bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Depression Status Change on Daily Cigarette Smoking Amount: a eleven-year follow up study of the Korea Welfare Panel Study
Authors: Kang Soo Hyun , Jeong Wonjeong , Jang Sung-In , Park Eun-Cheol
Published: August 2020

Background: In the past decade, the Korean smoking rate has only decreased by 3%, despite several smoking control policies. There is a need for such policies to take smokers’ psychological characteristics into account. Depression is a well-known contributor to failed smoking cessation. This study aimed to examine the effect of smokers’ depression status changes on their daily cigarette smoking amount (DCA).Methods: This study used a sample drawn from the Korea Welfare Panel Study (KoWePS) waves 3 (2008) to 13 (2018). The DCA refers to the number of the cigarettes smoked per day at the time of the survey. Depression was measured using an 11-item version of the Center for Epidemiologic Studies Depression Scale (CESD-11). A generalized estimating equation (GEE) model was employed to analyse the effect of change of depression status on DCA.Results: The Yes→No male depression status group had lower DCA (β=-0.631, p-value=0.0248) than the No→No group. The Yes→No male depression status group that began smoking before age 19 had lower DCA (β=-0.881, p-value: 0.0089) than the No→No group that started smoking before 19.Conclusions: We found that a change from depressed to non-depressed and non-depressed to depressed status is associated with decreasing and increasing DCA, respectively. Also, for smokers who began smoking before 19 years of age, the subgroup that went from depressed to non-depressed had much a lower DCA than general smokers. Thus, when treating people participating in smoking cessation programs, counsellors should check for depression symptoms and encourage individuals to pursue depression treatment simultaneously.
Alcohol Consumption and Sports-betting Among Young Male Motorcycle Taxi Bodaboda Riders in Urban Southwestern Uganda
Authors: Nabifo Stella Cheryl , Izudi Jonathan , Bajunirwe Francis
Published: August 2020

Introduction: The popularity of sports-betting is growing globally and may be associated with alcohol consumption among young adults. In this study, we examine the relationship between alcohol consumption plus other substances with sports-betting in a group of young adult males in Uganda. Methods: We conducted a cross-sectional study and interviewed male motorcycle taxi bodaboda riders in the southwestern Uganda town of Mbarara. We asked questions about alcohol consumption, smoking and history and frequency of sports-betting.Results: We enrolled 401 riders. The median age was 29.0 years, interquartile range 25-32. Seventy four (18.5%) had engaged in sports-betting in the past 30 days. Among those that reported sports-betting, 16(21.6%) engaged daily or almost daily. Alcohol use was significantly associated with gambling with an adjusted risk ratio (aRR) of 2.08(95% CI 1.36, 3.18) among moderate drinkers compared to low or non-drinkers but not among heavy drinkers. Cigarette smoking was significantly associated with sports-betting with an aRR 1.85(95% CI 1.13, 3.01). Conclusion: Our data show sports-betting is common among these relatively young male motorcycle riders, and is associated with alcohol consumption and cigarette smoking. Interventions to regulate sports-betting should be co-packaged with those to reduce alcohol consumption and cigarette smoking among young adult males.
Different Expression Pattern of Human Cytomegalovirus-Encoded microRNAs in Circulation from Virus Latency to Reactivation
Authors: Zhou Wanqing , Wang Cheng , Ding Meng , Bian Yuying , Zhong Yujie , Shen Han , Wang Junjun , Zhang Chen-Yu , Zhang Chunni
Published: August 2020

Background: Human cytomegalovirus (HCMV) is a beta-hersvirinae that has a high latent infection rate worldwide and can cause serious consequences in immunocompromised patients when reactivation; however, the mechanism of how HCMV convert from latent to reactivation has rarely been investigated. In the present study, we aimed to perform a comprehensive analysis of the HCMV-encoded microRNA (miRNA) profile in serum of patients upon HCMV reactivation from latency and to further evaluate its clinical significance for the disease monitoring and preventing usefulness.Methods: Serum samples from 60 viremia patients and 60 age-gender matched controls were enrolled in this study for screening and validation of different expression of HCMV miRNAs. Serum concentrations of 22 known HCMV miRNAs were determined by a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. HCMV DNA was measured by quantitative real-time PCR (qPCR) with the whole blood sample. Serum HCMV IgG and IgM were assessed using enzyme linked immunosorbent assay (ELISA). Another 47 samples from 5 patients at different time points were collected to evaluate the monitoring effectiveness and disease prediction ability of differential expression HCMV-miRNAs during the antiviral treatment. Results: The RT-qPCR analysis revealed that the serum levels of 16 of the 22 examined HCMV miRNAs were elevated in HCMV viremia patients compared with controls, and a profile of 8 HCMV miRNAs including hcmv-miR-US25-2-3p, hcmv-miR-US4-5p, hcmv-miR-US25-2-5p, hcmv-miR-US25-1-3p, hcmv-miR-US25-1, hcmv-miR-UL36, hcmv-miR-UL148D, hcmv-miR-US29-3p were markedly elevated (fold change > 2, P < 0.01). Receiver operating characteristic curve (ROC) analysis were performed on the selected HCMV-miRNAs in all of the patients and controls that enrolled in this study, and which ranged from 0.74 to 0.79 in the autoimmune patients. In addition, hcmv-miR-US25-1-3p levels were significantly correlated with HCMV DNA copies (r = 0.297，P = 0.022), and were obviously higher in the reactivation set than the latency set in the autoimmune patients, which could be a predictor for the monitoring of the antiviral treatment.Conclusions: HCMV miRNAs profile showed markedly shift-switch from latency to reactivation in circulation from HCMV infected patients and hcmv-miR-US25-1-3p may be served as a predictor for the switch upon reactivation from latency in patients suffered with autoimmune diseases.
Development and Internal Validation of a Model Predicting Safe, Early Discharge Among Patients Presenting to the Emergency Department with an Infection.
Authors: Mulders Merijn , Maaten Jan Ter , Boekhoud Lisanne , Olgers Tycho , Bouma Hjalmar R.
Published: August 2020

