bluuebunny/crossref_metadata_2025 huggingface dataset:
A mink (Neovison vison) model of self injury: effects of CBP-CREB axis on nerve injury and behavior
Authors: Liu Chunxiao , Guo Xiaolan , Si Huazhe , Li Guangyu
Published: July 2020

BackgroundSelf-injurious behavior (SIB) is a clinically challenging problem within both the general population and several clinical disorders. However, the precise molecular mechanism of SIB is still confused, and few animal models exist. Here, we systematic investigated the genesis and development of SIB based on behavioral and pathophysiology study in mink (Neovison vison) models.MethodWe used night-vision video to observe the mink behavior for four weeks,HE stain was performed to characteristic the pathology change of brain. We performed IHC assay to detect the protein level of Iba-1、p-CREB 、CBP and p300 in the brain tissues. Elisa assay used to examined the levels of NfL and NfH in serum and CSF of mink. qRT-PCR assay was mused to detected the expression of Bcl2, NOR1, FoxO4、c-FOS、CBP and p300 in brain tissues. Western blot was used to detect the protein levels of p-CREB、CBP and p300 in brain tissues. We also used Evans Blue as a tracer to detect whether the blood brain barrier was impaired in the brain of mink.RusultFirst we combine behavioral testing, histopathological and molecular biology experiments found that CBP was related with SIB. Mechanism analysis showed that the dysregulation of CBP in brain activated CREB signaling, resulting in nerve damage of brain and SIB symptoms in minks. Importantly, the CBP-CREB interaction inhibitor helped to relieve SIB and nerve damage in brain tissues.ConclusionOur results illustrate an induction of CBP and an activation of CREB, as a novel mechanism in the genesis of SIB. These finding indicate that CBP-CREB axis is critical for SIB and demonstrate the efficacy of the CBP-CREB interaction inhibitor in treating these behaviors.
Molecular dynamics simulation and experimental study of the surface-display of SPA protein via Lpp-OmpA system for screening of IgG
Authors: Vahed Majid , Ramezani Fatemeh , Tafakori Vida , Mirbagheri V.S. , Najafi Akram , Ahmadian Gholamreza
Published: July 2020

Staphylococcal protein A (SpA) is a major bacterial virulence factor of Staphylococcus aureus. S. aureus is capable of escaping from immune system recognition by the surface display of protein A. The SpA protein is broadly used to purify immunoglobulin G (IgG) antibodies. This study investigates the ability of the fusion of Lpp’-OmpA (46 − 159) to anchor and display five repeat domains of protein A with 295 residues length (SpA295) of S. aureus on the Escherichia coli cell surface to develop a novel bioadsorbent. First, the binding between Lpp’-OmpA-SPA295 and IgGFc and anticipation of this structure was investigated using molecular dynamics simulation. Then high IgG recovery from human serum by the surface-displayed system of Lpp’-OmpA-SPA295 performed experimentally. In silico analysis showed the binding potential of SPA295 to IgG after surface expression on LPP-OmpA. Surface-engineered E. coli displaying SpA protein and IgG-binding assay with SDS-PAGE analysis exhibited the high potential of the expressed complex on the surface of E. coli for IgG recapture from human serum which is applicable to conventional immune precipitation.
Integrated Blood Pressure-Chemical Sensing Epidermal Patch
Authors: Sempionatto Juliane , Lin Muyang , Yin Lu , Paz Ernesto de la , Pei Kexin , Sonsa-ard Thitaporn , Silva Andre de Loyola , Khorshed Ahmed , Zhang Fangyu , Tostado Nicholas , Xu Sheng , Wang Joseph
Published: July 2020

The growing demand for tracking the effects of diverse daily activities upon the body physiological response calls for continuous monitoring devices, with integrated hemodynamic and metabolic sensing modalities. This work presents the first demonstration of an integrated wearable sensor that monitors the blood pressure and heart rate via ultrasonic transducers, along with parallel non-invasive electrochemical detection of biomarker levels, such as glucose, lactate, caffeine, and alcohol, in sweat and interstitial fluid. Such simultaneous non-invasive blood-pressure/chemical sensing was implemented by monitoring the dynamic effects of everyday activities, such as exercise and intake of food and drinks, upon the user’s physiological states. Leveraging novel material selection and assembly processes, the multiplexed sensing modalities were optimized to ensure reliable sensing without crosstalk between individual sensors, along with mechanical resiliency and flexibility for conformal contact to curved skin surfaces. The simultaneous acoustic and electrochemical sensors were evaluated on multiple human subjects under different stimuli, and the dynamic correlation of the hemodynamic activities and corresponding metabolic variations was monitored and discussed. Such multimodal blood-pressure/chemical wearable sensor offers a collection of previously unavailable information towards enhancing our understanding of the body’s response to common activities while holding considerable promise for predicting abnormal cardiac events and improving remote, telemetric, and personalized healthcare medical outcome.
Hippocampal spatial and sequential representations of event structure scaffold precise episodic temporal order memory
Authors: Liu Chuqi , Ye Zhifang , Chen Chuansheng , Axmacher Nikolai , Xue Gui
Published: July 2020

