bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Factors Influencing the Seroprevalence of Dengue among Residents of the Forest Fringe Areas of Peninsular Malaysia
Authors: Abd-Jamil Juraina , Ngui Romano , Nellis Syahrul , Fauzi Rosmadi , Lim Ai Lian Yvonne , Chinna Karuthan , Khor Chee-Sieng , AbuBakar Sazaly
Published: May 2020

Dengue is an endemic mosquito-borne viral disease prevalent in many urban areas of the tropic, especially the Southeast Asia. Its presence among the indigenous population of Peninsular Malaysia (Orang Asli), however, has not been well described. The present study was performed to investigate the seroprevalence of dengue among the Orang Asli (OA) residing at the forest fringe areas of Peninsular Malaysia and determine the factors that could affect the transmission of dengue among the OA. Eight OA communities consisting of 491 individuals were recruited. From the study, at least 17% of the recruited study participants were positive for dengue IgG, indicating past exposure to dengue. Analysis on the demographic and socioeconomic variables suggested that high seroprevalence of dengue was significantly associated with those above 13 years old and a low household income of less than MYR500 (USD150). It was also associated with the vast presence of residential areas and the presence of a lake. Remote sensing analysis showed that higher land surface temperatures and lower land elevations also contributed to higher dengue seroprevalence. The present study suggested that both demographic and geographical factors contributed to the increasing risk of contracting dengue among the OA living at the forest fringe areas of Peninsular Malaysia. The OA, hence, remained vulnerable to dengue.
Liuweidihuang Pill Alleviates Inflammation of the Testis via AMPK/SIRT1/NF‐κB Pathway in Aging Rats
Authors: Wang Yuxin , Yang Zhangjie , Yang Lingling , Zou Qian , Zhao Shuai , Hu Na , Chen Dongmei , Cui Ruiqin , Ma Huiming
Published: May 2020

Liuweidihuang Pill (LP) is a traditional Chinese herbal formula that is often used in clinical practice to treat kidney deficiency syndrome. The present study investigated the antiaging effects of LP in a D‐galactose‐ (D‐Gal‐) induced subacute aging rat model. The study also attempted to explore whether anti‐inflammatory mechanisms that underpin the antiaging effects are mediated by the AMPK/SIRT1/NF‐κB signaling pathway. Rats were subcutaneously injected with D‐Gal at a dosage of 100 mg/kg/d for 8 weeks. Upon successful induction of aging in the rats, the animal was administered LP at 0.9 g/kg/d by gavage for 4 weeks. Proteins of the testis were subsequently examined by western blot analysis, and associated locations in the testicular tissue were determined by immunohistochemistry. We observed that LP exerted antiaging effects in aging rats following the activation of AMPK/SIRT1. It was also observed that LP inhibited the expression of NF‐κB, thereby further attenuating inflammation of the testis. Therefore, LP can alleviate inflammation of the testis via the AMPK/SIRT1/NF‐κB pathway in aging rats.
Expression Levels of IL-17A, IL-17F, IL-17RA, and IL-17RC in Prostate Cancer with Taking into Account the Histological Grade according to Gleason Scale in Comparison to Benign Prostatic Hyperplasia: In Search of New Therapeutic Options
Authors: Janiczek Marlena , Szylberg Łukasz , Antosik Paulina , Kasperska Anna , Marszałek Andrzej
Published: May 2020

Prostate cancer (PCa) is the second most commonly diagnosed malignant tumor and the fifth leading cause of cancer death in men in the world. The most common types of tumors are adenocarcinomas. Prostate cancer is a slow-growing cancer. The incidence increases with age. Evaluation of proinflammatory factors such as IL-17A, IL-17F, IL-17RA, and IL-17RC expression makes it possible to assess the impact of inflammatory process on progression of PCa. The aim of the study was to retrospectively assess the histological material of PCa divided into few groups using the Gleason score. Studies were carried out on archival tissue material in the form of paraffin blocks of 40 men with PCa after radical prostatectomy. The control group was composed of 10 men with benign prostatic hyperplasia (BPH). The material was obtained by the transurethral resection of the prostate (TURP). Immunohistochemistry was performed on prepared material using specific primary antibodies against IL-17A, IL-17F, IL-17RA, and IL-17RC. Expression of the antibody to be examined using light microscopy and the Remmele-Stegner score (IRS) in cancer staining was then evaluated. Expression of IL-17 RA was not shown in a group of patients with PCa and in the control group. In the group of patients with Gleason score 8 and 9 PCa, the expression of IL-17A was higher compared to that of IL-17F. In addition, in PCa with an increased grade of Gleason scale, a decrease in the expression of the study inflammatory parameters was found. The inflammatory process has an impact on PCa. A study on IL-17 may become a starting point for further research on an attempt to use, for example, immunotherapy in PCa.
Antidiabetic Activity of Aloe vera Leaves
Authors: Muñiz-Ramirez Alethia , Perez Rosa M. , Garcia Efren , Garcia Fabiola E.
Published: May 2020