Background: Prolonged hospitalization is associated with high costs and mortality, and increases the chance of adverse events. This study aimed to identify predictors of safe, early discharge in patients presenting to the Emergency Department (ED) with an infection. Methods: This prospective observational study was performed in the ED of a tertiary care teaching hospital. Adult non-trauma patients with suspected infection and at least two Systemic Inflammatory Response Syndrome (SIRS) criteria were included. Exclusion criteria were intensive care unit admission and transfer to another hospital. Safe, early discharge was defined as hospital-discharge within 24 hours without disease-related death or readmission to our hospital during the first 7 days. A prediction model for safe, early discharge was created using a multivariate logistic regression analysis and validated with k-fold cross-validation. Results: 1381 patients were included, of whom 354 (25.6%) met the safe, early discharge criteria. Parameters associated with safe, early discharge were younger age, absence of co-morbidities, living independently, yellow or green triage urgency, absence of ambulance transport, absence of general practitioner referral, normal clinical impression, (q)SOFA, PIRO, MEDS, NEWS and SIRS scores, absence of abnormal vital sign measurements and absence of kidney and respiratory failure. A prediction model for safe, early discharge was developed with an area under the curve (AUC) of 0.824. Internal validation generated a minimal drop in performance, indicating a good fit. Conclusion: By identifying predictors of clinical improvement and combining several readily available parameters in the ED setting, a model for safe, early discharge with good prognostic performance was created.
Monitoring Forest Fire using Geo-Spatial Information Techniques and Spatial Statistics: One Case Study of Forest fire in Margalla Hills, Islamabad, Pakistan
Authors: Tariq Aqil , Shu Hong , Siddiqui Saima
Published: August 2020

Background Understanding the spatial patterns of forest ﬁres is of key importance for ﬁre risk management with ecological implications. Fire occurrence, which may result from the presence of an ignition source and the conditions necessary for a fire to spread, is an essential component of fire risk assessment. Methods The aim of this research was to develop a methodology for analyzing spatial patterns of forest ﬁre danger with a case study of tropical forest fire at Margalla Hills, Islamabad, Pakistan. A geospatial technique was applied to explore inﬂuencing factors including climate, vegetation, topography, human activities, and 299 ﬁre locations. We investigated the spatial extent of burned areas using Landsat data and determined how these factors inﬂuenced the severity rating of ﬁres in these forests. The importance of these factors on forest ﬁres was analyzed and assessed using logistic and stepwise regression methods. Results The findings showed that as the number of total days since the start of fire has increased, the burned areas increased at a rate of 25.848 ha / day (R 2 = 0.98). The average quarterly mean wind speed, forest density, distance to roads and average quarterly maximum temperature were highly correlated to the daily severity rating of forest fires. Only the average quarterly maximum temperature and forest density affected the size of the burnt areas. Fire maps indicate that 22% of forests are at the high and very high level (> 0.65), 25% at the low level (0.45-0.65), and 53% at the very low level (0.25 – 0.45). Conclusion Through spatial analysis, it is found that most forest fires happened in less populated areas and at a long distance from roads, but some climatic and human activities could have influenced fire growth. Furthermore, it is demonstrated that geospatial information technique is useful for exploring forest fire and their spatial distribution.
Diagnostic Value of miR-106a-5p in Patients with Psoriasis and its Regulatory Role in Inflammatory Responses
Authors: Miao Xiaolin , Tong Xinyun , Hu Jingsang , Wang Juan
Published: August 2020

