds of genes that possess antioxidant response elements (ARE) in their promoter regions. Bach1 complexes bind to ARE sites and dominantly repress Nrf2 transcriptional activity. This transcriptional repression can be inactivated by heme binding to Bach1. We have discovered small molecule BACH1 inhibitors that increase HO-1 and FTH1 mRNA in HepG2 cells. Additionally, they restore glutathione levels and inhibit VCAM-1 expression in human primary aortic endothelial cells upon hemin or TNFα challenge. To investigate if Bach1 inhibitors could have an effect on vaso-occlusion in vivo, microvascular stasis was examined in Townes-SS mice with implanted dorsal skin-fold chambers. Townes-SS mice were orally gavaged with vehicle or Bach1 inhibitors at different doses once daily for 8 days. Microvascular stasis was determined in 20-25 preselected flowing subcutaneous venules in response to intravenous infusion of hemin (3.2 μmol/kg). Stasis was significantly inhibited by Bach1 inhibitors in a dose responsive manner. After stasis measurement, blood was collected and the F-cells were stained using the Kleihauer-Betke Test. F-cell % was significantly increased by Bach1 inhibitor treatment at all doses tested.

Disclosures

Belcher: Mitobridge, an Astellas Company: Consultancy, Research Funding. Biddle:Mitobrige, an Astellas Company: Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Stickens:Mitobridge, an Astellas Company: Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Olson:Mitobridge, an Astellas Company: Employment. Bell:Mitobridge, an Astellas Company: Employment. Vercellotti:Mitobridge, an Astellas Company: Consultancy, Research Funding.
A Busulfan Following Cyclophosphamide and Constant Cell Dose Protocol Improved Results in Alternative Donor Hematologic Stem Cell Transplantation in Thalassemia Major: A Result from Long-Term Large-Size Multi-Center Study
Authors: He Yuelin , Jiang Hua , Li Changgang , Zhu Yiping , Wu Xuedong , Sixi Liu , Yuhua Qu , Liao Jiangyu , Feng Xiaoqin , Liu Huaying , Peng Zhiyong , He Lan , Bu Chaoke , Mandeen Gautam , Wing Leung , Li Chunfu
Published: February 2020

Sibling donor transplantation (SDT) is a proven curative therapy for patients with thalassemia major (TM), NF-08-TM protocol improved the outcomes of unrelated donor transplantation (UDT) in single-center. This study aim was to determine whether outcomes of NF-08-TM protocol could be proved in multicenter and long-term follow-up and to compare the outcomes of full-matched (FM) and one-locus mismatch (WM) UDT. 586 patients from 4 pediatric BMT centers in China from Dec. 2008 to Jun. 2016 received NF-08-TM protocol, a newly designed Busulfan following Cyclophosphamide and constant cell dose protocol. With a median follow-up of 57 months (range, 21-116), the 9-year OS, TFS, GR, and TRM were 94.4%, 92.8%, 2.7%, and 5.6%, respectively, in total. The corresponding rates for SDTs (n=224) were 95.9%, 95.5%, 1.4% and 4.1%; for UDTs (n=275) were 92.4%, 89.9%, 4.3% and 7.6%; for parental donor transplantation (PDT, n=40) were 95.0%, 95.0%, 0% and 5.0%; and for cord blood transplantation (CBT, n=47) were 97.9%, 95.4%, 2.6% and 2.1%, respectively.The incidence of grade II-IV aGVHD, III-IV aGVHD, mild cGVHD and moderate/severe cGVHD of the entire cohort was 8.9%, 4.6%, 3.7%, and 1.4%, respectively. There was no statistically significant difference (SSD) in OS, TFS, TRM, and GR when comparing FM-SDTs with those of FM-PDTs, FM-UDTs or FM-CBTs. Among PDTs, no SSD was found in OS, TFS, TRM, GR, and GVHD in comparison of FM-PDTs and WM-PDTs. More moderate/severe cGVHD occurred in WM-UDTs than FM-UDTs. Compared FM-SDTs, WM-UDTs had worse OS, TFS, TRM, and a higher rate of grade II-IV aGVHD and cGVHD. Current study proved that Good outcomes of NF-08-TM protocol in single-center be proved in multicenter and long-term follow-up. Compared to the outcomes of FM-UDT) those of well-UDT was worse and was not recommended to thalassemia patients.

Disclosures

Wing: Miltenyi Biotec: Employment.
Multilocus phylogeny and cryptic diversity of white-toothed shrews (Mammalia, Eulipotyphla, Crocidura) in China
Authors: Chen Shunde , Qing Jiao , Liu Zhu , Liu Yang , Tang Mingkun , Murphy Robert W. , Pu Yingting , Wang Xuming , Tang Keyi , Guo Keji , Jiang Xuelong , Liu Shaoying
Published: February 2020

Background

Crocidura, the most speciose mammalian genus, occurs across much of Asia, Europe and Africa. The taxonomy of Chinese representatives has been studied primarily based on cursory morphological comparisons and their molecular phylogenetic analyses remain unexplored. In order to understand the phylogeny of this group in China, we estimated the first multilocus phylogeny and conducted species delimitation, including taxon sampling throughout their distribution range.