This research evaluated the potential of using the methanol extract of Aloe vera (L.) Burm.f (AVM) to prevent the formation of AGEs by means of the BSA/glucose assay, BSA‐methylglyoxal assay, arginine‐methylglyoxal assay, fructosamine, Nɛ‐(carboxymethyl) lysine (CML), thiol groups, and carbonyl protein in vitro. The effect of AVM was also evaluated with regard to inhibiting the enzymes α‐amylase, α‐glucosidase, and pancreatic lipase. For this, the plant was dried, ground, and subsequently macerated with methanol. Aloe vera methanol extract (AVM) significantly decreased the formation of AGEs, as well as the formation of fructosamine, CML, and carbonyl protein. The concentration of 5 mg/ml of AVM presented the best results. AVM significantly inhibited the α‐amylase and α‐glucosidase enzymes. As regards the content of thiol groups, a significant increase was observed during the four weeks of the experiment. So, we can conclude that Aloe vera methanol extract decreases the formation of AGEs and may inhibit the increase in postprandial glucose, suggesting that AVM can prevent diabetes complications associated with AGE.
Prospecting for Breast Cancer Blood Biomarkers: Death-Associated Protein Kinase 1 (DAPK1) as a Potential Candidate
Authors: Arko-Boham Benjamin , Owusu Bright Afriyie , Aryee Nii Ayite , Blay Richard Michael , Owusu Ewurama Dedea Ampadu , Tagoe Emmanuel Ayitey , Adams Abdul Rashid , Gyasi Richard Kwasi , Adu-Aryee Nii Armah , Mahmood Seidu
Published: May 2020

Background. Breast cancer is the commonest malignancy in women worldwide. It is estimated to affect approximately 1.5 million women annually and responsible for the greatest number of cancer-related mortalities among women. In 2018, breast cancer mortalities stood at 627,000 women representing approximately 15% of all cancer deaths among women. In Ghana, breast cancer is the second leading cause of cancer deaths, with an incidence of 2,900 cases annually; one of eight women with the disease die. This gives impetus to the fight for improved early detection, treatment, and/management. In this light, we investigated the potential of death-associated protein kinase 1 (DAPK1) as a biomarker for breast cancer. As a tumour suppressor, its expression is activated by several carcinogens to influence cellular pathways that result in apoptosis, autophagy, immune response, and proliferation. Aim. To investigate DAPK1 as a blood biomarker for breast cancer. Methods. Blood samples of participants diagnosed with breast cancer and healthy controls were collected and processed to obtain serum. Information on age, treatment, diagnosis, and pathology numbers was retrieved from folders. Pathology numbers were used to retrieve breast tissue blocks of patients at the Department of Pathology of the KBTH. Tissue blocks were sectioned and immunohistochemically stained with anti-DAPK1 and counterstained with hematoxylin to determine the DAPK1 expression levels. DAKP1 levels in blood sera were quantified using a commercial anti-DAPK1 ELISA kit. Case and control group means were compared using one-way ANOVA and Chi-square test. Statistical significance was set at p≤0.05. Results and Discussion. DAPK1 levels were higher in sera and breast tissues of breast cancer patients than controls. The augmented DAPK1 expression can be interpreted as a stress response survival mechanism to remediate ongoing deleterious events in the cells orchestrated by carcinogenesis. In the presence of abundant DAPK1, the proliferative power of cells (both cancerous and noncancerous) is increased. This may explain why high DAPK1 expression strongly associates with aggressive breast cancer phenotypes like the ER-negative breast cancers, especially the triple-negative breast cancers (TNBC) which are the most aggressive, fast-growing, and highly metastatic. Conclusion. DAPK1 is highly expressed in sera and breast tissues of breast cancer patients than nonbreast cancer participants. The elevated expression of DAKP1 in circulation rather than in breast tissues makes it a candidate for use as a blood biomarker and potential use as therapeutic target in drug development.
The Biology of Myxofibrosarcoma: State of the Art and Future Perspectives
Authors: Sambri Andrea , De Paolis Massimiliano , Spinnato Paolo , Donati Davide Maria , Bianchi Giuseppe
Published: May 2020

Background: Myxofibrosarcoma (MFS) is among the most highly complex sarcoma types. Molecular cytogenetic studies have identified a high level of genomic complexity. Summary: This review provides an update of the current research related to MFS, with particular emphasis on emerging mechanisms of tumorigenesis and their potential therapeutic impact. Many novel possible molecular markers have been identified, not only for prognostication in MFS, but also to serve as possible therapeutic targets, and thereby improve clinical outcomes. However, the molecular pathogenesis of MFS remains incompletely understood. Key Messages: Patients suffering from advanced MFS might benefit from expanded molecular evaluation in order to detect specific expression profiles and identify drug-able targets. Moreover, immunotherapy represents an intriguingly perspective due to the presence of “T-cell inflamed” tumor microenvironment.
ÔRÍ E MEMÓRIA: O PENSAMENTO DE BEATRIZ NASCIMENTO
Authors: Reis Rodrigo Ferreira dos
Published: May 2020

Este artigo tem como objetivo pensar os conceitos de Ôrí e Quilombo produzidos pela historiadora Beatriz Nascimento e suas interlocuções com os conceitos de memória e história. Para a produção deste estudo usamos como fonte os textos produzidos pela autora e publicados em diferentes jornais bem como sua obra oral “Ôrí”, apresentada no documentário produzido por Raquel Gerber. Primeiramente foi feita uma contextualização da vida e estudos de Beatriz Nascimento e sua ligação com os estudos pós-coloniais e, posteriormente, analisamos particularmente o conceito de Ôrí como possibilitador de uma memória coletiva ancorada no corpo negro e o quilombo como território corporal. Ôrí nos convoca como historiadores e acadêmicos a pensar o corpo, seus gestos, seus modos e sua linguagem como materialidade central para a produção de memória, de identidade e, portanto, de História.
RESENHA: “FEMINIZAÇÃO DA POBREZA NO SENEGAL E A DINÂMICA DAS RELAÇÕES SOCIAIS NAS FAMÍLIAS: O CASO DO SUBÚRBIO DE DAKAR”
Authors: Teixeira Dayane
Published: May 2020