Background: Psoriasis is a multifactorial, recurring, and chronic inflammatory skin disease. This study was designed to explore the potential role of microRNA-106a-5p (miR-106a-5p) in psoriasis.Methods: The expression levels of miR-106a-5p in the serum of psoriasis patients and healthy individuals were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic value of miR-106a-5p in serum was evaluated by the receiver operating characteristics curve (ROC). The levels of interleukin-22 (IL-22), interleukin-17A (IL-17A), and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme-linked immunosorbent assay.Results: The serum expression of miR-106a-5p was found to be up-regulated in psoriasis patients. ROC curve showed that miR-106a-5p had high specificity and sensitivity in the diagnosis of psoriasis. The correlation between the serum expression level of miR-106a-5p and PASI was positive. The relative expression levels of IL-17A, IL-22 and TNF-alpha in serum of psoriasis patients were significantly upregulated compared with that in healthy control, and showed positive association with serum miR-106a-5p levels. Cell experiments demonstrated that upregulation of miR-106a-5p could promote cell proliferation, and the levels of IL-22, IL-17A and TNF-alpha were upregulated significantly in M5-induced HaCaT cells.Conclusion: Considering the novel and vital role in psoriasis progression, miR-106a-5p is expected to be a new potent target for treatment of psoriasis. MiR-106-5p was expected to use for more immunity diseases research and therapy.
MiR-124 and small molecules synergistically regulate the direct generation of neuronal cells from rat cortical reactive astrocytes
Authors: Zheng Yangyang , Huang Zhehao , Xu Jinying , Hou Kun , Yu Yifei , Lv Shuang , Chen Lin , Li Yulin , Quan Chengshi , Chi Guangfan
Published: August 2020

Background：Irreversible neuron loss caused by central nervous system injuries usually lead to persistent neurological dysfunction. Reactive astrocytes, because of their high proliferative capacity, proximity to neuronal lineage, and significant involvement in glial scarring, are ideal starting cells for neuronal regeneration. Having previously identified several small molecules as important regulators of astrocyte-to-neuron reprogramming, our aim in this study was to explore whether other small molecules and miR-124, a key neural differentiation mediator, could co-regulate reactive astrocyte-to-neuron conversion.Methods: MiR-124, ruxolitinib, SB203580, and forskolin were used to induce postnatal rat cortex reactive astrocytes, and the neuronal phenotype of the induced cells was characterised. To understand the genetic changes, RNA-sequencing analyses were performed on reactive astrocytes, induced neurons, and rat neurons, and the mechanisms underlying the regulatory role of miR-124 during the neuronal conversion was explored.Results：MiR-124, ruxolitinib, SB203580, and forskolin could co-convert rat cortical reactive astrocytes into neurons. The induced cells had reduced astroglial properties, displayed typical neuronal morphologies, and expressed neuronal markers, reflecting 25.9% of cholinergic neurons. Gene analysis revealed that induced neuron gene expression patterns were more similar to that of primary neurons than of initial reactive astrocytes. On the molecular level, miR-124-driven neuronal differentiation of reactive astrocytes was via targeting of the SOX9-NFIA-HES1 axis to inhibit HES1 expression.Conclusions：Providing a novel approach for inducing endogenous rat cortical reactive astrocytes into neurons by co-regulation involving miR-124 and three small molecules, our research has potential implications for inhibiting glial scar formation and promoting neuronal regeneration after central nervous system injury or disease.
Both Aerobic and Resistance Exercise Ameliorate Nonalcoholic Fatty Liver Disease Even in the Absence of Weight Reduction in High-fat Diet-induced Obese Mice
Authors: Bae Ju Yong
Published: August 2020

Background: This study aimed at analyzing how aerobic and resistance exercise without dietary restriction could affect fat accumulation in the liver of high-fat diet (HFD)-induced obese mice.Methods: Mice, divided into normal (CO) and high-fat diet (HF) groups, were fed normal or 60 % HFD diets for 8 weeks, respectively. The HF group was then subdivided into HFD + sedentary (HF), HFD + aerobic training (HFAT), and HFD + resistance training (HFRT) groups. The mice in the training groups underwent treadmill or ladder climbing training for 8 weeks.Results: Although the HFAT and HFRT group body weight did not decrease, fat mass significantly decreased in the training groups than that in the HF group. Liver triglyceride levels in the HF group significantly increased compared to the CO group while no significant difference was detected in the training groups. HFD significantly induced an increase of liver cannabinoid-1 receptor, Sterol-regulatory element binding protein 1 (SREBP-1), and fatty acid synthase. Both aerobic and resistance training significantly induced the increase of liver carnitine palmitoyltransferase1, phosphor AMP-activated protein kinase (p-AMPK), and p-AMPK/AMPK while inducing a decrease of liver SREBP-1. However, the type of exercise did not cause any significant difference.Conclusions: Both aerobic and resistance exercise effectively improved fat mass and NAFLD even without weight reduction in HFD-induced obese mice. Therefore, a selected sustainable type of exercise based on the fitness level, type of disease, musculoskeletal disorders status, and preference of subjects, would be the best exercise intervention for alleviating NAFLD.
The YAP/HIF-1α/miR-182/EGR2 Axis is Implicated in Asthma Severity by Control of Th17 Cell Differentiation
Authors: Zhou Jing , Zhang Ning , Zhang Wei , Lu Caiju , Xu Fei
Published: August 2020