Results

We obtained one mitochondrial gene (cytb) (~ 1, 134 bp) and three nuclear genes (ApoB,BRCA1,RAG1) (~ 2, 170 bp) for 132 samples from 57 localities. Molecular analyses identified at least 14 putative species that occur within two major well-supported groups in China. PolyphyleticC. wuchihensisappears to be composed of two putative species. Two subspecies,C. rapax rapaxandC. rapax kurodaishould be elevated to full species status. A phylogenetic tree based on mitochondrial gene from AsianCrociduraspecies showed that theC. rapax rapaxis embedded withinC. attenuata, making the latter a paraphyletic group. Three strongly supported undescribed species (C.sp.1,C.sp.2 andC.sp.3) are revealed from Zada County of Tibet (Western China), Hongjiang County of Hunan Province (Central China) and Dongyang County of Zhejiang Province (Eastern China), Motuo County of Tibet, respectively. The divergence time estimation suggested that China’sCrociduraspecies began to diversify during the late Pliocene (3.66 Ma) and the Early Pleistocene (2.29 Ma), followed by a series of diversifications through the Pleistocene.

Conclusions

The cryptic diversity found in this study indicated that the number of species is strongly underestimated under the current taxonomy. We propose that the three undescribed species should be evaluated using extensive taxon sampling and comprehensive morphological and morphometric approaches. Climate change since the late Pliocene and the uplift of the Qinghai-Tibet Plateau may result in the diversification and speciation of China’sCrociduraspecies. In short, the underestimated diversity underlines the need for a taxonomic revision of ChineseCrociduraspecies.
Cost-effectiveness analysis of chromosomal microarray as a primary test for prenatal diagnosis in Hong Kong
Authors: Chung Claudia Ching Yan , Chan Kelvin Yuen Kwong , Hui Pui Wah , Au Patrick Kwok Cheung , Tam Wai Keung , Li Samuel Kai Man , Leung Gordon Ka Chun , Fung Jasmine Lee Fong , Chan Marcus Chun Yin , Luk Ho Ming , Mak Annisa Shui Lam , Leung Kwok Yin , Tang Mary Hoi Yin , Chung Brian Hon Yin , Kan Anita Sik Yau
Published: February 2020

Background

Chromosomal microarray (CMA) has been shown to be cost-effective over karyotyping in invasive prenatal diagnosis for pregnancies with fetal ultrasound anomalies. Yet, information regarding preceding and subsequent tests must be considered as a whole before the true cost-effectiveness can emerge. Currently in Hong Kong, karyotyping is offered free as the standard prenatal test while genome-wide array comparative genome hybridization (aCGH), a form of CMA, is self-financed. A new algorithm was proposed to use aCGH following quantitative fluorescent polymerase chain reaction (QF-PCR) as primary test instead of karyotyping. This study aims to evaluate the cost-effectiveness of the proposed algorithm versus the current algorithm for prenatal diagnosis in Hong Kong.

Methods

Between November 2014 and February 2016, 129 pregnant women who required invasive prenatal diagnosis at two public hospitals in Hong Kong were prospectively recruited. The proposed algorithm was performed for all participants in this demonstration study. For the cost-effectiveness analysis, cost and outcome (diagnostic rate) data were compared with that of a hypothetical scenario representing the current algorithm. Further analysis was performed to incorporate women’s willingness-to-pay for the aCGH test. Impact of government subsidies on the aCGH test was explored as a sensitivity analysis.

Results

The proposed algorithm dominated the current algorithm for prenatal diagnosis. Both algorithms were equally effective but the proposed algorithm was significantly cheaper (p ≤ 0.05). Taking into account women’s willingness-to-pay for an aCGH test, the proposed algorithm was more effective and less costly than the current algorithm. When the government subsidy reaches 100%, the maximum number of diagnoses could be made.

Conclusion

By switching to the proposed algorithm, cost saving can be achieved whilst maximizing the diagnostic rate for invasive prenatal diagnosis. It is recommended to implement aCGH as a primary test following QF-PCR to replace the majority of karyotyping for prenatal diagnosis in Hong Kong.
Membrane and synaptic defects leading to neurodegeneration in Adar mutant Drosophila are rescued by increased autophagy
Authors: Khan Anzer , Paro Simona , McGurk Leeanne , Sambrani Nagraj , Hogg Marion C. , Brindle James , Pennetta Giuseppa , Keegan Liam P. , O’Connell Mary A.
Published: February 2020

Background

In fly brains, theDrosophilaAdar (adenosine deaminase acting on RNA) enzyme edits hundreds of transcripts to generate edited isoforms of encoded proteins. Nearly all editing events are absent or less efficient in larvae but increase at metamorphosis; the larger number and higher levels of editing suggest editing is most required when the brain is most complex. This idea is consistent with the fact thatAdarmutations affect the adult brain most dramatically. However, it is unknown whetherDrosophilaAdar RNA editing events mediate some coherent physiological effect. To address this question, we performed a genetic screen for suppressors ofAdarmutant defects.Adar5G1null mutant flies are partially viable, severely locomotion defective, aberrantly accumulate axonal neurotransmitter pre-synaptic vesicles and associated proteins, and develop an age-dependent vacuolar brain neurodegeneration.

Results

A genetic screen revealed suppression of allAdar5G1mutant phenotypes tested by reduced dosage of theTorgene, which encodes a pro-growth kinase that increases translation and reduces autophagy in well-fed conditions. Suppression ofAdar5G1phenotypes by reduced Tor is due to increased autophagy; overexpression ofAtg5, which increases canonical autophagy initiation, reduces aberrant accumulation of synaptic vesicle proteins and suppresses allAdarmutant phenotypes tested. Endosomal microautophagy (eMI) is another Tor-inhibited autophagy pathway involved in synaptic homeostasis inDrosophila. Increased expression of the key eMI protein Hsc70-4 also reduces aberrant accumulation of synaptic vesicle proteins and suppresses allAdar5G1mutant phenotypes tested.

