bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ1-42 decrease with age, whereas NT1 tau and NfL increase
Authors: Mengel David , Liu Wen , Glynn Robert J. , Selkoe Dennis J. , Strydom Andre , Lai Florence , Rosas H. Diana , Torres Amy , Patsiogiannis Vasiliki , Skotko Brian , Walsh Dominic
Published: December 2019

Background: Down syndrome (DS) is the most common genetic cause of Alzheimer’s Disease (AD), but diagnosis of AD in DS is challenging due to the intellectual disability which accompanies DS. When disease-modifying agents for AD are approved, reliable biomarkers will be required to identify when and how long people with DS should undergo treatment. Three cardinal neuropathological features characterize AD, and AD in DS – Aβ amyloid plaques, tau neurofibrillary tangles, and neuronal loss. Here, we quantified plasma biomarkers of all 3 neuropathological features in a large cohort of people with DS aged from 3 months to 68 years.Methods: Using ultra-sensitive single molecule array (Simoa) assays, we measured 3 analytes in plasmas of 100 individuals with DS and 100 age- and sex-matched controls. The analytes were: Aβ1-42, NfL, and tau. The latter was measured by an assay (NT1) which detects forms of tau containing at least residues 6-198.Results: High Aβ1-42 and NT1 tau, and low NfL, were observed in infants. Across all ages, Aβ1-42 levels were higher in DS than controls. Levels of Aβ1-42 decreased with age in both DS and controls, but this decrease was greater in DS than controls and became prominent in the third decade of life. NT1 tau fell in adolescents and young adults, but increased in older individuals with DS. NfL levels were low in infants, children, adolescents and young adults, but thereafter increased in DS compared to controls. Conclusions: High levels of Aβ1-42 and tau in both young controls and DS suggest these proteins are produced by normal physiological processes, whereas, the changes seen in later life are consistent with emergence of pathological alterations. Our plasma biomarker results are in good agreement with prior neuropathology studies and indicate that the third and fourth decades (i.e. 20 to 40 years of age) of life are pivotal periods during which AD processes manifest in DS. Application of the assays used here to longitudinal studies of individuals with DS aged 20 to 50 years of age, should further validate the use of these biomarkers, and in time may allow identification and monitoring of people with DS best suited for treatment with emerging AD therapies.
Is adiposity associated with objectively measured physical activity and sedentary time in older adults?
Authors: Zhu Wenfei , Cheng Zhiwei , Howard Virginia J. , Judd Suzanne E. , Blair Steven N. , Sun Yuliang , Hooker Steven P.
Published: December 2019

Background: Many older adults in the U.S. do not achieve the recommended amount of physical activity (PA) to fully realize a myriad of health benefits. Adiposity may be one of those important correlates of PA and sedentary behaviors. However, the full extent to which adiposity is associated with PA and sedentary time (SED) is uncertain. Therefore, we examined the association of adiposity with objectively measured PA and SED in black and white older adults. Methods: We conducted a cross-sectional study of older adults enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study 2003-2007 who participated in an ancillary accelerometer study 2009-2013. Assessment of body mass index (BMI) and waist circumference (WC) was completed during an in-home visit in the parent study. PA was measured by ActicalTM accelerometers, which provided estimates of moderate-to-vigorous-intensity PA (MVPA), light-intensity PA (LPA), and SED for 4-7 consecutive days. Data from accelerometers were standardized to square root percentages of total wear time per day (SqrtMVPA%, SqrtLPA%, and SqrtSED%). Interactions were tested for BMI and WC by race and sex, separately. Results: Data were available for 7,873 participants (69.8 ± 8.7 yr, 54.2% women, 31.5% African American). In mixed linear regression models, significant interactions existed in BMI by race and sex for the SqrtMVPA%, WC by race and sex for the SqrtMVPA% and the SqrtLPA% model(P<0.05). No interaction was significant for the logistic model of meeting the PA guideline or not. In subgroup analyses, BMI was inversely associated with SqrtMVPA%, SqrtLPA%, and positively related to SqrtSED% in black women, white men and white women after adjustments. Similar patterns were observed between WC and SqrtMVPA%, SqrtLPA%, and SqrtSED% in all groups, respectively. However, BMI was not associated with SqrtMVPA% in black men. Those with higher BMI or WC were less likely to meet the PA guideline in all groups. Conclusions: Adiposity was inversely associated with higher levels of MVPA/LPA and positively associated with higher levels of SED among black and white older adults. Prevention efforts aimed at promoting weight control may be beneficial to prevent physical inactivity and sedentary lifestyle among older adults.
Comparison of Seven in Silico methods for Evaluating of Ecotoxicological Acute Toxicity of Daphnia magna and Pimephales promelas: Case study on Chinese Priority Controlled Chemicals
Authors: Zhou Linjun , Fan Deling , Yin Wei , Gu Wen , Wang Zhen , Liu Jining , Xu Yanhua , Shi Lili , Liu Mingqing
Published: December 2019

