bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of nicotinamide adenine dinucleotide phosphate oxidase 4 on migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis
Authors: Lee Ha-Reum , Yoo Su-Jin , Kim Jinhyun , Yoo In Seol , Park Chan Keol , Kang Seong Wook
Published: March 2020

Background: Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and consequently, enhances cell migration. Despite the important interrelationship between RA, FLS, and ROS, the effect of NOX4 on RA pathogenesis remains unclear. Methods: FLS isolated from RA (n=5) and osteoarthritis (OA, n=5) patients were stimulated with recombinant interleukin 17 (IL-17; 10 ng/ml) and tumor necrosis factor alpha (TNF-α; 10 ng/ml) for 1 h. Cell migration, invasion, adhesion molecule expression, vascular endothelial growth factor (VEGF) secretion, and ROS expression were examined. The mRNA and protein levels of NOX4 were analyzed by RT-qPCR and western blotting, respectively. The NOX4 inhibitor GLX351322 and NOX4 siRNA were used to inhibit NOX4 to probe the effect of NOX4 on these cellular processes. Results: Migration of RA FLS was increased 2.48-fold after stimulation with IL-17 and TNF-α, while no difference was observed for OA FLS. ROS expression increased in parallel with invasiveness of FLS following cytokine stimulation. When the expression of NOX was examined, NOX4 was significantly increased by 9.73-fold in RA FLS compared to unstimulated FLS. Following NOX4 inhibition, cytokine-induced vascular cell adhesion molecule 1 (VCAM1), VEGF, and migration and invasion capacity of RA FLS were markedly decreased to unstimulated levels. Conclusion: NOX4 is a key contributor to cytokine-enhanced migration and invasion via modulation of ROS, VCAM1, and VEGF in RA FLS.
Acute Mechanical Stress in Primary Porcine RPE Cells Induces Angiogenic Factor Expression and in vitro Angiogenesis
Authors: Farjood Farhad , Ahmadpour Amir , Ostvar Sassan , Vargis Elizabeth
Published: March 2020

Background Choroidal neovascularization (CNV) is a major cause of blindness in patients with age-related macular degeneration. CNV is characterized by new blood vessel growth and subretinal fluid accumulation, which results in mechanical pressure on retinal pigment epithelial (RPE) cells. The overexpression of RPE-derived angiogenic factors plays an important role in inducing CNV. In this work, we investigated the effect of mechanical stress on the expression of angiogenic factors in porcine RPE cells and determined the impact of conditioned medium on in-vitro angiogenesis. Results The goal of this study was to determine whether low levels of acute mechanical stress during early CNV can induce the expression of angiogenic factors in RPE cells and accelerate angiogenesis. Using a novel device, acute mechanical stress was applied to primary porcine RPE cells and the resulting changes in the expression of major angiogenic factors, VEGF, ANG2, HIF-1α, IL6, IL8 and TNF - α, were examined using immunocytochemistry, qRT-PCR, and ELISA. An in vitro tube formation assay was used to determine the effect of secreted angiogenic proteins due to mechanical stress on endothelial tube formation by human umbilical vein endothelial cells (HUVECs). Our results showed an increase in the expression of VEGF, ANG2, IL-6 and IL-8 in response to mechanical stress, resulting in increased in vitro angiogenesis. Abnormal epithelial-mesenchymal transition (EMT) in RPE cells is also associated with CNV and further retinal degeneration. Our qRT-PCR results verified an increase in the expression of EMT genes, CDH2, VIM and FN1, in RPE cells. Conclusions In conclusion, we showed that acute mechanical stress induces the expression of major angiogenic and EMT factors and promotes in vitro angiogenesis, suggesting that mechanical stress plays a role in promoting aberrant angiogenesis in AMD.
The relationship between physical activity, apolipoprotein E ε4 carriage and brain health
Authors: de Frutos-Lucas Jaisalmer , Cuesta Pablo , Lopez-Sanz David , Peral-Suarez Africa , Cuadrado-Soto Esther , Ramirez-Toraño Federico , Brown Belinda M , Serrano Juan M , Laws Simon M , Rodriguez-Rojo Inmaculada C , Verdejo-Roman Juan , Bruña Ricardo , Delgado-Losada Maria L , Barabash Ana , Lopez-Sobaler Ana M , Lopez-Higes Ramon , Marcos Alberto , Maestu Fernando
Published: March 2020

BACKGROUND: Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer’s disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon. METHOD: The relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition and mood was also investigated. RESULTS: A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, in ε4 carriers and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory). CONCLUSIONS: PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, specially ε4 carriers.
Psychological, social, and motivational factors in persons who use drugs
Authors: Shahrabadi Sana , Jalali Amir , Jalali Rostam , Gholami Ali
Published: March 2020