Conclusions

These findings linkDrosophila Adarmutant synaptic and neurotransmission defects to more general cellular defects in autophagy; presumably, edited isoforms of CNS proteins are required for optimum synaptic response capabilities in the brain during the behaviorally complex adult life stage.
Two novel protein chips for the detection of antibodies against porcine parvovirus
Authors: Wu Yue , Wu Xudan , Hou Jinxiu , Chen Xiongnan , Huang Xiaobo , Zhou Bin
Published: February 2020

Background

PPV is one of the most important pathogens causing porcine reproductive disorder. It has been shown in clinical cases to be a commonly mixed infection with other important swine diseases which can aggravate the severity of the disease and bring serious economic losses to the pig industry. Serological methods, such as hemagglutination inhibition assays (HAI), serum neutralization (SN), and the modified direct complement-fixation (MDCF) test were utilized earlier, whereas the enzyme-linked immunosorbent assay (ELISA) is the most frequently applied assay to detect PPV-specific antibodies.

Results

We establish the visible protein chip and the cyanine dye 3 (Cy3)-labeled protein chip to detect the clinical serum from pigs. In this study, the recombinant protein VP2 of PPV was expressed in E.coli, purified with nickel magnetic beads, and then printed onto epoxy-coated glass slides for preparation of the protein chip. After a series of experiments, the conditions of antigen protein concentration, incubation time of primary antibody or secondary antibody, and optimal serum dilution fold were optimized, resulting in a successful visible protein chip and Cy3-labeled protein chip. The results showed that the positive serum, diluted up to 6000-fold, can be detected by the visible protein chip, and the positive serum, diluted up to 12,800-fold, can be detected by the Cy3-labeled protein chip, suggesting the high sensitivity of these protein chips. Moreover, the positive detection ratio, sensitivity, and specificity of these two kinds of protein chips were higher than those of commercial ELISA antibody detection kits.

Conclusion

Overall, these two protein chips can be used to rapidly diagnose clinical samples with high throughput.
Correction to: Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy
Authors: Ren Daixi , Hua Yuze , Yu Boyao , Ye Xin , He Ziheng , Li Chunwei , Wang Jie , Mo Yongzhen , Wei Xiaoxu , Chen Yunhua , Zhou Yujuan , Liao Qianjin , Wang Hui , Xiang Bo , Zhou Ming , Li Xiaoling , Li Guiyuan , Li Yong , Zeng Zhaoyang , Xiong Wei
Published: February 2020

After publication of the article [1], authors found out that Fig. 1 was inadvertently replaced.
Systemic microbial TLR2 agonists induce neurodegeneration in Alzheimer’s disease mice
Authors: Lax Neta , Fainstein Nina , Nishri Yossi , Ben-Zvi Ayal , Ben-Hur Tamir
Published: February 2020

Background

Accumulating data suggest a central role for brain microglia in mediating cortical neuronal death in Alzheimer’s disease (AD), and for Toll-like receptor 2 (TLR2) in their toxic activation. Amyloid deposition in preclinical AD is associated with microglial activation but not directly with neurodegeneration. We examined in transgenic 5xFAD mice the hypothesis that systemic TLR2 agonists, derived from common infectious agents, may accelerate neurodegeneration in AD.

Methods

Microbial wall-derived TLR2 agonists zymosan and lipoteichoic acid were administered intraperitoneally or intracerebroventricularly to 7-month-old wild-type or 5xFAD mice. Immunofluorescent stainings were used to quantify cortical neurons and evaluate tissue reaction. Microglial activation was assessed using functional assays, RNA expression, and FACS analysis.

Results

Repeated low-dose systemic administration of zymosan or lipoteichoic acid killed cortical neurons in 5xFAD mice but not in wild-type mice. Direct CNS delivery of a selective TLR2 antagonist blocked the neurotoxicity of systemically administered zymosan, indicating that CNS TLR2 mediates this effect. Systemically administered zymosan crossed the disrupted blood-brain barrier in 5xFAD mice and entered brain parenchyma. By intracerebroventricular delivery, we found a dose- and exposure time-dependent acute neurotoxic effect of the microbial TLR2 agonist, killing cortical neurons. 5xFAD mice exhibited significantly increased vulnerability to TLR2 agonist-induced neuronal loss as compared to wild-type mice. Microbial TLR2-induced neurodegeneration was abolished by inhibiting microglia. The vulnerability of 5xFAD mice brains was mediated by an increase in number and neurotoxic phenotype of TLR2-expressing microglia.

Conclusions

We suggest that repeated exposure to microbial TLR2 agonists may facilitate neurodegeneration in AD by their microglial-mediated toxicity to the hyper-vulnerable environment of the AD brain.
Stereotactic radiosurgery combined with targeted/ immunotherapy in patients with melanoma brain metastasis
Authors: Hadi Indrawati , Roengvoraphoj Olarn , Bodensohn Raphael , Hofmaier Jan , Niyazi Maximilian , Belka Claus , Nachbichler Silke Birgit
Published: February 2020

Background

There is limited data on the use of targeted or immunotherapy (TT/IT) in combination with single fraction stereotactic radiosurgery (SRS) in patients with melanoma brain metastasis (MBM). Therefore, we analyzed the outcome and toxicity of SRS alone compared to SRS in combination with TT/IT.

