The Impact of Systematic Review Automation Tools on Methodological Quality and Time Taken to Complete Systematic Review Tasks: Case Study.

Abstract:
BACKGROUND
Systematic reviews (SRs) are considered the highest level of evidence to answer research questions; however, they are time and resource intensive.

OBJECTIVE
When comparing SR tasks done manually, using standard methods, versus those same SR tasks done using automated tools, (1) what is the difference in time to complete the SR task and (2) what is the impact on the error rate of the SR task?

METHODS
A case study compared specific tasks done during the conduct of an SR on prebiotic, probiotic, and synbiotic supplementation in chronic kidney disease. Two participants (manual team) conducted the SR using current methods, comprising a total of 16 tasks. Another two participants (automation team) conducted the tasks where a systematic review automation (SRA) tool was available, comprising of a total of six tasks. The time taken and error rate of the six tasks that were completed by both teams were compared.

RESULTS
The approximate time for the manual team to produce a draft of the background, methods, and results sections of the SR was 126 hours. For the six tasks in which times were compared, the manual team spent 2493 minutes (42 hours) on the tasks, compared to 708 minutes (12 hours) spent by the automation team. The manual team had a higher error rate in two of the six tasks-regarding Task 5: Run the systematic search, the manual team made eight errors versus three errors made by the automation team; regarding Task 12: Assess the risk of bias, 25 assessments differed from a reference standard for the manual team compared to 20 differences for the automation team. The manual team had a lower error rate in one of the six tasks-regarding Task 6: Deduplicate search results, the manual team removed one unique study and missed zero duplicates versus the automation team who removed two unique studies and missed seven duplicates. Error rates were similar for the two remaining compared tasks-regarding Task 7: Screen the titles and abstracts and Task 9: Screen the full text, zero relevant studies were excluded by both teams. One task could not be compared between groups-Task 8: Find the full text.

CONCLUSIONS
For the majority of SR tasks where an SRA tool was used, the time required to complete that task was reduced for novice researchers while methodological quality was maintained.

systematic reviews
automation
case study
comparison study
methods evaluation
technology assessment


Effectiveness of magnetic resonance imaging-targeted biopsy for detection of prostate cancer in comparison with systematic biopsy in our countries with low prevalence of prostate cancer: our first experience after 3 years.

Abstract:
Background
Some men are subjected to multiple repeated biopsies because of ongoing suspicion of prostate cancer, which might subject them to complications. The aim of the study was to determine the diagnostic accuracy of magnetic resonance imaging (MRI)/target fusion-guided biopsy in comparison with systematic biopsy in our low prevalence prostate cancer population, in terms of validity measure, case detection rate, and detection of clinically significant cancer.

Methods
This is a retrospective cohort study. All consecutive patients who met the inclusion criteria (all men with persistent high prostate-specific antigen levels >4 ng/ml and/or subnormal finding in direct rectal examination, with suspicious regions identified on prebiopsy MRI) were subjected to transrectal MRI/ultrasound fusion-guided biopsy.

Results
A total of 165 cases met the inclusion criteria and were included in the study. The cancer detection rate (CDR) of target biopsy was significantly higher than that of standard biopsy (27.9% vs 14%, respectively), and 25 cases (52%) were missed by standard strategy and correctly classified by multiparametric MRI with targeted biopsy (MRI-TB). On the other hand, only 2 cases (4.3%) were misclassified by MRI-TB, and one of them was clinically significant. There was an exact agreement between the 2 strategies in 15 (31%) cases. Targeted biopsy diagnosed 41.5% more high-risk cancers vs systematic biopsy (41.6% vs 6.2%, P < .001). The difference between sensitivity, specificity, and negative predictive value of MRI-TG varies between 80% and 98%.

Conclusion
The CDR of prostate cancer in general and clinically significant cancer, in specific, is significantly higher with MRI-TG modality than with systematic modality. Yet, MRI-TG biopsy still misses some men with clinically significant prostate cancer. Hence, the addition of a 12-core biopsy is required to evade missing cases of clinically significant and insignificant cancer.

Arafa|Mostafa A|MA|
Rabah|Danny M|DM|
Khan|Farruhk K|FK|
Farhat|Karim H|KH|
Al-Atawi|Mohamed A|MA|

Countries with low prevalence of prostate cancer

Magnetic resonance imaging–targeted biopsy


Big brown bats (Eptesicus fuscus) emit intense search calls and fly in stereotyped flight paths as they forage in the wild.

Abstract: The big brown bat, Eptesicus fuscus, uses echolocation for orientation and foraging, and scans its surroundings by aiming its sonar beam at obstacles and prey. All call parameters are highly adaptable and determine the bat's acoustic field of view and hence its perception of the echo scene. The intensity (source level) and directionality of the emitted calls directly contribute to the bat's acoustic field of view; however, the source level and directionality of the big brown bat's sonar signals have not been measured in the field. In addition, for bats, navigation and prey capture require that they process several streams of acoustic information. By using stereotypic flight paths in known areas, bats may be able to reduce the sensory processing load for orientation and therefore allocate echo processing resources to prey. Here we recorded the echolocation calls from foraging E. fuscus in the field with a microphone array and estimated call intensity and directionality, based on reconstructed flight trajectories. The source levels were intense with an average maximum source level of 138 dB (root mean square re. 20 µPa at 0.1 m). Furthermore, measurements taken from a subset of calls indicate that the echolocation signals in the field may be more directional than estimated in the laboratory (half-amplitude angle 30 deg at 35 kHz). We also observed that E. fuscus appear to follow stereotypic flight paths, and propose that this could be a strategy to optimize foraging efficiency by minimizing the sensory processing load.

Hulgard|Katrine|K|
Moss|Cynthia F|CF|
Jakobsen|Lasse|L|
Surlykke|Annemarie|A|

Flight path
Source level
Directionality
Attention
Bat echolocation
Sensory load


Role of Online Retailers' Post-sale Services in Building Relationships and Developing Repurchases: A Comparison-Based Analysis Among Male and Female Customers.

Abstract: Customers are skeptical about shopping online because e-commerce environments are typically considered impersonal. To assure product quality and to enhance customer proclivity in such environments, post-sale services (i.e., product returns, exchange, and maintenance) may be considered to alleviate customers' skepticism. Therefore, this study's objective is to investigate the role of an online retailer's post-sale services (i.e., product return, exchange, and maintenance) on customers' attitudinal (building relationships) and behavioral aspects (developing customers' repurchase intentions). Structural equation modeling is applied to data collected through an online survey answered by 409 online customers of jd.com (after missing data were removed). Research findings show that product return, exchange, and maintenance services are strongly predictive of online customer satisfaction, and satisfaction significantly impacts customer trust. Both customer satisfaction and trust, as indicators of relationship quality, further mediate the links between product return, exchange, and maintenance services and online customer repurchase intention. In addition, differences between male and female customers were found in various aspects of online retailers' product return, exchange, and maintenance services. This is the first empirical study that not only examines the influence of all three dimensions of online retailers' post-sale services on customers' online shopping perceptions and decisions, but also considers differences between male and female customers. Finally, this research provides theoretical and managerial implications based on conceptual and empirical evidence.

Javed|Muhammad Kashif|MK|
Wu|Min|M|
Qadeer|Talat|T|
Manzoor|Aqsa|A|
Nadeem|Abid Hussain|AH|
Shouse|Roger C|RC|

product return
repurchase intention
customer satisfaction
trust
product exchange
product maintenance


Effect of hydroalcoholic extract of ginger on the liver of epileptic female rats treated with lamotrigine.

Abstract:
OBJECTIVE
Lamotrigine is an antiepileptic drug, widely used in the treatment of epilepsy; long-term use of this drug can cause hepatotoxicity. Zingiber officinale Roscoe (ginger) possesses antioxidant properties. In present research, the effect ofhydroalcoholic extract of ginger (HEG) on the liver of lamotrigine-treated epileptic rats was investigated Material and Methods: Forty-eight female Wistar rats were selected and allocated to 8 groups of 6 each. Group 1: Negative controls were treated with normal saline. Group 2: Positive controls were treated with lamotrigine (LTG) (10 mg/kg) daily by gavages for 4 consecutive weeks. Epilepsy was induced in treatment groups by i.p. injection of pentylenetetrazol (PTZ) (40 mg/kg). Group 3: Epileptic group received normal saline (10 ml/kg). Group 4: Epileptic group was treated with LTG (10 mg/kg). Groups 5 and 6: Epileptic groups received HEG (50 and 100 mg/kg). Groups 7 and 8: Epileptic groups received LTG and HEG (50 and 100 mg/kg). At the end of 28 days, blood samples were drawn and their livers were processed for light microscopy.

RESULTS
The mean values of TG, CHOL, AST, and ALT activity significantly rose (p<0.01) in groups 2, 3, and 4, while in rats treated with HEG (groups 5, 6, 7, and 8), the levels of liver enzymes significantly decreased (p<0.05) compared with epileptic group treated with lamotrigine (group 4). Histopathological changes of liver samples were comparable with respective control.

CONCLUSION
These results suggest that hydroalcoholic extract of ginger improves liver function in lamotrigine-induced hepatotoxicity.

Liver
Rat
Lamotrigine
Epilepsy
Zingiber officinale


Zero-Valent Iron Nanoparticles for Soil and Groundwater Remediation.

Abstract: Zero-valent iron has been reported as a successful remediation agent for environmental issues, being extensively used in soil and groundwater remediation. The use of zero-valent nanoparticles have been arisen as a highly effective method due to the high specific surface area of zero-valent nanoparticles. Then, the development of nanosized materials in general, and the improvement of the properties of the nano-iron in particular, has facilitated their application in remediation technologies. As the result, highly efficient and versatile nanomaterials have been obtained. Among the possible nanoparticle systems, the reactivity and availability of zero-valent iron nanoparticles (NZVI) have achieved very interesting and promising results make them particularly attractive for the remediation of subsurface contaminants. In fact, a large number of laboratory and pilot studies have reported the high effectiveness of these NZVI-based technologies for the remediation of groundwater and contaminated soils. Although the results are often based on a limited contaminant target, there is a large gap between the amount of contaminants tested with NZVI at the laboratory level and those remediated at the pilot and field level. In this review, the main zero-valent iron nanoparticles and their remediation capacity are summarized, in addition to the pilot and land scale studies reported until date for each kind of nanomaterials.

D052918:Environmental Restoration and Remediation

stabilized zero-valent iron nanoparticles


Metagenomics reshapes the concepts of RNA virus evolution by revealing extensive horizontal virus transfer.