Feminização da pobreza no Senegal (2003), escrito pela socióloga e jornalista senegalesa Codou Bop, é fruto de uma comunicação apresentada pela mesma durante o Colloque International de la Recherche Feministe Francophone, ocorrido na França em setembro de 2002, e que foi traduzido e disponibilizado na plataforma da revista eletrônica Labrys- Estudos Feministas pela Prof.a Dra. Tania Navarro Swain.
Effect of matching relation of multi-scale, randomly distributed pores on geometric distribution of induced cracks in hydraulic fracturing
Authors: Peng Peihuo
Published: May 2020

Reservoir rock contains many multi-scale, unevenly distributed pores, and the pore structures of shale in different reservoirs and geological environments vary greatly. Because the seepage velocity and pressure field are related to the pore spatial variations, the inhomogeneity of the seepage is superimposed on the anisotropy of the rock’s physical properties, which will affect the distribution of the induced cracks. A method for calculating the pore size in the bonded particle model, based on Delaunay triangulation, is proposed. A modeling approach capable of simulating the multi-scale pore distribution of actual rock is presented based on the proposed method. To understand how microcracks connect micropores in the process of fracturing, several bonded particle model samples with different pore structures were established, and numerical experiments were conducted based on the coupling calculation of the discrete seepage algorithm and discrete element method. The focus of this study was on the interactions between the distribution characteristics of multi-scale pores, the specific physical properties of the fracturing fluid, and the distribution differences of the induced cracks caused by the special seepage characteristics when using different fracturing fluids. The numerical results showed that the advantages of supercritical CO2 fracturing are maximized in deep reservoirs (high in-situ stress) and that a suitable in-situ stress condition is required (i.e. a stress ratio close to 1).
B(l)ack By Popular Demand: An Analysis of Positive Black Male Characters in Television and Audiences’ Community Cultural Wealth
Authors: Stamps David L.
Published: May 2020

Often media research interrogating Black male characters featured in television does so from a deficit-based framework. To shift the conversation and showcase affirmative examples of Black male roles in scripted television, the following essay analyzes portrayals in the series This Is Us (2016–current), Unbreakable Kimmy Schmidt (2015–2019), S.W.A.T. (2017–current), and A Million Little Things (2018–current). This work adopts critical race theory and community cultural wealth as mechanisms to examine depictions of Black male television characters to illustrate how each offers various forms of cultural capital, including aspirational and resistant capital, for minority audiences. The portrayals discussed here demonstrate a shift in depictions of Black men in television as characters express nonaggressive idiosyncrasies, display vulnerability, and engage in social support with other characters.
Ascending aorta mechanics in bicuspid aortopathy: controversy or fact?
Authors: Iliopoulos Dimitrios C , Sokolis Dimitrios P
Published: May 2020

Bicuspid aortic valve is the most common congenital cardiovascular defect, often associated with proximal aortic dilatation, and the ideal management strategy is debated. The inconsistency in previous and present guideline recommendations emphasizes the insufficiency of the maximal diameter as the sole criterion for prophylactic repair. Our ability to guide clinical decisions may improve through an understanding of the mechanical properties of ascending thoracic aortic aneurysms in bicuspid compared to tricuspid aortic valve patients and non-aneurysmal aortas, because dissection and rupture are aortic wall mechanical failures. Such an understanding of the mechanical properties has been attempted by several authors, and this article addresses whether there is a controversy in the accumulated knowledge. The available mechanical studies are briefly reviewed, discussing factors such as age, sex, and the region of mechanical examination that may be responsible for the lack of unanimity in the reported findings. The rationale for acquiring layer-specific properties is presented along with the main results from our recent study. No mechanical vulnerability of ascending thoracic aortic aneurysms was evidenced in bicuspid aortic valve patients, corroborating present conservative guidelines concerning the management of bicuspid aortopathy. Weakening and additional vulnerability was evidenced in aged patients and those with coexisting valve pathology, aortic root dilatation, hypertension, and hyperlipidemia. Discussion of these results from age- and sex-matched subjects, accounting for the region- and layer-specific aortic heterogeneity, in relation to intact wall results and histologic confirmation, helps to reconcile previous findings and affords a universal interpretation of ascending aorta mechanics in bicuspid aortopathy.
Effects of levosimendan on weaning and survival in adult cardiogenic shock patients with veno-arterial extracorporeal membrane oxygenation: systematic review and meta-analysis
Authors: Burgos Lucrecia María , Seoane Leonardo , Furmento Juan Francisco , Costabel Juan Pablo , Diez Mirta , Vrancic Mariano , Aissaoui Nadia , Benzadón Mariano Noel , Navia Daniel
Published: May 2020

Introduction:

Veno-arterial extracorporeal membrane oxygenation may be used to support patients with refractory cardiogenic shock. Many patients can be successfully weaned, the ability of some medications to facilitate weaning from veno-arterial extracorporeal membrane oxygenation were reported. To date, there are limited studies investigating the impact of levosimendan on veno-arterial extracorporeal membrane oxygenation weaning. The objective of this systematic review and meta-analysis was to assess the effects of levosimendan on successful weaning from veno-arterial extracorporeal membrane oxygenation and survival in adult patients with cardiogenic shock.