Methods

Patients with MBM treated with single session SRS at our department between 2014 and 2017 with a minimum follow-up of 3 months after first SRS were included. The primary endpoint of this study was local control (LC). Secondary endpoints were distant intracranial control, radiation necrosis-free survival (RNFS), and overall survival (OS). The local/ distant intracranial control rates, RNFS and OS were analyzed using the Kaplan-Meier method. The log-rank test was used to test differences between groups. Cox proportional hazard model was performed for univariate continuous variables and multivariate analyses.

Results

Twenty-eight patients (17 male and 11 female) with 52 SRS-lesions were included. The median follow-up was 19 months (range 14–24 months) after first SRS. Thirty-six lesions (69.2%) were treated with TT/IT simultaneously (4 weeks before and 4 weeks after SRS), while 16 lesions (30.8%) were treated with SRS alone or with sequential TT/IT. The 1-year local control rate was 100 and 83.3% for SRS with TT/IT and SRS alone (p = 0.023), respectively. The estimated 1-year RNFS was 90.0 and 82.1% for SRS in combination with TT/IT and SRS alone (p = 0.935). The distant intracranial control rate after 1 year was 47.7 and 50% for SRS in combination with TT/IT and SRS alone (p = 0.933). On univariate analysis, the diagnosis-specific Graded Prognostic Assessment including the BRAF status (Melanoma-molGPA) was associated with a significantly improved LC. Neither gender nor SRS-PTV margin had a prognostic impact on LC. V10 and V12 were significantly associated with RNFS (p < 0.001 and p = 0.004).

Conclusion

SRS with simultaneous TT/IT significantly improved LC with no significant difference in radiation necrosis rate. The therapy combination appears to be effective and safe. However, prospective studies on SRS with simultaneous TT/IT are necessary and ongoing.

Trial registration

The institutional review board approved this analysis on 10th of February 2015 and all patients signed informed consent (UE nr. 128–14).
The effect of human gene therapy for RPE65-associated Leber’s congenital amaurosis on visual function: a systematic review and meta-analysis
Authors: Wang Xue , Yu Chaofeng , Tzekov Radouil T. , Zhu Yihua , Li Wensheng
Published: February 2020

Background

RPE65-associated LCA (RPE65-LCA) is an inherited retinal degeneration caused by the mutations of RPE65 gene and gene therapy has been developed to be a promising treatment. This study aims to evaluate the association between changes in visual function and application of gene therapy in patients with RPE65-LCA.

Methods

Several databases (PubMed, Cochrane Library, and Web of Science) were searched for results of studies describing efficacy of gene therapy in patients with RPE65-LCA. Six studies, which included one randomized and five prospective non-randomized clinical trials, 164 eyes met our search criteria and were assessed.

Results

The BCVA significantly improved in treated eyes at 1 yr post treatment by − 0.10 logMAR (95% CI, − 0.17 - -0.04; p = 0·002), while there was no significant difference at 2–3 years post treatment (WMD: 0.01; 95% CI, − 0.00 - 0.02; p = 0·15). FST sensitivity to blue flashes also improved by 1.60 log (95% CI, 0.66–2.55; p = 0.0009), but no significant difference to red flashes (WMD: 0.86; 95% CI, − 0·29–2.01; p = 0.14) at 1 yr. There was no significant difference in central retinal thickness at 1 yr, but central retina in treated eyes appeared thinner at 2–3 years post treatment by 19.21 μm (95% CI, − 34.22 - -4.20; p = 0.01).

Conclusions

Human gene therapy is a pioneering treatment option for RPE65-LCA. Although its efficacy appears to be limited to less than 2 yrs after treatment, it carries the potential for further improvement and prolongation of efficacy.
Short and long term effect of treatment non-pharmacological and lifestyle in patients with metabolic syndrome
Authors: Brandão Ana Denise , da Silva Jeferson Hernandes , Mariane Oliveira Lima Sarah , Lima Leiciane , Loize Bhianca , de Castro Antônio Adolfo Mattos , Kümpel Claudia , Porto Elias Ferreira
Published: February 2020

Background

Metabolic syndrome (MS) is a complex disorder represented by a set of cardiovascular risk factors usually related to central fat deposition, insulin resistance, hypertension and dyslipidemia. It is associated with accelerated atherosclerosis in response to chronic inflammation and vascular endothelial dysfunction, increasing overall mortality. The objective to evaluate the short and long term effect of the comprehensive cardiac rehabilitation program and intensive lifestyle intervention in metabolic syndrome patients.

Methods

This is longitudinal interventional study. All patients underwent a 20-session cardiac rehabilitation program with aerobic and resisted exercises as well as an educational program for lifestyle changes and follow up 1 year.

Results

Forty seven patients participated in the present study, but only 28 concluded the follow up. 77.7% were females and the majority was older than 60 years (63.1%). After cardiac rehabilitation, the percentage of overweight (0.04) patients who controlled the SBP (0.04) increased, and obesity levels I and II were reduced, as well as a significant reduction in total cholesterol and triglycerides (0.01 and 0.05), all of these variables remained similar after 1 year of follow-up. After cardiac rehabilitation all participants were practicing the five factors of healthy lifestyle, and reduced to 73% after follow up.