Abstract: Virus metagenomics is a young research filed but it has already transformed our understanding of virus diversity and evolution, and illuminated at a new level the connections between virus evolution and the evolution and ecology of the hosts. In this review article, we examine the new picture of the evolution of RNA viruses, the dominant component of the eukaryotic virome, that is emerging from metagenomic data analysis. The major expansion of many groups of RNA viruses through metagenomics allowed the construction of substantially improved phylogenetic trees for the conserved virus genes, primarily, the RNA-dependent RNA polymerases (RdRp). In particular, a new superfamily of widespread, small positive-strand RNA viruses was delineated that unites tombus-like and noda-like viruses. Comparison of the genome architectures of RNA viruses discovered by metagenomics and by traditional methods reveals an extent of gene module shuffling among diverse virus genomes that far exceeds the previous appreciation of this evolutionary phenomenon. Most dramatically, inclusion of the metagenomic data in phylogenetic analyses of the RdRp resulted in the identification of numerous, strongly supported groups that encompass RNA viruses from diverse hosts including different groups of protists, animals and plants. Notwithstanding potential caveats, in particular, incomplete and uneven sampling of eukaryotic taxa, these highly unexpected findings reveal horizontal virus transfer (HVT) between diverse hosts as the central aspect of RNA virus evolution. The vast and diverse virome of invertebrates, particularly nematodes and arthropods, appears to be the reservoir, from which the viromes of plants and vertebrates evolved via multiple HVT events.

Dolja|Valerian V|VV|
Koonin|Eugene V|EV|

Virus evolution
Horizontal virus transfer
Virus metagenomics
RNA viruses
Metaviromics


Glycoproteogenomics: A Frequent Gene Polymorphism Affects the Glycosylation Pattern of the Human Serum Fetuin/α-2-HS-Glycoprotein.

Abstract: Fetuin, also known as α-2-HS-glycoprotein (gene name: AHSG), is one of the more abundant glycoproteins secreted into the bloodstream. There are two frequently occurring alleles of human AHSG, resulting in three genotypes (AHSG*1, AHSG*2, and heterozygous AHSG1/2). The backbone amino acid sequences of fetuin coded by the AHSG*1 and AHSG*2 genes differ in two amino acids including one known O-glycosylation site (aa position 256). Although fetuin levels have been extensively studied, the originating genotype is often ignored in such analysis. As fetuin has been suggested repeatedly as a potential biomarker for several disorders, the question whether the gene polymorphism affects the fetuin profile is of great interest. In this work, we describe detailed proteoform profiles of fetuin, isolated from serum of 10 healthy and 10 septic patient individuals and investigate potential glycoproteogenomics correlations, e.g. how gene polymorphisms affect glycosylation. We established an efficient method for fetuin purification from individuals' serum using ion-exchange chromatography. Subsequently, we performed hybrid mass spectrometric approaches integrating data from native mass spectra and peptide-centric MS analysis. Our data reveal a crucial effect of the gene polymorphism on the glycosylation pattern of fetuin. Moreover, we clearly observed increased fucosylation in the samples derived from the septic patients. Our serum proteoform analysis, targeted at one protein obtained from 20 individuals, exposes the wide variability in proteoform profiles, which should be taken into consideration when using fetuin as biomarker. Importantly, focusing on a single or few proteins, the quantitative proteoform profiles can provide, as shown here, already ample data to classify individuals by genotype and disease state.

Lin|Yu-Hsien|YH|
Zhu|Jing|J|
Meijer|Sander|S|
Franc|Vojtech|V|
Heck|Albert J R|AJR|

fetuin
Glycoproteins*
Glycoproteomics
Plasma or serum analysis
Post-translational modifications*
Protein Identification*


DNA Knot Malleability in Single-Digit Nanopores.

Abstract: Knots in long DNA molecules are prevalent in biological systems and serve as a model system for investigating static and dynamic properties of biopolymers. We explore the dynamics of knots in double-stranded DNA in a new regime of nanometer-scale confinement, large forces, and short time scales, using solid-state nanopores. We show that DNA knots undergo isomorphic translocation through a nanopore, retaining their equilibrium morphology by swiftly compressing in a lateral direction to fit the constriction. We observe no evidence of knot tightening or jamming, even for single-digit nanopores. We explain the observations as the malleability of DNA, characterized by sharp buckling of the DNA in nanopores, driven by the transient disruption of base pairing. Our molecular dynamics simulations support the model. These results are relevant not only for the understanding of DNA packing and manipulation in living cells but also for the polymer physics of DNA and the development of nanopore-based sequencing technologies.

DNA knots
Solid-state nanopores
polymers
DNA sequencing
knot dynamics


Hierarchical multifunctional graphene oxide cancer nanotheranostics agent for synchronous switchable fluorescence imaging and chemical therapy.

Abstract: A nanotheranostics platform was synthesized based on PEGylated graphene oxide-gold nanoparticles and specified with aptamer toward the MUC-1-positive tumor cells. Subsequently, it was loaded with doxorubicin, used for non-invasive fluorescence imaging and therapy of breast and colon tumors. The success of the nano-coating at each synthesis step was characterized through FTIR, XRD, TGA, FE-SEM, EDAX, Zeta-potential, and fluorescence spectroscopy. Besides, the ability of the designed platform in targeted imaging, drug delivery, and in vitro therapy were evaluated using fluorescence microscopy and flow cytometry. The selected aptamer acts as a quencher, resulting in an "on/off" fluorescence biosensor. When the aptamer specifically binds to the MUC-1 receptor, its double strands separate, leading to the drug release and the recovery of the fluorescence of ("On" state) at the excitation wavelength of 300 nm. Based on cell toxicity results, this platform has more toxicity toward the MUC-1-positive tumor cells (HT-29 and MCF-7) compared  to MUC-1-negative cells (Hep-G2), representing its selective performance. Thus, this nano-platform can be introduced as a multifunctional cancer nanotheranostics system for tracing particular biomarkers, non-invasive imaging, and targeted chemotherapy. Graphical abstract.

Graphene oxide
Cancer nanotheranostics
Aptamer
Non-invasive imaging
Targeted therapy


Comparison of eye movement desensitization and reprocessing therapy, cognitive behavioral writing therapy, and wait-list in pediatric posttraumatic stress disorder following single-incident trauma: a multicenter randomized clinical trial.

Abstract:
BACKGROUND
Practice guidelines for childhood posttraumatic stress disorder (PTSD) recommend trauma-focused psychotherapies, mainly cognitive behavioral therapy (CBT). Eye movement desensitization and reprocessing (EMDR) therapy is a brief trauma-focused, evidence-based treatment for PTSD in adults, but with few well-designed trials involving children and adolescents.

METHODS
We conducted a single-blind, randomized trial with three arms (n = 103): EMDR (n = 43), Cognitive Behavior Writing Therapy (CBWT; n = 42), and wait-list (WL; n = 18). WL participants were randomly reallocated to CBWT or EMDR after 6 weeks; follow-ups were conducted at 3 and 12 months posttreatment. Participants were treatment-seeking youth (aged 8-18 years) with a DSM-IV diagnosis of PTSD (or subthreshold PTSD) tied to a single trauma, who received up to six sessions of EMDR or CBWT lasting maximally 45 min each.

RESULTS
Both treatments were well-tolerated and relative to WL yielded large, intent-to-treat effect sizes for the primary outcomes at posttreatment: PTSD symptoms (EMDR: d = 1.27; CBWT: d = 1.24). At posttreatment 92.5% of EMDR, and 90.2% of CBWT no longer met the diagnostic criteria for PTSD. All gains were maintained at follow-up. Compared to WL, small to large (range d = 0.39-1.03) intent-to-treat effect sizes were obtained at posttreatment for negative trauma-related appraisals, anxiety, depression, and behavior problems with these gains being maintained at follow-up. Gains were attained with significantly less therapist contact time for EMDR than CBWT (mean = 4.1 sessions/140 min vs. 5.4 sessions/227 min).

CONCLUSIONS
EMDR and CBWT are brief, trauma-focused treatments that yielded equally large remission rates for PTSD and reductions in the severity of PTSD and comorbid difficulties in children and adolescents seeking treatment for PTSD tied to a single event. Further trials of both treatments with PTSD tied to multiple traumas are warranted.

de Roos|Carlijn|C|
van der Oord|Saskia|S|
Zijlstra|Bonne|B|
Lucassen|Sacha|S|
Perrin|Sean|S|
Emmelkamp|Paul|P|
de Jongh|Ad|A|

D057169:Eye Movement Desensitization Reprocessing


Changes in physiotherapy students' beliefs and attitudes about low back pain through pre-registration training.

Abstract:
BACKGROUND
Implementation of best-practice care for patients with low back pain (LBP) is an important issue. Physiotherapists' who hold unhelpful beliefs are less likely to adhere to guidelines and may negatively influence their patients' beliefs. Pre-registration education is critical in moving towards a biopsychosocial model of care. This study aimed to investigate the changes in 2nd year physiotherapy students' beliefs about LBP after a module on spinal pain management and determine whether these changes were maintained at the end of academic training.

METHODS
During three consecutive calendar years, this longitudinal cohort study assessed physiotherapy students' beliefs with the Back Pain Attitudes Questionnaires (Back-PAQ) in their 1st year, before and after their 2nd year spinal management learning module, and at the end of academic training (3rd year). Unpaired t-tests were conducted to explore changes in Back-PAQ score.

RESULTS
The mean response rate after the spinal management module was 90% (128/143 students). The mean (± SD) Back-PAQ score was 87.73 (± 14.21) before and 60.79 (± 11.44) after the module, representing a mean difference of - 26.95 (95%CI - 30.09 to - 23.80, p < 0.001). Beliefs were further improved at the end of 3rd year (- 7.16, 95%CI - 10.50 to - 3.81, p < 0.001).

CONCLUSIONS
A spinal management learning module considerably improved physiotherapy students' beliefs about back pain. Specifically, unhelpful beliefs about the back being vulnerable and in need of protection were substantially decreased after the module. Improvements were maintained at the end of academic training one-year later. Future research should investigate whether modifying students' beliefs leads to improved clinical practice in their first years of practice.

Low back pain
Education
Biopsychosocial
Psychological factors


The Effect of Tympanic Membrane Perforation Site, Size and Middle Ear Volume on Hearing Loss.

Abstract:
Objective
The aim of this study was to analyze the location and the size of perforation in cases with tympanic membrane perforation, its relation to the manubrium mallei and middle ear volume, and to investigate how these are correlated with the severity and frequencies of conductive hearing loss.

Methods
This prospectively designed study included the patients who presented to the the Department of Otorhinolaryngology at the Dokuz Eylül University with hearing loss or tinnitus complaints in the period from June 2014 through June 2017 and were identified to have tympanic membrane perforation in their otoscopic examination. Patients who underwent myringoplasty and type 1 tympanoplasty and whose air-bone gap was found lower than 10 dB in the postoperative audiological examination were included in the study. Effects of the perforation size, the perforation site, and the relationship of the perforation with the manubrium, as well as the effects of the middle ear volume on the severity and frequency of conductive hearing loss were compared.

Results
The study included 44 ears of 38 patients (13 male and 25 female) of whom six had tympanic membrane perforation in both ears. Air conduction threshold and air-bone gap were significantly found higher if the perforation area was wide (p<0.05), the perforation involved both the anterior and the posterior quadrants (p<0.05), had contact with the manubrium mallei (p<0.05), and the middle ear volume reduced (p<0.05).

Conclusion
Solely tympanic membrane perforation affects hearing function; nevertheless, hearing function are better in cases, which have perforations small in size, no contact with manubrium mallei and well pneumatized middle ears.

tympanic membrane perforation
Conductive hearing loss
audiometry
tympanometry


A Selective Fluorescence Sensor for Fe (III) Based on Phenanthroimidazole Imine Compound.