Background: Persons who use drug needs family and society’s support in the pross of treatment and rehabilitation. Therefore, it is imperative to find the psychological, social, and motivational factors that can help them in the treatment process. The present study was an attempt to determine the relationship of psychological, social, and motivational factors and demographics of the persons who use drugs (PWUD).
Methods: An analytical cross-sectional study was carried out. Psychological, Social, and Motivational Performance Questionnaire for the PWUD was first translated into Farsi and validated after securing permission from the copyright holder of the tool. Participants were 250 PWUD under methadone therapy who were selected through convenient sampling. Before analyzing the collected data, validity and reliability of the tool were confirmed using confirmatory and exploratory factor analyses. Given the scale of demographical data, descriptive and analytic statistics were used to analyze the relationship between demographical variables and psychological, social, and motivational factors.
Results: The results of exploratory and confirmatory factor analyses showed that out of 83 statements in the original questionnaire, 55 statements categorized into 11 aspects were usable for Iranian population. The results showed that gender, income, and marital status were effective in Psychological functioning of the PWUD (P<0.05). However, education level, domicile, and type of drug and consumption did not have a significant relationship with social functioning of the participants (p>0.05). There was a significant relationship between age, number of children, and history of using drug and Psychological functioning of the participants (P<0.01). The results showed that the demographics did not have a notable effect on the participants’ motivation for treatment; only marital status had a significant relationship with the participants’ treatment readiness (P<0.05).
Conclusion: As the results showed, the demographical variables could affect physical, psychological, and motivational readiness in the participants.
Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer's disease spectrum patients: A randomized, double-blind, placebo-controlled study and a two-period extension study
Authors: Novak Gerald , Streffer Johannes Rolf , Timmers Maarten , Henley David , Brashear H Robert , Bogert Jennifer , Russu Alberto , Janssens Luc , Tesseur Ina , Tritsmans Luc , Nueten Luc Van , Engelborghs Sebastiaan
Published: March 2020

Background

Atabecestat, a potent brain-penetrable inhibitor of BACE1 activity that reduces CSF amyloid beta (Aβ), was developed for oral treatment for Alzheimer’s disease (AD).
The long-term safety and effect of atabecestat on cognitive performance in participants with predementia AD in two phase 2 studies were assessed.

Methods

In the placebo-controlled double-blind parent ALZ2002 study, participants aged 50 to 85 years were randomized (1:1:1) to placebo or atabecestat 10 or 50 mg once-daily (later reduced to 5 and 25 mg) for six months. Participants entered ALZ2004, a 12-month-treatment extension with placebo or atabecestat 10 or 25 mg, followed by an open-label phase. Safety, changes in CSF biomarker levels, brain volume, and effects on cognitive performance were assessed.

Results

Of 114 participants randomized in ALZ2002, 99 (87%) completed, 90 entered the ALZ2004 double-blind phase, and 77 progressed to open-label phase. CSF Aβ fragments and sAPPβ were reduced dose-proportionately. Decreases in whole brain and hippocampal volumes were greater in participants with mild cognitive impairment (MCI) due to AD than in preclinical AD, but were not affected by treatment. In ALZ2004, change from baseline in RBANS trended toward worse scores for atabecestat versus placebo. Elevated liver enzyme adverse events reported in 12 participants on atabecestat resulted in dosage modification and increased frequency of safety monitoring. Treatment discontinuation normalized ALT or AST in all except one with pretreatment elevation, which remained mildly elevated. No case met ALT/AST >3X ULN; total bilirubin >2X ULN (Hy’s law).

Conclusion

Atabecestat was associated with trend toward declines in cognition, and elevation of liver enzymes.
Quality of Sleep in People Living With HIV
Authors: Medeiros Rafaela Catherine da Silva Cunha de , Silva Tatiane Andreza Lima da , Santos Isis Kelly dos , Andrade Ricardo Dias de , Barboza Renata Rangel , Medeiros Jason Azevedo de , Araújo Juliany de Souza , Varela Phelipe Wilde de Alcântara , Knackfuss Maria Irany , Cabral Breno Guilherme de Araújo Tinoco , Dantas Paulo Moreira Silva
Published: March 2020

Background: Throughout the history of AIDS, changes in behavior patterns, sleep quality, development of depressive symptoms, low self-esteem, low levels of self-care, fear and anxiety were observed. The aim of this study is to analyze the factors associated with sleep quality in people living with HIV/AIDS (PLHA). Methods: It is a cross-sectional study with 314 PLHA. The Pittsburgh Sleep Quality Index was used to assess sleep quality. Socioeconomic, clinical and lifestyle habits were investigated through a structured anamnesis. Using the bivariate analysis, the differences between the sleep quality components in relation to the independent study variables were verified (p <0.10). Linear regression was performed following a multilevel hierarchical model for each sleep quality component (p ≤ 0.5). Results: Regarding the sleep quality domains, there was an association with socioeconomic and clinical factors. Sleep latency with marital status; usual efficiency with marital status and use of HAART and sleep disorders with schooling. Conclusions: The study concludes that sleep latency and usual efficiency in PLHA are associated with marital status, while sleep quality with gender and sleep disturbance with schooling.
Placenta-Specific Protein 1 Enhances Liver Metastatic Potential and is Associated with the PI3K/AKT/NF-κB Signaling Pathway in Colorectal Cancer
Authors: Ma Jiachi , Li Lei , Du Jun , Pan Chengwu , Zhang Chensong , Chen Yuzhong
Published: March 2020