The hippocampus plays an important role in representing spatial locations and sequences and for transforming representations via pattern separation and completion. How these representational structures and operations support memory for the temporal order of random items is still poorly understood. We addressed this question by leveraging the method of loci (MOL), a powerful mnemonic strategy for temporal order memory that particularly recruits hippocampus-dependent computations of spatial locations and associations. Applying representational similarity analysis to fMRI activation patterns revealed that hippocampal subfields contained representations of both temporal context and multiple features of sequence structure, including location identity, distance, and sequence boundaries. Critically, the hippocampal CA1 and CA23DG exhibited spatial and sequential pattern separation, respectively, enabling the encoding of multiple items in the same location and reducing swap errors across adjacent locations. Our results suggest that the hippocampus can flexibly reconfigure multiplexed event structure representations to support accurate temporal order memory.
Gut microbiota and fecal metabolites in captive and wild North China leopard (Panthera pardus japonensis) by comparsion using 16s rRNA gene sequencing and LC/MS-based metabolomics
Authors: Cao Heqin , Hua Yan , Wang Jiao , He Fengping , Jiang Guangshun
Published: July 2020

Background: Gut microbes significantly contribute to nutrient digestion and absorption, intestinal health and immunity, and are essential for the survival and environmental adaptation of wild animals. However, there are few studies on the gut microbiota of captive and wild North China leopard (Panthera pardus japonensis). Results: A total of 10 mainly bacterial phyla were identified in the fecal microbiota of North China leopard, Lachnoclostridium (p = 0.003), Peptoclostridium (p = 0.005), Bacteroides (p =0.008), Fusobacterium (p = 0.017) and Collinsella (p = 0.019) were significantly higher than those of wild North China leopard. Distinct differences in the fecal metabolic phenotypes of captive and wild North China leopard were found, such as content of l-methionine, n-acetyl-l-tyrosine, pentadecanoic acid and oleic acid. Differentially abundant gut microbes were associated with fecal metabolites, especially the bacteria in Firmicutes and Bacteroidetes, involved in the metabolism of N-acetyl-L-alanine and D-quinovose.Conclusion: This study reports for the first time the differences in gut microbiota abundance between captive and wild North China leopard, as well as significant differences in fecal metabolic phenotypes between two groups.
Comparative Analysis of Human Microglial Models for Studies of HIV Replication and Pathogenesis
Authors: Rai Mohammad A , Hammonds Jason , Pujato Mario , Mayhew Christopher , Roskin Krishna , Spearman Paul
Published: July 2020

Background: HIV associated neurocognitive disorders cause significant morbidity and mortality despite the advent of highly active antiretroviral therapy. A deeper understanding of fundamental mechanisms underlying HIV infection and pathogenesis in the central nervous system is warranted. Microglia are resident myeloid cells of the brain that are readily infected by HIV and may constitute a CNS reservoir. We evaluated two microglial model cell lines (C20, HMC3) and two sources of primary cell-derived microglia (monocyte-derived microglia [MMG] and induced pluripotent stem cell-derived microglia [iPSC-MG]) as potential model systems for studying HIV-microglia interactions. Results: All four microglial model cells expressed typical myeloid markers with the exception of low or absent CD45 and CD11b expression by C20 and HMC3, and all four expressed the microglia-specific markers P2RY12 and TMEM119. Marked differences were observed upon gene expression profiling, however, indicating that MMG and iPSC-MG cluster closely together with primary human microglial cells, while C20 and HMC3 were similar to each other but very different from primary microglia. Expression of HIV-relevant genes also revealed important differences, with iPSC-MG and MMG expressing relevant genes at levels more closely resembling primary microglia. iPSC-MG and MMG were readily infected with R5-tropic HIV, while C20 and HMC3 lack CD4 and require pseudotyping for infection. Despite many similarities, HIV replication dynamics and HIV-1 particle capture by Siglec-1 differed markedly between the MMG and iPSC-MG. Conclusions: MMG and iPSC-MG appear to be viable microglial models that are susceptible to HIV infection and bear more similarities to authentic microglia than two transformed microglia cell lines. The observed differences in HIV replication and particle capture between MMG and iPSC-MG warrant further study.
Molecular Characterizations, Virulence Determinants and Antimicrobial Resistance Profiles of Methicillin-Resistant Staphylococcus aureus (MRSA) in the North of Iran
Authors: Kouhsari Ebrahim , Hosseini Mojgan , Ahmadi Alireza , Khadivar Parand , Rahimi Somayeh , Amini Abolfazl
Published: July 2020