Conclusion

A comprehensive cardiac rehabilitation program and lifestyle change is an effective approach in the treatment of patients with MS mainly, it has positive short and long term effects on weight control, reducing total cholesterol and triglycerides.
miR-765 inhibits the osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting BMP6 via regulating the BMP6/Smad1/5/9 signaling pathway
Authors: Wang Tao , Zhang Chao , Wu Cihu , Liu Jianyun , Yu Hui , Zhou Xiaoou , Zhang Jie , Wang Xinping , He Shan , Xu Xiaoyuan , Ma Baicheng , Che Xiangxin , Li Weidong
Published: February 2020

Background

The process of bone repair is heavily dependent on the ability of human bone marrow mesenchymal stem cells (hMSCs) to undergo osteogenic differentiation. MicroRNAs have been shown to regulate this osteogenic process. This study aimed to investigate the role of miR-765 in the osteogenic differentiation of hMSCs.

Methods

We transfected hMSCs with lentiviral constructs to knock down or overexpress this miRNA, allowing us to assess its role in osteogenesis via assessing the expression of the relevant markers alkaline phosphatase (ALP), runt-related gene-2 (RUNX-2), and osteocalcin (OCN), with further functional measurements made via quantifying ALP activity and conducting Alizarin Red S staining. The targeting of the 3′-untranslated region (UTR) of BMP6 by miR-765 was examined via luciferase assay. We used hMSCs with altered miR-765 expression to assess p-Smad1/5/9 levels via Western blotting over the course of osteogenic differentiation. We also assessed the osteogenic differentiation of hMSCs in which miR-765 was knocked down and at the same time as a BMP/Smad signaling inhibitor was added to disrupt Smad1/5/9 phosphorylation.

Results

We found miR-765 overexpression to inhibit osteogenesis-associated gene upregulation during osteogenic differentiation of hMSCs, whereas knockdown of this miRNA was associated with increased expression of these genes. Using luciferase reporter assays, we confirmed direct miR-765 binding to the 3′-untranslated region (UTR) of BMP6. We also found that miR-765 overexpression reduced Smad1/5/9 phosphorylation, and knockdown of this miRNA enhanced this phosphorylation on BMP6/Smad1/5/9 signaling. The osteogenic differentiation of hMSCs in which miR-765 had been knocked down was further weakened upon the addition of a BMP/Smad signaling inhibitor relative to miR-765 knockdown alone.

Conclusions

Together, these results thus suggest that miR-765 is able to inhibit hMSC osteogenic differentiation by targeting BMP6 via regulation of the BMP6/Smad1/5/9 signaling pathway. Our findings may offer molecular insights of value for the development of novel therapeutic treatments for bone diseases including osteoporosis.
Subdural haematomas drain into the extracranial lymphatic system through the meningeal lymphatic vessels
Authors: Liu Xuanhui , Gao Chuang , Yuan Jiangyuan , Xiang Tangtang , Gong Zhitao , Luo Hongliang , Jiang Weiwei , Song Yiming , Huang Jinhao , Quan Wei , Wang Dong , Tian Ye , Ge Xintong , Lei Ping , Zhang Jianning , Jiang Rongcai
Published: February 2020

Subdural haematomas (SDHs) are characterized by rapidly or gradually accumulated haematomas between the arachnoid and dura mater. The mechanism of haematoma clearance has not been clearly elucidated until now. The meningeal lymphatic vessel (mLV) drainage pathway is a novel system that takes part in the clearance of waste products in the central nervous system (CNS). This study aimed to explore the roles of the mLV drainage pathway in SDH clearance and its impacting factors. We injected FITC-500D, A488-fibrinogen and autologous blood into the subdural space of mice/rats and found that these substances drained into deep cervical lymph nodes (dCLNs). FITC-500D was also observed in the lymphatic vessels (LYVE+) of the meninges and the dCLNs in mice. The SDH clearance rate in SDH rats that received deep cervical lymph vessel (dCLV) ligation surgery was significantly lower than that in the control group, as evaluated by haemoglobin quantification and MRI scanning. The drainage rate of mLVs was significantly slower after the SDH model was established, and the expression of lymphangiogenesis-related proteins, including LYVE1, FOXC2 and VEGF-C, in meninges was downregulated. In summary, our findings proved that SDH was absorbed through the mLV drainage pathway and that haematomas could inhibit the function of mLVs.
Should we treat sepsis-induced DIC with anticoagulants?
Authors: Inata Yu
Published: February 2020

Background

Disseminated intravascular coagulation (DIC) is a common complication in sepsis because of crosstalk between the immune system and the coagulation system. Several anticoagulant agents have been tested in an attempt to improve the survival of patients with sepsis and sepsis-induced DIC. Here, we discuss the rationale against using anticoagulation therapy in septic DIC.

Main body of the abstract

Coagulopathy and DIC are associated with increased mortality in sepsis. Several anticoagulant agents have been tested in an attempt to improve the survival of patients with sepsis and sepsis-induced DIC, but have proven largely ineffective. This is because of two major factors. First, the coagulation system is complex and closely related to the immune system. When we manipulate one of the factors involved in these systems, we may disturb the delicate homeostasis between them. A second factor may be failure to identify patients who will benefit from anticoagulation therapy. This may be attributed partly to the fact that there is no gold standard for the diagnosis of DIC, and there are consequently several diagnostic criteria, none of which are specifically designed for sepsis-induced DIC. Application of precision medicine, of the kind currently being applied in other intensive care fields, may be the key to overcoming these challenges. Until we know the precise target population, we should not use anticoagulation therapy in sepsis-induced DIC outside a research setting.