Background: The acute toxicity on aquatic organisms are indispensable parameters in the ecological risk assessment priority chemical screening process (e.g. persistent, bioaccumulative and toxic chemicals). Currently, a number of predictive models for aquatic toxicity are available, however, the accuracy of in silico tools in priority assessment and risk assessment still remains to be further studied. Herein, this study evaluated the performance of seven Quantitative Structure–Activity Relationship (QSAR) in silico methods (Danish QSAR Database, Ecological Structure Activity Relationships, KAshinhou Tool for Ecotoxicity on PAS, Toxicity Estimation Software Tool, QSAR Toolbox, Read Across, and Virtual models for property Evaluation of chemicals within a Global Architecture) for assessing acute aquatic toxicity to Daphnia magna and Pimephales promelas using the first batch list of Priority Controlled Chemicals in China. Results: Based on the values for the median lethal dose and the US Environmental Protection Agency’s acute aquatic toxicity categories of concern, the acute toxicity grade was classified into six categories. According to the comparative prediction results, the accuracy of the Daphnia magna toxicity categories prediction was 25%–56%, the correlation coefficient ranged from 0.1236 to 0.6349, and the correlation coefficients of the applicability domain were 0.040 and 0.5148. The corresponding values for the Pimephales promelas toxicity categories prediction were 22%–44%, 0.1495–0.4144, 0.2156 and 0.6793. Conclusion: As the structure of chemicals of first batch list of Priority Controlled Chemicals in China are complex, the accuracy of model prediction is low, which depends on the quality of the constructed model and application domain. Although in silico methods can be used to preliminarily estimate aquatic toxicity, experimental data validation is still required for prioritizing environmental hazards assessments and risk assessments.
Role of C1q in spleen-derived neutrophil infiltration and neuroinflammation after ICH in mice
Authors: Tang Jun , Luo Tiantian , Geng Junjun , Zhang Bo , Niu Yin , Wang Ling , Jila Shiju , Feng Hua , Zhu Gang , Chen Zhi
Published: December 2019

Background: Neuroinflammation is a major detrimental role of secondary brain injury after spontaneously intracerebral hemorrhage (ICH). Neutrophil infiltration plays a key role in the pathophysiology of ICH, but the coming resource and mechanism is unknown. This study aims to investigate whether spleen-derived neutrophil infiltration accelerated neuroinflammation and the role of C1q classical pathway.Methods: Male C57 mice were subjected to collagenase-induced ICH. If necessary, splenectomy was performed 2 weeks prior to ICH induction or anti-C1q neutralizing antibody (50mg/kg) was injected intravenously into the tail vein 15 minutes prior. Immunohistochemistry, Propidium Iodide staining, western blotting, ELISA and qRT-PCR were used to study the change of molecular proteins, neuronal cells and inflammatory factors. 7.0T animal MRI was used to assess hydrocephalus.Results: At 0h, 6h, 12h, 24h and 48h post ICH induction, we found a significant increasing tendency of microglia activation and neutrophil infiltration around hematoma and that C1q upregulation was correlated with neuronal decrease, which peaked at 24h after ICH. Here, we demonstrated spleen atrophy and upregulation of neutrophil in spleen 24h after ICH. Splenectomy prior to ICH mice resulted in significant decrease of microglia and neutrophil infiltration compared with that in group of sham-splenectomy. Moreover, both anti-C1q antibody and splenectomy significantly attenuated neutrophil infiltration and neuron death, restored synapse VGAT, alleviated hydrocephalus and inflammatory factors, such as IL-1β, TNF-α and IL-6 after ICH.Conclusion: The study demonstrated that spleen is a major source of brain neutrophil infiltration after ICH. C1q-targeted inhibition of classic complement pathway could prevent spleen-derived neutrophil infiltration and attenuate ICH induced neuroinflammation, which provides a novel therapeutic approach for hemorrhagical stroke.
Construction of high copy number and highly stable Escherichia coli-Bacillus subtilis shuttle plasmids based on pWB980
Authors: Zhao XingYa , Xu JianYong , Tan Ming , Zhen Jie , Shu WenJu , Yang ShiBin , Ma YanHe , Zheng Hongchen , Song Hui
Published: December 2019

Background: pWB980 derived from pUB110 is a promising expression vector in Bacillus for its high copy number and high stability. However, the low transformation rate of recombinant plasmids to the wild cells limited the application of it. On the basis of pWB980, constructing an E. coli - B. subtilis shuttle plasmid could facilitate the transformation rate to Bacillus cells. Because the insertion site for E. coli replication origin sequence ( ori ) is not unique in pWB980, in order to investigate the best insertion site, eight shuttle plasmids (pUC980-1~pUC980-8) containing all possible insertion sites and directions were constructed.Results: The results showed that all the selected insertion sites could be used to construct shuttle plasmid but some sites required a specific direction. And different insertion sites led to different properties of the shuttle plasmids. The best shuttle plasmids pUC980-1 and pUC980-2, which showed copies more than 450 per cell and segregational stabilities up to 98%, were selected for heterologous expressions of an alkaline pectate lyase gene pelN , an alkaline protease spro1 and a pullulanase gene pulA11 , respectively. The highest extracellular activities of PelN, Spro1 and PulA11 were upto 5200 U/mL, 21537 U/mL and 504 U/mL correspondingly after 54 h, 60 h and 48 h fermentation in a 10 L fermentor. Notably, PelN and Spro1 showed remarkably higher yields in Bacillus than previous reports.Conclusion: In this work we can conclude that the optimum ori insertion site was the upstream region of BA3-1 in pWB980 which resulted in shuttle plasmids with higher copy numbers and higher stabilities. The novel shuttle plasmids pUC980-1 and pUC980-2 will be promising expression vectors in B. subtilis . And the ori insertion mechanism revealed in this work could provide theoretical guidance for further studies of pWB980 and constructions of other shuttle plasmids.
Study on Biodegradation Characteristics of Aryl Organophosphorus Flame Retardants (aryl-OPFRs) by Sphingobium yanoikuyae YC-XJ2
Authors: Li Xianjun , Wang Junhuan , Hlaing Thet Su , Jia Yang , Yan Yanchun
Published: December 2019

