bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral phospholipidic curcumin in juvenile idiopathic arthritis-associated uveitis
Authors: Miserocchi Elisabetta , Giuffrè Chiara , Cicinelli Maria Vittoria , Marchese Alessandro , Gattinara Maurizio , Modorati Giulio , Bandello Francesco
Published: December 2019

Purpose:

To evaluate the efficacy and the safety of curcumin-phosphatidylcholine complex in children affected by juvenile idiopathic arthritis–associated uveitis as an adjunctive treatment to chronic systemic immunosuppressive therapy.

Methods:

In this retrospective, longitudinal study, we treated patients affected by juvenile idiopathic arthritis–associated uveitis with residual low-grade inflammatory activity in the anterior chamber with one tablet of curcumin-phosphatidylcholine complex per day, over a year. Low-grade inflammatory activity was characterized by flare 1+ at slit-lamp examination and 10–50 photon counts per ms) at the FC500 laser flare meter. Inactivity of uveitis was defined as complete disappearance of flare at the slit-lamp examination and values <10 ph/ms at laser flare meter. Conversely, recurrence of the uveitis was defined as a one-step increase from baseline in anterior chamber cells levels or laser flare meter measurements >50 ph/ms.

Results:

A total of 22 out of 27 patients (81%) achieved inactivity at the end of the study. Five patients (19%) did not show a significant reduction in anterior chamber flare, remaining stable throughout the follow-up. Only three episodes of flare-ups in three different patients were recorded. Overall, the treatment was well tolerated by all patients and no ocular discomfort, ocular side effects, or allergic reactions were registered.

Conclusion:

Adjunctive therapy with curcumin in patients affected by juvenile idiopathic arthritis–associated uveitis improves mild chronic anterior chamber flare and presents a good safety profile. Despite being mild, anterior chamber inflammation should be minimized to avoid the development of sight-threatening complications in these patients.
Bioinformatics Workflows With NoSQL Database in Cloud Computing
Authors: Wercelens Polyane , da Silva Waldeyr , Hondo Fernanda , Castro Klayton , Walter Maria Emília , Araújo Aletéia , Lifschitz Sergio , Holanda Maristela
Published: December 2019

Scientific workflows can be understood as arrangements of managed activities executed by different processing entities. It is a regular Bioinformatics approach applying workflows to solve problems in Molecular Biology, notably those related to sequence analyses. Due to the nature of the raw data and the in silico environment of Molecular Biology experiments, apart from the research subject, 2 practical and closely related problems have been studied: reproducibility and computational environment. When aiming to enhance the reproducibility of Bioinformatics experiments, various aspects should be considered. The reproducibility requirements comprise the data provenance, which enables the acquisition of knowledge about the trajectory of data over a defined workflow, the settings of the programs, and the entire computational environment. Cloud computing is a booming alternative that can provide this computational environment, hiding technical details, and delivering a more affordable, accessible, and configurable on-demand environment for researchers. Considering this specific scenario, we proposed a solution to improve the reproducibility of Bioinformatics workflows in a cloud computing environment using both Infrastructure as a Service (IaaS) and Not only SQL (NoSQL) database systems. To meet the goal, we have built 3 typical Bioinformatics workflows and ran them on 1 private and 2 public clouds, using different types of NoSQL database systems to persist the provenance data according to the Provenance Data Model (PROV-DM). We present here the results and a guide for the deployment of a cloud environment for Bioinformatics exploring the characteristics of various NoSQL database systems to persist provenance data.
Applications of Next-Generation Sequencing Technologies and Computational Tools in Molecular Evolution and Aquatic Animals Conservation Studies: A Short Review
Authors: Tan Min Pau , Wong Li Lian , Razali Siti Aisyah , Afiqah-Aleng Nor , Mohd Nor Siti Azizah , Sung Yeong Yik , Van de Peer Yves , Sorgeloos Patrick , Danish-Daniel Muhd
Published: December 2019

Aquatic ecosystems that form major biodiversity hotspots are critically threatened due to environmental and anthropogenic stressors. We believe that, in this genomic era, computational methods can be applied to promote aquatic biodiversity conservation by addressing questions related to the evolutionary history of aquatic organisms at the molecular level. However, huge amounts of genomics data generated can only be discerned through the use of bioinformatics. Here, we examine the applications of next-generation sequencing technologies and bioinformatics tools to study the molecular evolution of aquatic animals and discuss the current challenges and future perspectives of using bioinformatics toward aquatic animal conservation efforts.
Development and psychometric testing of an instrument to assess psychosocial determinants of sleep hygiene practice
Authors: Murawski Beatrice , Plotnikoff Ronald C , Duncan Mitch J
Published: December 2019

This study examined the psychometric properties of a newly developed instrument to assess psychosocial determinants of sleep hygiene. Baseline data ( n = 160) from an m-health physical activity and sleep intervention were analyzed to examine scale validity. Additional participants ( n = 20) were recruited to compute test–retest reliability. Four of seven constructs correlated significantly with sleep hygiene practice ( r = −0.17 to −0.36). The scales generally displayed unidimensional component structures. Internal consistency was good to excellent ( α = 0.76–0.92). Test–retest reliability was good to excellent (ICC = 0.61–0.84). Though satisfactory, these findings warrant replication in larger samples.
Solid Evidence for a Thin Hypothesis
Authors: Shih Jerry
Published: December 2019