Abstract: Experimental studies in the aqueous solution are crucial for the detection of metal cations in environmental and biological media. Polymer materials allow to work in aqueous media for fluorescent substances which are insoluble in water. Fluorescence sensor studies of the phenanthroimidazole imine compound (PI) synthesized previously by our group were performed in the polymer medium and the selective response to Fe (III) cation was obtained. The resulting sensor exhibited a selective fluorescence quenching effect to Fe (III). A logarithmic calibration graph was obtained in the range of 5.0 × 10- 5 and 1.0 × 10- 2 M. The interference effects of other ions besides Fe (III) have been examined and it has been observed that PI compound behaves selectively to Fe (III) ion in aqueous media. In addition, regeneration and reproducibility studies were carried out to determine the long-term usage of PI doped polymer film and reproducible results have been obtained for Fe (III) cation.

Fluorescence sensor
Phenanthroimidazole
Polymer film
Fe (III) sensor


Compartment-Specific Screening Tools for Persistence: Potential Role and Application in the Regulatory Context.

Abstract: The persistence assessment under the European Union regulation Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) relies on compartment-specific degradation half-lives derived from laboratory simulation studies with surface water, aquatic sediment, or soil. Although these data are given priority, they are not available for most of the compounds. Therefore, according to the Integrated Assessment and Testing Strategy (ITS) for persistence assessment, results from ready biodegradability tests (RBTs) are used within a persistence screening to decide whether a substance is considered as "not persistent" or "potentially persistent." However, ready biodegradability is currently tested only in water. Consequently, there is a lack of approaches that include the soil and sediment compartments for persistence assessment at the screening level. In previous studies, compartment-specific screening tools for water-sediment (Water-Sediment Screening Tool [WSST]) and soil (Soil Screening Tool [SST]) were developed based on the existing test guideline Organisation for Economic Development and Co-operation (OECD TG 301C [MITI (Ministry of International Trade and Industry, Japan) test]). The test systems MITI, WSST, and SST were successfully applied to determine sound and reliable biodegradation data for 15 test compounds. In the present study, these results are used within the scope of a new alternative persistence screening approach, the Compartment-Specific Persistence Screening (CSPS). Compared to the persistence screening under REACH, the CSPS is a more conservative approach that provides additional reasonable results, particularly for compounds that sorb to sediment and soil, and for which the current standard persistence screening might be insufficient. Thus, the CSPS can be used to identify potentially persistent and nonpersistent compounds in the regulatory context by a comprehensive assessment that includes water, soil, and sediment. Moreover, experimentally determined half-lives from the compartment-specific screening tools can be used as input for multimedia models that estimate, for example, overall persistence (Pov ). The application of fixed half-life factors to extrapolate from water to soil and sediment, which is here demonstrated to be inappropriate, can thereby be avoided. Integr Environ Assess Manag 2019;00:000-000. © 2019 SETAC.

D001673:Biodegradation, Environmental
D004784:Environmental Monitoring
D005062:European Union
D019015:Geologic Sediments
D012989:Soil Pollutants

Persistence REACH Sediment Soil Biodegradation


Exercise in clinical cancer care: a call to action and program development description.

Abstract: A large and convincing body of evidence demonstrates the benefits of exercise for cancer survivors during and after treatment. Based on that literature, more cancer survivors should be offered exercise support and programming. Unfortunately, exercise programs remain an exception rather than the norm in cancer care. Not surprisingly, common barriers to the implementation of exercise programs in oncology include limited resources, expertise, and awareness of benefits on the part of patients and clinicians. To improve the accessibility and cost-effectiveness of cancer exercise programs, one proposed strategy is to combine the resources of hospital and community-based programs with home-based exercise instruction. The present paper highlights current literature regarding exercise programming for cancer survivors, describes the development of an exercise program for cancer patients in Toronto, Canada, and offers experiential insights into the integration of exercise into oncologic care.

Santa Mina|D|D|
Alibhai|S M H|SM|
Matthew|A G|AG|
Guglietti|C L|CL|
Steele|J|J|
Trachtenberg|J|J|
Ritvo|P G|PG|

Exercise program
exercise program development
knowledge translation
physical activity


Morphological, Molecular Identification and Distribution of Trypanosome-Transmitting Dipterans from Cattle Settlements in Southwest Nigeria.

Abstract:
INTRODUCTION
Glossina spp. (Glossinidae), Tabanus spp. (Tabanidae), Ancala spp. (Tabanidae), Atylotus spp. (Tabanidae) and Stomoxys spp. (Muscidae) are important transmitting vectors of African animal trypanosomosis in sub-Saharan Africa. There is paucity of information on the distribution and identification of these flies in cattle settlements in southwest Nigeria.

METHODS
The distribution patterns, genetic variations and diversities of dipteran flies in southwest Nigeria were described and identified using morphological and molecular analysis of the 28S rDNA gene.

RESULTS
Of the 13,895 flies examined morphologically between April 2016 and March 2017, tabanids were identified [Tabanus (0.34%), Ancala (0.03%), Atylotus (0.01%), Haematopota (0.014%) and Chrysops (0.11%)]. Two stomoxyine species were identified; Stomoxys niger niger Macquart (45.30%) and Stomoxys calcitrans Linnaeus (17.29%) and two Glossina spp. namely; Glossina p. gambiense Vanderplank, 1911 (0.46%) and Glossina tachinoides Westwood (0.51%) were identified. The identities were further confirmed in a BLAST search using their nucleotide sequences. The median-joining network of the 28S rDNA gene sequences indicated that fly species examined were genetically distinct. The apparent density of all the trapped flies was highest at a mean temperature of 26-28 ℃, humidity > 80% and rainfall of 150-220 mm/month. The distribution of flies was observed to increase as vegetation increased in density and decreased in areas with relatively high human population density (> 100/km2).

CONCLUSIONS
The population indices of the 28S rDNA gene of the flies suggest that analysis of nuclear DNA fragments may provide more information on the molecular ecology of these flies. Characterising fly species and assessing their impact are essential in distribution and monitoring AAT spread.

Morphology
Southwest nigeria
Horse fly
Phylogenetics
Stable fly
Tsetse flies


Binding of direct oral anticoagulants to the FA1 site of human serum albumin.

Abstract: The anticoagulant therapy is widely used to prevent and treat thromboembolic events. Until the last decade, vitamin K antagonists were the only available oral anticoagulants; recently, direct oral anticoagulants (DOACs) have been developed. Since 55% to 95% of DOACs are bound to plasma proteins, the in silico docking and ligand-binding properties of drugs apixaban, betrixaban, dabigatran, edoxaban, and rivaroxaban and of the prodrug dabigatran etexilate to human serum albumin (HSA), the most abundant plasma protein, have been investigated. DOACs bind to the fatty acid (FA) site 1 (FA1) of ligand-free HSA, whereas they bind to the FA8 and FA9 sites of heme-Fe(III)- and myristic acid-bound HSA. DOACs binding to the FA1 site of ligand-free HSA has been validated by competitive inhibition of heme-Fe(III) recognition. Values of the dissociation equilibrium constant for DOACs binding to the FA1 site (ie, calc KDOAC ) derived from in silico docking simulations (ranging between 1.2 × 10-8 M and 1.4 × 10-6 M) agree with those determined experimentally from competitive inhibition of heme-Fe(III) binding (ie, exp KDOAC ; ranging between 2.5 × 10-7 M and 2.2 × 10-6 M). In addition, this study highlights the inequivalence of rivaroxaban binding to mammalian serum albumin. Given the HSA concentration in vivo (~7.5 × 10-4 M), values of KDOAC here determined indicate that the formation of the HSA:DOACs complexes in the absence and presence of FAs and heme-Fe(III) may occur in vivo. Therefore, HSA appears to be an important determinant for DOACs transport.

human serum albumin:direct oral anticoagulant recognition


The Importance of Quantifying the Composition of the Amorphous Intermixed Phase in Organic Solar Cells.

Abstract: The relation of phase morphology and solid-state microstructure with organic photovoltaic (OPV) device performance has intensely been investigated over the last twenty years. While it has been established that a combination of donor:acceptor intermixing and presence of relatively phase-pure donor and acceptor domains is needed to get an optimum compromise between charge generation and charge transport/charge extraction, a quantitative picture of how much intermixing is needed is still lacking. This is mainly due to the difficulty in quantitatively analyzing the intermixed phase, which generally is amorphous. Here, fast scanning calorimetry, which allows measurement of device-relevant thin films (<200 nm thickness), is exploited to deduce the precise composition of the intermixed phase in bulk-heterojunction structures. The power of fast scanning calorimetry is illustrated by considering two polymer:fullerene model systems. Somewhat surprisingly, it is found that a relatively small fraction (<15 wt%) of an acceptor in the intermixed amorphous phase leads to efficient charge generation. In contrast, charge transport can only be sustained in blends with a significant amount of the acceptor in the intermixed phase (in this case: ≈58 wt%). This example shows that fast scanning calorimetry is an important tool for establishing a complete compositional characterization of organic bulk heterojunctions. Hence, it will be critical in advancing quantitative morphology-function models that allow for the rational design of these devices, and in delivering insights in, for example, solar cell degradation mechanisms via phase separation, especially for more complex high-performing systems such as nonfullerene acceptor:polymer bulk heterojunctions.

intermixing
organic solar cells
fullerene derivatives
organic electronics
semiconducting polymers


Polyclonal antibody targeting SOX11 cannot differentiate mantle cell lymphoma from B-cell non-Hodgkin lymphomas.

Abstract:
OBJECTIVES
To determine whether SOX11 is a diagnostic marker of mantle cell lymphoma (MCL).

METHODS
We analyzed SOX11 expression in 349 B-cell non-Hodgkin lymphomas (B-NHLs) via immunohistochemistry.

RESULTS
Nuclear staining of SOX11 was observed in 54 (93.1%) of 58 MCLs. We noticed that SOX11 protein was also expressed on the nuclei in 8 (21.6%) of 37 B-lymphoblastic lymphomas, 45 (32.6%) of 138 diffuse large B-cell lymphomas, 15 (44.1%) of 34 follicular lymphomas, 8 (30.8%) of 26 Burkitt lymphomas, 2 (10.0%) of 20 chronic lymphocytic leukemia/small cell lymphomas, and 3 (18.8%) of 16 marginal zone lymphomas.

CONCLUSIONS
Although the positive rate of SOX11 expression in MCL was significantly higher than other B-NHLs (P < .001), polyclonal antibody targeting SOX11 is not able to identify MCL from B-NHLs because the nuclear staining of SOX11 was widely positive in B-NHLs.

Zhang|Li-Na|LN| Cao|Xin|X| Lu|Ting-Xun|TX| Fan|Lei|L| Wang|Li|L| Xu|Ji|J| Zhang|Run|R| Zou|Zhi-Jian|ZJ| Wu|Jia-Zhu|JZ| Li|Jian-Yong|JY| Xu|Wei|W|

Polyclonal antibody
SOX11
Mantle cell lymphoma
B-cell non-Hodgkin lymphoma
Immunohistochemistry


Effect of Exogenous Nitro Oxide on Chilling Tolerance, Polyamine, Proline, and γ-Aminobutyric Acid in Bamboo Shoots (Phyllostachys praecox f. prevernalis).