The preprint has been retracted as all authors did not agree to posting.
County level mortality and morbidity associated with PM2.5-related cancers in China based on satellite-derived PM2.5 data from 1998 to 2016: a forecasting and spatial analysis
Authors: Ju Ke , Liao WeiBin , Zhou Qian , Gao YaMin , Pan Jay
Published: December 2019

Background: Ambient fine particulate matter (PM2.5) pollution is becoming increasingly serious in China, and is a major risk factor for various cancers. Moreover, recent studies have indicated that there is an impact of PM2.5 from regional transport. We aimed to predict spatial distribution of cancers related to PM2.5, and draw a series of forecasting maps of these cancers. Methods: A 1000-loops simulation was done to choose the optimal forecasting model between five alternative models: ridge regression, partial least square regression, regression tree, model tree, and the combined forecasting model. Then a kriging interpolation method was used to draw the forecasted cancer maps. Results: The trend showed a gradual increase in the mortality and morbidity of breast cancer, pancreatic cancer, and all-cause cancer. We found a significant spatial autocorrelation between cancer incidence and PM2.5. Our results from forecasting showed a constant growth in mortality and morbidity of all cancers, and the kriging method suggested a similar spatial pattern. High morbidity and mortality areas were mainly in central-east and south-east China. We found a similar distribution pattern between PM2.5 concentration and mortality and morbidity associated with PM2.5-related cancers. Conclusions: These findings serve as a valuable reference for the development of effective policies to reduce air pollution emissions, with the efforts from governments in high-risk areas.
Identification of stable reference genes for qPCR studies in common wheat (Triticum aestivum L.) seedlings under short-term drought stress
Authors: Dudziak Karolina , Sozoniuk Magdalena , Szczerba Hubert , Kuzdraliński Adam , Kowalczyk Krzysztof , Börner Andreas , Nowak Michał
Published: December 2019

Background: Quantitative PCR (qPCR) is one of the most common and accurate methods of gene expression analysis. However, the biggest challenge for this kind of examinations is normalization of the results, which requires the application of dependable internal controls. The selection of appropriate reference genes (RGs) is one of the most crucial points in qPCR data analysis and for correct assessment of gene expression. Because of the fact that many reports indicate that the expression profiles of typically used RGs can be unstable in certain experimental conditions, species or tissues, reference genes with stable expression levels should be selected individually for each experiment. In this study, we analysed a set of ten candidate RGs for wheat seedlings under short-term drought stress. Our tests included five ‘traditional’ RGs (GAPDH, ACT, UBI, TUB, and TEF1) and five novel genes developed by the RefGenes tool from the Genevestigator database.Results: Expression stability was assessed using five different algorithms: geNorm, NormFinder, BestKeeper, RefFinder and the delta Ct method. In the final ranking, we identified three genes: CJ705892, ACT, and UBI, as the best candidates for housekeeping genes. However, our data indicated a slight variation between the different algorithms that were used. We revealed that the novel gene CJ705892, obtained by means of in silico analysis, showed the most stable expression in the experimental tissue and condition. Conclusions: Our results support the statement, that novel genes selected for certain experimental conditions have a more stable level of expression in comparison to routinely applied RGs, like genes encoding actin, tubulin or GAPDH. Selected CJ705892 gene can be used as a housekeeping gene in the expression analysis in wheat seedlings under short-term drought. The results of our study will be useful for subsequent analyses of gene expression in wheat tissues subjected to drought.
Beyond Health System Contact: Measuring and Validating Quality of Childbirth Care Indicators in Primary Level Facilities of Northern Ethiopia
Authors: Weldearegay Haftom Gebrehiwot , Medhanyie Araya Abrha , Godefay Hagos , Kahsay Alemayehu Bayray
Published: December 2019

Background: Measurement of quality of health care has been largely overlooked and continues to be a major health system bottleneck in monitoring performance and quality to evaluate progress against defined targets for better decision making. Hence, metrics of maternity care are needed to advance from health service contact alone to content of care. We assessed the accuracy of indicators that describe the quality of basic care for childbirth functions both at the individual level as well as at the population level in Northern Ethiopia. Methods: A validation study was conducted by comparing women’s self-reported coverage of maternal and newborn health interventions during intra-partum and immediate postpartum care received in primary level care facilities of Northern Ethiopia against a gold standard of direct observation by a trained third party (n=478). Sensitivity, specificity and individual-level reporting accuracy via the area under the receiver operating curve (AUC) and inﬂation factor (IF) to estimate population-level accuracy for each indicator was applied for validity analysis.Findings: 455(97.5%) of women completed the survey describing health interventions. Thirty-two (43.2%) of the 93 basic quality child birth care indicators that were assessed could be accurately measure at the facility and population level (AUC>0.60 and 0.75<IF<1.25). Few of the valid indicators were: whether women and their companion were greeted respectfully, whether an HIV test was offered, and whether severe bleeding (hemorrhage) was experienced by the woman. An additional 21(28.4%) indicators accurately measure at the facility or individual level, but the indicators under or over estimate at population level. Thirteen other indicators could accurately measure at population level. Eight (8.6%) indicators didn’t meet either of the validity criteria. Conclusion: Women were able to accurately report on several indicators of quality for basic child birth care. For those few indicators that required a technical understanding tended to have higher don’t know response from the women. Therefore, valid indicators should be included as a potential measurement of quality for the childbirth care process to ensure that essential interventions are delivered.
In vivo comparison of the biodistribution and toxicity of InP/ZnS quantum dots with different surface functional groups
Authors: Li Li , Chen Yajing , Xu Gaixia , Liu Dongmeng , Yang Zhiwen , Chen Tingting , Wang Xiaomei , Jiang Wenxiao , Xue Dahui , Lin Guimiao
Published: December 2019