[Box: see text]
Compounds From the Root of Pueraria peduncularis (Grah. ex Benth.) Benth. and Their Antitumor Effects
Authors: Chen Huabao , Qian Yong , Zhao Xiaomin , Lv Tianxing , Wang Bin , Gong GuoShu , Qiu Xiaoyan , Luo Liya , Zhang Min , Qin GuangWei , Khaskheli Muhammad Ibrahim , Yang Chunping
Published: December 2019

Pueraria peduncularis belongs to the genus Pueraria DC., and has a wide range of medicinal and agricultural values. Previous studies have shown that methanol extracts of P. peduncularis had broad range bioactivities against different pests such as insects, phytopathogens, and snails; however, the specific studies with regard to active compounds against these pests have not been reported. In the current study, we systematically assessed the effects of P. peduncularis root extract against cancer cells, and we also isolated, purified, and analyzed the active ingredients of 8 different compounds from the root of P. peduncularis. To the best of our knowledge, coumestrol (compound 1), lupinalbin A (compound 2), wighteone (compound 6), and erythrinin C (compound 4) were the first isolated from the P. peduncularis root in our study. The extract of the P. peduncularis root had a significantly strong cytotoxic activity on the lung adenocarcinoma cell line A549 (31.0%) and breast cancer cell line MCF-7 (33.0%), respectively. Lupinalbin A (compound 2), erythrinin C (compound 4), pedunsaponin A (compound 7), and pedunsaponin C (compound 8) had more than 40% inhibitory effects on the lung adenocarcinoma line A549. Whereas erythrinin C (compound 4) and pedunsaponin C inhibited more than 47% breast cancer cell lines MCF-7. These results indicate that P. peduncularis is rich in anticancer substances that laid the foundation for a further understanding of P. peduncularis and need to be further explored for other diseases.
Absorbency and utensilency: A spectrum for analysing children’s digital play practices
Authors: Lundtofte Thomas Enemark , Odgaard Ane Bjerre , Skovbjerg Helle Marie
Published: December 2019

This article explores 4- to 7-year-old children’s tablet computer (tablet) use, drawing on empirical data from day-care institutions, primary schools and private home settings in Denmark. Data were gathered via video observations in two different studies: (a) a media ethnography on children’s tablet play practices in home settings and (b) a socioculturally informed, design-based study involving children as co-producers in institutional settings. We understand children’s tablet use via practice theory, framing tablets as actor-enacted objects in play practices expressed through play moods in qualitatively distinguishable ways. We suggest a conceptual spectrum (not dichotomy) for understanding how sociomateriality is articulated in children’s tablet play practices, ranging from absorbent to utensilent. Within sociomaterially absorbent practices, the tablet is foregrounded in intense involvement, thus mediating a focused play mood which relies on not being disturbed by outside actors. Within sociomaterially utensilent practices, the tablet is backgrounded as a node or nexus, thus mediating a distributed play mood of involvement with places and agents beyond the tablet. We contribute to previous findings by Marsh framed within the post-humanist approach as we suggest the empirically observed complexity in children’s digital play can be approached by tracing the relationally generated object positions. We add to this by proposing an analytical spectrum ranging from absorbent to utensilent sociomaterial practices that can be employed when analysing children’s digital play.
Liver transplantation in a patient with hereditary haemorrhagic telangiectasia and pulmonary hypertension
Authors: Ejiri Kentaro , Akagi Satoshi , Nakamura Kazufumi , Amioka Naofumi , Ichikawa Keishi , Yagi Takahito , Ito Hiroshi
Published: December 2019

Hereditary haemorrhagic telangiectasia or Rendu‐Osler‐Weber syndrome is a systemic vascular disease with autosomal dominant inheritance, mucocutaneous telangiectasia, and repeated nasal bleeding due to vascular abnormalities. Hereditary haemorrhagic telangiectasia may occasionally lead to complications, including arteriovenous malformations and pulmonary hypertension. We present a case of a 52‐year‐old female patient with hereditary haemorrhagic telangiectasia who was referred to our hospital for treatment of pulmonary hypertension. She had been diagnosed with hereditary haemorrhagic telangiectasia during adolescence and was being followed up. Six months prior to presentation, she had undergone coil embolization for pulmonary haemorrhage due to pulmonary arteriovenous malformations. She was in World Health Organization functional class IV, with a mean of pulmonary arterial pressure of 38 mmHg, a pulmonary capillary wedge pressure of 10 mmHg, and a right atrial pressure of 22 mmHg. A contrast‐enhanced computed tomography angiography showed large arteriovenous malformations in the liver. Right heart catheterization revealed an increase in oxygen saturation in the inferior vena cava between the supra‐ and infra‐hepatic veins, low pulmonary vascular resistance, and high right atrial pressure. Hence, she was diagnosed with hereditary haemorrhagic telangiectasia with pulmonary hypertension due to major arteriovenous shunt resulting from arteriovenous malformations in the liver. Therefore, we considered liver transplantation as an essential treatment option. She underwent cadaveric liver transplantation after a year resulting in dramatic haemodynamic improvement to World Health Organization functional class I. Liver transplantation is a promising treatment in patients with hereditary haemorrhagic telangiectasia and pulmonary hypertension resulting from arteriovenous shunt caused by arteriovenous malformations in the liver.
Schistosomiasis on prostate biopsy, adenocarcinoma on transurethral resection of prostate specimens
Authors: Mukendi Alain Mwamba , Doherty Sean , Ngobese Lungile
Published: December 2019

In bilharzia-endemic areas, schistosomiasis is a common infection. Prostate cancer is also a common urological condition affecting people in both bilharzia and non-bilharzia-endemic areas. The association of these familiar conditions is infrequent and the relationship between these entities still controversial. We are adding to the literature a rare case of prostatic bilharzia on needle biopsy, and the subsequent finding of prostatic adenocarcinoma on transurethral resection of prostate specimens.