Background: Emergence and prevalence of Methicillin-Resistant Staphylococcus aureus (MRSA) has become a major universal health concern, limiting therapeutic options. Methods: In the North side of Iran, during the years 2015 to 2017, a total number of 37 MRSA isolates, including 19 clinical isolates from hospitalized patients and 18 colonizing isolates from health care workers were identified from three hospitals, in Gorgan, North of Iran. Antimicrobial susceptibility test was performed using the disk diffusion method and E-test. The presence of virulence and antibiotic resistance determinants were evaluated by PCR. The genotypic characterization was further analyzed using multi-locus sequence, spa, SCCmec, and agr typing.Results: The frequency of MRSA among S. aureus isolates was 38.14% (37/97). The most frequent S. aureus resistant isolates were found to be obstinate against penicillin (98%) and gentamicin (82.5%). Additionally, the lowest resistance rates were found against daptomycin (0%), vancomycin (2.7%), and quinupristin-dalfopristin (5.4%). All MRSA isolates were susceptible to daptomycin with MIC50/MIC90 of 0.25/0.5 µg/ml. One isolate belonging to the ST239-SCCmecIII/t037 clone (MIC≥16μg/ml) was resistant to vancomycin. All but one isolate that shares the ST22-SCCmec IV/t790 strain were positive for both tsst and pvl genes. The most predominant MRSA isolates (27%) were associated with the ST239-SCCmec III/t037 clone; and followed by ST239-SCCmec III/t924 (16.2%).Conclusions: In our study, circulating MRSA strains were genetically diverse with a high prevalence of the ST239-SCCmecIII/t037 clone. These findings emphasize the need for future and continuous surveillance studies on MRSA to prevent the dissemination of multidrug resistance and existing MRSA clones in an effective manner.
The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects
Authors: Kim Yoo-Mi , Choi Jin-Ho , Kim Gu-Hwan , Sohn Young Bae , Ko Jung-Min , Lee Beom Hee , Cheon Chong Kun , Lim Han Hyuk , Heo Sun-Hee , Yoo Han-Wook
Published: July 2020

Background
Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients.
Results
The study cohort included 63 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harboured the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (10%). Of the 18 patients harbouring the p.G85E mutation, their median age at diagnosis was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years.
Conclusion
The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.
Central Serous Chorioretinopathy And Selective Serotonin Reuptake Inhibitors
Authors: ALTUN Ahmet , Atmaca Fatih , Icagasioglu Ahmet , Cekmeceli Selcuk
Published: July 2020

Aim: To investigate the relationship between central serous chorioretinopathy (CSC) and selective serotonin reuptake inhibitor (SSRI) antidepressant drugs.Methods: The files of patients diagnosed with CSC who applied to our clinics were analyzed retrospectively. Group 1 was formed from patients who had never used any antidepressant drug. Group 2 and Group 3 were composed of patients who did not stop and stopped using SSRI after the third month, respectively. Ophthalmological examinations, optical coherence tomography and fundus fluorescein angiography images of the patients were analyzed and the groups were compared with each other. Results: Group 1, Group 2 and Group 3 had 122, 8, 12 eyes, respectively. The time for complete resolution of subretinal fluid (SRF) in Group 3 was statistically significantly shorter than Group 1 and Group 2 (p ˂ 0.01). In Group 2, the time for complete resolution of SRF was significantly longer than Group 1 (p ˂ 0.05). Conclusion: SSRI group antidepressant drugs might be an important factor in CSC etiology and prognosis. Discontinuation of these drugs may accelerate subretinal fluid resolution.
Effect of Toe Exercises and Toe-grip Strength on the Treatment of Primary Metatarsalgia
Authors: Amaha Kentaro , Arimoto Tatsuya , Kitamura Nobuto
Published: July 2020

Background
The relationship of metatarsalgia and toe function is poorly understood. We investigated the efficacy of toe exercises for the treatment of metatarsalgia.
Methods
Forty-one (56 feet) metatarsalgia patients (age mean ± SD: 63.4 ± 10.6) underwent toe strength measurement. We recorded pre- and post-treatment visual analogue scale (VAS), The American Orthopaedics Foot & Ankle Society (AOFAS) score, marble pickup, and single-leg standing time (SLST) and compared in two subgroups to evaluate impact of disease duration on treatment outcome.
Results
Post treatment, toe plantarflexion strength improved (all p < 0.01); VAS scores decreased (p < 0.01); and AOFAS scores, marble pickup, and SLST improved (all p < 0.01). Patients symptomatic for > 1 year had significantly lower changes in VAS scores (p < 0.01). Multivariate analysis showed patients with longer disease duration and larger body mass index had significantly lower improvement in VAS scores (p = 0.029 and p = 0.036, respectively). Device consistency assessed by Intraclass Correlation Coefficients (ICC) was excellent (0.89–0.97).
Conclusion
Toe function and metatarsalgia is improved by toe exercises, suggesting that they are closely related.
Impact of Health Human Resources on the Output Efficiency of Residents’ Health Status in China
Authors: Cheng Jingjing , Kuang Xianming , Zeng Linghuang
Published: July 2020

Background: Along with the development of the Chinese economy, there has been an increasing demand for resident health care services. Human resources for health (HRH) are a cornerstone in the medical system and have a significant influence on the health status of residents. Methods: This study employed the data envelopment analysis (DEA) to explore the output efficiency of residents’ health status. The input variable was medical services and the output variable was the health status of residents. We examined aspects of the provincial and national dimensions in China and used a Tobit regression analysis to explore the impact of HRH on output efficiency scores. Results: We found that in the provincial dimension, all kinds of HRH (except for technicians) had a significantly positive impact on the output efficiency of residents’ health status. In the national dimension, licensed (assistant) doctors, registered nurses, and village doctors had a significantly positive effect on the efficiency in the “with surgical procedures” model. In the “without surgical procedures” model, the effect factors changed to registered nurses and pharmacists. Most importantly, pharmacists played a critical role in both the provincial and national output efficiency scores. For pharmacists, the influence coefficient was three times higher than licensed (assistant) doctors and 11 times higher than registered nurses.Conclusions: There is asymmetry between the demand for drug therapy and the lack of clinical pharmacists. Optimizing the allocation of HRH should be a top priority for healthcare systems and the government should adopt a long-term perspective.
Midwives’ Challenges and Factors that Motivate them to Remain in Their Workplace in the Democratic Republic of Congo – An Interview Study
Authors: Bogren Malin , Grahn Malin , Kaboru Berthollet Bwira , Berg Marie
Published: July 2020