Background: Asthma is a heterogeneous chronic inflammatory disease of the airways, with reversible airflow limitations and airway remodeling. T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. However, there is hitherto little data about signaling pathways controlling Th17 cell differentiation in asthma. The aim of this study was to ascertain whether the YAP/HIF-1α/miR-182/EGR2 axis underpins Th17 cell differentiation and asthma severity.Methods: The study included 29 pediatric patients with asthma, 22 healthy volunteers, ovalbumin (OVA)-induced murine asthma models, and mouse naive CD4+ T. The subpopulation of Th17 cells was examined by flow cytometry. The level of IL-17A was determined by ELISA method. ChIP-qPCR assay and dual-luciferase reporter gene assay were performed to examine interaction between HIF-1α and miR-182, miR-182 and EGR2.Results: YAP, HIF-1α, and miR-182 were found to be up-regulated but EGR2 was down-regulated in human and mouse peripheral blood mononuclear cells (PBMCs) in the context of asthma. Abundant expression of YAP and HIF-1α promoted miR-182 expression and then inhibited EGR2, a target of miR-182, thus enhancing Th17 differentiation and deteriorating asthma and lipid metabolism dysfunction. In addition, in vivo findings revealed that over-expression of EGR2 undermined the promoting effect of the YAP/HIF-1α/miR-182 axis on asthma and lipid metabolism dysfunction.Conclusion: These results shed light on that the activation of the YAP/HIF-1α/miR-182/EGR2 axis may promote Th17 cell differentiation, exacerbate asthma development, and aggravate lipid metabolism dysfunction, providing a potential therapeutic target in asthma.
Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway
Authors: Zhao Xiuhao , Zhou Jin , Liang Wenhua , Sheng Qingfeng , Lu Li , Chen Tong , Chen Jianglong , Tan Kezhe , lv Zhibao
Published: August 2020

Background: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated.Results: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor (PXR) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components.Conclusions: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhancing the function of the barrier.
Community Assembly as the Basis for Species Selection for Tropical Forest Restoration in Global Change Scenario
Authors: Meira-Neto João Augusto Alves , Oliveira-Júnior Neil Damas de , Silva Nathália , Oliveira-Filho Ary Teixeira de , Bueno Marcelo Leandro , Pontara Vanessa , Gastauer Markus
Published: August 2020

Background Tropical forests hold high biodiversity, which challenges the selection of species for forest restoration. For a site-specific restoration is required the understanding of the main influences ruling the assemblages. We aimed to answer three questions. 1) how do environmental variables influence taxonomic, phylogenetic diversities, and the phylogenetic structure in the of Rio Doce Basin (TFRD)? 2) How do environmental variables, phylogenetic structure and the main types of seed dispersal relate to each other? 3) Which information of the TFRD assemblages can be used for ecological restoration and conservation in global change scenario? We used 78 sites with their checklists to calculate taxonomic, and phylogenetic diversities, phylogenetic structures, and dispersal proportions. Then, we related the diversities of the sites to their bioclimatic variables and built GLM models.Results Species richness was influenced negatively by water excess duration, by water deficit duration, and positively by maximum temperature, and temperature seasonality. Water regime drives diversity and phylogenetic community structure in the TFRD more than other variables. Annual precipitation and maximum temperature presented the clearer influences on diversity and phylogenetic structure. Zoochory was positively, and anemochory, autochory were negatively related to sesMPD. Conclusions By choosing the lineages with high fitness for each site, the functioning and the stability of ecosystems should increase. The addition of species with anemochory and autochory increases functional and phylogenetic diversity in areas with extreme water excess or water deficit, important in a global change scenario. A high proportion of zoochory allows the communities to function conserving dispersers, biodiversity, and services.
A Clearance Period After Soluble Lead Nanoparticle Inhalation did not Ameliorate the Negative Effects on Target Tissues Due to Decreased Immune Response
Authors: Dumkova Jana , Smutná Tereza , Vrlikova Lucie , Docekal Bohumil , Kristekova Daniela , Vecera Zbynek , Husakova Zuzana , Jakesova Veronika , Jedlickova Adriena , Mikuska Pavel , Capka Lukas , Coufalik Pavel , Tvrdonova Michaela , Krumal Kamil , Vaculovic Tomas , Kanicky Viktor , Hampl Ales , Buchtova Marcela
Published: August 2020

Background: The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover possible differences in the effects of lead exposure on individual target organs and to reveal potential variability in the clearance of lead from organs after inhalation of soluble and insoluble lead particles. Mice were exposed to Pb(NO3)2 NPs in whole-body inhalation chambers for up to 11 weeks. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs (lung, liver, kidney, spleen, bone and blood). Results: After exposure to Pb(NO3)2 NPs, the lead concentration was the highest in femur at all designated time points with the exception of 3-day inhalation. In contrast to other organs, the ability to clear the lead from the femur was very low. In the lungs, Pb(NO3)2 NP inhalation induced serious structural changes; lung damage was present even after a 5-week clearance period despite the lead being almost completely eliminated from the lung tissue. Furthermore, in secondary target organs (kidney and liver), Pb(NO3)2 NPs induced several morphological defects, with alterations that remained visible after the clearance period even though the tissue lead concentrations decreased to minimal values. The numbers of lung and liver macrophages were significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, was increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines (tumour necrosis factor alpha [TNF-α], transforming growth factor beta 1 [TGFβ1], interleukin 6 [IL-6], IL-1α and IL-1β) displayed a tissue-specific response to lead exposure. Conclusions: Taken together, diminished inflammatory response in lung and liver after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by enhanced pathological changes in target organs, even after a 5-week clearance period that contrasts to the stronger effect observed previously after the clearance of insoluble lead nanoparticles.
Withholding and Withdrawal of Life Support in Mechanically Ventilated Stroke Patients
Authors: Montmollin Etienne de , Schwebel Carole , Dupuis Claire , Garrouste-Orgeas Maité , Silva Daniel da , Azoulay Elie , Laurent Virginie , Thiéry Guillaume , Grinea Alexandra , Marcotte Guillaume , Oziel Johanna , Gainnier Marc , Siami Shidasp , Reignier Jean , Sztrymf Benjamin , Adrie Christophe , Ruckly Stephane , Sonneville Romain , Timsit Jean-François
Published: August 2020