Abstract
Background: To better explore the underlying mechanism of liver metastatic formation by placenta-specific protein 1 (PLAC1) in human colorectal cancer, we investigated the proliferation, invasion and angiogenic capabilities of human colorectal cancer cell lines with different liver metastatic potentials as well as the mechanism of action of PLAC1 in the metastatic process.
Methods: The expression of PLAC1 was detected by reverse transcriptase PCR, western blot and real-time PCR. The effect of PLAC1 on metastatic potential was determined by proliferation, invasion, and angiogenesis assays, including an in vitro coculture system consisting of cancer cells and vascular endothelial cells that were used to detect the relationship between cancer cells and angiogenesis. In addition, we also determined PLAC1 downstream targets that preferentially contribute to the metastatic process.
Results: PLAC1 was expressed in HT-29, WiDr and CaCo-2 colorectal cancer cells but not in Colo320 colorectal cancer cells. PLAC1 not only enhanced significantly the proliferation of CoLo320 and human umbilical vein endothelial cells (HUVECs), but also promoted the invasion of CoLo320 cells. The angiogenesis of HUVECs was enhanced by PLAC1 in a dose-dependent manner. In cocultured systems, angiogenesis was significantly increased by coculture with HT-29 cells. In addition, PLAC1 could promote angiogenesis in coculture with HT-29 cells. Furthermore, PLAC1-enhanced metastatic potential of colorectal cancer cells was dependent on activation of the PI3K/Akt/NF-κB pathway.
Conclusions: The activation of PI3K/Akt/NF-κB signaling by PLAC1 may be critical for the metastasis of colorectal cancer cells. According to our results, we suggest that modification of PLAC1 function might be a promising new therapeutic approach to inhibit the aggressive spread of colorectal cancer.
Two nuclear localization signals regulate intracellular localization of the Duck enteritis virus UL13 protein
Authors: Yang Linjiang , Hu Xixia , Cheng Anchun , Wang Mingshu , Jia Renyong , Yang Qiao , Wu Ying , Chen Shun , Liu Mafeng , Zhu Dekang , Ou Xumin , Wen Xingjian , Mao Sai , Sun Di , Zhang Shaqiu , Zhao Xinxin , Huang Juan , Gao Qun , Liu Yunya , Yu Yanling , Zhang Ling , TIan Bin , Pan Leichang , Rehman Mujeeb Ur , Chen Xiaoyue
Published: March 2020

Background UL13 multifunctional tegument protein duck enteritis virus (DEV) is predicted as conserved herpesvirus protein kinase (CHPK); however, little is known about its subcellular localization signal. Results In this study, by transfection with two predicted nuclear signals of DEV UL13 fused to enhanced green fluorescent protein (EGFP), two bipartite nuclear localization signals (NLS) were identified. We found that the NLSs block its nuclear import using ivermectin and proved that nuclear localization signal of DEV UL13 is a classical importin α/β-dependent process. And we constructed the DEV UL13 mutant strain, with the NLSs of DEV UL13 deleted, to explore whether it can affect the virus replication Conclusions The DEV pUL13 amino acids 4 to 7 and 90 to 96 was predicted, and proved that this nuclear import occurs via the classical importin α/β-dependent process. We also found NLSs of pUL13 have no effect on DEV replication in cell culture. Our study enhances the understanding of DEV pUL13. Taken together, these results would provide significant information for the biological function of pUL13 during DEV infection.
Stigma for Common Mental Disorders in Racial Minorities and Majorities: A Systematic Review and Meta-Analysis
Authors: Eylem Ozlem , de Wit Leonore , straten Annemieke van , Steubl Lena , Melissourgaki Zaneta , Danışman Gözde Topgüloğlu , de Vries Ralph , Kerkhof Ad J.F.M , Bhui Kamaldeep , Cuijpers Pim
Published: March 2020

Background There is a strong stigma attached to mental disorders preventing those affected from getting psychological help. The consequences of stigma are worse for racial and/or ethnic minorities compared to racial and/or ethnic majorities since the former often experience other social adversities such as poverty and discrimination within policies and institutions. This is the first systematic review and meta-analysis summarizing the evidence on the impact of differences in mental illness stigma between racial minorities and majorities. Methods This systematic review and meta-analysis included cross-sectional studies comparing mental illness stigma between racial minorities and majorities. Systematic searches were conducted in the bibliographic databases of PubMed, PsycINFO and EMBASE until 20 th December 2018. Outcomes were extracted from published reports, and meta-analyses, and meta-regression analyses were conducted in CMA software. Results After screening 2,787 abstracts, 29 studies with 193,418 participants (N=35,836 in racial minorities) were eligible for analyses. Racial minorities showed more stigma than racial majorities (g=0.20 (95% CI: 0.12~0.27) for common mental disorders. Sensitivity analyses showed robustness of these results. Multivariate meta-regression analyses pointed to the possible moderating role of the number of studies with high risk of bias on the effect size. Racial minorities have more stigma for common mental disorders when compared with majorities. Limitations included moderate to high risk of bias, high heterogeneity, few studies in most comparisons, and the use of non-standardized outcome measures. Conclusions Mental illness stigma is higher among ethnic minorities than majorities. An important clinical implication of these findings would be to tailor anti-stigma strategies related with mental illnesses according to specific racial and/or ethnic backgrounds with the intention to improve mental health outreach.
Application of a new 68Ga-labeled cNGR dimer peptide to microPET imaging of ovarian cancer
Authors: Yang Yi , Zhang Jun , Zou Huifeng , Shen Yang , Wu Yiwei
Published: March 2020