Background: The Democratic Republic of Congo (DRC) has high maternal mortality and a low number of midwives, which undermines the achievement of Goal 3 of the Sustainable Development Goals (SDGs) for 2030, specifically the health of mother and newborn. Scaling up the midwifery workforce in relation to number, quality of healthcare, and retention in service, are therefore critical. The aim of this study was to investigate midwives’ challenges and factors that motivate them to remain in their workplace in the DRC. Methods: A qualitative content analysis method was used. Data was collected through ten focus-group discussions with a total of 63 midwives working at ten different healthcare facilities. Results: Loving one’s work made it worthwhile for the midwives to remain in the workplace. To be a midwife was not just a profession; it was a calling and made them proud, despite low professional status. The organisational system at facility level was unsupportive, with insufficient work-related security, no remuneration system, and rigid hierarchical management structures. A lack of resources and insufficient competence gave the midwives inadequate pre-conditions for carrying out their professional work.Conclusion: Midwives in the DRC are driven by a strong professional conscience to provide the best possible care for women during childbirth, despite a difficult work environment and low professional status. To attract and retain midwives and ensure that they are working to their full scope of practice, we suggest coordinated actions at the regional and national levels in the DRC and in other low-income countries with similar challenges, including: i) conducting midwifery education programmes following international standards; ii) prioritising and enforcing policies to include adequate remuneration for midwives; iii) involving midwives’ associations in policy and planning about the midwifery workforce; and iv) ensuring that midwives’ working environments are safe and well equipped.
Childhood Obesity, Weight Loss and Long Term Development in Quality-of-Life: A Longitudinal Follow-Up Study.
Authors: Jørgensen Rasmus Møller , Vestergaard Esben Thyssen , Kremke Britta , Bahnsen Rikke Frederiksen , Nielsen Bent Windelborg , Bruun Jens Meldgaard
Published: July 2020

Background To evaluate long-term effects of a multifactorial lifestyle intervention on measures of quality-of-life (QoL) in children with obesity. Methods One hundred and twenty children age 4-17 years with a BMI standard deviation score (BMI-SDS) >2 participated in a multifactorial lifestyle intervention. QoL and wellbeing were measured by a 6-item Visual Analogue Scale (VAS) throughout the intervention.Results Follow-up time was 26.4 months (13.9 SD). VAS scores decreased on bullying (0.6 vs. 0.0 median) and in motivation (10.0 vs. 9.6). QoL increased in children with a BMI-SDS reduction (0.65 (2.49 SD)) opposite children with no-change or increasing BMI-SDS who reported reduced QoL (-0.36 (1.55 SD) and -0.96 (2.27 SD)). Boys experienced reduced appetite (6.7 (2.3 SD) to 5.7 (2.6 SD)), bullying (median 0.4 vs. 0.0) and motivation (median 10.0 vs. 8.9), while girls experienced reduction in bullying (median 0.6 vs. 0.0) and an enhancement in Joy of Life compared to boys (0.73 (2.10 SD) vs. -0.04 (2.08 SD)).Conclusion Multifactorial lifestyle intervention for children with obesity induces long-term BMI-SDS reduction for the majority, and exerts significant reduction in bullying and improves QoL if weight loss is obtained and maintained.
Living with Chronic Illness Scale: Validation in a Type 2 Diabetes Mellitus Population
Authors: Caro-Bautista Jorge , Rodriguez-Blázquez Carmen , Perez-Manchon David , Timonet Eva , Carvajal Gloria , Fuentes-Ramírez Alejandra , Corchon Silvia , Aranda-Gallardo Marta , Ambrosio Leire
Published: July 2020

Background: Worldwide, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases and one of those producing greatest impact on patients’ day-to-day quality of life. Our study aim is to validate the “Living with Chronic Illness Scale” for a Spanish-speaking T2DM population.Methods: In this observational, international, cross-sectional study, 582 persons with T2DM were recruited in primary health care and outpatient hospital consultations, in Spain and Colombia, during the period from May 2018 to June 2019. The properties analysed were feasibility/acceptability, internal consistency, reliability, precision and (structural) content-construct validity. The COSMIN checklist was used to assess the methodological/psychometric quality of the instrument.Results: The instrument has adequate internal consistency and test retest reliability (Cronbach’s alpha = 0.90; intraclass correlation coefficient = 0.96, respectively). In addition, the instrument is accurate (standard error of measurement = 3.34, with values <½SD = 8.52 considered acceptable) and correlates positively with social support (DUFSS) (rs = 0.56), quality of life (WHOQOL) (rs = 0.51-0.30) and satisfaction (SLS-6) (rs = 0.50-0.38). The questionnaire discriminates by the level of severity of the illness (Patient Based Global Impression of Severity Scale), associating lower values with greater severity, and also by male gender. The COSMIN checklist is favourable for all the properties analysed, although some weaknesses are detected for content validity.Conclusions: “Living with T2DM” (LW-T2DM) is a valid, reliable and accurate instrument for use in clinical practice to determine how a person’s life is affected by the presence of diabetes. This instrument correlates well with the associated constructs of social support, quality of life and satisfaction. Additional research is needed to determine how well the questionnaire structure performs when robust factor analysis methods are applied.
Impact of CRP on continuous bladder irrigation in hemorrhagic cystitis patients after hematopoietic stem cell transplantation
Authors: Yang Wenbo , Qu Zhan , Du Yiqing , Bai Wenjun , Yu Luping , Zhang Xiaopeng , Wang Qi , Zhang Xiaowei , Li Qing , Xu Tao
Published: July 2020