Background. The determinants of decisions to limit life support (withholding or withdrawal) in ventilated stroke patients have been poorly investigated.Methods. In a prospective multicenter observational cohort (2005-2016), we evaluated limitation of life support in ventilated stroke patients compared to a non-brain-injured population and identified factors associated with such decisions in stroke patients using Fine and Gray competing risk models.Results. We identified 373 stroke patients (ischemic, n=167 (45%); hemorrhagic, n=206 (55%)), and 5683 non-brain-injured patients. Decisions to limit life support were taken in 41% of ischemic stroke cases (vs. non-brain-injured patients, sHR 3.59 [95% CI 2.78-4.65]) and in 33% of hemorrhagic stroke cases (vs. non-brain-injured patients, sHR 3.9 [95% CI 2.97-5.11]). Time from ICU admission to the first limitation was longer in ischemic than in hemorrhagic stroke (5 [3 - 9] vs 2 [1 - 6] days, p<0.01). Limitation of life support preceded ICU death in 70% of ischemic strokes and 45% of hemorrhagic strokes (p<0.01). Life support limitation in ischemic stroke was associated with a vertebrobasilar location (vs. anterior circulation, sHR, 1.61 [95% CI 1.01 - 2.59]) and in hemorrhagic stroke, it was associated with an age>70 years (2.29 [1.43 - 3.69]), a Glasgow score<8 (2.15 [1.08 - 4.3]) and a lower non-neurologic admission SOFA score (per point, 0.89 [0.82 - 0.97]).Conclusions. In ventilated stroke patients, decisions to limit life support are more than 3 times more frequent than in non-brain injured patients, with different timing and associated risk factors between ischemic and hemorrhagic strokes.
Mutational Analysis of Ocriplasmin to Reduce Proteolytic and Autolytic Activity in Pichia Pastoris
Authors: Baghban Roghayyeh , Farajnia Safar , Ghasemi Younes , Hoseinpoor Reyhaneh , Safary Azam , Mortazavi Mojtaba , Zarghami Nosratollah
Published: August 2020

Background: Ocriplasmin (Jetrea) is using for the treatment of symptomatic vitreomacular adhesion. This enzyme undergoes rapid inactivation and limited activities duration as a result of its autolytic and proteolytic nature after injection within the eye. Moreover, the proteolytic activities can cause photoreceptor damage, which may result in visual impairment in the more serious cases.Results: The present research aimed to reduce the disadvantages of ocriplasmin using site-directed mutagenesis. To reduce the autolytic activity of ocriplasmin in the first variant, lysine 156 changed to glutamic acid and in the second variant for the proteolytic activity reduction, alanine 59 mutated to threonine. The third variant contained both the mutations. Expression of wild type and three mutant variants of ocriplasmin constructs were done in Pichia pastoris expression system. The mutant variants analyzed in silico and in vitro and compared to the wild type. The kinetic parameters of ocriplasmin variants showed both variants with K156E substitution were more resistant to autolytic degradation than wild-type. These variants also exhibited reduced Kcat and Vmax values. An increase in their Km values, leading to a decreased catalytic efficiency (the Kcat/Km ratio) of autolytic and mix variants. Moreover, in variant with A59T mutation, Kcat and Vmax values have reduced compared to wild type. The mix variants showed the most increase in Km value (almost 2-fold) as well as reduced enzymatic affinity to the substrate. Thus, the results indicated combine mutations at ocriplasmin sequence were more effective compared with single mutations. Conclusions: The results indicated such variants represent valuable tools for the investigation of therapeutic strategies aiming at non-surgical resolution of vitreomacular adhesion.
Impact of antifungal stewardship interventions on the susceptibility of Candida species in pediatric patients with malignancy
Authors: Amanati Ali , Badiee Parisa , Jafarian Hadis , Ghasemi Fatemeh , Nematolahi Samane , Haghpanah Sezaneh , Hamzavi Seyedeh Sedigheh
Published: August 2020

Background

There is a worldwide concern with respect to the antimicrobial resistance and the inappropriate use of antifungal agents, which had led to an ever-increasing antifungal resistance. This study aimed to identify the antifungal susceptibility of Candida species isolated from the pediatric patients with cancer and also to evaluate the clinical impact of antifungal stewardship (AFS) ‎interventions on antifungal susceptibility of Candida species.
Methods

In this study, Candida species colonization were evaluated among hospitalized children with cancer in a tertiary teaching hospital, Shiraz 2017-18. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) for polyenes (amphotericin B), echinocandins (caspofungin), and azoles (voriconazole, fluconazole, posaconazole, and itraconazole). Antifungal susceptibility of Candida species was compared with our previous study results to determine the clinical impact of AFS interventions on the antifungal susceptibility.
Results