Abstract: The effects of exogenous nitro oxide (NO) on chilling resistance and the metabolism of polyamine, proline, and γ-aminobutyric acid of bamboo shoots were investigated. Bamboo shoots were dipped in 0.07 mM sodium nitroprusside (SNP) and stored at 1 °C for 56 days. During the storage, the development of chilling injury of SNP treated bamboo shoots was inhibited with decreased accumulation of malonaldehyde and electrical leakage. At the end of storage, the chilling injury incidence of treated bamboo shoots decreased by 37.9% while their malonaldehyde content and electrical leakage were 8.8% and 18.6% lower than that of the control, respectively. Interestingly, the endogenous NO, polyamines, γ-aminobutyric acid, and proline contents of treated bamboo shoot also significantly increased. Consistently, the metabolisms of these nitrogenous compounds were stimulated in treated bamboo shoots, according to their higher (20.2%-49.8%) related enzyme activities, including nitric oxide synthase, arginine decarboxylase, ornithine decarboxylase, glutamate decarboxylase, orn-δ-aminotransferase, and Δ1-pyrroline-5-carboxylate synthetase. The results indicated that the SNP treatment enhanced chilling tolerance of bamboo shoots, which might associate with the activated metabolism of polyamines, γ-aminobutyric acid, and proline. SNP treatment might be an alternative technology to avoid chill injury during cold storage of bamboo shoots.

D002262:Carboxy-Lyases
D003080:Cold Temperature
D005968:Glutamate Decarboxylase
D009569:Nitric Oxide
D019001:Nitric Oxide Synthase
D009955:Ornithine Decarboxylase
D010940:Plant Proteins
D018520:Plant Shoots
D006109:Poaceae
D011073:Polyamines
D011392:Proline
D005680:gamma-Aminobutyric Acid

nitro oxide
polyamine
proline
bamboo shoot
chilling injury
GABA


Species-specific molecular signature of Commiphora species of Saudi Arabia inferred from internal transcribed spacer sequences of nuclear ribosomal DNA.

Abstract: The deciduous habit and tendency to produce flowers prior to developing leaves, and a predominantly dioecious system of breeding in the genus Commiphora leads to difficulties in its taxonomic identification at species level. The characteristics of easy amplification by universal primer, shorter length and higher discrimination power at the species level makes the internal transcribed spacer (ITS) sequence of nuclear ribosomal DNA (nrDNA) to a smart gene for generating species-specific phylogenetic inferences in most of the plants groups. The present study deals the ITS sequence of nrDNA based molecular genotyping of seven species of the genus Commiphora of Saudi Arabia. The molecular phylogenetic analysis of ITS sequences of nrDNA of Commiphora species distributed in Saudi Arabia reveals the the occurrence of C. madagascariens in Saudi Arabia.

Commiphora
Saudi Arabia
ITS
nrDNA
Molecular genotyping
Burseraceae


Extracellular histones disarrange vasoactive mediators release through a COX-NOS interaction in human endothelial cells.

Abstract: Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone-mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose-dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) mRNA and protein expression, decreased COX-1 mRNA levels and did not change thromboxane A2 synthase (TXAS) expression. Moreover, extracellular histones decreased both, eNOS expression and NO production in HUVEC. The impaired NO production was related to COX-2 activity and superoxide production since was reversed after celecoxib (10 μmol/l) and tempol (100 μmol/l) treatments, respectively. In conclusion, our findings suggest that extracellular histones stimulate the release of endothelial-dependent mediators through an up-regulation in COX-2-PGIS-PGI2 pathway which involves a COX-2-dependent superoxide production that decreases the activity of eNOS and the NO production. These effects may contribute to the endothelial cell dysfunction observed in histone-mediated pathologies.

Pérez-Cremades|Daniel|D|
Bueno-Betí|Carlos|C|
García-Giménez|José Luis|JL|
Ibañez-Cabellos|José Santiago|JS|
Hermenegildo|Carlos|C|
Pallardó|Federico V|FV|
Novella|Susana|S|

D061307:Human Umbilical Vein Endothelial Cells

extracellular histones
endothelial cells
prostanoids
nitric oxide
vascular mediators


Pressure RElieving Support SUrfaces: a Randomised Evaluation 2 (PRESSURE 2): study protocol for a randomised controlled trial.

Abstract:
BACKGROUND
Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual's functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers.

METHODS/DESIGN
PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 'high-risk' patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee.

DISCUSSION
The double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design.

TRIAL REGISTRATION
ISRCTN01151335 . Registered on 14 May 2013. Protocol version: 5.0, dated 25 September 2015 Trial sponsor: Clare Skinner, Faculty Head of Research Support, University of Leeds, Leeds, LS2 9JT; 0113 343 4897; C.E.Skinner@leeds.ac.uk.

Brown|Sarah|S|0000-0002-1840-3786
Smith|Isabelle L|IL|
Brown|Julia M|JM|
Hulme|Claire|C|
McGinnis|Elizabeth|E|
Stubbs|Nikki|N|
Nelson|E Andrea|EA|
Muir|Delia|D|
Rutherford|Claudia|C|
Walker|Kay|K|
Henderson|Valerie|V|
Wilson|Lyn|L|
Gilberts|Rachael|R|
Collier|Howard|H|
Fernandez|Catherine|C|
Hartley|Suzanne|S|
Bhogal|Moninder|M|
Coleman|Susanne|S|
Nixon|Jane E|JE|

D001513:Beds
D002985:Clinical Protocols
D003362:Cost-Benefit Analysis
D004867:Equipment Design
D017721:Hospital Costs
D006801:Humans
D010781:Photography
D011312:Pressure
D003668:Pressure Ulcer
D011788:Quality of Life
D012107:Research Design
D013222:State Medicine
D011795:Surveys and Questionnaires
D013997:Time Factors
D016896:Treatment Outcome
D006113:United Kingdom
D014945:Wound Healing

Double triangular group sequential design


Curcumin a potent cancer preventive agent: Mechanisms of cancer cell killing.

Abstract: There is no doubt that diet could effectively improve health and halt cancers. Dietary phytochemical compounds and their derivatives represent a cornucopia of effectively anticancer compounds. This review discusses existing data on the anticancer activities of curcumin, and then offers possible explanations for and mechanisms of its cancer-preventive action. This review also offers insights into the molecular mechanism and targets through which curcumin modulates cell cycle, apoptotic signals, anti-apoptotic proteins, miRNAs, Wnt/beta-catenin signaling, protein kinases, nuclear factor-κB, proteasome activation, epigenetic regulation including DNA methylation and histone modification. Finally, this review provides explanations for how curcumin reverses the multi-drug resistance (MDR) of cancer cells.

apoptotic signals
miRNAs
proteasomes
DNA methylation
histone modification
cell cycle arrest


Evaluation of homocysteine in the diagnosis and prognosis of coronary slow flow syndrome.

Abstract: Aim: To identify the exact molecular markers related to coronary slow flow syndrome (CSFS) and its prognosis. Patients & methods: Data from 54 patients with CSFS diagnosed by coronary angiography and 101 normal control patients were collected and analyzed. Results: Logistic regression analysis confirmed that homocysteine (Hcy; odds ratio: 1.107; 95% CI: 1.018-1.205; p = 0.018) was associated with CSFS. Receiver-operating characteristic curve analysis identified an Hcy value of 17.1 μmol/l as an effective cut-off point for predicting CSFS. Cox survival analysis showed a relationship between high admission Hcy level (odds ratio: 1.19; 95% CI = 1.05-1.34; p = 0.005) and recurrent angina. Conclusion: Our results showed positive correlations of Hcy with CSFS and cardiac events.

Li|Nan|N| Tian|Liuyang|L| Ren|Jiefeng|J| Li|Yang|Y| Liu|Yuqi|Y|0000-0001-5792-5723

homocysteine
prognosis
coronary slow flow syndrome
correlation
predictor


The Effect of Melatonin on Mitochondrial Function and Autophagy in In Vitro Matured Oocytes of Aged Mice.

Abstract:
Objective
This study examined the in vitro effect of melatonin on the protein synthesis of mitochondria, as well as autophagy in matured oocytes of aged mice.

Materials and Methods
In this experimental study, germinal vesicles (GV) oocytes were collected from aged (with the age of six-months-old) and young mice (with age range of 6-8 weeks old) and then cultured in the in vitro culture medium (IVM) for 24 hours to each metaphase II (MII) oocytes and then supplemented with melatonin at a concentration of 10 μM. The culture medium of MII oocytes was devoid of melatonin. Afterward, the expression of the SIRT-1 and LC3 was assessed by immunocytochemistry. ATP-dependent luciferin-luciferase bioluminescence assay was employed for the measurement of the ATP contents. Intracellular reactive oxygen specious (ROS) was detected by DCFH-DA, and the total antioxidant capacity (TAC) level was determined by TAC assay.

Results
The expression of SIRT-1 and LC3, as well as the measurement of the ATP content, was significantly increased in oocytes treated with melatonin compared with the oocytes receiving no treatment. Moreover, TAC was considerably higher in melatonin-treated oocytes than oocytes receiving no treatment. On the other hand, the level of ROS was significantly decreased in oocytes treated with melatonin in comparison with the untreated oocytes. The results indicated that melatonin considerably improved the development of oocytes as well.

Conclusion
According to the data, melatonin increased mitochondrial function and autophagy via an increase in the expression of SIRT1 and LC3, as well as the ATP contents while it decreased the levels of ROS and increased TAC in oocytes derived from aged mice.

Nasheed Hamad Almohammed|Zahraa|Z|
Moghani-Ghoroghi|Fatemeh|F|
Ragerdi-Kashani|Iraj|I|
Fathi|Rouhollah|R|
Tahaei|Leila Sadat|LS|
Naji|Mohamad|M|
Pasbakhsh|Parichehr|P|

Melatonin
Autophagy
Aged Mice
Mitochondria


James Astor in conversation with Warren Colman.

Abstract: In this interview with Warren Colman, James Astor speaks about his development as a Jungian analyst from his own experience of personal analysis in the 1960s to his recent retirement from clinical practice. The discussion covers his long association with Michael Fordham, the child analytic training at the SAP, the infant observation seminars with Fordham and Gianna Henry through which Fordham was able to make new discoveries about infant development, his experience of supervision with Donald Meltzer and the development of his own thinking through a series of papers on the analytic process, supervision and the relation between language and truth. The interview concludes with reflections about the legacy of Michael Fordham and the future of analytic work.

Michael Fordham
child analytic training
infant observation
Donald Meltzer
Society of Analytical Psychology


Warble infestations by Hypoderma tarandi (Diptera; Oestridae) recorded for the first time in West Greenland muskoxen.

Abstract: In the northern hemisphere, Caribou (Rangifer spp.) populations are known to be infested with the skin-penetrating ectoparasite, Hypoderma tarandi (Diptera; Oestridae). Although regarded as host specific, H. tarandi has been reported from other species, and has become of increasing concern as a zoonosis infecting humans. In February 2012, concurrent with the hunting of muskoxen, we examined carcasses for muscle and tissue parasites, and recorded warble larvae infestations. DNA extracted from samples of larvae was amplified targeting 579 bp of the COI gene, and subsequently sequenced, to be confirmed as H. tarandi. Infestation by oestrid flies has not previously been reported in muskoxen in West Greenland.