Level of evidence: 4
Psychological Case Conference Following the Death of a Patient With Neuromuscular Disease: A Source of Emotional Support for Participating Medical Staff
Authors: Fujino Haruo , Matsumura Tsuyoshi , Saito Toshio , Fujimura Harutoshi , Imura Osamu
Published: December 2019

Healthcare professionals involved in the treatment and care of patients with intractable diseases, such as muscular dystrophy, increasingly encounter situations that can elicit emotional distress for them as well as the patients. Therefore, medical professionals also need support. This article describes a psychological case conference of multidisciplinary professionals involved in the treatment of a deceased patient with Duchenne muscular dystrophy. The conference aimed to support medical professionals in reflecting on and sharing their thoughts, feelings, and conflicts. Such a practice could support medical professionals in reflecting patients’ thoughts and sharing their personal experiences with other staff members, which may alleviate emotional and personal conflicts. Reflecting on their interactions and dealings with patients serves this supportive function. Psychological case conferences for medical staff may serve as an opportunity for participants to feel emotionally supported and may perhaps help prevent burnout.
Myeloid cell–targeted miR-146a mimic inhibits NF-κB–driven inflammation and leukemia progression in vivo
Authors: Su Yu-Lin , Wang Xiuli , Mann Mati , Adamus Tomasz P. , Wang Dongfang , Moreira Dayson F. , Zhang Zhuoran , Ouyang Ching , He Xin , Zhang Bin , Swiderski Piotr M. , Forman Stephen J. , Baltimore David , Li Ling , Marcucci Guido , Boldin Mark P. , Kortylewski Marcin
Published: December 2019

NF-κB is a key regulator of inflammation and cancer progression, with an important role in leukemogenesis. Despite its therapeutic potential, targeting NF-κB using pharmacologic inhibitors has proven challenging. Here, we describe a myeloid cell–selective NF-κB inhibitor using an miR-146a mimic oligonucleotide conjugated to a scavenger receptor/Toll-like receptor 9 agonist (C-miR146a). Unlike an unconjugated miR146a, C-miR146a was rapidly internalized and delivered to the cytoplasm of target myeloid cells and leukemic cells. C-miR146a reduced expression of classic miR-146a targets (IRAK1 and TRAF6), thereby blocking activation of NF-κB in target cells. IV injections of C-miR146a mimic to miR-146a–deficient mice prevented excessive NF-κB activation in myeloid cells, and thus alleviated myeloproliferation and mice hypersensitivity to bacterial challenge. Importantly, C-miR146a showed efficacy in dampening severe inflammation in clinically relevant models of chimeric antigen receptor (CAR) T-cell–induced cytokine release syndrome. Systemic administration of C-miR146a oligonucleotide alleviated human monocyte-dependent release of IL-1 and IL-6 in a xenotransplanted B-cell lymphoma model without affecting CD19-specific CAR T-cell antitumor activity. Beyond anti-inflammatory functions, miR-146a is a known tumor suppressor commonly deleted or expressed at reduced levels in human myeloid leukemia. Using The Cancer Genome Atlas acute myeloid leukemia data set, we found an inverse correlation of miR-146a levels with NF-κB–related genes and with patient survival. Correspondingly, C-miR146a induced cytotoxic effects in human MDSL, HL-60, and MV4-11 leukemia cells in vitro. The repeated IV administration of C-miR146a inhibited expression of NF-κB target genes and thereby thwarted progression of disseminated HL-60 leukemia. Our results show the potential of using myeloid cell–targeted miR-146a mimics for the treatment of inflammatory and myeloproliferative disorders.
Stem cell mutations can be detected in myeloma patients years before onset of secondary leukemias
Authors: Sridharan Ashwin , Schinke Carolina D. , Georgiev George , Da Silva Ferreira Mariana , Thiruthuvanathan Victor , MacArthur Ian , Bhagat Tushar D. , Choudhary Gaurav S. , Aluri Srinivas , Chen Jiahao , Pradhan Kith , Xia Yu , Panjikaran Maya , Sims Gregory , Bhagat Chirag K. , Bender Ryan , Keeler Lauryn , Graber Armin , Heuck Christoph , Fletcher Frederick A. , Alapat Daisy , Weinhold Niels , Johnson Sarah K. , Wickrema Amittha , Barlogie Bart , Morgan Gareth J. , Shastri Aditi , Steidl Ulrich , Will Britta , Verma Amit
Published: December 2019

Key Points

Leukemia-associated mutations can be detected many years before the onset of secondary leukemias in myeloma patients. Stem and progenitor cells can act as reservoirs of mutations before the onset of secondary MDS and AML after treatment of myeloma.
Capacitive Imaging Technique for the Inspection of Composite Sucker Rod
Authors: Wang Kefan , Yin Xiaokang , Li Chen , Li Wei , Chen Guoming
Published: December 2019