Background Continuous bladder irrigation (CBI) and proper adjustment of saline irrigation speed are important to avoid CBI failure in hemorrhagic cystitis (HC) patients after allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, too fast irrigation speed could take away the patient's much heat, contribute to blood coagulopathy, and increase the nursing workload. Evaluation of risk for CBI failure remains an unmet clinical need. Methods The general information, clinical characteristics, and consultation records of HC patients in 1380 patients with hematopoietic stem cell transplantation in our center from 2017 to 2019 were analyzed retrospectively. The receiver operating characteristic (ROC) curve was used to calculate the cutoff point of the continuous variable, and multivariate logistic regression was used to analyze the risk factors affecting CBI failure in HC patients. Results The incidence of HC after HSCT was 23%. A total of 227 patients with HC above grade 2 were included. Univariate analysis showed that CRP, age, platelet counts, onset time after transplantation, albumin, and hemoglobin were associated with CBI failure in the short-term (P < 0.05). ROC curve and multivariate logistic regression analysis showed that CRP > 8.89 ng/ml (RR = 7.828, 95% CI 2.885–21.244), age < 14.5 years (RR = 9.940, 95% CI 3.219–30.697), and onset time of HC༞37d after transplantation (RR = 7.021, 95% CI 2.204–22.364), were independent risk factors for failure of CBI (P < 0.05). Conclusions The study identified CRP > 8.89 ng/ml, age < 14.5 years, and onset time of HC after HSCT > 37d are independent factors for failure of CBI, which could be combined to allow stratification of HC after HSCT patients into low-, intermediate- and high-risk subgroups of CBI failure.
Identification of Core Genes and Pathways in Major Depressive Disorder Applying Bioinformatics
Authors: Yang Wenshan , Yin Hong , Wang Yichen , Liu Ping , Hu Yuan
Published: July 2020

Background: Although extensive study efforts on major depressive disorder (MDD), the pathogenesis related to the biological factors are not fully understood and present therapeutic regimen are ineffective in some depressive patients. This study aims to identify key genes and pathways associated with the molecular biological mechanisms of major depressive disorder through bioinformatics analysis in the Gene Expression Omnibus (GEO) public database of the National Center for Biotechnology Information (NCBI) website.Materials and methods: The whole-transcriptome brain expression profile dataset (GSE101521) was obtained from the GEO database. Differentially-expressed genes (DEGs) in normal group (non-psychiatric human) and MDD group (depressive patients) were identified applying Networkanalyst online database. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to function annotation and enrichment analysis. After that, STRING online database was conducted to protein–protein interaction (PPI) network, and Cytoscape.3.7.2 software was performed to module analysis. Results: Out of the 41 DEGs identified from normal tissue samples and MDD, 39 were upregulated and 2 were downregulated. GO enrichment analysis discovered that DEGs were primarily involved in inflammatory response, and KEGG pathway analysis suggested that the most chiefly pathway related to MDD were IL-17 signaling pathway, TNF signaling pathway and NOD-like receptor signaling pathway. Six hub genes (IL6, CXCL8, IL1B, FOS, CCL2 and CXCL2) were identified by PPI network and module analysis. Conclusion: Our current study detected novel markers and targets involved immune system, which are involved in pivotal biological mechanisms related to the pathogenesis of major depression. Looking forward, these findings still need to be validated in future experimental studies.
Evaluation of Curcumin and Copper Acetate Against Salmonella Typhimurium Infection, Intestinal Permeability, and Cecal Microbiota Composition in Broiler Chickens
Authors: Leyva-Diaz Anaisa A. , Hernandez-Patlan Daniel , Solis-Cruz Bruno , Adhikari Bishnu , Kwon Young Min , Latorre Juan D. , Hernandez-Velasco Xochitl , Fuente-Martinez Benjamin , Hargis Billy M. , Lopez-Arellano Raquel , Tellez Guillermo
Published: July 2020