Methods:

We performed a systematic review and meta-analysis (PubMed, the Cochrane Library, and the International Clinical Trials Registry Platform published from the year 2000 onwards) investigating whether levosimendan offers advantages compared to standard therapy or placebo, in cardiogenic shock adult patients treated with veno-arterial extracorporeal membrane oxygenation. The primary outcome was veno-arterial extracorporeal membrane oxygenation successful weaning, whereas secondary outcome was all-cause mortality at the longest follow-up available. We pooled risk ratio and 95% confidence interval using fixed and random effects models according to the heterogeneity.

Results:

A total of five non-randomized clinical trials comprising 557 patients were included, 299 patients for levosimendan and 258 patients for control groups. The pooled prevalence of veno-arterial extracorporeal membrane oxygenation successful weaning was 61.4% (95% confidence interval 39.8-82.9%), and all-cause mortality was 36% (95% confidence interval 29.6-48.8%). There was a significant increase in veno-arterial extracorporeal membrane oxygenation successful weaning with levosimendan compared to the controls (risk ratio = 1.42 (95% confidence interval 1.12-1.8), p for effect = 0.004, I2 = 71%). A decrease risk of all-cause mortality in the levosimendan group was also observed, risk ratio = 0.62 (95% confidence interval 0.44-0.88), p for effect = 0.007, I2 = 36%.

Conclusion:

The use of levosimendan on adult patients with cardiogenic shock may facilitate the veno-arterial extracorporeal membrane oxygenation weaning and reduce all-cause mortality. Few articles of this topic are available, and prospective, randomized multi-center trials are warranted to conclude decisively on the benefits of levosimendan in this setting.
Immediate versus wait-and-gradual discontinuation in antipsychotic switching: A meta-analysis
Authors: Takeuchi Hiroyoshi , Remington Gary
Published: May 2020

Introduction:

In two previous meta-analyses of randomized controlled trials (RCTs) examining antipsychotic switching strategies in patients with schizophrenia, we showed no significant differences in any clinical outcomes between immediate versus gradual and gradual versus wait-and-gradual discontinuation of the pre-switch antipsychotic. In this report, we compared immediate versus wait-and-gradual antipsychotic discontinuation.

Methods:

We identified five RCTs examining immediate versus wait-and-gradual discontinuation of the pre-switch antipsychotic in antipsychotic switching involving patients with schizophrenia. However, no data were available from one RCT. The following clinical outcome data were extracted and meta-analyzed: study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events that were reported in two or more of the studies.

Results:

The meta-analysis included four RCTs involving 351 patients ( n=175 for immediate and n=176 for wait-and-gradual antipsychotic discontinuation). A significant difference was found in study discontinuation due to all causes ( n=4, n=351, risk ratio=1.58, 95% confidence interval 1.15–2.17, p=0.005, I2=0%) between the immediate and wait-and-gradual antipsychotic discontinuation groups, while there was no significant difference in any other clinical outcomes. The group difference in study discontinuation due to all causes remained significant for the studies adopting immediate antipsychotic initiation but not for the studies switching to ziprasidone.

Conclusion:

Findings suggest that wait-and-gradual antipsychotic discontinuation may be preferable when a more cautious antipsychotic switch is needed. However, further long-term, double-blind RCTs are needed to confirm the present findings.
Promoting Media Literacy Among Older People: A Systematic Review
Authors: Rasi Päivi , Vuojärvi Hanna , Rivinen Susanna
Published: May 2020

The aim of this study was to advance understanding of how to foster media literacy among older people. A systematic review was conducted of 40 empirical studies published between January 2005 and April 2019. The literature review provided information and practical implications for researchers, designers, and providers of media-literacy education for older people. Based on the review, it can be concluded that interventions aimed at fostering media literacy in older people need further development and creative enrichment in terms of aims, content, providers, recipients, and pedagogical approaches.
Qualitative Methods in Health Policy and Systems Research: A Framework for Study Planning
Authors: Fisher Michael P. , Hamer Mika K.
Published: May 2020

Qualitative methodologies and methods are commonly used in health policy and systems research but have not been extensively characterized. We describe how qualitative approaches are used within the field and present a framework to aid researchers in study planning. To achieve these aims, we conducted a scoping literature review of 1 year of selected health policy and systems research and then coded publications based on their primary analytical foci. Four core themes emerged: policy or program content, an analysis of the substance of policies or program documents; policy or program environment, a study of the landscape of policies or programs; policy or program implementation, a study of the planned or actual execution of a policy or program; and organization or system operations, a study of the structure or function of health organizations or systems. We provide guidance on utilizing the framework and adhering to qualitative best practices during the process.
Parameter identification of the dynamic Winkler soil–structure interaction model using a hybrid unscented Kalman filter–multi-objective harmony search algorithm
Authors: Naranjo-Pérez Javier , Jiménez-Alonso Javier Fernando , Sáez Andrés
Published: May 2020