Introduction: Peptides containing the asparagine-glycine-arginine (NGR) sequence have been found to specifically bind to cluster of differentiation 13 (CD13) (aminopeptidase N), a tumor neovascular biomarker that is overexpressed on the surface of angiogenic blood vessels and various tumor cells and plays an important role in angiogenesis and tumor progression. The aim of this study was to evaluate the efficacy of a gallium-68 ( 68 Ga)-labeled dimeric cyclic NGR (cNGR) peptide as a new molecular probe that binds to CD13 in vitro and in vivo .Materials and Methods: A dimeric cNGR peptide conjugated with 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) and DOTA-c(NGR) 2 was synthesized and labeled with 68 Ga. In vitro uptake and binding analysis was performed in two ovarian tumor cell lines, ES2 and SKOV3, each of which have different expression levels of CD13. An in vivo biodistribution study was performed in normal mice, and micro positron emission tomography (PET) imaging was performed in nude mice xenografts with ES2 and SKOV3 tumors. Results : 68 Ga-DOTA-c(NGR) 2 with high radiochemical purity (>95%) was obtained and found to be stable at room temperature and when incubated with bovine serum at 37°C for 3 h. In vitro studies showed that uptake of 68 Ga-DOTA-c(NGR) 2 in ES2 cells increased over time, was higher than that in SKOV3 cells at all time points, and could be blocked by cold DOTA-c(NGR) 2 . Biodistribution studies demonstrated that 68 Ga-DOTA-c(NGR) 2 was mainly excreted from the kidney and rapidly cleared from blood. MicroPET imaging of ES2 tumor xenografts showed that focal uptake in tumors was distinctly observed from 1 to 1.5 h post-injection of 68 Ga-DOTA-c(NGR) 2 . Clear and high-contrast tumor visualization occurred at 1 h, which corresponded to the highest tumor/background ratio of 10.30±0.26. Moreover, accumulation of the probe in ES2 tumors apparently declined with pretreatment of unlabeled peptide, which further proved the specificity of 68 Ga-DOTA-c(NGR) 2 . In SKOV3 tumor models, the tumor was not obviously displayed under the same imaging protocols. Conclusion : We conclude that 68 Ga-DOTA-c(NGR) 2 might be a potential molecular probe for evaluating the expression levels of CD13 in different tumors, thereby providing a basis for targeting angiogenesis in cancer therapy.
Heritability and correlation analysis of morphological and yield traits in genetically modified cotton
Authors: Rehman Abdul , Mustafa Nida , Xiongming Du , Azhar Muhammad Tehseen
Published: March 2020

Background Cotton is known for its fiber and it is grown in tropical and sub-tropical areas of the world. It has a significant role in GDP of Pakistan. Therefore, present two years research was conducted to estimate heritability and association among various yield contributing parameters of cotton. The selected genotypes of cotton were hybridized in green house of the department. The F 0 cotton seed along with parents were planted in the field conditions during May, 2018. The sowing of this experiment was completed in three replications followed by RCBD. The data was recorded at maturity for various agronomic traits including plant height, number of bolls per plant, number of sympodial branches per plant, seed cotton yield, boll weight, seed index, ginning out turn, fiber length, fiber strength, and fiber fineness. Level of significance of data was computed by ANOVA to assess the difference among cotton genotypes which was used for estimation of heritability and correlation analysis among the related traits. Results Association analysis revealed that seed cotton yield had significant positive relationship with plant height, number of bolls per plant, number of sympodial branches per plant, ginning out turn, staple length and fiber strength. Staple length and fiber strength were negatively linked with each other. Estimates of heritability were high for all observed traits except number of sympodial branches per plant and boll weight. Conclusion The parent IUB-222 was found best for plant height, number of bolls per plant, boll weight, ginning out turn, seed cotton yield and seed index. NIAB-414 and VH-367 were identified best parents for fiber length, strength and fineness. Among crosses NIAB-414 × IUB-222 was best for number of bolls per plant, seed index, seed cotton yield and fiber fineness. Whereas, cross NIAB-414 × CIM-632 was good for plant height. The combination of A555 × CIM-632 was best for number of sympodial branches per plant, boll weight, fiber length and strength. VH-367 × CIM-632 proved best for ginning out turn. The correlation results from this study would be helpful to breed cotton cultivars with good yield and quality characters. Broad sense heritability was high for all of parameters which provides the strong evidence that selection in early generations can improve the performance of these traits.
Longitudinal Microglial Activation in Tau Transgenic P301S Mice Predicts Increased Tau Accumulation and Deteriorated Spatial Learning
Authors: Eckenweber Florian , Luque Jose Medina , Blume Tanja , Sacher Christian , Biechele Gloria , Wind Karin , Deussing Maximilian , Briel Nils , Lindner Simon , Boening Guido , von Ungern-Sternberg Barbara , Unterrainer Marcus , Albert Nathalie L. , Zwergal Andreas , Levin Johannes , Bartenstein Peter , Cumming Paul , Rominger Axel , Höglinger Günter U. , Herms Jochen , Brendel Matthias
Published: March 2020