The prevalence of Candida albicans in the present study was significantly higher than other Candida species. Candida albicans species were completely susceptible to the azoles. The sensitivity rate of C. albicans to amphotericin B and caspofungin was 93.1% and 97.1%, respectively. The results confirm the positive effect of optimized antifungal usage and bedside intervention on the susceptibility of Candida species after the implementation of the AFS program. C. albicans and C. glabrata exhibited significant increase in sensitivity after the execution of AFS program.
Conclusions

Improving the antifungal agent usage can improve antifungal ‎susceptibility and reduce resistance. The AFS is recommended to be addressed, applied, and regularly assessed in centers.
Origanum Vulgare L. Extract-mediated Synthesis of Silver Nanoparticles, Their Characterization and Antibacterial Activities
Authors: Hambardzumyan Syuzanna , Sahakyan Naira , Petrosyan Margarit , Nasim Muhammad Jawad , Jacob Claus , Trchounian Armen
Published: August 2020

Plant extracts serve as reducing and coating agents and are, therefore, commonly employed for the generation of silver (Ag) nanoparticles (NPs). Plant extract mediated synthesis of Ag NPs is a green, environmentally friendly and cost-effective technique which offers a new and potential alternative to chemically synthesized NPs, decreasing the utilization of hazardous and toxic chemicals and protecting the environment. Origanum vulgare L. extracts were evaluated for total flavonoid and phenol content. The free radical scavenging activity was determined employing 2,2-diphenyl-1-picrylhydrazyl assay. Ag NPs were produced exploiting ethanolic extracts of O. vulgare L. leaves. The generation of Ag NPs was carried out both in light and dark conditions. The biosynthesized Ag NPs were characterized employing microscopic and spectroscopic techniques. Antibacterial activities of Ag NPs were determined following appropriate methods. The results revealed that energy of photons was required to reduce Ag+ to Ag0. According to scanning electron microscopy reports, biologically formed Ag NPs ranged in size from 1 to 50 nmand were presented instability causing aggregation. They indicated that O. vulgare L. extracts were rich in flavonoids and phenols and exhibited strong antioxidant activity. Ag NPs exhibited good antibacterial activity immediately after production. Gram-positive strains showed higher sensitivity to Ag NPs compared to Gram-negative stains. Ag NPs can serve as an effective antibacterial agent against antibiotic-resistant strains. The kanamycin-resistant strain was more sensitive to Ag NPs than the ampicillin-resistant strain. Thus, Origanum extract-mediated synthesized Ag NPs can be recommended as alternative effective antibacterial agents, but their activity depended on bacterial species and strains.
Longitudinal Analysis of Socioecological Obesogenic Factors in a National Sample of U.S. Children
Authors: Kim Taeeung , KWON JUNHYE , Lee Chung Gun , Jang Chang-Yong
Published: August 2020

Background: Childhood obesity is a serious public health threat. Although many researchers conducted research on socioecological determinants of childhood obesity, their longitudinal effects remain inconclusive especially among young children. This study examined socioecological factors and associated transitions of children’s body mass index (BMI) status throughout children’s kindergarten to elementary school years, using data from a national longitudinal sample.Methods: The baseline sample of this study included 1,264 children (weighted N=379,297) extracted from the Early Childhood Longitudinal Study (baseline mean age: 5.24 years). The socioecological framework guided selection of socioecological obesogenic variables (e.g., family activity and parental involvement). Longitudinal ordered logistic regressions were performed to determine the associations between socioecological obesogenic variables and unhealthy/healthy changes in BMI status that captured transitions between healthy and unhealthy weight status (i.e., overweight, obesity, and severe obesity).Results: Children with Hispanic ethnicity and nonwhite race, less socioeconomic and environmental support, and living in households with fewer family members were more likely than their counterparts to have unhealthy BMI status changes over time (all ps<0.05). Over the study period, girls were more likely than boys to experience transitions to unhealthy BMI status (all ps<0.05).Conclusion: As hypothesized a priori, the findings of the current affirmed multiple dimensions of how sociological obesogenic factors may influence children’s BMI status changes in a longitudinal setting. In order to maintain children’s long-term healthy weight, more attention should be paid to socioeconomic obesogenic factors surrounding children as well as individual determinants of obesity (e.g., being physically active and having well-balanced nutrition).
Long Term Outcome for OnabotulinumtoxinA (Botox) Therapy in Chronic Migraine: A 2-Year Follow up of Patients Attending the Hull (UK) Migraine Clinic
Authors: Ahmed Fayyaz , Buture Alina , Tanvir Taukir , Khalil Modar
Published: August 2020