Soil–structure interaction is a key aspect to take into account when simulating the response of civil engineering structures subjected to dynamic actions. To this end, and due to its simplicity and ease of implementation, the dynamic Winkler model has been widely used in practical engineering applications. In this model, soil–structure interaction is simulated by means of spring–damper elements. A crucial point to guarantee the adequate performance of the approach is to accurately estimate the constitutive parameters of these elements. To this aim, this article proposes the application of a recently developed parameter identification method to address such problem. In essence, the parameter identification problem is transformed into an optimization problem, so that the parameters of the dynamic Winkler model are estimated by minimizing the relative differences between the numerical and experimental modal properties of the overall soil–structure system. A recent and efficient hybrid algorithm, based on the combination of the unscented Kalman filter and multi-objective harmony search algorithms, is satisfactorily implemented to solve the optimization problem. The performance of this proposal is then validated via its implementation in a real case-study involving an integral footbridge.
Return to Sport following Isolated Lateral Opening Wedge Distal Femoral Osteotomy
Authors: Agarwalla Avinesh , Liu Joseph N. , Garcia Grant H. , Gowd Anirudh K. , Puzzitiello Richard N. , Yanke Adam B. , Cole Brian J.
Published: May 2020

Purpose. The aims of this study were to (1) examine the timeline of return to sport (RTS) following isolated lateral opening wedge distal femoral osteotomy (DFO), (2) evaluate the degree of participation on RTS, and (3) identify risk factors for failure to RTS. Methods. Nineteen consecutive patients undergoing isolated lateral opening wedge DFO were reviewed retrospectively at a minimum of 2 years postoperatively. Patients completed a sports questionnaire, visual analogue scale for pain (VAS-Pain), Single Assessment Numerical Evaluation (SANE), and a satisfaction questionnaire. Results. Seventeen patents (89.5%; age 32.1 ± 10.1 years; gender 9 males, 52.9%) were contacted at 7.3 ± 4.4 years (range 2.0-13.8 years). Twelve patients (70.6%) resumed playing ≥1 sport at an average time of 9.5 ± 3.3 months (range 3-12 months). Of these 12 patients, 6 returned to a lower level of participation (50.0%). Seven patients (41.2%) had returned to the operating room for further surgery, which included removal of hardware (5.9%) and total knee arthroplasty (5.9%). The average VAS-Pain, SANE, and Marx scores were 3.4 ± 2.6 (range 0-8), 56.2 ± 18.7 (range 20-85), and 5.0 ± 5.3 (range 0-16), respectively. Fourteen patients (82.4%) were at least somewhat satisfied with their procedure. Conclusion. In patients with isolated lateral compartment osteoarthritis and valgus deformity, lateral opening wedge DFO allows 70.6% of patients to RTS by 9.5 ± 3.3 months. However, most patients may be unable to return to their presymptomatic level of function. Patient expectations regarding RTS can be appropriately managed with adequate preoperative patient education. Level of Evidence. IV, case series.
LipF increases rifampicin and streptomycin sensitivity in a Mycobacterium tuberculosis surrogate
Authors: Arriaga-Guerrero Ana Leticia , Hernández-Luna Carlos E. , Rigal-Leal Joyce , Robles-González Rene J. , González-Escalante Laura Adiene , Silva-Ramírez Beatriz , Mercado-Hernández Roberto , Vargas-Villarreal Javier , Bermúdez de León Mario , Peñuelas-Urquides Katia
Published: May 2020

Background

Mortality due to tuberculosis (TB) has increased due to the development of drug resistance, the mechanisms of which have not been fully elucidated. Our research group identified a low expression of lipF gene in Mycobacterium tuberculosis clinical isolates with drug resistance. The aim of this work was to evaluate the effect of lipase F (LipF) expression on mycobacterial drug resistance.

Results

The effects of expressing lipF from Mycobacterium tuberculosis in Mycobacterium smegmatis on resistance to antituberculosis drugs were determined with resazurin microtiter assay plate and growth kinetics. Functionality of ectopic LipF was confirmed. LipF expression reduced the rifampicin (RIF) and streptomycin (STR) minimum inhibitory concentration (MIC) from 3.12 μg/mL to 1.6 μg/mL and 0.25 μg/mL to 0.06 μg/mL respectively, moreover a reduced M. smegmatis growth in presence of RIF and STR compared with that of a control strain without LipF expression (p < 0.05 and p < 0.01) was shown.

Conclusions

LipF expression was associated with increased RIF and STR sensitivity in mycobacteria. Reduced LipF expression may contribute to the development of RIF and STR resistance in Mycobacterium species. Our findings provide information pertinent to understanding mycobacterial drug resistance mechanisms.
Precision genome editing in plants: state-of-the-art in CRISPR/Cas9-based genome engineering
Authors: Wada Naoki , Ueta Risa , Osakabe Yuriko , Osakabe Keishi
Published: May 2020

Traditionally, generation of new plants with improved or desirable features has relied on laborious and time-consuming breeding techniques. Genome-editing technologies have led to a new era of genome engineering, enabling an effective, precise, and rapid engineering of the plant genomes. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) has emerged as a new genome-editing tool, extensively applied in various organisms, including plants. The use of CRISPR/Cas9 allows generating transgene-free genome-edited plants (“null segregants”) in a short period of time. In this review, we provide a critical overview of the recent advances in CRISPR/Cas9 derived technologies for inducing mutations at target sites in the genome and controlling the expression of target genes. We highlight the major breakthroughs in applying CRISPR/Cas9 to plant engineering, and challenges toward the production of null segregants. We also provide an update on the efforts of engineering Cas9 proteins, newly discovered Cas9 variants, and novel CRISPR/Cas systems for use in plants. The application of CRISPR/Cas9 and related technologies in plant engineering will not only facilitate molecular breeding of crop plants but also accelerate progress in basic research.
Differential effects and mechanisms of local anesthetics on esophageal carcinoma cell migration, growth, survival and chemosensitivity
Authors: Zhu Guanhua , Zhang Ling , Dan Jiapeng , Zhu Qiong
Published: May 2020

Background

Retrospective analysis and pre-clinical studies suggest that local anesthetics have anti-tumoral effects. However, the association between cancer recurrence and the use of local anesthesia is inconclusive and most reports are based on single local anesthetic results.