Samuelsson|Fredrik|F|
Nejsum|Peter|P|
Raundrup|Katrine|K|
Hansen|Tina Vicky Alstrup|TV|
Kapel|Christian Moliin Outzen|CM|

Hypoderma tarandi
Greenland
Caribou
Cross contamination
Muskox


The Protective Effect of Apocynin on Cyclosporine A-Induced Hypertension and Nephrotoxicity in Rats.

Abstract: Cyclosporine A (CsA) is the prototype of immunosuppressant drugs that has provided new perspectives in human and veterinary medicine to prevent organ transplant rejection and to treat certain autoimmune diseases and dermatologic diseases. Unfortunately, the treatment with CSA is often limited by severe adverse effects such as hypertension and nephrotoxicity. Some data suggest that reactive oxygen species (ROS) and the oxidative stress play an important role in its pathogenesis, in particular the superoxide (O2 (-)) that is the most powerful free radical generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase present mainly in the kidney. The present study has been designed to investigate the role of Apocynin a selective inhibitor of NADPH oxidase activity on cyclosporine-induced adverse effect. In this study, we have evaluated the effect of CsA, used alone or in association with Apocynin on blood pressure (BP), on glomerular filtration rate (GFR), on absoluted fluid reabsorption (Jv) in proximal tubule (PT), on O2 (-) concentration, and on nitric oxide (NO) production. We have demonstrated that CsA administration increases superoxide concentration in the aorta, decreases the NO concentration, reduces GFR and the Jv in PT, and induces a significant increase in BP. Moreover, we have shown that Apocynin treatment restores these hemodynamic alterations, as well as NO and superoxide productions. In conclusion, the reported data indicate that CsA induced nephrotoxicity and hypertension are related to NADPH oxidase activity, in fact Apocynin protects the kidney function and BP from toxic effects induced by CsA through the inhibition of NADPH oxidase activity.

Ciarcia|Roberto|R|
Damiano|Sara|S|
Florio|Alessia|A|
Spagnuolo|Manuela|M|
Zacchia|Enza|E|
Squillacioti|Caterina|C|
Mirabella|Nicola|N|
Florio|Salvatore|S|
Pagnini|Ugo|U|
Garofano|Tiziana|T|
Polito|Maria Sole|MS|
Capasso|Giovambattista|G|
Giordano|Antonio|A|

APOCYNIN
CYCLOSPORINE A
REACTIVE OXYGEN SPECIES
NITRIC OXIDE


Altered expression of the core circadian clock component PERIOD2 contributes to osteoarthritis-like changes in chondrocyte activity.

Abstract: In osteoarthritis, chondrocytes undergo a phenotype shift characterised by reduced expression of SOX9 (sry-box 9) and increased production of cartilage-degrading enzymes, e.g. MMP13 (matrix metalloproteinase 13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5). The chondrocyte clock is also altered. Specifically, the peak level of PER2 is elevated, but peak level of BMAL1 reduced in osteoarthritic chondrocytes. The purpose of this study was to determine whether increased PER2 expression causes disease-associated changes in chondrocyte activity and to identify whether known risk factors for osteoarthritis induce changes in PER2 and BMAL1 expression. Primary human chondrocytes isolated from macroscopically normal cartilage were serum-starved overnight then re-fed with serum-replete media with/without interleukin 1β (IL-1β) (10 ng/mL), hydrogen peroxide (100 µM) or basic calcium phosphate (BCP) crystals (50 µg/mL). Peak level of BMAL1 was lower, whereas PER2 levels remained elevated for longer, in chondrocytes treated with IL-1β, hydrogen peroxide or BCP crystals compared to untreated cells. Levels of SOX9 were lower, whereas levels of ADAMTS5 and MMP13 were higher, in chondrocytes exposed to any of the three treatments compared to untreated cells. Knockdown of PER2 using siRNA partially abrogated the effects of each treatment on chondrocyte phenotype marker expression. Similarly, in chondrocytes isolated from osteoarthritic cartilage PER2 knockdown was associated with increased SOX9, reduced ADAMTS5 and reduced RNA and protein levels of MMP13 indicating partial mitigation of the osteoarthritic phenotype. Conversely, further ablation of BMAL1 expression in osteoarthritic chondrocytes resulted in a further reduction in SOX9 and increase in MMP13 expression. Overexpression of PER2 in the H5 chondrocyte cell line led to increased ADAMTS5 and MMP13 and decreased SOX9 expression. Localised inflammation, oxidative stress and BCP crystal deposition in osteoarthritic joints may contribute to disease pathology by inducing changes in the chondrocyte circadian clock.

Rong|Jing|J|
Zhu|Mark|M|
Munro|Jacob|J|
Cornish|Jillian|J|
McCarthy|Geraldine M|GM|
Dalbeth|Nicola|N|
Poulsen|Raewyn C|RC|

matrix metalloproteinases
interleukin 1β
oxidative stress
Peripheral clocks
chondrocyte hypertrophy
crystal arthropathy
osteoarthritis pathogenesis


Novel Template Plasmids pCyaA'-Kan and pCyaA'-Cam for Generation of Unmarked Chromosomal cyaA' Translational Fusion to T3SS Effectors in Salmonella.

Abstract: The type III secretion systems (T3SS) encoded in pathogenicity islands SPI-1 and SPI-2 are key virulence factors of Salmonella. These systems translocate proteins known as effectors into eukaryotic cells during infection. To characterize the functionality of T3SS effectors, gene fusions to the CyaA' reporter of Bordetella pertussis are often used. CyaA' is a calmodulin-dependent adenylate cyclase that is only active within eukaryotic cells. Thus, the translocation of an effector fused to CyaA' can be evaluated by measuring cAMP levels in infected cells. Here, we report the construction of plasmids pCyaA'-Kan and pCyaA'-Cam, which contain the ORF encoding CyaA' adjacent to a cassette that confers resistance to kanamycin or chloramphenicol, respectively, flanked by Flp recombinase target (FRT) sites. A PCR product from pCyaA'-Kan or pCyaA'-Cam containing these genetic elements can be introduced into the bacterial chromosome to generate gene fusions by homologous recombination using the Red recombination system from bacteriophage λ. Subsequently, the resistance cassette can be removed by recombination between the FRT sites using the Flp recombinase. As a proof of concept, the plasmids pCyaA'-Kan and pCyaA'-Cam were used to generate unmarked chromosomal fusions of 10 T3SS effectors to CyaA' in S. Typhimurium. Each fusion protein was detected by Western blot using an anti-CyaA' monoclonal antibody when the corresponding mutant strain was grown under conditions that induce the expression of the native gene. In addition, T3SS-1-dependent secretion of fusion protein SipA-CyaA' during in vitro growth was verified by Western blot analysis of culture supernatants. Finally, efficient translocation of SipA-CyaA' into HeLa cells was evidenced by increased intracellular cAMP levels at different times of infection. Therefore, the plasmids pCyaA'-Kan and pCyaA'-Cam can be used to generate unmarked chromosomal cyaA' translational fusion to study regulated expression, secretion and translocation of Salmonella T3SS effectors into eukaryotic cells.

Fernández|Paulina A|PA|
Zabner|Marcela|M|
Ortega|Jaime|J|
Morgado|Constanza|C|
Amaya|Fernando|F|0000-0001-6424-108X
Vera|Gabriel|G|
Rubilar|Carolina|C|
Salas|Beatriz|B|
Cuevas|Víctor|V|
Valenzuela|Camila|C|0000-0002-5642-6188
Baisón-Olmo|Fernando|F|
Álvarez|Sergio A|SA|
Santiviago|Carlos A|CA|

translational fusion
T3SS
effector
Salmonella
secretion
SPI-1
SPI-2
translocation
adenylate cyclase
cyaA’


Remote Estimation of Rice Yield With Unmanned Aerial Vehicle (UAV) Data and Spectral Mixture Analysis.

Abstract: The accurate assessment of rice yield is crucially important for China's food security and sustainable development. Remote sensing (RS), as an emerging technology, is expected to be useful for rice yield estimation especially at regional scales. With the development of unmanned aerial vehicles (UAVs), a novel approach for RS has been provided, and it is possible to acquire high spatio-temporal resolution imagery on a regional scale. Previous reports have shown that the predictive ability of vegetation index (VI) decreased under the influence of panicle emergence during the later stages of rice growth. In this study, a new approach which integrated UAV-based VI and abundance information obtained from spectral mixture analysis (SMA) was established to improve the estimation accuracy of rice yield at heading stage. The six-band image of all studied rice plots was collected by a camera system mounted on an UAV at booting stage and heading stage respectively. And the corresponding ground measured data was also acquired at the same time. The relationship of several widely-used VIs and Rice Yield was tested at these two stages and a relatively weaker correlation between VI and yield was found at heading stage. In order to improve the estimation accuracy of rice yield at heading stage, the plot-level abundance of panicle, leaf and soil, indicating the fraction of different components within the plot, was derived from SMA on the six-band image and in situ endmember spectra collected for different components. The results showed that VI incorporated with abundance information exhibited a better predictive ability for yield than VI alone. And the product of VI and the difference of leaf abundance and panicle abundance was the most accurate index to reliably estimate yield for rice under different nitrogen treatments at heading stage with the coefficient of determination reaching 0.6 and estimation error below 10%.

Duan|Bo|B| Fang|Shenghui|S| Zhu|Renshan|R| Wu|Xianting|X| Wang|Shanqin|S| Gong|Yan|Y| Peng|Yi|Y|

rice
yield
unmanned aerial vehicle (UAV)
remote sensing (RS)
vegetation index (VI)
spectral mixture analysis (SMA)


Sustaining elevated levels of nitrite in the oral cavity through consumption of nitrate-rich beetroot juice in young healthy adults reduces salivary pH.

Abstract:
BACKGROUND
Dietary inorganic nitrate (NO3-) and its reduced forms nitrite (NO2-) and nitric oxide (NO), respectively, are of critical importance for host defense in the oral cavity. High concentrations of salivary nitrate are linked to a lower prevalence of caries due to growth inhibition of cariogenic bacteria.

OBJECTIVE
In-vitro studies suggest that the formation of antimicrobial NO results in an increase of the pH preventing erosion of tooth enamel. The purpose of this study was to prove this effect in-vivo.

METHODS
In a randomized clinical study with 46 subjects we investigated whether NO3- rich beetroot juice exhibits a protective effect against caries by an increase of salivary pH.

RESULTS
Our results show that, in comparison to a placebo group, consumption of beetroot juice that contains 4000 mg/L NO3- results in elevated levels of salivary NO2-, nitrite NO3-, and NO. Furthermore, we determined an increase of the mean pH of saliva from 7.0 to 7.5, confirming the anti-cariogenic effect of the used NO3--rich beetroot juice.

CONCLUSIONS
Taken together, we have found that NO3--rich beetroot juice holds potential effects against dental caries by preventing acidification of human saliva.

TRIAL REGISTRATION
C-87-15 (Ethics Commissions of Upper Austria).