Background: Interest in the use of natural feed additives as an alternative to antimicrobials in the poultry industry has increased in recent years because of the risk of bacterial resistance. One of the most studied groups are polyphenolic compounds, given their advantages over other types of additives and their easy potentiation of effects when complexes are formed with metal ions. Therefore, the objective of the present study was to evaluate the impact of dietary supplementation of Copper Acetate (CA), Curcumin (CR), and their combination (CA-CR) against Salmonella Typhimurium colonization, intestinal permeability, and cecal microbiota composition in broiler chickens.Results: The obtained results showed that in two independent studies, all experimental treatments were able to significantly reduce the S. Typhimurium colonization in cecal tonsils (CT, p < 0.05) compared to the positive control (PC) group. However, CR and CA-CR were the best treatments reducing S. Typhimurium counts. Furthermore, the serum fluorescein isothiocyanate dextran (FITC-d) concentration in chickens treated with CR was significantly lower when compared to PC (p < 0.05). The effect of dietary treatments in reducing S. Typhimurium colonization was further supported by the Linear discriminant analysis effect size (LEfSe) analysis of microbiome data, where Salmonella was significantly enriched in PC group (LDA score > 2.0 and p<0.05). In addition, Coprobacillus, Eubacterium, and Clostridium were significantly higher in the PC group compared to other treatment groups. On the contrary, Fecalibacterium and Enterococcus at CR, unknown genus of Erysipelotrichaceae at CA-CR, and unknown genus of Lachnospiraceae at CA were significantly abundant respectively.Conclusions: CR treatment was the most effective treatment to reduce S. Typhimurium intestinal colonization and intestinal permeability associated with variations in the cecae microbiota structure in broiler chickens.
Etoposide and topoisomerase II inhibition for aggressive prostate cancer: data from a translational study.
Authors: Cattrini Carlo , Capaia Matteo , Boccardo Francesco , Barboro Paola
Published: July 2020

Background. Etoposide phosphate (VP-16) is a topoisomerase 2 (TOP2) inhibitor that demonstrated limited activity in patients with metastatic castration-resistant prostate cancer (mCRPC). In our study, we investigated the sensitivity of prostate cancer (PCa) cells (LNCaP, 22Rv1, PC3, DU145, PDB and MDB) to VP-16 and the possible relationship between VP-16 activity and TOP2 expression. We also compared the activity of VP-16 with that of docetaxel, enzalutamide and olaparib. In the datasets analysis, we explored the prevalence and clinical significance of TOP2 genetic and transcriptomic alterations in mCRPC. Methods. Cell cultures and crystal violet cell proliferation assays were performed. Specific antibodies were used in western blots analyses of cell protein extracts. Large scale datasets were analyzed in cBioportal and STRING was used for the functional enrichment analysis. Results. VP-16 was active in all PCa cell lines analyzed and this drug demonstrated increased activity in the aggressive PC3 and DU145 cells. VP-16 was more cytotoxic compared to the other treatments, except for LNCaP and 22Rv1, which were more sensitive to docetaxel. Of note, the maintainment of antiandrogen treatment in bicalutamide-resistant MDB and PDB increased sensitivity to VP-16, docetaxel and enzalutamide. Compared to LNCaP, TOP2A was found to be overexpressed in 22Rv1, DU145 and PC3, whereas TOP2B was overexpressed in 22Rv1 and PDB. In the mCRPC datasets analysis, TOP2A mRNA overexpression was associated with worse patients’ prognosis, with the molecular features of neuroendocrine prostate cancer (NEPC) and with lower androgen receptor (AR) score. Patients overexpressing TOP2A mRNA were more likely to harbor RB1 loss. Conclusions. Specific subpopulations of patients with aggressive variant prostate cancer (AVPC) could benefit from VP-16 treatment. TOP2A overexpression, rather than TOP2B, might be a good biomarker to predict response to VP-16. Further investigations are warranted to determine the role of TOP2A in mCRPC and to assess the efficacy of VP-16, alone or in combination with other agents, for the treatment of patients with mCRPC.Key points: · Etoposide is a chemotherapeutic agent that shows significant activity in preclinical models of prostate cancer and increased activity is observed in the most aggressive cells.· Overexpression of topoisomerase II alfa and decreased functionality of the androgen receptor signaling seem to be associated with response to etoposide.· Specific patients with castration-resistant prostate cancer could benefit from etoposide treatment, alone or in combination with other agents.
Pacemaker-Generated Stress Fracture of The Second Rib: A Case Report
Authors: Ksela Jus , Racman Mark , Zbacnik Rok , Djordjevic Anze , Jan Matevz
Published: July 2020

Background: Pocket-related complications following the implantation of cardiovascular implantable electronic devices primarily include pocket hematoma, infection, skin erosion or decubitus, device migration, and Twiddler's syndrome, with other pathologies such as nerve impairment or bone lesions being extremely rarely encountered. We report a case of a 20-year old asthenic, non-athlete female patient presenting with a device-generated fracture of the second rib several months after sub-muscular permanent pacemaker implantation due to repeated bilateral pre-pectoral pocket infections.Case presentation: A 20-year old female patient was readmitted to our institution 9 months following sub-pectoral implantation of a permanent pacemaker, complaining of severe pocket-related pain, which arose spontaneously in the absence of direct trauma, intense physical activity or vigorous coughing, and was associated with normal day-to-day activity. To rule out a pacemaker re-infection, a native computed tomography and a positron emission tomography - computed tomography of the thorax were performed. Both modalities excluded an infection but showed a healing fracture and a focus of enhanced metabolic activity in the anterolateral part of the right second rib, indicating a non-traumatic or stress fracture of the bone. Consequently, a complete extraction of the pulse generator and both leads was performed and the smallest available single-chamber pulse generator with a single atrial electrode was implanted in the sub-fascial, pre-muscular pocket in the now recovered and uninfected left subclavicular region, alleviating patient’s severe pain symptoms and significantly enhancing her quality of life.Conclusions: In the absence of direct trauma, intense physical activity or vigorous coughing, we assume that in this asthenic girl a normal day-to-day motion of the right shoulder has persistently forced the sub-muscularly placed pulse generator toward thoracic wall, putting increased repetitive pressure force on the underlying bones, finally causing a fatigue stress fracture of the second rib. In asthenic phenotype patients with small thorax and short subclavicular distance, a sub-muscular pacemaker implantation can potentially cause unique and unexpected pocket-related adverse events necessitating advanced diagnostics and timely treatment.
Administration of Herb Formulation Enhanced Blastocyst Implantation via Iκb Activation in Mouse Endometrium
Authors: Jeon Songhee , Liu Quan Feng , Cai Hua , Jeong Ha Jin , Kim Su-Hyun , Kim Dong-Il , Lee Ju-Hee
Published: July 2020