Composite sucker rod has been extensively used due to its high strength, light weight and corrosion resistive nature. However, such composite sucker rod is difficult for conventional non-destructive evaluation (NDE) techniques to inspect because of its complex material and/or structure. It is thus useful to embark research on developing novel NDE technique to comply the inspection requirement. This work demonstrates the feasibility of using the capacitive imaging (CI) technique for the inspection of composite sucker rod. Finite element (FE) models were constructed in COMSOL to simulate the detection of defects in the glass-fiber layer and on the carbon core surface. An FE Model based inversion method is proposed to obtain the profile of the carbon core. Preliminary CI experimental results are then presented, including the detection of surface wearing defect in the glass-fiber layer, and obtaining the profile of the carbon core. A set of accelerated aging experiments were also carried out and the results indicate that the CI technique is potentially useful in evaluating the ageing status of such composite sucker rod. The CI technique described in this work shows great potential to target some challenging tasks faced in the non-destructive evaluation of composite sucker rod, including quality control, defect detection and ageing assessment.
Ag Nanoparticles Sensitized In2O3 Nanograin for the Ultrasensitive HCHO Detection at Room Temperature
Authors: Zhou Shiqiang , Chen Mingpeng , Lu Qingjie , Zhang Yumin , Zhang Jin , Li Bo , Wei Haitang , Hu Jicu , Wang Huapeng , Liu Qingju
Published: December 2019

Formaldehyde (HCHO) is the main source of indoor air pollutant. HCHO sensors are therefore of paramount importance for timely detection in daily life. However, existing sensors do not meet the stringent performance targets, while deactivation due to sensing detection at room temperature, for example, at extremely low concentration of formaldehyde (especially lower than 0.08 ppm), is a widely unsolved problem. Herein, we present the Ag nanoparticles (Ag NPs) sensitized dispersed In2O3 nanograin via a low-fabrication-cost hydrothermal strategy, where the Ag NPs reduces the apparent activation energy for HCHO transporting into and out of the In2O3 nanoparticles, while low concentrations detection at low working temperature is realized. The pristine In2O3 exhibits a sluggish response (Ra/Rg = 4.14 to 10 ppm) with incomplete recovery to HCHO gas. After Ag functionalization, the 5%Ag-In2O3 sensor shows a dramatically enhanced response (135) with a short response time (102 s) and recovery time (157 s) to 1 ppm HCHO gas at 30 °C, which benefits from the Ag NPs that electronically and chemically sensitize the crystal In2O3 nanograin, greatly enhancing the selectivity and sensitivity.
BEST: a web server for brain expression Spatio-temporal pattern analysis
Authors: Guo Liyuan , Lin Wei , Zhang Yidan , Li Wenhan , Wang Jing
Published: December 2019

Background

Dysregulated gene expression patterns have been reported in several mental disorders. Limited by the difficulty of obtaining samples, psychiatric molecular mechanism research still relies heavily on clues from genetics studies. By using reference data from brain expression studies, multiple types of comprehensive gene expression pattern analysis have been performed on psychiatric genetic results. These systems-level spatial-temporal expression pattern analyses provided evidence on specific brain regions, developmental stages and molecular pathways that are possibly involved in psychiatric pathophysiology. At present, there is no online tool for such systematic analysis, which hinders the applications of analysis by non-informatics researchers such as experimental biologists and clinical molecular biologists.

Results

We developed the BEST web server to support Brain Expression Spatio-Temporal pattern analysis. There are three highlighted features of BEST: 1) visualization: it generates user-friendly visual results that are easy to interpret, including heatmaps, Venn diagrams, gene co-expression networks and cluster-based Manhattan gene plots; these results illustrate the complex spatio-temporal expression patterns, including expression quantification and correlation between genes; 2) integration: it provides comprehensive human brain spatio-temporal expression patterns by integrating data from currently available databases; 3) multi-dimensionality: it analyses input genes as both a whole set and several subsets (clusters) which are enriched according to co-expression patterns, and it also presents the correlation between genetic and expression data.

Conclusions

To the best of our knowledge, BEST is the first data tool to support comprehensive human brain spatial-temporal expression pattern analysis. It helps to bridge disease-related genetic studies and mechanism studies, provides clues for key gene and molecular system identification, and supports the analysis of disease sensitive brain region and age stages. BEST is freely available at http://best.psych.ac.cn.
Population size influences the type of nucleotide variations in humans
Authors: Subramanian Sankar
Published: December 2019

Background

It is well known that the effective size of a population (Ne) is one of the major determinants of the amount of genetic variation within the population. However, it is unclear whether the types of genetic variations are also dictated by the effective population size. To examine this, we obtained whole genome data from over 100 populations of the world and investigated the patterns of mutational changes.

Results

Our results revealed that for low frequency variants, the ratio of AT→GC to GC→AT variants (β) was similar across populations, suggesting the similarity of the pattern of mutation in various populations. However, for high frequency variants,βshowed a positive correlation with the effective population size of the populations. This suggests a much higher proportion of high frequency AT→GC variants in large populations (e.g. Africans) compared to those with small population sizes (e.g. Asians). These results imply that the substitution patterns vary significantly between populations. These findings could be explained by the effect of GC-biased gene conversion (gBGC), which favors the fixation of G/C over A/T variants in populations. In large population, gBGC causes highβ. However, in small populations, genetic drift reduces the effect of gBGC resulting in reducedβ. This was further confirmed by a positive relationship betweenNeandβfor homozygous variants.