ObjectiveThe objective of this prospective analysis was to determine the long-term outcome of patients diagnosed with chronic migraine who were treated with OnabotulinumtoxinA for the prevention of chronic migraine.BackgroundThe long-term outcomes of patients treated with OnabotulinumtoxinA remains uncertain, including information on the number of cycles and duration of OnabotulinumtoxinA needed to successfully convert chronic migraine to episodic migraine, development of resistance to treatment and sustainability of response after stopping treatment.MethodsA total of 655 adult patients diagnosed with chronic migraine who received OnabotulinumtoxinA at the Hull Migraine Clinic were followed up prospectively for a minimum of 2 years. OnabotulinumtoxinA was delivered as per the PREEMPT study protocol and patients were asked to keep a headache diary for at least 30 days prior to and continuously after receiving OnabotulinumtoxinA. The primary outcome was either the number of patients who achieved a ≥50% reduction in headache days or migraine days or an increment in crystal clear days twice that of baseline in a 30-day period. Patients were also assessed for analgesic medication overuse.ResultsTreatment data were available for 655 patients who commenced treatment between July 2010 and October 2016 and followed for at least 2 years (24–70 months). Of the 655 patients, 380 patients responded to treatment after two cycles and went on to receive the third cycle. Of these, 152 patients were still on active treatment at 2 years. Of the 228 patients who stopped treatment, 112 were successfully converted to episodic migraine and showed a sustained response, 28 reverted to chronic migraine after the initial response inspite of continuing treatment (developed resistance), 14 were lost to follow up and 61 patients after achieving remission relapsed after a mean of 9 months (range 4–24 months) and recommenced treatment with OnabotulinumtoxinA. ConclusionAfter a minimum of 2 years, 29.4% of patients with chronic migraine who initially responded to treatment were successfully converted to episodic migraine and maintained a sustained response. Forty percent of the initial cohort of responders continued therapy with OnabotulinumtoxinA to manage their chronic migraine.
Safety of Measles, Mumps, and Rubella Vaccine in Egg Allergy:in Vivo and in Vitro Management
Authors: Magistà Stefania , Albanesi Marcello , Chaoul Nada , Bona Danilo Di , Leo Elisabetta Di , Nettis Eustachio , Caiaffa Maria Filomena , Macchia Luigi
Published: August 2020

Background Egg allergy is the second most prevalent form of food allergy in childhood. In spite of the evidence accumulated, inoculating egg allergy children with attenuated vaccines grown on chick embryo cell cultures, such as the measles, mumps, and rubella (MMR) vaccine, is regarded (erroneously) as potentially dangerous or even anaphylactogenic, by many. An issue perceived as particularly conflicting also by Health Professionals.Case presentation A 15-year-old boy, with a history of severe egg allergy in early infancy, who was still sensitized to egg allergens, including baked egg, had never received MMR vaccination, in fear of possible anaphylaxis, in spite of the fact that this vaccination is mandatory in the first year of life, in Italy. Because of that, he was not allowed to attend school, longer, and was referred to us in order to assess the potential risk of MMR vaccination. Upon thorough allergological workup, sensitization to MMR vaccine components was excluded by an in vivo approach, consisting in skin prick tests, intradermal tests, and subcutaneous injection test, corroborated by vaccine-specific B-lymphocyte proliferation assay, ex vivo. T-cell proliferation in response to MMR vaccine was also excluded. Eventually, the boy was inoculated with MMR vaccine and was readmitted to school.Conclusions The diagnostic strategy adopted appears feasible and easy-to-perform and may be adopted in controversial cases (as the one reported), characterized by previous severe allergic reactions to egg. The B-lymphocyte proliferation assay we developed may represent a useful and reliable tool not only in research but also in clinical practice.
Survey on patients’ organisations’ knowledge and position paper on screening for  inherited neuromuscular diseases in Europe
Authors: Lamy François , Ferlini Alessandra , Board EURO-NMD Patient Advisory , Evangelista Teresinha
Published: August 2020

BackgroundThe development of new genetic testing methods and the approval of the first treatments raises questions regarding when and how to perform screening for inherited neuromuscular conditions. Screening directives and access to the different techniques is not uniform across Europe. The patient advisory board of the European reference network for rare neuromuscular diseases (NMD) conducted a qualitative study to understand the state of play of screening for inherited NMD in Europe and the patients’ needs. ResultsWe collected answers from 30 patient organisations (POs) from 18 European countries. Fifteen acknowledge the existence of pre-implantation genetic diagnosis in their country. Regarding prenatal screening, we had 25 positive answers and 5 negative ones. Twenty-four POs mentioned that newborn screening was available in their country. We had some contradicting answers from POs from the same country and in some cases; diseases said to be part of the screening programmes were not hereditary disorders. Twenty-eight organisations were in favour of testing. The reasons for the two negative answers were lack of reimbursement and treatment, religious beliefs and eventual insurance constrains. Most POs (21) were in favour of systematic screening with the option to opt-out. Regarding the timing for screening, “at birth” reunites most of the responses.The main priority to perform screening for NMDs was early access to treatment, followed by shorter time to diagnostic, preventive care and genetic counselling. ConclusionsThis is the first study to assess knowledge and needs of POs concerning screening for NMDs. The knowledge of POs regarding screening techniques is quite uneven. This implies that, even in communities highly motivated and knowledgeable of the conditions they advocate for, there is a need for better information. Differences in the responses to the questions “how and when to screen” shows that the screening path depends on the disease specificity and the presence of a disease modifying treatment.The unmet need for screening inherited NMDs should follow an adaptive pathway related to the fast moving medical landscape of NMDs. International coordination leading to a common policy would certainly be a precious asset tending to harmonize the situation amongst European countries.
Bacterial Community Assemblages in Classroom Floor Dust of 50 Public Schools in a Large City: Characterization Using 16s rRNA Sequences and Associations with Environmental Factors
Authors: Park Ju-Hyeong , Lemons Angela R. , Roseman Jerry , Green Brett J. , Cox-Ganser Jean M.
Published: August 2020