BackgroundBaelan Chagsang Bang (BCB), consisting of a mixture of 11 herbs, may be prescribed as a reproductive function supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Oriental Medicine. This study aimed to investigate the effects and mechanisms of action of water-extracted BCB on endometrial receptivity and blastocyst implantation in a mifepristone (RU486)-induced implantation failure model.MethodsIn in vitro, antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and DCFH-DA assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically. BCB was administrated from 7 days before pregnancy until the end of the experiment. They were housed with male mice until pregnancy was confirmed. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure.ResultsAdministration of the BCB water extract increased the number of newborn pups in BCB-treated mice compared to that of sham-treated mice and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein expression level of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression level of matrix metalloproteinases (MMPs) at the uterus implantation site was up-regulated in the BCB-treated group compared to that of the RU486-treated group. To determine the mechanisms of action of BCB, the anti-oxidative effect of BCB was examined via in vitro assay. The BCB water extract showed strong anti-oxidative effects in the DPPH assay and the superoxide anion free-radical scavenging activity assay.ConclusionOur findings provide evidence that BCB has therapeutic potential against poor endometrial receptivity.
Identification of Candidate Genes Controlling Fiber Quality Traits in Upland Cotton Through Integration of Meta-QTL, Significant SNP and Transcriptomic Data
Authors: Shudi XU , Pan Zhenyuan , Yin Feifan , Yang Qingyong , Lin Zhongxu , Wen Tianwang , Zhu Longfu , Zhang Dawei , Nie Xinhui
Published: July 2020

Background
Meta-analysis of quantitative trait locus (QTL) is a computational technique to identify consensus QTL and refine QTL positions on the consensus map from multiple mapping studies. The combination of meta-QTL intervals, significant SNPs and transcriptome analysis has been widely used to identify candidate genes in various plants.
Results
In our study, 884 QTL associated with cotton fiber quality traits from 12 studies were used for meta-QTL analysis based on reference genome TM-1, as a result, 74 meta-QTL were identified, including 19 meta-QTL for fiber length (FL), 18 meta-QTL for fiber strength (FS), 11 meta-QTL for fiber uniformity (FU), 11 meta-QTL for fiber elongation (FE), and 15 meta-QTL for micronaire (MIC). Combined with 8589 significant SNPs associated with fiber quality traits collected from 15 studies, 297 candidate genes were identified in the meta-QTL intervals, 20 of which showed high expression specifically in the developing fibers. According to the function annotations, some of the 20 key candidate genes are associated with the fiber development.
Conclusions
This study provides not only stable QTLs used for marker-assisted selection (MAS), but also candidate genes to uncover the molecular mechanisms for cotton fiber development.
Aptamer-Protamine-siRNA Nanoparticles in Targeted Therapy of ErbB3 Positive Breast Cancer Cells
Authors: Xu Xiangshang , Li Li , Li Xiaolan , Tao Deding , Zhang Peng , Gong Jianping
Published: July 2020

Background: RNAi-based technology has achieved good results in both in vitro and in vivo applications, and it is expected to become a good genetic treatment for some diseases, especially neoplastic diseases. But there are still many obstacles in the in vivo application, the most important thing is the lack of an efficient and safe carrier.Methods: In this study, we designed and constructed a new siRNA delivery, which was named as aptamer-protamine-siRNA nanoparticle (APR). APR was consisted of ErbB3 aptamer, protamine and siRNA. We used Zeta nanosize to detect the size of APR to verify whether it is a nano-scale compound. We use the FAMRNA to replace the siRNA to detect whether APR could recognize and enter ErbB3 positive MCF-7 cells. The we replaced the siRNA as oncogene suvivin siRNA to detect whether APR could inhibit tumor growth by silence surviving, and replaced siRNA to CDK1 siRNA to detect the cell cycle blocking effect. At last we tested the anticancer effect and safety of APR by carrying survivin siRNA in MCF-7 bearing nude mice. Results: APR was identified as a nanoscale compound. It showed specific targeting for ErbB3-positive MCF-7 cancer cells. APR has demonstrated the characteristics of inhibiting tumor growth by carrying siRNA against oncogene survivin. APR could also block cell cycle of MCF-7 cells by delivering CDK1 siRNAs. In the ErbB3 positive breast cancer xenograft mice model, APR nanoparticles could inhibit tumor growth and cause tumor regression without any toxicity. Conclusions: In both in vivo and in vitro applications, APR nanoparticles could be targeted to recognize and enter ErbB3 positive tumor cells, and play a corresponding role by silencing targeted gene expression. APR nanoparticle is expected to become a good tumor treatment option.
Long Noncoding RNA HOXA-AS2 Functions as an Oncogene by Binding to EZH2 and Suppressing LATS2 in AML
Authors: Feng Yubin , Hu shuang , Li lanlan , Peng xiaoqing , Chen Feihu
Published: July 2020