Background: P301S tau transgenic mice show age-dependent accumulation of neurofibrillary tangles in brainstem, hippocampus, and neocortex, leading to neuronal loss and cognitive deterioration. However, there is hitherto only sparse documentation of the role of neuroinflammation in tau mouse models. Thus, we analyzed longitudinal microglial activation by small animal 18kDa translocator protein positron-emission-tomography (TSPO µPET) imaging in vivo , in conjunction with terminal assessment of tau pathology, spatial learning, and cerebral glucose metabolism. Methods: Transgenic P301S (n=33) and wild-type (n=18) female mice were imaged by 18 F-GE-180 TSPO µPET at the ages of 1.9, 3.9 and 6.4 months. We conducted behavioral testing in the Morris water maze, 18 F-fluordesoxyglucose ( 18 F-FDG) µPET and AT8 tau immunohistochemistry at 6.3-6.7 months. Terminal microglial immunohistochemistry served for validation of TSPO µPET results in vivo, applying target regions in brainstem, cortex, cerebellum and hippocampus. We compared the results with our historical data in amyloid -β mouse models. Results: TSPO expression in all target regions of P301S mice increased exponentially from 1.9 to 6.4 months, leading to significant differences in the contrasts with wild-type mice at 6.4 months (+11-23%, all p<0.001), but the apparent microgliosis proceeded more slowly than in our experience in amyloid-β mouse models. Spatial learning and glucose metabolism of AT8-positive P301S mice were significantly impaired at 6.3/6.5 months compared to the wild-type group. Longitudinal increases in TSPO expression predicted greater tau accumulation and lesser spatial learning performance at 6.7/6.3 months. Conclusions: Monitoring of microglial activation in P301S tau transgenic mice by TSPO µPET indicates a delayed time course when compared to amyloid-β mouse models. Detrimental associations of microglial activation with outcome parameters are opposite to earlier data in amyloid-β mouse models. The contribution of microglial response to pathology accompanying amyloid-β and tau over-expression merits further investigation.
Changes of Health Related Quality of Life during Pregnancy based on Pregnancy Context: A prospective study
Authors: Kazemi Ashraf , Dadkhah Aazam , Torabi Fatemeh
Published: March 2020

Background: The significance of planned pregnancy is an accepted principle for improving the health of pregnant women; and quality of life, as one of the important indicators of women's health, is reduced in high-risk pregnancies. The aim of this research was to investigate the changes in the health related quality of life (HRQL) in low risk pregnancies in different groups based on pregnancy context. Methods: The present study was a longitudinal prospective study conducted on 250 pregnant women divided into three groups of women with planned pregnancy, unplanned/wanted pregnancy and unwanted pregnancy. Then, using WHOQOL-26 questionnaire, the quality of life of these women was measured in physical, psychological, social and environmental dimensions at the beginning of pregnancy as well as at the end of the first, second and third trimesters. Results: Based on the results, the mean score of environmental-HRQL in women with unwanted pregnancy was significantly lower than the other two groups. All dimensions on HRQL were influenced by time and group. However, changes in the physical, psychological and social dimensions of HRQL varied within the groups. Physical- HRQL changes were different within the groups. The intergroup effect on environmental dimension of quality of life changes was significant.Conclusion: It was observed in this study that HRQL in the women with unwanted pregnancy was lower than the women with planned pregnancy and those with unplanned /wanted pregnancy. Moreover, increase in gestational age would lower quality of life, but this decline had a similar pattern in different groups.
Evaluation of the anaesthetic theatre educational environment at the University of the Witwatersrand.
Authors: Khan Saad Ali , Perrie Helen , Scribante Juan , Green-Thompson Lionel
Published: March 2020

Background The educational environment impacts on various aspects of students’ professional development and well-being and is an important aspect of medical education programmes. Limited research investigating the theatre educational environment has been identified in South Africa and there is limited understanding of this environment at the University of the Witwatersrand (Wits). This study aims to describe the educational environment in theatre for registrars in the Department of Anaesthesiology at Wits. Methods A prospective, descriptive study design was followed, involving anaesthetic registrars at Wits, using the adapted Anaesthetic Theatre Educational Environment Measure (ATEEM) questionnaire between April and June 2019. A convenience sampling method was implemented to administer the anonymous questionnaire. Categorical variables were described using numbers and percentages. Descriptive statistics were used to calculate the total scores. The independent t-test or analysis of variance test was used to make comparisons. Results A total of 85 anaesthetic registrars participated in this study. The mean total (SD) adapted ATEEM score was 116.5 (16.9) out of a total of 164. The total score for male and female registrars was 118.4 (13.5) and 115.3 (18.7) respectively (p=0.419). First-year registrars scored 121.6 (14.3), second years 111.1 (19.0), third years 111.4 (14.6) and fourth years 122.3 (18.7) (p=0.003). Junior and senior registrars scored 117.1 (17.0) and 115.7 (17.1) respectively (p=0.708). The three hospitals were scored 112.3 (19.5), 119.8 (16.4) and 115.4 (12.0) respectively (p=0.187). The mean scores for the five domains were autonomy 25.4/32 (3.1), perception of atmosphere 31.6/44 (5.4), workload/supervision/support 17.3/28 (3.5), perception of teachers and teaching 14.3/20 (2.9), and learning opportunities and orientation to learning 27.9/40 (5.1). Conclusion The theatre educational environment is perceived as more positive than negative, but with room for improvement. The specific domains that require attention to further improve the educational environment were perception of atmosphere, workload/supervision/support, perception of teachers and teaching, and learning opportunities and orientation to learning. With the availability of a validated instrument to assess the educational environment objectively and quantitatively, regular quality assessments of the educational environment should be included in the training institution’s practice.
Short-course Rifaximin therapy is effective and safe in patients with Diarrhea-Predominant Irritable Bowel Syndrome
Authors: Zhuang Xiaojun , Tian Zhenyi , Luo Mei , Xiong Lishou
Published: March 2020