Hohensinn|Barbara|B| Haselgrübler|Renate|R| Müller|Ulrike|U| Stadlbauer|Verena|V| Lanzerstorfer|Peter|P| Lirk|Gerald|G| Höglinger|Otmar|O| Weghuber|Julian|J|

Nitrite
Beetroot juice
Nitrate
Nitric oxide
Caries
Salivary pH


Social and sex differences in psychiatric comorbidity and psychosocial functioning among adolescents with depression.

Abstract:
BACKGROUND
To determine social and sex differences in psychosocial functioning and psychiatric comorbidity among adolescents with depression.

METHODS
A cohort-based study in Stockholm, Sweden. Adolescents who turned 13 years during 2001-2007, were followed in registers until they turned 18 in 2005-2011, (n = 169,262). In the current study, those with depression at age 13-17 were included (n = 6,439).

RESULTS
Adolescents with parents with low (OR=1.5, CI 1.1-2.2) education were more likely to have low psychosocial functioning. Those with parents with low education and low household income were more likely to have comorbid internalizing (OR=1.3, CI 1.0-1.7/1.3, CI 1.0-1.7) and externalizing disorders (OR=2.5, CI 1.5-4.0/2.4, CI 1.4-4.2). Adolescents with parents born outside the Nordic countries were more likely to have comorbid externalizing disorders (OR=1.6, CI 1.1-2.4). No social differences were evident in relation to family receipt of unemployment benefits. Social differences were found for both girls and boys in relation to psychosocial functioning and comorbidity but the magnitude of social differences in depression with comorbidity was overall larger for boys than girls.

LIMITATIONS
The findings of the current study can only be generalized to adolescents that have sought care for and been diagnosed with depression, within a setting similar to this study, e.g. with free access to care.

CONCLUSION
Adolescents with depression and with more disadvantaged social circumstances in the childhood run a higher risk of psychiatric comorbidity and low psychosocial functioning, which can indicate a lengthy clinical course and poorer response to treatment. Both boys and girls follow this path but partly in different kinds of psychiatric comorbidity.

Wirback|Therese|T| Möller|Jette|J| Larsson|Jan-Olov|JO| Engström|Karin|K|

Comorbidity
Psychosocial functioning
Adolescence
Depression
Social differences


MR mammography using diffusion-weighted imaging in evaluating breast cancer: a correlation with proliferation index.

Abstract:
PURPOSE
To evaluate whether the variation of the apparent diffusion coefficient (ADC) values obtained with DWI can predict elevated levels of Ki67 proliferation index and aggressive subtypes in patients with breast cancer.

MATERIALS AND METHODS
Breast MRI studies of 115 patients (mean age 57.3 years, range 36-81 years) with a biopsy-proven breast cancers were evaluated in this retrospective IRB-approved study. Examinations were performed on a 1.5 T magnet and included a Single-Shot Echoplanar DWI sequence with b values of 0 and 1000 s/mm(2). For each target lesion, ADC was measured. ADC values were compared considering Ki67 status (≥20 % or <20 %), histology, grade (G1, G2 or G3) and clinical-pathological classification (Luminal A, Luminal B HER2-positive, Luminal B HER-2 negative, HER-2 enriched and Triple Negative). Mann-Whitney U test and Kruskal-Wallis test were used for comparisons and receiver operating characteristic (ROC) curves were obtained. Inter- and intra-reader variability was evaluated in a subset of 40 patients, using interclass correlation coefficient (ICC) and Bland-Altman plots.

RESULTS
Of 115 lesions, 53 (46.1 %) were assessed as Ki67 positive and 62 (53.9 %) as Ki67 negative. ADC values were significantly (p < 0.0001) lower in Ki67-positive patients (median 0.86 × 10(-3) mm(2)/s; interquartile range 0.75-0.92) compared to Ki67-negative (median 1.03 × 10(-3) mm(2)/s; interquartile range 0.92-1.13). Median ADC was also lower in G2 and G3 cancer and in the Luminal B Her2-negative subtype (p = 0.0015). No differences were found when evaluating histology. ROC curve showed a sensitivity and specificity of 83.0 and 66.1 %, respectively, when using a cutoff of 0.95 s/mm(2) to differentiate Ki67-positive from Ki67-negative cancers. Inter- and intra-reader variability was moderate (ICC = 0.623; ICC = 0.548, respectively). No systematic differences were identified with Bland-Altman plots.

CONCLUSIONS
Lower ADC values are associated with elevated Ki67 proliferation index and more aggressive pathologic features. Moderate agreement in ADC measurement could be a limitation.

Molinari|Cristina|C| Clauser|Paola|P| Girometti|Rossano|R| Linda|Anna|A| Cimino|Elisa|E| Puglisi|Fabio|F| Zuiani|Chiara|C| Bazzocchi|Massimo|M|

D038524:Diffusion Magnetic Resonance Imaging

Diffusion-weighted imaging
Breast neoplasms
Ki67 antygen
Magnetic resonance imaging
Tumor markers


Analysis of pH Dose-dependent Growth of Sulfate-reducing Bacteria.

Abstract: Lower intraluminal colonic pH is an indication for the development of inflammatory bowel disease including active ulcerative colitis. Involvement of intestinal sulfate-reducing bacteria in decreasing bowel pH by the production of H2S and acetate as well as their sensitivity has never been reported before. The study of the relative pH and survival of Desulfovibrio piger Vib-7 by monitoring sulfate reduction parameters was the aim of this work. Monitoring was done through the measurement of bacterial growth (biomass), dissimilatory sulfate reduction parameters: sulfate consumption, lactate oxidation, hydrogen sulfide and acetate production. According to our results, we observed that lower pH (<5) significantly inhibited D. piger Vib-7 growth. This inhibition was also noticed when alkaline media (>9 pH) was used, though the reduction was not at the rate as in media with pH of 4. The research indicates that the growth of D. piger Vib-7 is inhibited at pH of 4 which is not as low as the pH found in people with severely developed inflammatory bowel diseases such as ulcerative colitis. Certainly the interaction (synergistic effect) between both hydrogen sulfide and acetate accumulation can also play an important etiological role in the development of bowel inflammation in humans and animals.

Sulfate-reducing bacteria
Ulcerative colitis
Hydrogen sulfide
Toxicity
pH gut


Traumatic brain injury among female offenders in a prison population: results of the FleuryTBI study.

Abstract:
AIM
The study was designed to estimate the prevalence of traumatic brain injury (TBI) in a French prison population of female offenders, study the variables known to be associated with TBI, and compare our results with those obtained among male offenders as described in a previous paper.

PARTICIPANTS
All female offenders (adults and juveniles) consecutively admitted to Fleury-Mérogis prison over a 3-month period were included in the study.

METHOD
During the admission procedure, female offenders were interviewed by healthcare staff using a self-reported questionnaire.

RESULTS
In all, 100 female offenders were included. The rate of self-reported TBI was high, with a prevalence of 21%. The first cause of TBI was violence related (35%) and a majority of female offenders with a history of TBI reported having sustained more than one TBI. When compared with those who did not report a TBI, epilepsy and use of alcohol were higher among female offenders with a history of TBI. Perceived health was significantly worse for women who reported a TBI.

CONCLUSIONS
This study findings provide additional evidence that TBI among offender populations is serious and that specific actions need to be developed and implemented in correctional settings such as screening for TBI upon arrival.

Durand|Eric|E| Watier|Laurence|L| Lécu|Anne|A| Fix|Michel|M| Weiss|Jean-Jacques|JJ| Chevignard|Mathilde|M| Pradat-Diehl|Pascale|P|

traumatic brain injury
female prisoners
head injury
inmates
neuropsychology


Amalgam Phase-Down Part 2: UK-Based Knowledge, Opinions, and Confidence in the Alternatives.

Abstract:
INTRODUCTION
Amalgam use has recently been phased down, and the potential for a phase-out is being investigated.

OBJECTIVES
The study aimed to identify knowledge of the phase-down and opinions of a potential phase-out of amalgam by UK primary care clinicians and assess their confidence in using different materials in different situations.

METHODS
An anonymized, prepiloted cross-sectional e-survey was used to assess primary care clinicians' knowledge and opinions of the amalgam phase-down and potential phase-out and their confidence in using amalgam and the alternatives in different situations. In total, 11,902 invitations were distributed through British dentist and therapist associations. Prior hypotheses were tested alongside descriptive statistics.

RESULTS
Response rate was 13% (n = 1,513). Knowledge of the amalgam phase-down was low, with just 3% clinicians correctly identifying all patient groups in whom amalgam use should be avoided in the United Kingdom. Postgraduate education on posterior composite placement was high (88%), but a large majority had personal and patient-centered concerns over the suitability of the alternatives and lacked confidence when placing composite in comparison to amalgam in difficult situations (P < 0.0001). Logistic regressions revealed that the best predictors of high confidence in placing mesio-occluso-distal composites and composites in difficult situations were being a private general dentist or being primarily a composite user.

CONCLUSION
Primary care clinicians have major personal and patient-centered concerns regarding the amalgam phase-down (of which they have limited knowledge) and potential phase-out. Many lack confidence in using the alternative, composite, to restore posterior teeth in difficult situations, whereas confidence in using amalgam in similar situations is high. Effective education of clinicians and understanding patients' needs, alongside policy changes, are required to enable a successful amalgam phase-down and potential phase-out.

KNOWLEDGE TRANSFER STATEMENT
This study shows that UK primary care clinicians are worried about the phase-down of amalgam for themselves and their patients. Many lack confidence in the alternative, composite, when used in difficult situations, which is in stark contrast to amalgam. Knowledge of the phase-down is limited. There is a need for more effective education of clinicians, an understanding of patients' values, and policy changes to ensure the success of the phase-down and potential phase-out of amalgam.

caries treatment
clinical outcomes
composite materials
health services research
restorative dentistry
restorative materials


A Case of Zoonotic Ancylostoma ceylanicum Infection in a Suburban Area of Selangor, Malaysia.

Abstract:
INTRODUCTION
The animal hookworm, Ancylostoma ceylanicum, is a dominant hookworm species of dogs and cats. However, it has increasingly been found infecting humans in Southeast Asia.

PURPOSE
We report an autochthonous case of A. ceylanicum in a suburban area of Selangor, Malaysia. A 66-year-old Indian lady who is an avid gardener presented with chronic diarrhea of 4 months' duration.

METHODS
The patient was examined clinically and colonoscopy was performed. Adult parasites obtained via colonoscopy were subjected to microscopy and molecular investigations.

RESULTS
Clinical examinations were unremarkable, and blood investigation revealed normochromic normocytic anemia. Stool occult blood was positive but negative for ova, cyst and adult parasites. Colonoscopy performed showed multiple diverticulae and worm infestation from the terminal ileum to sigmoid colon. Morphological examination on the adult worms showed the specific characteristics of Ancylostoma species. Molecular investigations further confirmed the nematode as Ancylostoma ceylanicum. She was treated with albendazole 400 mg daily for 3 days with symptomatic improvements sustained 3 months later. It is suspected that the patient had ingested or contacted soil contaminated with filariform larvae while gardening.

CONCLUSION
Information on the A. ceylanicum infection in humans, especially in urban and suburban areas, is limited, necessitating further epidemiological and clinical studies.