Background: Indium phosphide (InP) quantum dots (QDs) have shown a broad application prospect in the fields of biophotonics and nanomedicine. However, the potential toxicity of InP QDs has not been systematically evaluated. In particular, the effects of different surface modifications on the biodistribution and toxicity of InP QDs is still unknown, which hinders their further developments. The present study aims to investigate the biodistribution and in vivo toxicity of three types of InP/ZnS QDs with different surface modifications, hQDs (QDs-OH), aQDs (QDs-NH2), and cQDs (QDs-COOH) respectively. These InP/ZnS QDs with 2.5 mg/kg BW or 25 mg/kg BW were intravenously injected into BALB/c mice. Biodistribution of three QDs was determined through cryosection fluorescence microscopy and ICP-MS analysis. The subsequent effects of InP/ZnS QDs on histopathology, hematology and blood biochemistry were evaluated at 1, 3, 7, 14 and 28 days post-injection.Results: The results showed these types of InP/ZnS QDs QDs were rapidly distributed in the major organs of mice, mainly in the liver and spleen, and lasted for 28 days. No abnormal behavior, weight change or organ index were observed during the whole observation period, except that 2 mice died on Day 1 after 25 mg/kg BW hQDs treatment. The results of H&E staining showed that no obvious histopathological abnormalities were observed in the main organs (including heart, liver, spleen, lung, kidney, and brain ) of all mice injected with different surface functionalized QDs. Low concentration exposure of three QDs hardly caused obvious toxicity, while high concentration exposure of the three QDs could cause some changes in hematological parameters or biochemical parameters related to liver function or cardiac function. More attention need to be paid on cQDs as high dose exposure of cQDs induced death, acute inflammatory reaction and slight changes in liver function in mice.Conclusions: Generally speaking, the surface modification and exposure dose can influence the biological behavior and in vivo toxicity of QDs. The surface chemistry should be fully considered in the design of InP-based QDs for their biomedical applications. Keywords: InP/ZnS quantum dots, surface chemistry, in vivo, biodistribution, nanotoxicology
Treatment Characteristics and Outcomes in 58 Children with Spinal Cord Injury
Authors: Li Yongqiang , Ge Panli , Huang Yingjun , Wang Yingjie , Li Jianan
Published: December 2019

Background: Spinal cord injury (SCI) can change an individual’s life significantly and usually irreversibly. Recently, the incidence of spinal SCI in children has shown an upward trend. Many of them arise from back bends in dances. SCI can cause great suffering and dysfunction to children because they are still in the physical development stage and the degree of injury and prognosis are different from adults. This study aimed to analyze the characteristics of children with SCI and their prognosis, to study the causes of these injuries, and to explore rehabilitation strategies for children with SCI. Methods: The clinical data of children with SCI, including general conditions, cause and degree of injury, and effects of rehabilitation were analyzed and evaluated. Results: Out of the 58 patients, 22 (37.93%) had SCI at and above T6, 34 (58.62%) at T7-T12, and 2 (3.45%) at and below L1. The injuries were caused by a back bend in 35 cases (60.34%) and by traffic accidents in eight cases (13.79%). Upon discharge, seven patients (12.07%) achieved independent walking ability, 33 (56.90%) realized wheelchair independence, and 46 (79.31%) attained basic or complete self-care ability. Fifty-six (96.55%) of these children with SCI experienced bladder dysfunction, 55 (94.83%) experienced rectal dysfunction, and 20 (34.48%) had scoliosis. Conclusions: Children with incomplete SCI are able to gain a great degree of functional recovery while children with complete SCI can achieve better independent living ability through active comprehensive rehabilitation training.
Popular Perceptions of Bats Hinder Conservation Actions in Maranhão, Northern Brazil
Authors: Silva Janete Santos , Silva Naiara Pereira , Santana Ewaldo Eder Carvalho , Andrade Fernanda Atanaena Gonçalves , Fraga Elmary Costa , Barros Maria Claudene , Olímpio Ana Priscila Medeiros
Published: December 2019