BackgroundLong noncoding RNAs (lncRNAs) plays an important role in the development of physiology and pathology. Many reports have shown that LncRNA HOXA cluster antisense RNA 2 (HOXA-AS2) is a carcinogen and plays an important role in many tumors, but there are few reports on its role in Acute myeloid leukemia (AML). MethodsThe expression of HOXA-AS2 in AML cell line was detected by qRT-PCR. AML cases from the public database (GEPIA) were also included in this study. Cell counting kit-8 (CCK-8) assay, flow cytometry, immunofluorescence and Western blot were used to detect the role of HOXA-AS2 in AML cells. Luciferase reporter gene detection, RIP, RNA pull-down and RNA-ChIP detection were used to demonstrate the molecular biological mechanism of HOXA-AS2 in AML.ResultsOur results show that HOXA-AS2 was upregulated in AML cell lines and tissues, and the overexpression of HOXA-AS2 is negatively correlated with the survival of patients. Silencing HOXA-AS2 can inhibit the proliferation and induce differentiation of AML cells in vitro and in vivo. After overexpressing HOXA-AS2, it will show the opposite result. Moreover, more in-depth mechanism studies show that HOXA-AS2 exerts its carcinogenicity mainly by binding with the epigenetic inhibitor Enhancer of zeste homolog 2 (EZH2) and then inhibiting the expression of Large Tumor Suppressor 2 (LATS2). ConclusionsTaken together, our results highlight the important role of HOXA-AS2 in AML, suggesting that HOXA-AS2 may be an effective therapeutic target for patients with AML.
Factors Influencing the Deterioration from Cognitive Decline of Normal Aging to Dementia among Nursing Home Residents
Authors: Hayajneh Audai A. , Rababa Mohammad , Alghwiri Alia A. , Masha'al Dina
Published: July 2020

Background: A dearth of differential research exists regarding the determinants of mild cognitive impairment (MCI) and moderate cognitive impairment or dementia among nursing home residents. This study aimed to identify and examine the factors that lead to progression of MCI to moderate cognitive impairment or dementia in nursing home residents.Methods: A cross-sectional design was used in this study. Convenience sampling of 182 participants was conducted in nursing homes located in the central part of Jordan. Montreal cognitive assessment (MoCA) was used to screen both MCI and moderate cognitive impairment or dementia. Bivariate analysis, including t-test and ANOVA test, and logistic and linear regression models were used to examine and identify the predictors of dementia.Results: Most nursing home residents had MCI (87.4%) compared to a few with moderate cognitive impairment or dementia. Age (t = -2.773), number of comorbidities (t = -4.045), depression (t = -4.809), frailty (t = -4.038), and quality of life physical (t = 3.282) and mental component summaries (t = 2.469) were significantly different between the stages of cognitive impairment. Marital status (t = -4.050, p < 0.001), higher-income (t = 3.755, p < 0.001), recent hospitalization (t = 2.622,p = 0.01), depression (t = -2.737, p = 0.007), and frailty (t = 2.852, p = 0.005) were significantly associated with mental ability scores among nursing home residents.Conclusion: The coexistence of comorbidities and depression among nursing home residents with MCI necessitates prompt management by healthcare providers to combat depressive symptoms in order to delay the dementia trajectory among at-risk residents.
Age-Related Changes in Postural Control: transitional task
Authors: Michalska Justyna , Kamieniarz Anna , Sobota Grzegorz , Stania Magdalena , Juras Grzegorz , Słomka Kajetan J
Published: July 2020

Background
Aging, being a natural process, involves many functional and structural changes within the body. Identifying the onset of age-related postural changes will provide insight into the role of aging on postural control during locomotion. The aim of this study was to identify age-related postural changes during a transitional task under different conditions.
Methods
Sixty healthy females divided into three age groups: A (50–60 y/o), B (60–70 y/o), and C (70–80 y/o). The transitional task was measured by two force platforms. The procedure consisted of three phases: quiet standing, transfer onto a second platform, and quiet standing on the second platform. Four different conditions were applied: unperturbed transfer, obstacle crossing, step-up, and step-down. Double-support time, transit time, and stability time before and after the step task were analyzed.
Results
The transit time was longer by 30% for subjects over 70 y/o. The double-support time was longer by 11% among adults 60–70 y/o, while in people over 70 y/o it was longer by almost 50% compared to the 50–60 y/o subjects. The stability time before the transitional task was longer by 17% among adults over 60 y/o compared to middle-age subjects. The stability times before and after the transitional task were longer for adults in the 50–60 y/o category.
Conclusion
The proposed procedure is adequate for assessing age-related changes in postural control while undergoing a transitional task. An analysis of the double-support time and stability time before and after the step task enabled the detection of early signs of balance changes in middle-age adults. Independent of age, the transitional task parameters changed with the increasing difficulty of the tasks.