Short conclusion

There is no strong evidence to support the effectiveness of routine anticoagulation therapy in sepsis-induced DIC, and it should not be used clinically until more is known regarding the population of patients who may benefit from it.
Development of a diabetes self-management + mHealth program: tailoring the intervention for a pilot study in a low-income setting in Mexico
Authors: Whittemore Robin , Vilar-Compte Mireya , Burrola-Méndez Soraya , Lozano-Marrufo Annel , Delvy Roberta , Pardo-Carrillo Mariana , De La Cerda Selene , Pena-Purcell Ninfa , Pérez-Escamilla Rafael
Published: February 2020

Background

Type 2 diabetes (T2D) is a public health pandemic disproportionately affecting low- and middle-income countries. The purpose of this formative research was to adapt evidence-based diabetes self-management education programs to the context of Seguro Popular clinics in Mexico. A theory-based mHealth (pictorial text messaging) component was developed.

Method

Our formative research and development of the program protocol consisted of six phases: (1) interviews and focus groups with stakeholders on the challenges to T2D management, curriculum content needs, and the use of mHealth as a supplement to a DSME program; (2) review of the theoretical underpinning, curriculum, and interactive strategies of four evidence-based DSME programs and modification to meet the needs of adults with T2D and systems of care in Mexico City; (3) development of theory-based illustrated text messages; (4) evaluation of text messaging acceptability and access in adults with T2D via focus groups; (5) development of program manual; and (6) development of a training program for health care providers.

Results

The ¡Sí, Yo Puedo Vivir Sano Con Diabetes! included 7 group-based weekly lessons; simple, interactive content; weekly empowerment messages; video novellas; group activities; and goal setting. Adaptations to the cultural context of Mexico included content/activities on diabetes etiology (addressing cultural misconceptions), nutrition (indigenous foods and plate method), self-blood glucose monitoring, and diabetes-related stress/coping. We used the Health Action Process Approach to guide the text message development, which posits that adoption, initiation, and maintenance of health behaviors require the development of intentions, plans, coping, and self-efficacy. Our final text message bank consisted of 181 messages. There were approximately 20–30 messages for each process of behavior change (e.g., action planning, maintenance self-efficacy) and 30 messages for each content topic (e.g., eating healthy, physical activity). There were 96 messages that were illustrated. Training materials were also developed.

Discussion

We used a systematic approach, collaboration with stakeholders, and a well-established behavior change theory to develop an evidence-based intervention to an international context and system of care. Collectively, this process has the potential to enhance the feasibility, acceptability, and efficacy of the program.
Hospitalized cancer patients with acquired long QT syndrome-a matched case-control study
Authors: Lin Yajuan , Yu Haixu , Liu Fei , Chen Cheng , Zhang Yanli , Wang Binhao , Yang Yiheng , Liu Ying , Zhang Li , Xia Yunlong
Published: February 2020

Background

Our recent study has revealed that many hospitalized patients with acquired long QT syndrome (ALQTS) are cancer patients. This study aims to determine the risk factors and outcomes of hospitalized cancer patients with ALQTS.

Methods

We performed a matched case-control study within a cohort of 10,180 cancer patients hospitalized between September 2013 and April 2016. Among them, 150 patients defined as having severe ALQTS with a markedly prolonged QT interval (QTc ≥ 500 ms) were compared with 293 age-, sex- and cancer-type-matched controls (non-ALQTS). Death as the endpoint was followed for up to 2 years. Cox regression and Kaplan-Meier survival analyses were performed to assess the effects of particular clinical variables on all-cause mortality. Multivariate logistic regression was performed to calculate odds ratios (OR) for various predictors of QT prolongation.

Results

The mortality was significantly higher in ALQTS group (63.3% vs. 33.4%). Hypertension, hypokalemia, hypocalcemia, QT-prolonging drugs, infection, anemia, anti-microtubule agents were contributing factors to ALQTS. Renal insufficiency, male gender and hypokalemia were found to be independent risk factors for all-cause mortality in ALQTS group.

Conclusion

Markedly prolonged QT interval was seen in 1.5% of hospitalized cancer patients. The all-cause mortality was high in cancer patients with severe ALQTS.
The use of Infographics as an educational tool for the upcoming digital transition
Authors: Kelidou Elisavet , Siountri Konstantina
Published: February 2020

Infographics have been proved as one of the most efficient visual tools to convey messages in a variety of applications and contexts. From road signage to data visualization and education, infographic designers manage to give a visual explanation for less or more complex concepts through a decreased use of detail, visual elements and text. Infographics can be designed in more than one types but static and animated types are the most frequently used. Whether the two types mentioned are equally effective in achieving a learning outcome, is still a subject of research. Studies that have compared static and animated infographics give different findings, preventing a secure conclusion for both of them. In addition to the above infographics have been used as visual rhetorical figures for creating meaning that persuade and lead to conclusions, perceptions, and emotions that could, in some cases, have a behavioral impact.The prementioned use of infographics as a means of knowledge transfer has been widely used in recent years in the transmission of information to social groups that may have little or no familiarity with the innovation of ICT and the processing of complex technological advancements. Technological developments and achievements such as Smart Cities, 5G, Internet of Things, Cloud Computing, Blockchain, Artificial Intelligence, etc. will change our lives drastically soon. For that reason, organizations, companies and research centers are trying to communicate the imminent changes with citizens - potential consumers - and to inform them of the upcoming digital transition that many describe as the 4th Industrial Revolution, in a simple and brief way. This paper seeks to identify both the positive effects of infographics and the dangers of such simplification and homogenization through paradigms, especially regarding the cultural characteristics of different sites and communities.
Interactive multimedia information for digital Anatomy Museum
Authors: Kiourexidou Matina , Antonopoulos Nikos , Kiourexidou Eugenia , Kotsakis Rigas , Heliades George , Polykalas Spyros , Natsis Konstantinos
Published: February 2020