Conclusions

Our results highlight the huge variation in the types of homozygous and high frequency polymorphisms between world populations. We observed the same pattern for deleterious variants, implying that the homozygous polymorphisms associated with recessive genetic diseases will be more enriched with G or C in populations with largeNe(e.g. Africans) than in populations with smallNe(e.g. Europeans).
Stratified reconstruction of ancestral Escherichia coli diversification
Authors: Gonzalez-Alba José Maria , Baquero Fernando , Cantón Rafael , Galán Juan Carlos
Published: December 2019

Background

Phylogenetic analyses of the bacterial genomes based on the simple classification in core- genes and accessory genes pools could offer an incomplete view of the evolutionary processes, of which some are still unresolved. A combined strategy based on stratified phylogeny and ancient molecular polymorphisms is proposed to infer detailed evolutionary reconstructions by using a large number of whole genomes. This strategy, based on the highest number of genomes available in public databases, was evaluated for improving knowledge of the ancient diversification of E. coli. This staggered evolutionary scenario was also used to investigate whether the diversification of the ancient E. coli lineages could be associated with particular lifestyles and adaptive strategies.

Results

Phylogenetic reconstructions, exploiting 6220 available genomes in Genbank, established the E. coli core genome in 1023 genes, representing about 20% of the complete genome. The combined strategy using stratified phylogeny plus molecular polymorphisms inferred three ancient lineages (D, EB1A and FGB2). Lineage D was the closest to E. coli root. A staggered diversification could also be proposed in EB1A and FGB2 lineages and the phylogroups into these lineages. Several molecular markers suggest that each lineage had different adaptive trajectories. The analysis of gained and lost genes in the main lineages showed that functions of carbohydrates utilization (uptake of and metabolism) were gained principally in EB1A lineage, whereas loss of environmental-adaptive functions in FGB2 lineage were observed, but this lineage showed higher accumulated mutations and ancient recombination events. The population structure of E. coli was re-evaluated including up to 7561 new sequenced genomes, showing a more complex population structure of E. coli, as a new phylogroup, phylogroup I, was proposed.

Conclusions

A staggered reconstruction of E. coli phylogeny is proposed, indicating evolution from three ancestral lineages to reach all main known phylogroups. New phylogroups were confirmed, suggesting an increasingly complex population structure of E. coli. However these new phylogroups represent < 1% of the global E. coli population. A few key evolutionary forces have driven the diversification of the two main E. coli lineages, metabolic flexibility in one of them and colonization-virulence in the other.
The influence of dexmedetomidine and propofol on circulating cytokine levels in healthy subjects
Authors: Kallioinen Minna , Scheinin Annalotta , Maksimow Mikael , Långsjö Jaakko , Kaisti Kaike , Takala Riikka , Vahlberg Tero , Valli Katja , Salmi Marko , Scheinin Harry , Maksimow Anu
Published: December 2019

Background

Surgery and diseases modify inflammatory responses and the immune system. Anesthetic agents also have effects on the human immune system but the responses they induce may be altered or masked by the surgical procedures or underlying illnesses. The aim of this study was to assess how single-drug dexmedetomidine and propofol anesthesia without any surgical intervention alter acute immunological biomarkers in healthy subjects.

Methods

Thirty-five healthy, young male subjects were anesthetized using increasing concentrations of dexmedetomidine (n = 18) or propofol (n = 17) until loss of responsiveness (LOR) was detected. The treatment allocation was randomized. Multi-parametric immunoassays for the detection of 48 cytokines, chemokines and growth factors were used. Concentrations were determined at baseline and at the highest drug concentration for each subject.

Results

The changes in the concentration of eotaxin (decrease after dexmedetomidine) and platelet-derived growth factor (PDGF, increase after propofol) were statistically significantly different between the groups. Significant changes were detected within both groups; the concentrations of monocyte chemotactic protein 1, chemokine ligand 27 and macrophage migration inhibitory factor were lower in both groups after the drug administration. Dexmedetomidine decreased the concentration of eotaxin, interleukin-18, interleukin-2Rα, stem cell factor, stem cell growth factor and vascular endothelial growth factor, and propofol decreased significantly the levels of hepatocyte growth factor, IFN-γ-induced protein 10 and monokine induced by IFN-γ, and increased the levels of interleukin-17, interleukin-5, interleukin-7 and PDGF.

Conclusions

Dexmedetomidine seemed to have an immunosuppressive effect on the immune system whereas propofol seemed to induce mixed pro- and anti-inflammatory effects on the immune system. The choice of anesthetic agent could be relevant when treating patients with compromised immunological defense mechanisms.

Trial registration

Before subject enrollment, the study was registered in the European Clinical Trials database (EudraCT number 2013–001496-21, The Neural Mechanisms of Anesthesia and Human Consciousness) and in ClinicalTrials.gov (Principal Investigator: Harry Scheinin, number NCT01889004, The Neural Mechanisms of Anesthesia and Human Consciousness, Part 2, on the 23rd of June 2013).
Eosinophils and other peripheral blood biomarkers in glioma grading: a preliminary study
Authors: Huang Zhenxing , Wu Liang , Hou Zonggang , Zhang Pengfei , Li Gen , Xie Jian
Published: December 2019

Background

Many peripheral blood biomarkers are associated with glioma grade, but eosinophils (Eo) are scarcely reported. This study assessed preoperative peripheral eosinophil levels and other peripheral biomarkers presented in prior literature, probing their associations and diagnostic value in the grading of glioma, including its most aggressive type, glioblastoma (GBM).