Methods

The biological effects (growth, migration and survival) of four common local anesthetics on esophageal carcinoma cells were compared. Biochemical assays on molecules involved in cell migration and proliferation were analyzed.

Results

Ropivacaine and bupivacaine significantly inhibited esophageal carcinoma cell migration, at clinically relevant micromolar concentrations. Mepivacaine and lidocaine showed less potent cell migration inhibition than ropivacaine or bupivacaine. All four local anesthetics inhibited cell proliferation. Of note, the effective concentration of anti-proliferative activities requires higher doses. At millimolar concentrations of these local anesthetics, cell apoptosis was moderately affected. Drug combination analysis demonstrated that two of four local anesthetics augmented chemotherapeutic drugs in inhibiting migration. However, all four local anesthetics significantly augmented chemotherapeutic drugs in inhibiting growth and inducing apoptosis. The anti-growth and anti-survival effects of four local anesthetics were attributed to mitochondrial dysfunction and oxidative damage. The anti-migratory effect of local anesthetics is likely through decreasing Rac1 activity.

Conclusions

Our work demonstrates the differential effects and proposes the mechanisms of local anesthetics on esophageal carcinoma cell migration, growth, survival and chemosensitivity.
Awake intubation and extraluminal use of Uniblocker for one-lung ventilation in a patient with a large mediastinal mass a case report
Authors: Liu Zhuo , Jia Qianqian , Yang Xiaochun
Published: May 2020

Background

The anesthesia of patients with large mediastinal mass is at high-risk. Avoidance of general anesthesia in these patients is the safest option, if this is unavoidable, maintenance of spontaneous ventilation is the next safest technique. In these types of patients, it is not applicable to use double-lumen tube (DLT) to achieve one-lung ventilation (OLV) because the DLT has a larger diameter and is more rigid than single-lumen tube (SLT), so the mass may rupture and bleed during intubation. Even using a bronchial blocker, a small size of SLT is required for once the trachea collapses the SLT can pass through the narrowest part of trachea. However, it is difficult to control the fiberoptic bronchoscopy (FOB) and the bronchial blocker simultaneously within the lumen of a small size SLT with traditional intubation methods.

Case presentation

The current study presented a 66 years old female patient with a large mediastinal mass that presented with difficulty breathing when lying flat. In this case, we combined use of dexmedetomidine and remifentanil to preserve the patient’s spontaneous ventilation during intubation and achieved one-lung ventilation with extraluminal use of Uniblocker.

Conclusions

Extraluminal use of Uniblocker and maintenance of spontaneous ventilation during intubation may be an alternative to traditional methods of lung isolation in such patients with a large mediastinal mass.
The Peacock study: feasibility of the dynamic characterisation of the paediatric hypothalamic-pituitary-adrenal function during and after cardiac surgery
Authors: Fudulu Daniel Paul , Angelini Gianni Davide , Papadopoulou Fani Fanoula , Evans Jonathan , Walker-Smith Terrie , Kema Ido , van Faassen Martijn , Stoica Serban , Caputo Massimo , Lightman Stafford , Gibbison Benjamin
Published: May 2020

Background

Cortisol is the main stress hormone mobilised during surgery to establish homeostasis. Our current understanding of the hypothalamic-pituitary-adrenal axis physiology in children undergoing cardiopulmonary bypass is very limited due to: (1) very few cortisol time point measurements over long periods (2) difficulties of sampling in low weight babies and (3) the concomitant use of glucocorticoids at anaesthesia induction. This lack of understanding is reflected in a lack of consensus on the utility of glucocorticoids perioperatively in cardiac surgery with the use of cardiopulmonary bypass.

Methods

The Peacock Study is a prospective, two-centre, observational cohort study of 78 children (undergoing cardiopulmonary bypass procedures and non-surgical procedures - split by age/cyanosis) that aims to characterise in detail the hypothalamic-pituitary-adrenal axis physiology of children using the stress model of paediatric cardiac surgery. Also, we aim to correlate cortisol profiles with clinical outcome data. We herein describe the main study design and report the full cortisol profile of one child undergoing heart surgery, thus proving the feasibility of the method.

Results

We used an automated, 24-h tissue microdialysis system to measure cortisol and cortisone, every 20 min. We herein report one cortisol profile of a child undergoing heart surgery. Besides, we measured serum cortisol and adrenocorticotrophic hormone at seven-time points for correlation. Tissue concentrations of cortisol increased markedly several hours after the end of surgery. We also noted an increase in the tissue cortisol/cortisone ratio during this response.

Conclusion

We report for the first time, the use of an automated microdialysis sampling system to evaluate the paediatric adrenal response in children. Changes in cortisol and cortisone could be measured, and the concentration of cortisol in the tissues increased after the end of cardiac surgery. The method has wide application to measure other hormones dynamically and frequently without the limitation of the circulating blood volume. The data from the main study will clarify how these cortisol profiles vary with age, pathology, type of procedure and correlation to clinical outcomes.