Online technology advances and the reduction of their cost have facilitated their use by museums. Today, internet users visit museums’ websites around the world on regular basis. Website design helps to disseminate information and multimedia content from exhibitions and to attract visitors as well. The integrated communication strategy of the museums has changed due to digital museums development. The exhibits of anatomical museums present the complexity of human anatomy to medical students and to general public. Visiting of such museums could be difficult as the impact of their exhibits on visitors could lead to various reactions. These museums offer medical knowledge employing anatomical maps, bones, cadavers and various items explaining the history of anatomy and medicine. The aim of this research is to create and present a digital multimedia museum of Anatomy, located at the School of Medicine, Faculty of Health Sciences of Aristotle University of Thessaloniki. The results of this study focus on the development of a digital museum for citizens, that offers an integrated, open access experience for all. The research contributes to the construction of anatomical museums’ digital presence using online new technologies and multimedia content.
Production of the environmental documentary ''PLASTICLYSM''
Authors: Katsouris Michalis , Pavlogeorgatos Gerasimos
Published: February 2020

Documentary film is one of the strongest audiovisual means of communication. Its strength comes from the combination of image, audio and information it includes. The use of documentary film to raise public awareness towards many different topics is common throughout history. Nowadays, several environmental documentaries are produced every year. One of the most serious environmental problems that modern societies are facing is that of plastic pollution. In global scale, plastic production is estimated at 300 million tons annually. This paper discusses environmental documentary as a genre and describes the production process of the environmental documentary “PLASTICLYSM”.
Documentary genres. Criteria and dominant theories
Authors: Skopeteas Ioannis
Published: February 2020

The most popular genres in the documentary film theory today are the ones proposed by Bill Nichols (2010) who introduced six modes of representation: poetic, expository, participatory, observational, reflexive, and performative. These six modes “establish a loose framework of affiliation within which individuals may work; they set up conventions that a given film may adopt; and they provide specific expectations viewers anticipate having fulfilled”. However, is this division capable to cover all the elements of a documentary film and therefore construct fixed categories that can serve all the needs of theorists, practitioners and audience? This paper will support that the genre classification by Bill Nichols is only based on representation and its relation with the voice of the narrator. However, there are several other issues within the documentary film that may lead to other classifications. To name some of them, the theme and the subject of the documentary, the narrative structure and the actuality depicted.  In such a way, a full table of documentary genres will be provided at the end of the paper, which will cover all the aspects of this type of film.
Editorial Comments and Symposium Info
Authors: And Symposium Info Editorial Comments
Published: February 2020

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New developments in neutrino physics
Authors: Alberico W. M. , Bilenky S. M.
Published: February 2020

A review of the problems of neutrino mass, mixing and oscillations is given. Possible phenomenological schemes of neutrino mixing are discussed. The most important consequences of neutrino mixing-neutrino oscillations are considered in some detail. The data of atmospheric, solar and LSND experiments are discussed. The results of phenomenological analysis of the data under the assumption of the mixing of three and four massive neutrinos are briefly presented.
Proton decay in general SU(S) models
Authors: Gómez M. E.
Published: February 2020

We discuss proton decay induced by dimension-5 operators in supersymmetric models containing extra hypercharge-1/3 colour-triplets. We derive a general formula relating dimension-5 operator to the colour-triplet mass matrix. We show that certain zeros in the triplet mass-matrix together with some triplet coupling selection rules can lead to elimination of dimension-5 operators. We apply this mechanism to SU(5) and flipped 517(5) theories with extended Higgs sectors.
Applications of the relativistic mean-field model to finite nuclei.
Authors: Lalazissis G. A.
Published: February 2020

The relativistic mean-field theory (RMF) provides a framework in which the nuclear many-body problem is described as a self-consistent system of nucléons and mesons. We review recent applications of the RMF theory to the structure of finite nuclei.
Mass determination of the charged pion, using high precision X-ray spectroscopy
Authors: Anagnostopoulos, et al. D. F.
Published: February 2020

X-ray transitions in pionic nitrogen were measured using a curved crystal spectrometer. From the transition energy, calibrated with the help of the copper Ka1,2 electronic transition, a value for the charged pion mass of (139.57071± 0.00053) MeV/c2 was deduced. In order to reduce the uncertainty of the charged pion mass in the level of 1 ppm, we propose the determination of pionic transition energy based on the more precisely known energies and line shapes of muonic transitions.
Modification of pillared layered clays for scavenging radiostrontium from acidic aqueous environments
Authors: Papachristodoulou C. A. , Assimakopoulos P. A. , Gangas N.-H. , Karamanis D. T.
Published: February 2020