Background: Bats play an important role in the ecology of many environments, although the general lack of knowledge on the relevance of these animals hinders initiatives that contribute to the development of favorable attitudes and participative measures that promote the conservation of these animals and the ecosystems they inhabit. In the present study, 398 residents of eight neighborhoods of the town of Caxias in Maranhão, Brazil, were interviewed to verify their perceptions of bats.Methods: A total of 398 individuals were interviewed during the present study. The interviewees were between 17 and 91 years old, and two-thirds (263; 66%) were women, while the other 135 were men (34%).Results: Most of the interviewees described bats as ugly and disgusting animals that look like rats, feed primarily on fruit, and frighten people. These individuals also confirmed that bats are important for Nature and should be protected simply because they are living creatures. The analyses indicate a significant association between a fear of bats and the belief that all these animals are vampires, and also that women are more likely to have a fear of bats than men. There was also an association between a low education level and the belief that all bats are vampires.Conclusions: The present study provides important insights into the perception of bats by the local population, highlighting the prevalence of mythical beliefs, which hinder the implementation of effective conservation measures. The results of this study reinforce the need for initiatives in environmental education that provide more reliable information on the biology of bats and their ecological importance, thereby contributing to the conservation of bat diversity.
The independent indicators of contrast-enhanced ultrasound for predicting renal cell carcinoma
Authors: Cao Hongli , Fang Liang , Chen Lin
Published: December 2019

Background: The value of contrast-enhanced ultrasound (CEUS) in differentiating between renal cell carcinoma (RCC) and angiomyolipoma (AML) was analyzed. The purpose of this study was to identify the independent indicators of CEUS for predicting RCC. Methods: A total of 172 renal tumors (150 RCCs, 22 AMLs) in 165 patients underwent conventional ultrasound (CUS) and CEUS examinations before radical or partial nephrectomy, and the features on CUS and CEUS were analyzed. Results: There were significant differences in echogenicity, blood flow signals in color Doppler flow imaging (CDFI), peak intensity, homogeneity of enhancement, wash in, wash out, and perilesional rim-like enhancement between RCC and AML (P<0.05 for all). Multivariate analysis indicated that perilesional rim-like enhancement (P=0.035, odds ratio [OR]=9.907, 95% confidence interval [CI]: 1.169-83.971) and fast wash out (P=0.001, OR =9.755, 95%[CI]: 2.497-38.115) were independent indicators for predicting RCC. The area under the receiver operating characteristic (ROC) curve (AUC) for perilesional rim-like enhancement was 0.838 (95% CI:0.774-0.890) with 76.7% sensitivity and 90.9% specificity, while the AUC of fast wash out was 0.833 (95% CI:0.768-0.885) with 74.7% sensitivity and 81.8% specificity. Conclusions: This study indicated that CEUS has value in differentiating RCC and AML. Present perilesional rim-like enhancement and fast wash out may be important indicators for predicting RCC.
The Application and Accuracy of Feature Matching on Automated Cephalometric Superimposition
Authors: Jiang Yiran , Song Guangying , Yu Xiaonan , Dou Yuanbo , Li Qingfeng , Liu Siqi , Han Bing , Xu Tianmin
Published: December 2019

Background: The aim of this study was to establish a computer-aided automated method for cephalometric superimposition and evaluate the accuracy of this method based on free-hand tracing. Methods: 28 pairs of pre-treatment (T1) and post-treatment (T2) cephalograms were selected. Structural superimpositions of the cranial base, maxilla and mandible were independently completed by three operators performing traditional hand tracing methods and by computerized automation using the feature matching method. To quantitatively evaluate the differences between the two methods, the manually superimposed patterns were digitized. In addition to registering automated and manual superimposition to digital T1 films, landmark distances between corresponding automated and manual T2 cephalometric landmarks were measured, and differences in manual superimposition among the operators were calculated. Results: The T2 landmark differences in hand tracing between the operators ranged from 0.61 mm to 1.65 mm for the three types of superimposition. There were no significant differences in accuracy between manual and automated superimposition (p > 0.05). Conclusions: Computer-aided cephalometric superimposition provides comparably accurate results to those of traditional hand tracing and will provide a powerful tool for academic research in the era of digital cephalograms and big data. Trial registration: The clinical trial has been registered in April 1st 2016, the registration number is ChiCTR1800017694, URL is: http://www.chictr.org.cn/showproj.aspx?proj=29144
Combination of Antibiotic, Efflux Pump Inhibitor and Autolysis Inhibitor Protects Mice from S. aureus Peritonitis by Inhibiting α-hemolysin-induced MAPKs/NF-κB/NLRP3 Activation
Authors: Luan Wenjing , Liu Xiaolei , Wang Xuefei , An Yanan , Wang Yang , Wang Chao , Ni Lihui , Ma Fangxue , Zhou Hong , Liu Mingyuan , Yu Lu
Published: December 2019

Background: The infection of staphylococcus aureus (S. aureus) is difficult to treat, our aim was to investigate the antibacterial abilities of a combination of antibiotic cloxacillin, efflux pump inhibitor thioridazine and autolysis inhibitor tetracycline and its anti-inflammation properties through inhibiting α-hemolysin induced MAPKs/NF-κB/NLRP3 activation in vitro and in vivo. Methods: The antibacterial susceptibility test and three-dimensional checkerboard method were utilized to investigate the synergistic antibacterial activity of the three-drug combination cloxacillin/thioridazine/tetracycline, α-hemolysin test and scanning electron microscope were used to assay the inhibition effects of the combination on the secretion of α-hemolysin and membrane-derived vesicles production from S. aureus, Western blot and pharmacological inhibition assays were performed to test α-hemolysin -induced MAPKs/NF-κB/NLRP3 activation in macrophage in vitro. Results: In vitro, the three-drug combination showed synergistic antistaphylococcal activity; the subinhibitory concentration of the combination significantly inhibited the secretion of α-hemolysin related to the number of vesicles produced by S. aureus and significantly inhibited the expression of MAPKs/NF-κB/NLRP3 proteins in the macrophages induced by S. aureus α-hemolysin. In vivo, the drug combination significantly reduced bacterial colony-forming unit counts of the viscera in mouse peritonitis model of S. aureus infection, the combination therapy reduced the primary inflammatory pathology and the release of bacterial-stimulated cytokines such as IL-1β and TNF-α, and inhibited the expression of MAPKs/NF-κB/NLRP3 proteins in peritoneal macrophage. Conclusions: Combination of antibiotic, efflux pump inhibitor and autolysis inhibitor owns good antistaphylococcal activity and significantly inhibit staphylococcal α-hemolysin and its inflammation, thus, the combination is a novel strategy of antibacterial and anti-inflammation.
Molecular epidemiology of drug resistant Mycobacterium tuberculosis in Africa: a systematic review
Authors: Chisompola Namaunga Kasumu , Streicher Elizabeth Maria , Muchemwa Chishala Miriam Kapambwe , Warren Robin Mark , Sampson Samantha Leigh
Published: December 2019