Trial registration

ISCRTN registry, number: 982586.
Reliability of prehospital patient classification in helicopter emergency medical service missions
Authors: Heino A. , Laukkanen-Nevala P. , Raatiniemi L. , Tommila M. , Nurmi J. , Olkinuora A. , Virkkunen I. , Iirola T.
Published: May 2020

Background

Several scores and codes are used in prehospital clinical quality registries but little is known of their reliability. The aim of this study is to evaluate the inter-rater reliability of the American Society of Anesthesiologists physical status (ASA-PS) classification system, HEMS benefit score (HBS), International Classification of Primary Care, second edition (ICPC-2) and Eastern Cooperative Oncology Group (ECOG) performance status in a helicopter emergency medical service (HEMS) clinical quality registry (CQR).

Methods

All physicians and paramedics working in HEMS in Finland and responsible for patient registration were asked to participate in this study. The participants entered data of six written fictional missions in the national CQR. The inter-rater reliability of the ASA-PS, HBS, ICPC-2 and ECOG were evaluated using an overall agreement and free-marginal multi-rater kappa (Κfree).

Results

All 59 Finnish HEMS physicians and paramedics were invited to participate in this study, of which 43 responded and 16 did not answer. One participant was excluded due to unfinished data entering. ASA-PS had an overall agreement of 40.2% and Κfree of 0.28 in this study. HBS had an overall agreement of 44.7% and Κfree of 0.39. ICPC-2 coding had an overall agreement of 51.5% and Κfree of 0.47. ECOG had an overall agreement of 49.6% and Κfree of 0.40.

Conclusion

This study suggests a marked inter-rater unreliability in prehospital patient scoring and coding even in a relatively uniform group of practitioners working in a highly focused environment. This indicates that the scores and codes should be specifically designed or adapted for prehospital use, and the users should be provided with clear and thorough instructions on how to use them.
Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy
Authors: Mhandire Doreen Z. , Mhandire Kudakwashe , Magadze Mulalo , Wonkam Ambroise , Kengne Andre P. , Dandara Collet
Published: May 2020

Background

Maternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll-like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans.

Methods

In a cross-sectional study, 110 women in late gestation who included 36 CMV infected cases and 74 CMV uninfected, age and HIV status matched controls were enrolled. Twenty single nucleotide polymorphisms in 10 genes which code for proteins involved in immunity against CMV were genotyped using Iplex GOLD SNP genotyping protocol on the Agena MassARRAY® system. Statistical analyses were performed using Stata SE and the ‘Genetics’ and ‘SNPassoc’ packages of the statistical package R.

Results

TheTLR7rs179008A > T (p < 0.001) polymorphism was associated while theTLR9rs352139T > C (p = 0.049) polymorphism was on the borderline for association with CMV positive (CMV+) status. In contrast, the interleukin (IL)-6rs10499563T > C (p < 0.001) andTLR2rs1816702C > T (p = 0.001) polymorphisms were associated with CMV negative (CMV-) status. Furthermore, allele frequencies of SNPs inTLR2, TLR4, TLR9, TLR7,IL-6,IL-10,IL-28B,IL-1Aand interferon AR1 (IFNAR1) genes are being reported here for the first time in a Zimbabwean population. The allele frequencies in the Zimbabwean population are generally comparable to other African populations but different when compared to European and Asian populations.

Conclusions

Toll-like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population previously exposed to CMV infection.
Chronic kidney disease in Russia: the Ural eye and medical study
Authors: Bikbov Mukharram M. , Zainullin Rinat M. , Kazakbaeva Gyulli M. , Gilmanshin Timur R. , Rakhimova Ellina M. , Rusakova Iulia A. , Bolshakova Natalia I. , Safiullina Kamila R. , Panda-Jonas Songhomitra , Yakupova Dilya F. , Nikitin Nikolai A. , Jonas Jost B.
Published: May 2020

Background

To examine the prevalence of chronic kidney disease (CKD) and its associations in a Russian population.

Methods

Out of 7328 eligible individuals, the population-based cross-sectional Ural Eye and Medical Study included 5899 (80.5%) individuals aged 40+ years and undergoing a detailed medical examination. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic-Kidney-Disease-Epidemiology-Collaboration (CKD-EPI) equation.