A Pillared Layered Clay (PILC), code-named FREZEN, has been developed as a potential antidote for trapping radiostrontium in the gastrointestinal tract of ruminants. The ion exchange behaviour of FREZEN has been studied, with particular emphasis on Sr+2 exchange in acidic solutions. As for most sorbents and ion ex­ changers, strontium uptake by FREZEN remains sufficiently good over a pH range of 5-11, but a sharp diminution is observed at pH values below 4. Furthermore, at lower pH values, hydronium ions (H3O+) successfully compete with strontium cations already uptaken by FREZEN. An extended "back-exchange" effect, charac­terized by fast kinetics, is thus observed. In order to impede the diffusion and prevalence of Η3Ο+, a modification of the microporous space in FREZEN has been carried out via intercalation of suitable organic molecules. Work currently underway reveals that this approach is capable of improving the performance properties of the PILC. Experimental results with glycerol as the intercalated organic agen will be presented and discussed.
Standardization, Metrology and conformity assessment
Authors: Nikolaeva Mariya , Kartashova Larisa
Published: February 2020

Describes the basic concepts and components of standardization, Metrology, assessment and confirmation of compliance, the normative-legal base of these activities with the accounting requirements, including newly adopted Federal laws.
Meets the requirements of Federal state educational standards of higher education of the last generation.
Designed for students of higher educational institutions in the areas of "trade", "commodity" (the degree qualification "bachelor"). Can be useful for students of institutions of secondary professional education on specialties "commodity research and quality expertise of consumer goods", "Commerce (on branches)", "Technology of catering products", "Organization of service in public catering".
Economic mechanism of development of housing and communal complex of the major cities of Russia
Authors: Nemkin Pavel
Published: February 2020

The monograph is devoted to one of the main infrastructural sectors of the economy major cities of our country. Outlines the main tasks of increase of efficiency of system of housing and communal services of big cities of Russia, and also proposes specific activities.
Of interest for employees of the enterprises of housing and communal services and employees of state authorities of the Russian Federation.
Math 100 points
Authors: Zhukova Galina , Rushaylo Margarita
Published: February 2020

In the tutorial proposed a systematic presentation of all the major sections of school mathematics which necessarily demanded in various kinds of control and independent works, Olympiads, math exams (MSE, CSE) and introductory tests in high schools, where they are completely aligned with the exam. When studying each topic for her mastery and the acquisition of practical skills given the necessary theoretical and background material, as well as analyzed and resolved a large number of examples and problems. To control the quality of the knowledge offered numerous assignments (with answers) for independent solving.
Can be used by students when doing homework, preparing for quizzes, exams, and Olympiads in mathematics. It is recommended teachers to work with students in the classroom, in clubs, in the preparatory training courses for OGE, exam etc. Will be useful for pupils and students with self-preparation for admission to the University, pupils of schools-eksternaty, teachers and students of the preparatory departments of universities.
History of training University teachers in Russia in the XIX century
Authors: Karnaukh Nadezhda
Published: February 2020

The monograph attempts to use a retrospective analysis to find out the factors that influenced the formation of the system of training Russian teachers for Russian universities in the XIX century, to consider the stages passed by this system, to systematize the requirements for the professionalism of a Professor at a Russian University in different historical periods.
The book is addressed to high school teachers, graduate students, and undergraduates.
Prediction of the development and susceptibility to acute mountain sickness (AMS) by monitoring oxygen saturation (SpO2) – literature review
Authors: Mazur Karol , Machaj Dominik , Jastrzębska Sandra , Płaczek Alicja , Mazur Dominika
Published: February 2020

The hypoxia is the main cause of altitude sickness, that usually starts from the benign form - acute mountain sickness (AMS), that being untreated can progress to the life-threatening states, like high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE).The aim of this study was to evaluate the role of monitoring oxygen saturation in prediction of the of the development and susceptibility to acute mountain sickness (AMS). Our study material consisted of publications, which were found in PubMed, ResearchGate and Google Scholar databases. The first step was to find proper publications from the last 25 years .The second step was to carry out an overview of the found publications. Based on this criteria, six publications have been qualifed for the study.There is strong relationship between development and susceptibility to acute mountain sickness (AMS) and hypoxia. But this topic is not fully understood and needs to be better researched. Monitoring oxygen saturation could prevent from the development and predcit the susceptibility to AMS. Pulse oxymetry could be also the indicator of adequate or inadequate acclimatization and high altitude performance.
Wpływ feministycznej krytyki języka na ustawodawstwo i język polityki w krajach niemieckojęzycznych
Authors: Bierzyński Zbigniew
Published: February 2020

The Influence of Feminist Criticism of Language Usage over Legislation and Language of Politics in German Language States In this article it is assumed that the feminist criticism of language usage had a significant influence over legislation and language of politics in German‑speaking countries, especially in Germany and Austria. This phenomenon is noticed for example in the General Act on Equal Treatment, the Austrian Federal Equal Treatment Act, the General Act of city Wädenswil in Switzerland, statements of German and Austrian political parties and politicians. This impact is shown in specific examples of law texts and statements of politicians. Furthermore, the aim of this article is to present the key points of feminist criticism of German language usage and the key ideas of language respecting both of genders (die geschlechtergerechte Sprache) or of gender‑neutral language (die geschlechtsneutrale Sprache). It is necessary to add that this article is only a short presentation of phenomenon of the feminism’s affect on German language of politics.