Background The burden of drug resistant tuberculosis (TB) in Africa is largely driven by the emergence and spread of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis strains. The highest burden of drug resistant TB is seen in countries further experiencing an HIV epidemic, resulting in high HIV/TB co-morbidity rates. The molecular mechanisms of drug resistance as well as the evolution of drug resistant TB strains have been widely studied using various genotyping tools. Viewed as a whole, this can give a better insight into the transmission dynamics of drug resistant TB in Africa.Methods A systematic review was performed on peer reviewed original research extracted from PubMed reporting on the molecular epidemiology of drug resistant TB from African countries. The search terms “Tuberculosis AND drug resistance AND Africa AND (spoligotyping OR molecular epidemiology OR IS6110 OR MIRU OR DNA fingerprinting OR RFLP OR VNTR OR WGS)” were used to identify relevant articles reporting the molecular epidemiology of drug resistant TB in Africa. Only studies reporting on the molecular epidemiology of drug resistant TB in Africa were included in the analysis.Results Diverse genotypes are associated with drug resistant TB in Africa, with variations in strain predominance within the continent. It has been demonstrated that drug resistant TB strains are associated with community and nosocomial outbreaks. Outbreaks have been described both in immunocompromised and immunocompetent individuals, involving MDR- and XDR-TB strains. Furthermore, the role of migration in the transmission of drug resistant TB strains has been demonstrated in certain parts of Africa. Of concern is the under-use of molecular epidemiological tools, resulting in gaps in knowledge of the transmission dynamics of drug resistant TB on the continent.Conclusions Genetic diversity of M. tuberculosis strains has been demonstrated across Africa implying that diverse genotypes are driving the epidemiology of drug resistant TB across the continent. To address knowledge gaps, there is a need for routine surveillance and extensive epidemiological investigations across the continent.
Risk factors associated with scrub typhus infection: A case-control study from Luhe, China
Authors: Musa Taha Hussein
Published: December 2019

Background: Globally, Scrub typhus (ST) is a serious public health issues in the rural of Asia-Pacific area. This study aimed to determine the risk factors associated with ST infection in Luhe District, China. Methods: The case-control study was conducted which involved (N=116) cases consisted of a patient who diagnosed with scrub typhus, and nearest neighbours control (N=232) subjects were selected by matching for occupation, place of residence and age (within 5-years) and lacked a history of scrub typhus. Statistical analysis was performed using SPSS version 25.0 for Windows. Results: The mean age of confirmed cases was 58.1(10.15) years, while that of control subjects were 56.14 (11.57). The ratio of farmers in cases and controls subjects was 90 (77.6%) and 187 (80.6%) respectively. There are no significant differences in the demographic characteristics of the study population (P>0.05). Factors including residential site (χ2=8.57, P=0.05), raising small animal and livestock (χ2=31.53, P<0.001), living in the house near to grassland and vegetable (χ2=16.61, P<0.001), piling weeds in the yard (χ2=15.48, P<0.001), piling weed inside the house and around the house (χ2=56.64, P<0.001), and presence of mouse activities in the house (χ2= 3.88, P<0.054) are significant associated with developing of ST infection. The logistic regression analysis showed that Two out of five general exposure factors were identified which include morning exercise in the park (AOR=3.848, 95% CI=1.018-4.544, P=0.047), and working as labourers in vegetable fields (AOR =1.792, 95% CI=1.12-2.87, P=0.016) posed a significant association with ST infection. Conclusions: The people who tend to involved in outdoor activities are exposure to ST infection. The findings derived from this study provide an information in the control and prevention of ST in Luhe, China.
Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis
Authors: Searson Peter , Linville Raleigh M. , Arevalo Diego , Maressa Joanna C. , Zhao Nan
Published: December 2019