Background and Aim Gut dysbiosis has been implicated in the pathogenesis of irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO), a manifestation of gut dysbiosis, is associated with diarrhea-predominant IBS (IBS-D). Rifaximin could effectively and safely improve IBS symptoms. The aim of this study was to investigate the effect of rifaximin on Chinese IBS-D patients.Methods This study included 78 IBS-D patients defined by the Rome IV criteria. Patients received 400 mg rifaximin twice daily for 2 weeks and participated in a 10-week follow-up. Gastrointestinal (GI) symptoms, quality of life (QOL) and lactulose hydrogen breath test (LHBT) results were assessed before and after treatment. Results All participants showed significant improvements in all GI symptom subdomains after rifaximin treatment (all P < 0.05), which were maintained for at least 10 weeks of follow-up. Additionally, QOL scores were increased with concomitant improvement of clinical symptoms (all P < 0.05). The 45 rifaximin-responsive patients (57.7%) achieved significantly greater GI-symptom improvement than non-responders (all P < 0.05). No GI symptoms were associated with the presence of SIBO (all P > 0.05). SIBO normalization after rifaximin treatment measured by LHBT was found in 44.4% (20/45) of patients with SIBO before treatment. Conclusion A short course (2 weeks) of rifaximin effectively and safely improved GI symptoms and QOL in Chinese patients with IBS-D. However, it did not eradicate SIBO completely, indicating that rifaximin might not be closely associated with LHBT normalization and that an additional therapeutic mechanism of rifaximin is urgently needed.
Circ_0072995 promotes cell carcinogenesis via up-regulating miR-149-5p-mediated SHMT2 in breast cancer
Authors: Qi Chuang , Qin Xianxiong , Zhou Zuozhi , Wang Yan , Yang Qin , Liao Tianzhi
Published: March 2020

Background Circ_0072995 is a novel identified circRNA and has been identified to involve in the metastasis of breast cancer. However, the detailed function and mechanism of circ_0072995 in the biological property of breast cancer cell remain vague. Methods The expression of circ_0072995, microRNA (miR)-149-5p and serine hydroxymethyltransferase 2 (SHMT2) mRNA was detected using quantitative real-time polymerase chain reaction. Western blot was used to detect levels of SHMT2, hexokinase-2 (HK-2), lactate dehydrogenase a chain (LDHA), glucose transporter 1 (GLUT1) and phosphoinositide 3-kinase (PI3K)/p-protein kinase B (AKT) pathway/mammalian target of rapamycin (mTOR) pathway-related protein. Cell proliferation, apoptosis, migration, and invasion were analyzed using cell counting kit-8 assay, flow cytometry, caspase-3 activity analysis, cell adhesion assay and transwell assay, respectively. Glucose metabolism was calculated by measuring glucose uptake, lactate production, and adenosine triphosphate (ATP) levels. The interaction between miR-149-5p and circ_0072995 or SHMT2 was confirmed by dual-luciferase reporter assay. In vivo tumorigenesis was performed using the murine xenograft model. Results Circ_0072995 and SHMT2 were up-regulated in breast cancer tissues and cell lines, and knockdown of circ_0072995 or SHMT2 suppressed cell malignant properties and anaerobic glycolysis; importantly, SHMT2 overexpression attenuated the anticancer action of si-Circ_0072995 in breast cancer. Besides, we also found miR-149-5p directly bound to circ_0072995 or SHMT2 in breast cancer cells, and circ_0072995 promoted the expression of SHMT2 by competitively binding to miR-149-5p. Moreover, circ_0072995 activated PI3K/AKT/mTOR pathway via elevating SHMT2 through miR-149-5p in vitro and in vivo. Additionally, xenograft tumors analysis showed circ_0072995 silence suppressed tumor growth via regulating SHMT2 and miR-149-5p. Conclusion This study demonstrated that circ_0072995 promoted cell malignant phenotypes and anaerobic glycolysis in breast cancer via up-regulating SHMT2 through sponging miR-149-5p, and activated PI3K/AKT/mTOR pathway via miR-149-5p/ SHMT2 axis, indicating a promising molecular target for breast cancer treatment.
Application of treatment planning system assisted large-aperture computed tomography simulator in percutaneous biopsy: initial experience by a radiation therapist
Authors: Lin Xiaoyi , Hong Jun-qiang , Luo Shui-ying , Lai You-qun , Dai Yong-liang , Kong Xiang-quan
Published: March 2020