Characterizing indoor microbial communities using molecular methods provides insight into bacterial assemblages present in environments that can influence occupants’ health. We conducted an environmental assessment as part of an epidemiologic study of 50 elementary schools in a large city in the northeastern United States. We vacuumed dust from the edges of the floor in 500 classrooms accounting for 499 processed dust aliquots for 16S Illumina MiSeq sequencing to characterize bacterial assemblages. DNA sequences were organized into operational taxonomic units (OTUs) and identified using a database derived from the National Center for Biotechnology Information. Bacterial diversity and ecological analyses were performed at the genus level. We identified 29 phyla, 57 classes, 148 orders, 320 families, 1,193 genera, and 2,045 species in 3,073 OTUs. The number of genera per school ranged from 470 to 705. The phylum Proteobacteria was richest, followed by Firmicutes, Actinobacteria, Bacteroidetes, and Cyanobacteria while Firmicutes was most abundant. The most abundant order included Lactobacillales, Spirulinales, Clostridiales, Bacteroidales, Pseudomonadales, and Micrococcales. Halospirulina was the most abundant genus (the only genus within the order Spirulinales), followed by Lactobacillus, Streptococcus, Sphingomonas, Clostridium, and Pseudomonas. Gram-negative bacteria were more abundant and richer (relative abundance=0.53;1,632 OTUs) than gram-positive bacteria (0.47; 1,441). The Bray-Curtis dissimilarity index ranged from 0.22 to 0.63, with a median of 0.40. Effects of school location, degree of water damage, building condition, number of students, air temperature and humidity, floor material, and classroom’s floor level on the bacterial richness or community composition were statistically significant but subtle. Our study indicates that classroom floor dust had a characteristic bacterial community represented by more gram-negative bacteria, in comparison to typical house dust that is represented by more gram-positive bacteria. Health implications of exposure to the microbiomes in classroom floor dust may be different from those in homes for school staff and students.
Atractylenolide-I suppresses tumorigenesis of breast cancer by inhibiting toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway
Authors: Long Fangyi , Lin Hong , Zhang Xiqian , Zhang Jianhui , Xiao Hongtao , Wang Ting
Published: August 2020

Background: Toll-like receptor 4 (TLR4) is an essential sensor related to tumorigenesis, and overexpression of TLR4 in human tumors often correlates with poor prognosis. Atractylenolide I (AT-I) is a major bioactive component from Rhizoma Atractylodes Macrocephalae. Emerging evidence suggests that AT-I exerts anti-tumor effects on various cancers such as colorectal cancer, bladder cancer and melanoma. Nevertheless, the effects of AT-I on mammary tumorigenesis remain unclear.Methods: In order to ascertain the correlation of TLR4/NF-κB pathway with breast cancer, the expression of TLR4 and NF-κB in normal breast tissues and cancer tissues with different TNM-stages was detected by human tissue microarray (TMA) and immunohistochemistry technology. The effects of AT-I on tumorigenesis were investigated by cell viability, colony formation, apoptosis, migration and invasion assays in two breast cancer cells (MCF-7 and MDA-MB-231), and N-Nitroso-N-methylurea (NMU) induced rat breast cancer models were developed to evaluate the anti-tumor effects of AT-I in vivo. The possible underlying mechanisms were further explored by western blot and ELISA assays after a series of LPS treatment and TLR4 knockdown experiments.Results：We found that TLR4 and NF-κB were significantly up-regulated in breast cancer tissues, and was correlated with advanced TNM-stages. AT-I could inhibit TLR4 mediated NF-κB signaling pathway and decrease NF-κB-regulated cytokines in breast cancer cells, thus inhibiting cell proliferation, migration and invasion, and inducing apoptosis of breast cancer cells. Furthermore, AT-I could inhibit NMU-induced rat mammary tumor progression through TLR4/NF-κB pathway.Conclusions: Our findings demonstrated that TLR4 and NF-κB were over expressed in breast cancer, and AT-I could suppress tumorigenesis of breast cancer via inhibiting TLR4-mediated NF-κB signaling pathway.
On the low-energy description for tunnel-coupled one-dimensional Bose gases
Authors: van Nieuwkerk Yuri Daniel , Essler Fabian
Published: August 2020

We consider a model of two tunnel-coupled one-dimensional Bose gases
with hard-wall boundary conditions. Bosonizing the model and retaining
only the most relevant interactions leads to a decoupled theory
consisting of a quantum sine-Gordon model and a free boson, describing
respectively the antisymmetric and symmetric combinations of the phase
fields. We go beyond this description by retaining the perturbation
with the next smallest scaling dimension. This perturbation carries
conformal spin and couples the two sectors. We carry out a detailed
investigation of the effects of this coupling on the non-equilibrium
dynamics of the model. We focus in particular on the role played by
spatial inhomogeneities in the initial state in a quantum quench setup.