Background: During brain development, chemical cues released by developing neurons, cellular signaling with pericytes, and mechanical cues within the brain extracellular matrix (ECM) promotes angiogenesis occurs of brain microvascular endothelial cells (BMECs). During brain disease, angiogenesis can also occur due to pathological chemical, cellular, and mechanical signaling. Existing in vitro and in vivo models of brain angiogenesis have key limitations. Methods: Here, we develop a high-throughput in vitro BBB bead assay of brain angiogenesis utilizing 150 μm diameter beads coated with induced pluripotent stem-cell (iPSC)-derived human BMECs (dhBMECs). After embedding the beads within a 3D matrix, we introduce various chemical cues and extracellular matrix components to explore their effects on angiogenic behavior. Based on the results from the bead assay, we generate a multi-scale model of the human cerebrovasculature within perfusable three-dimensional tissue-engineered blood-brain barrier (BBB) microvessels. Results: A sprouting phenotype is optimized in confluent monolayers of dhBMECs using chemical treatment with vascular endothelial growth factor (VEGF) and wnt ligands, and the inclusion of pro-angiogenic ECM components. As a proof-of-principle that the bead angiogenesis assay can be applied to study pathological angiogenesis, we show that oxidative stress can exert concentration-dependent effects on angiogenesis. Finally, we demonstrate the formation of a hierarchical microvascular model of the human blood-brain barrier displaying key structural hallmarks. Conclusions: We develop two in vitro models of brain angiogenesis: the BBB bead assay and the tissue-engineered BBB microvessel model. These platforms provide a tool kit for studies of physiological and pathological brain angiogenesis, with key advantages over existing two-dimensional models.
Meta-analysis of the pharmacogenetics of ARMS2 A69S polymorphism and the response to advanced age-related macular degeneration
Authors: Zhang Jun , Liu Zhaohui , Hu Shuqiong , Qi Jian
Published: December 2019

Background Age-related macular degeneration (AMD) causes irreversible vision loss, and targeted anti-vascular endothelial growth factor (VEGF) therapy is now the most common and effective treatment. The aim of this meta-analysis is to discuss whether genetic polymorphism of ARMS2 A69S could confer susceptibility to advanced AMD with the response to anti-VEGF treatment.Methods We performed a meta-analysis of relevant published studies selected through electronic databases. A total of 21 preferred studies regarding the association between ARMS2 gene and anti-VEGF treatment response in advanced AMD were generally included in the meta-analysis.Results The pooled results demonstrated that the carriage of G allele for ARMS2 A69S presented a better clinical prognosis for advanced AMD treated with anti-VEGF drugs (OR=1.38, 95% CI=1.13-1.69, P=0.002). Additionally, in the subgroup analysis based on ethnicity, ARMS2 polymorphisms were more likely to be a positive responder for East Asian patients (OR=1.67, 95% CI=1.29-2.16, P<0.001).Conclusion This meta-analysis through a series of rigorous methodology data demonstrated a significant association between ARMS2 A69S polymorphism and the anti-VEGF treatment response in advanced AMD, especially among East Asian population. Numerous well-designed, randomized, multicenter clinical trials with large sample size are required to validate the association.
Mindfulness-based interventions for children and adolescents: A scoping review protocol
Authors: Perrier Marie-France , Flowers Heather , Gurgel-Juarez Nalia Cecilia , McCormick Anna , Short Sarah J.
Published: December 2019

Background and purpose: Although mindfulness-based interventions (MBIs) are becoming increasingly popular, the application of MBIs with children and adolescents is still in its infancy. Mapping the existing literature is necessary to help guide pediatric mindfulness interventions. Our purpose is to synthesize the evidence of reported MBIs for children and adolescents with and without physical, mental, and cognitive disorders. Accordingly, we aim to identify trends and gaps in the literature, so that we can provide direction to researchers who seek to advance the evidence base for using MBIs in pediatric populations. Methods: Our search strategy will be conducted following Arksey and O’Malley’s methodological framework. It will include a comprehensive search of published studies in 7 databases, the grey literature, conference proceedings, and citations of selected articles. Two independent reviewers will evaluate all abstracts and full articles that: i) have a pediatric sample (children 2-18 years), ii) use MBIs to promote development or to remediate underlying disorders, and iii) are written in English or French. We will identify the definitions and concepts from MBIs, categorize accepted studies according to etiology and rehabilitation type, describe intervention methodology, and report outcomes of selected studies. Discussion: Our review will provide a comprehensive overview of the pediatric mindfulness intervention literature to date, involving a range of mental, cognitive and physical outcomes for healthy children and adolescents and for those with a variety of disorders in clinical and institutional settings. We will disseminate results to mindfulness practitioners and provide guidance to future pediatric researchers in their development and application of mindfulness interventions, thereby contributing to the scientific understanding of mindfulness for the ultimate betterment of child and adolescent well-being and life-long functioning. Systematic review registration: PROSPERO does not accept scoping review protocols.
A retrospective study in Chinese infertility patients to investigate pregnancy outcomes of gonadotropin-releasing hormone antagonist in in vitro fertilization/intracytoplasmic sperm injection cycles: The FASSION study
Authors: Li Rong , Yang Rui , Sheng Yan , Gong Fei , Liu Jianqiao , Ding Ying , Chang Peter , Qiao Jie
Published: December 2019