Background and purpose To evaluate the application of treatment planning system (TPS) assisted large-aperture computed tomography (CT) simulator in percutaneous biopsy, and report our initial experience of the accuracy and safety of this procedure.Methods From November 2018 to December 2019, treatment planning system assisted large-aperture CT simulator guided percutaneous biopsy was performed on 38 cases, with 34 of percutaneous lung biopsy, three of abdominal lesions biopsy, and one case of deep supraclavicular lymph node biopsy. The major results including planned and actual puncture parameters, the success rate, pathological information and complications were recorded. The analyses of puncture accuracy were accomplished by pared-t test and Wilcoxon rank sum test. And the risk factors of puncture accuracy and complications were further identified.Results The entire cohort achieved one-time success of biopsy. No significant differences were presented between planned and actual puncture depth and direction (P = 0.436 and 0.382), indicating the precision of the process. And the pulmonary puncture location was related to the accuracy of puncture direction (P = 0.033). Biopsy specimens were successfully obtained in 38 cases. The diagnostic rate of malignancy was 76%, of which 80% for initial treatment group and 69% for treated group, respectively. For patients with pulmonary biopsy, 12 had minor pneumothorax and 2 progressed to massive pneumothorax. Only three cases suffered needle track bleeding, and no other complications were observed. Additionally, the regression analysis found a significant correlation between puncture angle and the incidence of pneumothorax (P = 0.027).Conclusions TPS assisted large-aperture CT simulator improved the procedure of percutaneous biopsy by combining the advantages of radiotherapy specialty. The initial results suggested the increase of puncture accuracy and success rate, with satisfactory safety simultaneously. It might offer new insights into the field of CT-guided percutaneous biopsy.
Validation of machine learning models to predict dementia-related neuropsychiatric symptoms in real-world data
Authors: Mar Javier , Gorostiza Ania , Ibarrondo Oliver , Cernuda Carlos , Arrospide Arantzazu , Iruin Álvaro , Larrañaga Igor , Tainta Mikel , Ezpeleta Enaitz , Alberdi Ane
Published: March 2020

Background Neuropsychiatric symptoms (NPS) are the leading cause of the social burden of dementia but their role is underestimated. The objective of the study was to validate predictive models to separately identify psychotic and depressive symptoms in patients diagnosed with dementia using clinical databases representing the whole population (real-world data). Methods First, we searched the electronic health records of 4,003 patients with dementia to identify NPS. Second, machine learning (random forest) algorithms were applied to build in the training sample (N=3,003) separate predictive models for psychotic and depressive symptoms. In order to evaluate the classification ability of the models, the following statistics were calculated for each model: the area under the receiver operating curve (AUC), sensitivity, specificity, accuracy, no-information rate and Kappa index. Third, calibration and discrimination were assessed in the validation sample (N= 1,000) to assess the performance of the models. A calibration curve was drawn by plotting the predicted probabilities for groups on the x-axis and the mean observed values on the y-axis. Results Neuropsychiatric symptoms were noted in the electronic health record of 58% of patients. The AUC reached 0.80 for the psychotic symptoms model and 0.74 for the depressive symptoms model. The Kappa index and accuracy also showed better discrimination in the psychotic model. Calibration plots indicated that both types of model had less predictive accuracy when the probability of neuropsychiatric symptoms was < 25%. The most important variables in the psychotic symptom model were use of risperidone, level of sedation, quetiapine and haloperidol and the number of antipsychotics prescribed. In the depressive symptom model, the most important variable was number of antidepressants prescribed, use of escitalopram, level of sedation and age. Conclusions More than half of the sample had NPS as identified by the presence of key terms in the electronic health record. Although NPS are not encoded, they are treated with antipsychotics and antidepressants, which allows developing valid predictive models by joining machine learning tools and real-world data. Given their good performance, the predictive models can be used to estimate prevalence of NPS in population databases.
Factors associated with the burden of family caregivers of elderly patients with femoral neck fracture: a cross-sectional study
Authors: Xiao Peifeng , Zhou Yongchun
Published: March 2020

Background This study aimed to study the factors associated with caregiver burden among caregivers of elderly patients with femoral neck fracture. Methods This cross-sectional study was based on a non-probabilistic sampling of 183 elderly postoperative patients (aged 65 years or older) with femoral neck fracture who were hospitalized in the orthopaedic centre in our hospital and their primary caregivers. Data were collected from January 2016 to June 2019. Patients and primary caregivers completed the sociodemographic questionnaire. The Social Support Rating Scale (SSRS), the General Self-Efficacy Scale (GSE) and the Chinese version of the Zarit Burden Interview (ZBI) were used to evaluate social support, self-efficacy and caregiver burden, respectively. By analysing the clinical data of patients and primary caregivers and combining the factors that affect the caregiver burden in parallel studies, we selected the factors that affected the caregiver burden in this study and conducted a multivariate analysis of these factors. P <0.05 was considered statistically significant. Results We observed 176 caregivers aged 69.28 ± 7.19 years old, among whom 52.3% were male, 58.0% lived in the city, 84.0% were spouses of the patients, and 67.0% had a primary school educational background. The ZBI score of the primary caregivers was 37.8 ± 8.9, and 82.7% of the caregivers were under a moderate to severe burden. The patient’s functional status, Harris score, and pain score and the caregiver’s SSRS scores, GSE scores, and monthly income were factors that affected the caregiver burden. Conclusions Most primary caregivers of elderly patients with femoral neck fracture are subject to a considerable care burden, and social support and self-efficacy intervention are conducive to reducing the caregiver burden.
Effects of strontium ions with potential antibacterial activity on in vivo bone regeneration
Authors: Baheiraei Nafiseh , Eyni Hossein , bakhshi Bita , Najafloo Raziyeh
Published: March 2020

Background

Bioactive glasses (BGs) have attracted added attention in the structure of the scaffolds for bone repair applications. Different metal ions could be doped in BGs to induce specific biological responses. Among these ions, strontium (Sr) is considered as an effective and safe doping element with promising effects on bone formation and regeneration.