Methods

Patients newly diagnosed with neuroepithelial tumors were included and divided into low-grade glioma (LGG)/high-grade glioma (HGG) groups and non-GBM/GBM groups separately. Preoperative peripheral biomarkers were collected, such as the counts of Eo, neutrophils (Neu), and lymphocytes (Ly), and values such as the eosinophil to lymphocyte ratio (ELR) and neutrophil to lymphocyte ratio (NLR) were calculated. Correlation analyses were also performed between these biomarkers and the groups. Receiver operating characteristic curves were utilized to assess the individual and joint diagnostic values of the biomarkers.

Results

The HGG patients presented lower Eo and ELR values, which had negative correlations with glioma grade. The diagnostic efficiency of Eo and ELR could be enhanced when combined other biomarkers. In the non-GBM vs GBM analysis, GBM patients displayed reduced Eo and a negative correlation between Eo and a GBM diagnosis The combination of Eo and other biomarkers enhanced the diagnostic efficiency.

Conclusions

A negative correlation between peripheral eosinophils and glioma grade was found in our study. Numerous cytokines derived from eosinophils could regulate the immune response and affect the tumor microenvironment; moreover, eosinophils may inhibit the tumorigenesis of glioma, which should be explored in the future and may enlighten some new paths for glioma therapy.
Maternal healthcare services use in Mwanza Region, Tanzania: a cross-sectional baseline survey
Authors: Orwa James , Mantel Michaela , Mugerwa Micheal , Brownie Sharon , Pallangyo Eunice Siaity , Mwasha Loveluck , Isangula Kahabi , Subi Leonard , Mrema Secilia , Edwards Grace , Siso David , Selestine Edna , Mwansisya Tumbwene , Mbekenga Columba , Temmerman Marleen
Published: December 2019

Background

Improving maternal health by reducing maternal mortality/morbidity relates to Goal 3 of the Sustainable Development Goals. Achieving this goal is supported by antenatal care (ANC), health facility delivery, and postpartum care. This study aimed to understand levels of use and correlates of uptake of maternal healthcare services among women of reproductive age (15–49 years) in Mwanza Region, Tanzania.

Methods

A cross-sectional multi-stage sampling household survey was conducted to obtain data from 1476 households in six districts of Mwanza Region. Data for the 409 women who delivered in the 2 years before the survey were analyzed for three outcomes: four or more ANC visits (ANC4+), health facility delivery, and postpartum visits. Factors associated with the three outcomes were determined using generalized estimating equations to account for clustering at the district level while adjusting for all variables.

Results

Of the 409 eligible women, 58.2% attended ANC4+, 76.8% delivered in a health facility, and 43.5% attended a postpartum clinic. Women from peri-urban, island, and rural regions were less likely to have completed ANC4+ or health facility delivery compared with urban women. Education and early first antenatal visit were associated with ANC4+ and health facility delivery. Mothers from peri-urban areas and those who with health facility delivery were more likely to attend postpartum check-ups.

Conclusion

Use of ANC services in early pregnancy influences the number of ANC visits, leading to higher uptake of ANC4+ and health facility delivery. Postpartum check-ups for mothers and newborns are associated with health facility delivery. Encouraging early initiation of ANC visits may increase the uptake of maternal healthcare services.
HER2 gene (ERBB2) amplification is a rare event in non-liver-fluke associated cholangiocarcinogenesis
Authors: Albrecht Thomas , Rausch Melina , Rössler Stephanie , Albrecht Michael , Braun Jana Dorothea , Geissler Veronika , Mehrabi Arianeb , Vogel Monika Nadja , Pathil-Warth Anita , Mechtersheimer Gunhild , Renner Marcus , Rupp Christian , Weiss Karl Heinz , Busch Elena , Köhler Bruno , Springfeld Christoph , Schirmacher Peter , Goeppert Benjamin
Published: December 2019

Background

Cholangiocarcinoma is a rapidly fatal cancer entity with a median survival of less than one year. In contrast to many other malignancies, no substantial therapeutic breakthrough has been made in the past few decades, thereby limiting the treatment to cytotoxic chemotherapy with little beneficial effect for most patients. Targeted therapy tailored to the individual has shown substantial success in the recent past as a promising avenue for cancer therapy.

Methods

In this study, we determined the frequency of amplification of the HER2 gene in a comprehensive and well-characterized European cholangiocarcinoma cohort encompassing 436 patients including intrahepatic (n = 155), proximal (n = 155) and distal (n = 126) cholangiocarcinoma by strict application of a combined immunohistochemical and in situ hybridization algorithm following the current guidelines for HER2 assessment in gastric cancer.

Results

We identified a proportion of 1.4% (n = 6) patients that demonstrated HER2 gene amplification, with the highest rate among the distal cholangiocarcinoma patients (2.4%). None of the patients with equivocal (2+) immunohistochemical staining results exhibited gene amplification molecularly. In four of the five patients with HER2 positivity, gene amplification was already present in concomitantly tested high-grade biliary intraepithelial neoplasia (80%). HER2 gene amplification was not significantly associated with other clinical parameters, including survival.