Ceylanicum
Malaysia
Colonoscopy
Ancyclostoma
Ancylostomiasis
Zoonotic hookworm


New pharmacotherapy options for noninfectious posterior uveitis.

Abstract:
INTRODUCTION
Noninfectious inflammation of the posterior eye segment represents an important cause of visual impairment. It often affects relatively young people and causes a significant personal and social impact. Although steroids and nonbiologic- Disease-Modifying Antirheumatic Drugs (nbDMARDs) are effective both in acute and long- lasting diseases, however they are increasingly being replaced by biologic (DMARDs). bDMARD. This article therefore aims to identify recent advances in the therapy of noninfectious posterior segment uveitis.

METHODS
A Medline-search was conducted using the terms: nbDMARD, bDMARD, posterior uveitis, intermediate uveitis, treatment, corticosteroid. In addition, clinical studies were included as registered at ClinicalTrials.gov.

RESULTS
Currently two major lines of treatments can be identified: (1) the intraocular application of anti-inflammatory agents and (2) the introduction of new agents, e.g., (bDMARDs) and small-molecule-inhibitors. Whereas intravitreal treatments have the advantage to avoid systemic side effects, new systemic agents are progressively earning credit on the basis of their therapeutic effects.

CONCLUSION
Even when current treatment strategies are still hampered by the limited number of randomized controlled trials, promising progress and continuous efforts are seen.

Uveitis nbDMARD bDMARD Therapy Corticosteroid tsDMARD


The effect of protein supplement concentration in embryo transfer medium on clinical outcome of IVF/ICSI cycles: a prospective, randomized clinical trial.

Abstract: The aim of this prospective, randomized clinical trial (RCT) was to evaluate whether the supplemental protein concentration in embryo transfer (ET) medium affects the clinical outcomes in IVF-ET. A total of 750 patients undergoing IVF-ET who met the inclusion criteria were randomly divided into three groups, according to the concentration of synthetic serum substitute (SSS) in ET medium as follows: 10% (Group A), 20% (Group B) and 50% (Group C). The patient characteristics and embryology data were all similar among the groups. The rates of implantation, clinical pregnancy and live birth were compared. Clinical pregnancy (44.61%, 48.79% and 45.49%), multiple pregnancy (24.18%, 28.71% and 25.0%), implantation (28.21%, 30.68% and 29.86%) and live birth (41.67%, 43.96% and 41.70%) rates in the three groups (A, B and C, respectively) showed no significant differences. This RCT demonstrates that supplemental protein concentration in the ET medium does not affect the treatment outcomes in IVF-ET. There was no statistical evidence to support the hypothesis that supplemental protein concentration in the ET medium influences treatment outcomes in IVF-ET.

Huang|Jianying|J| Chen|Hua|H| Lu|Xiaosheng|X| Wang|Xiaona|X| Xi|HaiTao|H| Zhu|ChunFang|C| Zhang|Fan|F| Lv|Jieqiang|J| Ge|Hongshan|H|

transfer medium
clinical outcomes
prospective randomized controlled trial
serum albumin


Vessel wall enhancement in herpes simplex virus central nervous system vasculitis.

Abstract: Infection is a well-known cause of cerebral vasculopathy and vasculitis. We report a 36-year-old woman with cerebral vasculitis and ischemic stroke secondary to herpes simplex virus (HSV). MRI studies revealed a pontine stroke with basilar artery stenosis and vessel wall gadolinium enhancement. This case demonstrates the ability of HSV to cause a focal brainstem vasculitis and the utility of enhanced MRI in the diagnosis of stroke related to HSV central nervous system vasculitis.

Guerrero|Waldo R|WR|
Dababneh|Haitham|H|
Hedna|Shushrutha|S|
Johnson|James A|JA|
Peters|Keith|K|
Waters|Michael F|MF|

D020293:Vasculitis, Central Nervous System

Herpes simplex virus
Vasculitis
Imaging
Meningitis


Emerging corneal pathogens: First report of Pseudopestalotiopsis theae keratitis.

Abstract: A 55-year-old lady developed a corneal ring infiltrate following trauma with a wooden stick. 10% KOH mount of corneal scrapings revealed septate hyaline fungal filaments. White feathery colonies with shiny black dots grew on potato dextrose agar. Characteristic features of Pestalotiopsis spores were seen on Lactophenol cotton blue mount. DNA sequencing showed 99% similarity with Pseudopestalotiopsis theae. Complete resolution was noted with topical and oral antifungals. To the best of our knowledge, this is the first report of Pseudopestalotiopsis keratitis following trauma with vegetative matter highlighting the role of DNA sequencing in identification of rare fungi.

Sane|Sayali|S| Sharma|Savitri|S| Konduri|Ranjith|R| Fernandes|Merle|M|

Pseudopestalotiopsis theae
trauma
Fungal keratitis
phylogenetic analysis


Psychiatry Clinical Skills Evaluation: Interrater Reliability of the American Board of Psychiatry and Neurology Required Assessment.

Abstract:
OBJECTIVE
The American Board of Psychiatry and Neurology (ABPN) requires applicants to successfully complete at least 3 Clinical Skills Evaluations (CSE) as part of the credentialing requirements to sit for the psychiatry certification examination. The authors examined a database of CSE assessments conducted at a single site to determine the interrater and test-retest reliability of the evaluation.

METHODS
The authors examined 159 CSE assessments of 51 practicing psychiatrists who completed residency prior to the implementation of CSEs, but did not previously sit for the ABPN examination and later required CSEs to do so. Of these, 36 were simultaneously observed by 2 evaluators, at least 1 of whom had extensive experience with the CSE and 8 of whom were novice evaluators. At least 3 CSEs were done on the same day by each candidate.

RESULTS
The intraclass correlations for CSEs observed by 2 evaluators for the 3 clinical skills assessed (patient-physician relationship, conduct of the interview, and case presentation), were in the low-moderate "good" range for interrater reliability. Test-retest reliability for all candidates was in the moderate-high "good" range. Significant learning took place between the 1st and 3rd CSEs, with a mean improvement of 0.42-0.49 points on an 8-point scale (p < 0.01).

CONCLUSIONS
These data demonstrate good interrater reliability for the CSE even when conducted by novice faculty evaluators and good test-retest reliability despite significant learning that occurred over the series of assessments. The study supports both the educational and assessment value of the CSE.

Psychiatry
Evaluation
Interrater reliability
Certification
Test-retest reliability
Education


Varicella zoster virus antibody detection: A comparison of four commonly used techniques.

Abstract:
BACKGROUND
Antibody tests for the varicella zoster virus (VZV) include neutralization, fluorescent antibody to membrane antigen (FAMA), immune adherence hemagglutination (IAHA), enzyme immunoassay (EIA), glycoprotein-based enzyme-linked immunosorbent assay (gpELISA), and complement fixation (CF) tests. Of these, FAMA is considered the most sensitive. However, in Japan, the EIA method is most frequently employed.

OBJECTIVE
The VZV antibody detection rate of the FAMA, EIA, gpELISA, and IAHA methods was compared.

METHODS
Four types of antibody tests were conducted with sera collected from 83 college students. The relationships between two antibody tests were examined using Pearson's correlation coefficients.

RESULTS
All 83 subjects were observed to be VZV antibody-positive using the FAMA method. The Pearson correlation coefficients of gpELISA, EIA, and IAHA relative to FAMA were 0.808, 0.782, and 0.356, respectively. The positive agreement rate of IAHA relative to FAMA was 88.0% (73/83), whereas those of gpELISA and EIA were both 97.6% (81/83). Furthermore, EIA showed 100% positive agreement with gpELISA and a high correlation coefficient of 0.911, whereas these values for IAHA compared to gpELISA were much lower (90.1% and 0.530). The calculated Pearson correlation coefficient for comparison of the EIA and IAHA methods was 0.498, with a positive agreement rate of 90.1% (73/81).

CONCLUSIONS
The EIA method should be employed in Japan based on the similarity of the positivity between EIA and gpELISA, as it is more available and practical than gpELISA.

Otani|Naruhito|N| Tanaka|Miyuki|M| Maeda|Kazuhiro|K| Gomi|Yasuyuki|Y| Nakajima|Kazuhiko|K| Tanimura|Susumu|S| Takesue|Yoshio|Y| Shima|Masayuki|M| Okuno|Toshiomi|T|

Varicella zoster virus
Antibody
FAMA
EIA
Vaccine


Wet-Spinning Assembly of Continuous, Highly Stable Hyaluronic/Multiwalled Carbon Nanotube Hybrid Microfibers.

Abstract: Effective multiwalled carbon nanotube (MWCNT) fiber manufacturing methods have received a substantial amount of attention due to the low cost and excellent properties of MWCNTs. Here, we fabricated hybrid microfibers composed of hyaluronic acid (HA) and multiwalled carbon nanotubes (MWCNTs) by a wet-spinning method. HA acts as a biosurfactant and an ionic crosslinker, which improves the dispersion of MWCNTs and helps MWCNT to assemble into microfibers. The effects of HA concentration, dispersion time, injection speed, and MWCNT concentration on the formation, mechanical behavior, and conductivity of the HA/MWCNT hybrid microfibers were comprehensively investigated through SEM, UV-Vis spectroscopy, tensile testing, and conductivity testing. The obtained HA/MWCNT hybrid microfibers presented excellent tensile properties in regard to Young's modulus (9.04 ± 1.13 GPa) and tensile strength (130.25 ± 10.78 MPa), and excellent flexibility and stability due to the superior mechanical and electrical properties of MWCNTs. This work presents an effective and easy-to-handle preparation method for high-performance MWCNT hybrid microfibers assembly, and the obtained HA/MWCNT hybrid microfibers have promising applications in the fields of energy storage, sensors, micro devices, intelligent materials, and high-performance fiber-reinforced composites.

wet-spinning
multiwalled carbon nanotube
microfibers
hyaluronic acid
tensile properties
microstructures


Translocation, trophic transfer, accumulation and depuration of polystyrene microplastics in Daphnia magna and Pimephales promelas.

Abstract: In recent years, reports of plastic debris in the gastrointestinal (GI) tract of fish have been well documented in the scientific literature. This, in turn, increased concerns regarding human health exposure to microplastics through the consumption of contaminated fish. Most of the available research regarding microplastic toxicity has focused on marine organisms through direct feeding or waterborne exposures at the individual level. However, little is known about the trophic transfer of microplastics through the aquatic food chain. Freshwater zooplankton Daphnia magna (hereafter Daphnia), and the fathead minnow Pimephales promelas (FHM), are well-known model species used in standard toxicological studies and ecological risk assessments that provide a simple model for trophic transfer. The aim of this study was to assess the tissue translocation, trophic transfer, and depuration of two concentrations (20 and 2000-part ml-1) of 6 μm polystyrene (PS) microplastics particles between Daphnia and FHM. Bioconcentration factors (BCF) and bioaccumulation factors (BAF) were determined. Fluorescent microscopy was used to determine the number of particles in the water media and within the organs of both species. Throughout the five days of exposure, PS particles were only found within the GI tract of both species. The BCF for Daphnia was 0.034 ± 0.005 for the low concentration and 0.026 ± 0.006 for the high concentration. The BAF for FHM was 0.094 ± 0.037 for the low concentration and 0.205 ± 0.051 for the high concentration. Between 72 and 96 h after exposure all microplastic particles were depurated from both species. The presence of food had a significant effect on the depuration of microplastic particles from Daphnia but not for FHM. Based on the low BCF and BAF values for both species, rapid depuration rates, and null translocation of microplastic particles to organs and tissues from the GI tract, there is a low probability that microplastics will bioconcentrate and bioaccumulate under environmental conditions.