Background The prevalence of infertility among Chinese women of reproductive age was estimated to be 25.0%. Currently, assisted reproductive technology, such as in vitro fertilization (IVF), is considered the most effective treatment for infertility. Cetrorelix is a subcutaneously administered gonadotropin-releasing hormone antagonist approved for clinical use in IVF therapy. To improve IVF outcomes, there is a need to identify predictive markers of successful clinical pregnancy with gonadotropin-releasing hormone antagonists.Methods The retrospective FASSION study assessed clinical outcomes and factors associated with clinical pregnancy rates of Chinese patients undergoing fertility treatment with cetrorelix and IVF/intracytoplasmic sperm injection (ICSI) cycles. We analyzed medical records of infertile women aged ≤35 years, with baseline serum follicle-stimulating hormone level ≤10 mIU/mL, body mass index ≤30 kg/m2 and normal uterine cavity, who underwent IVF/ICSI cycles using cetrorelix at four centers in China. The primary objective was identifying factors associated with clinical pregnancy rates by validating a predictive model for clinical outcome evaluation. Secondary objectives were clinical outcomes and safety.Results In total, 2972 women were included. After adjusting for confounders, on the day of human chorionic gonadotropin triggering, an increased endometrial thickness was associated with a higher probability of pregnancy outcome (p=0.0001) and a higher progesterone level was associated with a lower probability of pregnancy outcome after fresh embryo transfer (ET) per initiated cycle (p=0.0256). Per ET cycle, the ongoing pregnancy and clinical pregnancy rates were 45.2% and 53.0%, respectively, with an implantation rate of 37.3% per ET. The early miscarriage and cycle cancellation rates were 13.4% and 5.7%, respectively. A total of 970 live births were reported. The live birth rate per initiated cycle was 32.6% and that per ET cycle was 45.2%. Fifty-one patients (1.7%) reported an ovarian hyperstimulation syndrome event, with severe events in 17 (0.6%) patients.Conclusions This prediction model may be useful for the preliminary screening of IVF patients and help improve clinical pregnancy outcomes.
Exclusive breastfeeding practice and associated factors among first time mothers in Bahir Dar city, North West Ethiopia, 2016: A cross sectional study.
Authors: Ayalew Tilksew Abitie
Published: December 2019

Background: Exclusive breastfeeding means infants were fed only breast milk, not even water, one day (24 hrs.) before the survey was conducted. It is considered as core practice to achieve almost all 2030 Sustainable Development Goals, specifically sustainable development goal 2 which focuses in ending hunger and improving nutrition and goal 3 which focuses in reducing child and maternal mortality. The objective of this study was to assess the prevalence of exclusive breastfeeding practice and its associated factor among first time mothers in Bahir Dar city, North West Ethiopia.Method: A community based quantitative cross sectional study was carried out from March to April, 2016 among 423 first time mothers in Bahir Dar city. Study participants were selected by busing simple random sampling method i.e., lottery method. Data on infant feeding practice were collected by trained interviewers who used a structured questionnaire. Both binary and multivariable logistic regression were used to determine factors associated with exclusive breastfeeding. Statistical significance was declared at P -value <0.05.Results: Prevalence of exclusive breastfeeding practice 24 hours before the survey was 57.3 %( 95%CL: 52.3%, 62%). Mothers not being married (AOR 2.787,95 %CI: 1.083, 7.171), were supported by their husband (AOR 3.658, 95%CI: 2.132, 6.278), with no breast complication (AOR 3.658, 95% CI: 2.132, 6.278), who had four or more antenatal care follow up (AOR 2.512, 95%CI: 1.494, 4.233) were more likely to practice exclusive breastfeeding. On the other hand, mothers who were living in nuclear family (AOR 0.48, 95%CI: 0.231, 1.001) were less likely to practice exclusive breastfeeding. Conclusion: The prevalence of exclusive breastfeeding practice in the study area was lower than the national recommended level. In this study maternal age, number of antenatal care visits, husband support, breast complication and type of family were predictors of exclusive breastfeeding. Involving partners during infant feeding counseling and education, creating awareness about breastfeeding, special attention for the first time mothers, and prenatal education for expectant parents were recommended to improve exclusive breastfeeding among first time mothers.
Risky Sexual Behaviors and Condom Use Barriers in Women with Substance Use Disorders, Iran
Authors: Khoei Effat Merghati , Mohraz Minoo , Rezaei Zahed , Azadi Nammam Ali , Bayat Alireza , Salimi Farahnaz , Killeen Therese , Korte Jeffrey E.
Published: December 2019

Background Scant information exists on Iranian women's protective behaviors mainly constant condom use. This seems prevalent among women with drug abuse problems. We aimed to investigate risky sexual behaviors (RSBs) and condom use barriers in Iranian female with substance use disorders (SUDs).Methods In our cross-sectional study, we recruited 300 women who sought treatments for their SUDs from outpatient drug free (ODF) and Methadone Maintenance Therapy (MMT) centers. We selected active centers in Tehran, Iran (N#6). We use three batteries including demographic questionnaire, the Risky Sexual Behavior Questionnaire (RSBQ), and the Condom Barriers Scale (CBS). The statistical software R, analysis of variance post hoc and multivariate analysis of variance (MANOVA) logistic regression tests were used in data analysisFindings we recruited 300 women who sought treatments for their SUDs from outpatient drug free (ODF) and Methadone Maintenance Therapy (MMT) centers. We use three batteries including demographic questionnaire, the Risky Sexual Behavior Questionnaire (RSBQ), and the Condom Barriers Scale (CBS). Analysis of variance post hoc and multivariate analysis of variance (MANOVA) logistic regression tests were used in data analysisConclusion RSBs was prevalent among our study population. Our results suggest that RSBs and condom use barriers are significantly interwoven. The condom use barriers were highly associated with the types of sexual encounters such as group sex or casual sexual relations than specific mean of sexual performance (i.e anal sex). Gender-specific SRB, STIs/HIV/AIDS prevention program is recommended for women with SUDs.