Methods

In this experiment, we evaluated the antibacterial activities of the gelatin-BG (Gel-BG) and Gel-BG/Sr scaffolds in vitro. The osteogenic properties of the prepared scaffolds were also assessed in rabbit calvarial bone defects for 12 weeks. Alizarin Red, Hematoxylin & Eosin (H&E) and Masson’s Trichrome staining were performed to assess bone regeneration and the obtained results were compared with those without Sr. Also, histomorphometric data were obtained to evaluate the new bone, residual graft, and connective tissue.

Results

Both scaffolds showed in vivo bone formation during 12 weeks with the newly formed bone area in Gel-BG/Sr scaffold was higher than that in Gel-BG scaffolds after the whole period. Based on the histological results, Gel-BG/Sr exhibited acceleration of early-stage bone formation in vivo. The results of antibacterial investigation showed that although both Gel-BG/Sr and Gel-BG effectively inhibited the growth of Escherichia coli (E. coli) but, only Gel-BG/Sr structure could lead to a 3 log reduction in Staphylococcus aureus (S. aureus). Conclusions: Our results confirmed that Sr doped BG is a favorable candidate for bone tissue engineering with superior antibacterial activity and bone regeneration capacity compared with similar counterparts having no Sr ion.
Can relative rotation angle serve as a sensitive predictor for the development of adjacent segment degeneration after single-segment PLIF?
Authors: Liu Xiao , Liu Haonan , Yang Xiaosong , Liu Zhongjun , liu xiaoguang , Yu Miao
Published: March 2020

Background: Adjacent segment degeneration (ASD) is a major issue after posterior lumbar interbody fusion (PLIF). Several studies have reported the potential causes of ASD based on radiography. However, the postoperative dynamic changes in the adjacent segments are not clear. This study aimed to determine the effect of PLIF on ASD using a formetric 4D system and to compare the effectiveness of this system with that of traditional radiography for the prediction of ASD. Methods: Eighty-five consecutive patients who underwent PLIF of a single-segmen t were included. The formetric 4Dsystem was used to calculate the relative rotation angle between the fusion segment and the upper and lower adjacent vertebrae preoperatively and at 6, 12 and 24 months postoperatively. The range of motion (ROM) and disc height (DH) of the adjacent segments were measured using radiography preoperatively and at 24 months postoperatively. At the final follow-up, the visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate the surgical outcome. The patients were divided into two groups according to the occurrence of radiographic ASD: the ASD group with progression of degeneration and the N-ASD group without progression of degeneration. The clinical outcomes and measurement data between the two groups were compared and analyzed. Results: The index fusion segments included L2-3 to L5-S1. Preoperatively, the relative rotation angles between the fused segment and the upper and lower adjacent vertebrae were 5.1°±2.2°and 3.3°±2.0°,respectively, and both angles increased significantly at all time-points after surgery ( p <0.05). The angles changed most significantly during L2-3 fusion . Radiographic ASD was noted in 13 of 85 patients (15.3%) at 24 months. There was no significant difference in the DH, ROM, or clinical outcome between the two groups ( p >0.05), while the relative rotation angle with the upper adjacent vertebra was greater in the ASD group than in the N-ASD group ( p <0.05). Conclusion: The relative rotation angle with the adjacent vertebra increased significantly after lumbar fusion surgery. It may be a more sensitive predictor for the development ofradiographic ASD than flexion-extension ROM and DH.
Construction of a sensitive and specific lead biosensor using a genetically engineered bacterial system with a luciferase gene reporter
Authors: Nourmohammadi Esmail , Hosseinkhani Saman , Nedaeinia Reza , Khoshdel-Sarkarizi Hoda , Nedaeinia Mozhdeh , Ranjbar Maryam , Ebrahimi Neshat , Farjami Zahra , Nourmohammadi Mohammad , Mahmoudi Ali , Goli Mohammad , A.Ferns Gordon , Sadeghizadeh Majid
Published: March 2020

Background A bacterial biosensor refers to genetically engineered bacteria that produces an assessable signal in the presence of a physical or chemical agent in the environment. Methods We designed and evaluated a bacterial biosensor expressing a luciferase-reporting gene that is controlled by pbr and cadA promoters in Cupriavidus metallidurans (previously Ralstonia metallidurans ) CH34 and pI258 plasmids of Staphylococcus aureus , respectively, for detection of heavy metals. In the present study, we produced biosensor plasmids designated pGL3-luc/pbr -biosensor and pGL3-luc/cad -biosensor, which were based on the expression of luc+ under the control of the cad promoter and the cadC gene of S. aureus plasmid pI258 and pbr promoter and pbrR gene from plasmid pMOL30 of Cupriavidus metallidurans . Results: We found that the biodegradable pGL3-luc/pbr -biosensor could measure lead concentrations between 1-100 μM in the presence of other metals such as zinc, cadmium, tin and nickel, in the presence of which gene expression of the reporter was not observed. The pGL3-luc/cad -biosensor was able to detect lead concentrations between 10 nM to 10 μM. Conclusions: This biosensor was found to be a specific sensor for identifying lead ions in both environmental and biological samples.