Elizalde-Velázquez|Armando|A|
Carcano|Analicia M|AM|
Crago|Jordan|J|
Green|Micah J|MJ|
Shah|Smit A|SA|
Cañas-Carrell|Jaclyn E|JE|

Trophic transfer
Depuration
Microplastics
Bioconcentration
Bioaccumulation


Sample size calculation in multi-centre clinical trials.

Abstract:
BACKGROUND
Multi-centre randomized controlled clinical trials play an important role in modern evidence-based medicine. Advantages of collecting data from more than one site are numerous, including accelerated recruitment and increased generalisability of results. Mixed models can be applied to account for potential clustering in the data, in particular when many small centres contribute patients to the study. Previously proposed methods on sample size calculation for mixed models only considered balanced treatment allocations which is an unlikely outcome in practice if block randomisation with reasonable choices of block length is used.

METHODS
We propose a sample size determination procedure for multi-centre trials comparing two treatment groups for a continuous outcome, modelling centre differences using random effects and allowing for arbitrary sample sizes. It is assumed that block randomisation with fixed block length is used at each study site for subject allocation. Simulations are used to assess operation characteristics such as power of the sample size approach. The proposed method is illustrated by an example in disease management systems.

RESULTS
A sample size formula as well as a lower and upper boundary for the required overall sample size are given. We demonstrate the superiority of the new sample size formula over the conventional approach of ignoring the multi-centre structure and show the influence of parameters such as block length or centre heterogeneity. The application of the procedure on the example data shows that large blocks require larger sample sizes, if centre heterogeneity is present.

CONCLUSION
Unbalanced treatment allocation can result in substantial power loss when centre heterogeneity is present but not considered at the planning stage. When only few patients by centre will be recruited, one has to weigh the risk of imbalance between treatment groups due to large blocks and the risk of unblinding due to small blocks. The proposed approach should be considered when planning multi-centre trials.

D016032:Randomized Controlled Trials as Topic

Block randomisation
Random effects
Linear mixed model


Glycome characterization of immunoglobulin G from buffalo (Bubalus bubalis) colostrum.

Abstract: Immunoglobulin G (IgG) is a major glycoprotein in ruminant colostrum. First day buffalo colostrum protein was purified on Sephadex G-100 and its mass was determined by MALDI-TOF as 147.848 KDa. The PMF data of protein subunits revealed its homology to IgG, which was supported by the identification of peptide sequences LLIYGATSR and VYNEYLPAPIVR corresponding to light and heavy chains of IgG by CID MS/MS analysis. The N-glycan microheterogeneity was established based on chemoselective glycoblotting technique with the identification of high mannose, neutral complex/hybrid and sialylated complex/hybrid glycans. A complete structural assignment of 54 N-linked oligosaccharides were identified and the ratio of sialyl oligosaccharides was found to be higher compared to neutral saccharides. The fucosylation observed in more than 20 oligosaccharides, high mannose and trisialyl oligosaccharides were present in diminutive amount. The high non-fucosyl and sialyl oligosaccharides in buffalo colostrum IgG provide ample scope for its utilization in targeted therapies to elicit effective ADCC and anti-inflammatory responses.

Bhanu|L S Mamatha|LS|
Amano|M|M|
Nishimura|S-I|SI|
Aparna|H S|HS|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Immunoglobulin G
Bubalus bubalis
Colostrum
Glycoblotting
MALDI-TOF MS


iRGD peptide as effective transporter of CuInZnxS2+x quantum dots into human cancer cells.

Abstract: In this paper, iRGD peptide-mediated quantum dots (QDs) delivery was studied. In the first step, dodecanethiol-capped CuInZnxS2+x (ZCIS) QDs were prepared and subsequently transferred into water using a standard and facile ligand exchange approach involving 3-mercaptopropionic acid (MPA). ZCIS@MPA nanocrystals possess a photoluminescence quantum yield (PL QY) of 25%, a PL emission centered at ca. 640nm and low distributions in size and shape. Next, the iRGD peptide was electrostatically associated to ZCIS@MPA QDs. After cytotoxicity evaluation, the tumor-targeting and penetrating activities of the iRGD/QD assembly were investigated by confocal microscopy. The experiments performed on various cancer cell lines revealed a high penetration ability of the assembly, while the bare QDs were not internalized. Additionally, imaging experiments were conducted on three-dimensional multicellular tumor spheroids in order to mimic the tumor microenvironment in vivo. iRGD/QD assemblies were found to be evenly distributed throughout the whole HeLa spheroid contrary to normal cells where they were not present. Therefore, iRGD/QD assemblies have a great potential to be used as targeted imaging agents and/or nanocarriers specific to cancer cells.

Przysiecka|Łucja|Ł| Michalska|Martyna|M| Nowaczyk|Grzegorz|G| Peplińska|Barbara|B| Jesionowski|Teofil|T| Schneider|Raphaël|R| Jurga|Stefan|S|

iRGD peptide
Tumor spheroids
Cell labelling
CuInZn(x)S(2+x) QDs
Tumor-targeted delivery


Occurrence and spatial distribution of dioxin and dioxin-like compounds in topsoil of Taranto (Apulia, Italy) by GC-MS analysis and DR-CALUX® bioassay.

Abstract: The aim of the present study was to assess the occurrence and spatial distribution of PCDD/Fs and dioxin-like compounds in topsoils of Taranto (Apulia Region), one of the most heavily industrialized and contaminated area of Southern Italy. A combined approach of chemical analysis by GC-MS/MS and AhR reporter gene bioassay was applied in a subset of topsoil samples (n = 20) collected in 2017-18 from ten sites embracing three levels of risk (from high to low) in the framework of a large survey inside Taranto municipality. TCDD-BEQs and GC-MS/MS TEQWHO and TEQTHEORETICAL revealed a decreasing trend with the distance from main industrial settings and landfill areas. A strong correlation between TCDD-BEQs and TEQWHO values (R2 = 0.85) and TEQTHEORETICAL (R2 = 0.88) was also found. In 3 out of 10 topsoil investigated, BEQs and TEQWHO/THEORETICAL resulted above Italian National Regulatory Limits for ∑PCDD/Fs in green, private and recreational used soils (10 ng TEQ/kg d.w. D.Lgs 152/2006) and for ∑PCDD/F/dl-PCBs in agricultural and farming soil (6 ng TEQ/kg d.w. D.M. 46/2019). GC-MS/MS pattern revealed the highest prevalence of dl-PCBs in 6 out of 10 sites, followed by PCDFs and PCDDs. Those sites are all located in proximity of main industrial steel and iron ore sinter plant, steel plant's landfills and illegal dumping sites. An update on occurrence and spatial distribution of PCDD/Fs and dl-PCBs contamination of Taranto urban soils was obtained and the DR-CALUX® bioassay was further recommended as a suitable screening tool for environmental and human risk assessment.

Liberatori|Giulia|G|
Cotugno|Pietro|P|
Sturba|Lucrezia|L|
Vannuccini|Maria Luisa|ML|
Capasso|Gennaro|G|
Velardo|Raffaele|R|
Besselink|Harrie|H|
Massari|Federica|F|
Tursi|Angelo|A|
Corbelli|Vera|V|
Behnisch|Peter Alexander|PA|
Corsi|Ilaria|I|

Dioxins
Dioxin-like compounds
Topsoil
Taranto
DR-CALUX® bioassay
Polychlorinated biphenyls


Improved metagenomic analysis with Kraken 2.

Abstract: Although Kraken's k-mer-based approach provides a fast taxonomic classification of metagenomic sequence data, its large memory requirements can be limiting for some applications. Kraken 2 improves upon Kraken 1 by reducing memory usage by 85%, allowing greater amounts of reference genomic data to be used, while maintaining high accuracy and increasing speed fivefold. Kraken 2 also introduces a translated search mode, providing increased sensitivity in viral metagenomics analysis.

Wood|Derrick E|DE|
Lu|Jennifer|J|
Langmead|Ben|B|0000-0003-2437-1976

Metagenomics
Alignment-free methods
Metagenomics classification
Microbiome
Minimizers
Probabilistic data structures


Quantitative analysis of the ACL and PCL using T1rho and T2 relaxation time mapping: an exploratory, cross-sectional comparison between OA and healthy control knees.

Abstract:
BACKGROUND
Quantitative magnetic resonance imaging (MRI) methods such as T1rho and T2 mapping are sensitive to changes in tissue composition, however their use in cruciate ligament assessment has been limited to studies of asymptomatic populations or patients with posterior cruciate ligament tears only. The aim of this preliminary study was to compare T1rho and T2 relaxation times of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) between subjects with mild-to-moderate knee osteoarthritis (OA) and healthy controls.

METHODS
A single knee of 15 patients with mild-to-moderate knee OA (Kellgren-Lawrence grades 2-3) and of 6 age-matched controls was imaged using a 3.0 T MRI. Three-dimensional (3D) fat-saturated spoiled gradient recalled-echo images were acquired for morphological assessment and T1ρ- and T2-prepared pseudo-steady-state 3D fast spin echo images for compositional assessment of the cruciate ligaments. Manual segmentation of whole ACL and PCL, as well as proximal / middle / distal thirds of both ligaments was carried out by two readers using ITK-SNAP and mean relaxation times were recorded. Variation between thirds of the ligament were assessed using repeated measures ANOVAs and differences in these variations between groups using a Kruskal-Wallis test. Inter- and intra-rater reliability were assessed using intraclass correlation coefficients (ICCs).

RESULTS
In OA knees, both T1rho and T2 values were significantly higher in the distal ACL when compared to the rest of the ligament with the greatest differences in T1rho (e.g. distal mean = 54.5 ms, proximal = 47.0 ms, p < 0.001). The variation of T2 values within the PCL was lower in OA knees (OA: distal vs middle vs proximal mean = 28.5 ms vs 29.1 ms vs 28.7 ms, p = 0.748; Control: distal vs middle vs proximal mean = 26.4 ms vs 32.7 ms vs 33.3 ms, p = 0.009). ICCs were excellent for the majority of variables.

CONCLUSION
T1rho and T2 mapping of the cruciate ligaments is feasible and reliable. Changes within ligaments associated with OA may not be homogeneous. This study is an important step forward in developing a non-invasive, radiological biomarker to assess the ligaments in diseased human populations in-vivo.

Ranmuthu|Chanuka D S|CDS|
MacKay|James W|JW|
Crowe|Victoria A|VA|
Kaggie|Joshua D|JD|
Kessler|Dimitri A|DA|
McDonnell|Stephen M|SM|

D000070598:Anterior Cruciate Ligament Injuries

T2 mapping
Posterior cruciate ligament
Anterior cruciate ligament
Osteoarthritis
T1rho mapping