Conclusions

This study identifies HER2 gene amplification as a rare event in cholangiocarcinoma of the Western population, occurring already in high-grade BilIN in a subset of patients. Furthermore, we provide a robust testing algorithm that may be used prior to therapy administration in future clinical trials evaluating the role of HER2 as a predictive marker in cholangiocarcinoma.
UPLC-MS based urine untargeted metabolomic analyses to differentiate bladder cancer from renal cell carcinoma
Authors: Wang Zhan , Liu Xiaoyan , Liu Xiang , Sun Haidan , Guo Zhengguang , Zheng Guoyang , Zhang Yushi , Sun Wei
Published: December 2019

Background

To discover biomarker panels that could distinguish cancers (BC and RCC) from healthy controls (HCs) and bladder cancers (BC) from renal cell carcinoma (RCC), regardless of whether the patients have haematuria. In addition, we also explored the altered metabolomic pathways of BC and RCC.

Methods

In total, 403 participants were enrolled in our study, which included 146 BC patients (77 without haematuria and 69 with haematuria), 115 RCC patients (94 without haematuria and 21 with haematuria) and 142 sex- and age-matched HCs. Their midstream urine samples were collected and analysed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarker panels and altered metabolic pathways.

Results

The panel of α-CEHC, β-cortolone, deoxyinosine, flunisolide, 11b,17a,21-trihydroxypreg-nenolone and glycerol tripropanoate could distinguish the patients with cancer from the HCs (the AUC was 0.950) and the external validation also displayed a good predictive ability (the AUC was 0.867). The panel of 4-ethoxymethylphenol, prostaglandin F2b, thromboxane B3, hydroxybutyrylcarnitine, 3-hydroxyphloretin and N′-formylkynurenine could differentiate BC from RCC without haematuria. The AUC was 0.829 in the discovering group and 0.76 in the external validation. The metabolite panel comprising 1-hydroxy-2-oxopropyl tetrahydropterin, 1-acetoxy-2-hydroxy-16-heptadecyn-4-one, 1,2-dehydrosalsolinol and L-tyrosine could significantly discriminate BC from RCC with haematuria (AUC was 0.913). Pathway analyses revealed altered lipid and purine metabolisms between cancer patients and HCs, together with disordered amino acid and purine metabolisms between BC and RCC with haematuria.

Conclusions

UPLC-MS urine metabolomic analyses could not only differentiate cancers from HCs but also discriminate BC from RCC. In addition, pathway analyses demonstrated a deeper metabolic mechanism of BC and RCC.
Analyses of pathological cranial ultrasound findings in neonates that fall outside recent indication guidelines: results of a population-based birth cohort: survey of neonates in Pommerania (SNiP-study)
Authors: Weise Judith , Heckmann Matthias , Bahlmann Hagen , Ittermann Till , Allenberg Heike , Domanski Grzegorz , Lange Anja Erika
Published: December 2019

Background

Recent guidelines recommend a cranial ultrasound (CU) in neonates born at < 30 weeks gestation, admitted to the neonatal intensive care unit (NICU), or with a CU indication. Here, we addressed the need to extend these recommendations.

Methods

We retrospectively reviewed 5107 CUs acquired in the population-based Survey of Neonates in Pomerania, conducted in 2002 to 2008. Neonates with conspicuous CUs that were ≥ 30 weeks gestation without recent indications for CU were identified and assigned to the following groups: with (I) or without (II) admission to neonatal care. We designated CU conspicuities as mild (MC) or significant (SC), and we investigated related neurodevelopment during follow-up.

Results

Of 5107 neonates, 5064 were born at ≥30 weeks gestation and of those, 4306 received CUs without any indication for this examination. We found conspicuities in 7.7% (n = 47/610) of group I (n = 30 MC, n = 17 SC), and 3.2% (n = 117/3696) of group II (n = 100 MC, n = 17 SC). In group II, SC comprised, e.g., bilateral cysts, partial agenesis of the corpus callosum, and periventricular leukomalacia. Follow-up was available in 75% of infants in group II with MCs and SCs; of these, 12.8% had an abnormal neurological follow-up.

Conclusions

We detected a high number of conspicuities in neonates without a CU indication. However, we could not demonstrate that ultrasound findings were associated with the neurological follow-up or any advantage to an earlier diagnosis. Our data did not support extending current guidelines or a general CU screening policy for all neonates.
The coin model of privilege and critical allyship: implications for health
Authors: Nixon Stephanie A.
Published: December 2019

Health inequities are widespread and persistent, and the root causes are social, political and economic as opposed to exclusively behavioural or genetic. A barrier to transformative change is the tendency to frame these inequities as unfair consequences of social structures that result in disadvantage, without also considering how these same structures give unearned advantage, or privilege, to others. Eclipsing privilege in discussions of health equity is a crucial shortcoming, because how one frames the problem sets the range of possible solutions that will follow. If inequity is framed exclusively as a problem facing people who are disadvantaged, then responses will only ever target the needs of these groups without redressing the social structures causing disadvantages. Furthermore, responses will ignore the complicity of the corollary groups who receive unearned and unfair advantage from these same structures. In other words, we are missing the bigger picture. In this conceptualization of health inequity, we have limited the potential for disruptive action to end these enduring patterns.