Results

The mean eGFR was 72.3 ± 19.1 mL/min/1.73m2 (median:70.3 mL/min/1.73m2). Prevalence of CKD stage 3a (eGFR< 60 mL/min/1.73m2 and > 45 mL/min/1.73m2), CKD stage 3b (eGFR< 45 mL/min/1.73m2 and > 30 mL/min/1.73m2) and CKD stage 4+ (eGFR< 30 mL/min/1.73m2) were 1351/5841 (23.1%;95% confidence interval (CI):22.1,24.2), 294/5841 (5.0%;95%CI:4.5,5.6), and 29/5841 (0.5%;95%CI:0.3,0.7), respectively. The CKD stage 3+ prevalence increased (P < 0.001) from 11.1% (95%CI:8.4,13.9) in 40–44-year-olds to 56.8% (95%CI:52.8,60.8) in 75 + year-olds. In univariate analysis, CKD stage 3a + prevalence increased with higher systolic blood pressure (P < 0.001). In multivariable analysis, higher prevalence of CKD stage 3a + was associated with older age (P < 0.001;odds ratio (OR):1.06;95%CI:1.05,1.07), female sex (P < 0.001;OR:2.29;95%CI:1.94,2.69), rural region of habitation (P = 0.001;OR:1.29;95%CI:1.11,1.50), higher body mass index (P = 0.03;OR:1.02;95%CI:1.002,1.03), lower prevalence of house ownership (P = 0.02;OR:0.57;95%CI:0.35,0.92), higher prevalence of mostly sitting or standing during work (P < 0.001;OR:1.40;95%CI:1.20,1.64), higher serum concentration of triglycerides (P < 0.001;OR:1.23;95%CI:1.12,1.35) and blood urea nitrogen (P < 0.001;OR:1.33;95%CI:1.27,1.40), lower serum concentration of hemoglobin (P = 0.03;OR:0.99;95%CI:0.99,0.999), and lower prevalence of chronic obstructive pulmonary disease (P < 0.001;OR:0.57;95%CI:0.42,0.78).

Conclusions

In this population from Russia aged 40+ years, prevalence of CKD stage 3+ (28.7%;95%CI:27.5,29.8) was relatively high as compared to populations from other countries. Associated factors were older age, female sex, rural region, higher body mass index, a sedentary lifestyle, and lower socioeconomic background.
Percutaneous insertion of peritoneal dialysis catheter is a safe and effective technique irrespective of BMI
Authors: Xie Dayang , Zhou Jianhui , Cao Xueying , Zhang Qingtao , Sun Yanli , Tang Li , Huang Jing , Zheng Juanli , Lin Li , Li Zhenzhen , Cai Guangyan , Chen Xiangmei
Published: May 2020

Background

A large body mass index (BMI) has been considered as a relative contraindication for percutaneous catheter insertion, although this technique has many advantages. Up to now, there are few studies on peritoneal catheter placement and obesity. The aim of this study was to determine whether patients with large BMI can also choose the percutaneous technique for peritoneal dialysis catheter insertion.

Methods

One hundred eighty seven consecutive patients underwent peritoneal catheter insertions in the Chinese PLA General Hospital between January 1, 2015 and December 31, 2016, with 178 eligible cases being included in the analysis. Two groups were created based on the catheter insertion techniques, the percutaneous group (group P) and the surgical group (group S). Subgroups were created according to BMI > 28 or ≤ 28. The outcomes included catheter related complications and catheter survival.

Results

Total infectious complication rates were significantly lower in group P than in group S. There were no significant differences in peritonitis rate between group P and group S (1.20% vs. 3.16% with P = 0.71 in early stage, and 4.82% vs. 11.58% with P = 0.11 in late stage). All other measured complications were similar between the two groups. Though the one-year infection-free catheter survival in group P was 7.5% higher than group S, the difference was not significant. The one-year dysfunction-free catheter survival, one-year dysfunction-and-infection-free catheter survival, and overall catheter survival were similar between the two groups. Subgroup analyses showed a superior one-year infection-free catheter survival of percutaneous technique in patients with BMI > 28, which was confirmed by Kaplan-Meier analysis.

Conclusions

Despite the challenges that may be encountered with patients who have a large BMI, the percutaneous technique seems to be a safe and effective approach to placing a peritoneal dialysis catheter.
CT-based radiomics scores predict response to neoadjuvant chemotherapy and survival in patients with gastric cancer
Authors: Sun Kai-Yu , Hu Hang-Tong , Chen Shu-Ling , Ye Jin-Ning , Li Guang-Hua , Chen Li-Da , Peng Jian-Jun , Feng Shi-Ting , Yuan Yu-Jie , Hou Xun , Wu Hui , Li Xin , Wu Ting-Fan , Wang Wei , Xu Jian-Bo
Published: May 2020

Background

Neoadjuvant chemotherapy is a promising treatment option for potential resectable gastric cancer, but patients’ responses vary. We aimed to develop and validate a radiomics score (rad_score) to predict treatment response to neoadjuvant chemotherapy and to investigate its efficacy in survival stratification.

Methods

A total of 106 patients with neoadjuvant chemotherapy before gastrectomy were included (training cohort: n = 74; validation cohort: n = 32). Radiomics features were extracted from the pre-treatment portal venous-phase CT. After feature reduction, a rad_score was established by Randomised Tree algorithm. A rad_clinical_score was constructed by integrating the rad_score with clinical variables, so was a clinical score by clinical variables only. The three scores were validated regarding their discrimination and clinical usefulness. The patients were stratified into two groups according to the score thresholds (updated with post-operative clinical variables), and their survivals were compared.

Results

In the validation cohort, the rad_score demonstrated a good predicting performance in treatment response to the neoadjuvant chemotherapy (AUC [95% CI] =0.82 [0.67, 0.98]), which was better than the clinical score (based on pre-operative clinical variables) without significant difference (0.62 [0.42, 0.83], P = 0.09). The rad_clinical_score could not further improve the performance of the rad_score (0.70 [0.51, 0.88], P = 0.16). Based on the thresholds of these scores, the high-score groups all achieved better survivals than the low-score groups in the whole cohort (all P < 0.001).

Conclusion

The rad_score that we developed was effective in predicting treatment response to neoadjuvant chemotherapy and in stratifying patients with gastric cancer into different survival groups. Our proposed strategy is useful for individualised treatment planning.