The goal of this article is to advance understanding and action on health inequities and the social determinants of health by introducing a framework for transformative change: the Coin Model of Privilege and Critical Allyship. First, I introduce the model, which explains how social structures produce both unearned advantage and disadvantage. The model embraces an intersectional approach to understand how systems of inequality, such as sexism, racism and ableism, interact with each other to produce complex patterns of privilege and oppression. Second, I describe principles forpracticing critical allyshipto guide the actions of people in positions of privilege for resisting the unjust structures that produce health inequities. The article is a call to action for all working in health to (1) recognize their positions of privilege, and (2) use this understanding to reorient their approach from saving unfortunate people to working in solidarity and collective action on systems of inequality.
Inaccuracies in survey reporting of alcohol consumption
Authors: Gilligan Conor , Anderson Kristen G. , Ladd Benjamin O. , Yong Yun Ming , David Michael
Published: December 2019

Background

Alcohol consumption estimates in public health predominantly rely on self-reported survey data which is likely to underestimate consumption volume. Surveys tend to ask specifically about standard drinks and provide a definition or guide in an effort to gather accurate estimates. This study aimed to investigate whether the inclusion of the term standard drinks with pictorial guide is associated with an adjustment in self-reported alcohol volume.

Methods

A web-based survey was administered with AUDIT-C questions repeated at the beginning and end of the survey with and without the standard drink term and guide. The order in which respondents were presented with the different question types was randomised. Two cohorts of university/college students in NSW Australia (n = 122) and the US Pacific Northwest (n = 285) completed the survey online.

Results

Australian students did not adjust their responses to questions with and without the standard drink term and pictorial guide. The US students were more likely to adjust their responses based on the detail of the question asked. Those US students who drank more frequently and in greater volume were less likely to adjust/apply a conversion to their consumption.

Conclusions

This study supports previous findings of the inaccuracy of alcohol consumption volume in surveys, but also demonstrates that an assumption of underestimation cannot be applied to all individual reports of consumption. Using additional questions to better understand drink types and serving sizes is a potential approach to enable accurate calculation of underestimation in survey data.
Effect of exogenous surfactant on Paediatric Bronchoalveolar lavage derived macrophages’ cytokine secretion
Authors: van Rensburg Lyné , van Zyl Johann M. , Smith Johan , Goussard Pierre
Published: December 2019

Background

Bronchoalveolar lavage is a useful bronchoscopy technique. However, studies in “normal” children populations are few. Furthermore, the anti-inflammatory effects of exogenous pulmonary surfactants on the bronchoalveolar cellular components are limited.

Methods

Thirty children, aged 3 to 14 years, underwent diagnostic bronchoscopy and bronchoalveolar lavage. Differential cytology, cytokine and chemokine measurements were performed on the fluid after exogenous surfactant exposure. The aim of the study was to investigate the potential anti-inflammatory effects of exogenous surfactants on the bronchoalveolar lavage fluid, specifically alveolar macrophages of healthy South African children.

Results

Alveolar macrophages were the predominant cellular population in normal children. Patients with inflammatory pneumonopathies had significantly more neutrophils. Levels of inflammatory cytokines were significantly lower after exogenous surfactant exposure. Moreover, IL-10 and IL-12 cytokine secretion increased after exogenous surfactant exposure.

Conclusion

This study provides the first data on bronchoalveolar lavage of healthy South African children. Bronchoalveolar lavage fluid from patients with pulmonary inflammation was characterised by neutrophilia. Finally, we propose that exogenous surfactant treatment could help alleviate inflammation in diseased states where it occurs in the tracheobronchial tree.
Anterior gland focal cryoablation: proof-of-concept primary prostate cancer treatment in select men with localized anterior cancers detected by multi-parametric magnetic resonance imaging
Authors: Sze Christina , Tsivian Efrat , Tay Kae Jack , Schulman Ariel A. , Davis Leah G. , Gupta Rajan T. , Polascik Thomas J.
Published: December 2019

Background

Due to their location away from the nerve bundles, anterior prostate cancers (APC) represent a rational target for image-guided cryoablation. This report describes the feasibility and short-term outcomes of anterior focal cryosurgery.

Methods

A retrospective review between 2012 and 2016 of patients with clinically localized APC treated with anterior gland cryoablation was performed. Descriptive statistics were used to report: age, PSA, prostate volume, prostate cancer grade group (PGG), median time to follow-up, and changes in functional status measured with the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) score.

Results

A total of 17 patients underwent anterior focal cryoablation with a median follow-up of 15 months. Median age and PSA at diagnosis were 67 years and 8.7 ng/mL. Pre-operative PGG1 was identified in 12 (71%) men and PGG2 in 5 (29%) men. Median (IQR) lesion volume was 2 mL(0.86, 3.1). Preoperative median IIEF-5 and IPSS scores were 19.5 and 5, and decreased to 19 and 4, post-operatively. All patients remained continent with no change in sexual function. All post-procedure targeted biopsies of the treated cancers were negative.

Conclusion

Our pilot study demonstrates the feasibility of treating APCs with image-guided targeted focal cryoablation as a good balance between short-term oncologic control and near complete preservation of genitourinary function. Further follow-up is necessary to examine the potential benefits long-term.