CRISPR-FOCUS: A web server for designing focused CRISPR screening experiments.

CRISPR-FOCUS: A web server for designing focused CRISPR screening experiments.

PLoS One. 2017;12(9):e0184281

Authors: Cao Q, Ma J, Chen CH, Xu H, Chen Z, Li W, Liu XS

Abstract
The recently developed CRISPR screen technology, based on the CRISPR/Cas9 genome editing system, enables genome-wide interrogation of gene functions in an efficient and cost-effective manner. Although many computational algorithms and web servers have been developed to design single-guide RNAs (sgRNAs) with high specificity and efficiency, algorithms specifically designed for conducting CRISPR screens are still lacking. Here we present CRISPR-FOCUS, a web-based platform to search and prioritize sgRNAs for CRISPR screen experiments. With official gene symbols or RefSeq IDs as the only mandatory input, CRISPR-FOCUS filters and prioritizes sgRNAs based on multiple criteria, including efficiency, specificity, sequence conservation, isoform structure, as well as genomic variations including Single Nucleotide Polymorphisms and cancer somatic mutations. CRISPR-FOCUS also provides pre-defined positive and negative control sgRNAs, as well as other necessary sequences in the construct (e.g., U6 promoters to drive sgRNA transcription and RNA scaffolds of the CRISPR/Cas9). These features allow users to synthesize oligonucleotides directly based on the output of CRISPR-FOCUS. Overall, CRISPR-FOCUS provides a rational and high-throughput approach for sgRNA library design that enables users to efficiently conduct a focused screen experiment targeting up to thousands of genes. (CRISPR-FOCUS is freely available at http://ift.tt/2iZ4tpA).

PMID: 28873439 [PubMed - in process]

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Differential expression of virulence genes in Legionella pneumophila growing in Acanthamoeba and human monocytes.

Differential expression of virulence genes in Legionella pneumophila growing in Acanthamoeba and human monocytes.

Virulence. 2017 Sep 05;:0

Authors: Mou Q, Leung PHM

Abstract
Legionella pneumophila, the causative agent of Legionnaires' disease, is widely distributed throughout natural and artificial water systems and can replicate in macrophages and amoebae. Amoebae are the natural hosts of L. pneumophila, whereas macrophages are incidentally infected. The life cycle of L. pneumophila comprises a replicative phase within the Legionella-containing vacuole (LCV) and a transmissive phase during which bacterial cells become motile and are released via killing of the host. Although the host death mechanisms induced by L. pneumophila have been studied, the expression patterns of related L. pneumophila genes have not been reported. The present study compared the expression patterns of host cell death-associated genes in L. pneumophila grown in the human monocytic cell line THP-1 and Acanthamoeba castellanii. Notably, when L. pneumophila was grown in THP-1, expression of the gene flaA, which is involved in the induction of pyroptosis, was downregulated during the course of infection. In contrast, sdhA associated indirectly with host death, was upregulated. Expression of the genes vipD and sidF, which are involved in the induction and suppression of apoptosis, changed by less than 2-fold. Notably, a lower percentage of pyroptotic cells was observed among infected THP-1 cells relative to uninfected cells, and the latter exhibited stronger expression of caspase-1. A different pattern was observed when L. pneumophila was grown in A. castellanii: flaA and vipD were activated, whereas sdhA and sidF were downregulated during the later stage of replication. The percentage of non-viable (annexin-V(+) PI(+) or annexin-V(+)PI(-)) A. castellanii organisms increased with Legionella infection, and the expression of metacaspase-1, which is involved in encystation was up-regulated at late infection time. In summary, L. pneumophila can multiply intracellularly in both amoebae and macrophages to induce cell death and secondary infection, and this characteristic is essential for its survival in water and the lungs. The gene expression profiles observed in this study indicated the increased cytotoxicity of L. pneumophila in A. castellanii, suggesting an increased adaptation of Legionella to this host.

PMID: 28873330 [PubMed - as supplied by publisher]

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Accelerated 4D self-gated MRI of tibiofemoral kinematics.

Accelerated 4D self-gated MRI of tibiofemoral kinematics.

NMR Biomed. 2017 Sep 05;:

Authors: Mazzoli V, Schoormans J, Froeling M, Sprengers AM, Coolen BF, Verdonschot N, Strijkers GJ, Nederveen AJ

Abstract
Anatomical (static) magnetic resonance imaging (MRI) is the most useful imaging technique for the evaluation and assessment of internal derangement of the knee, but does not provide dynamic information and does not allow the study of the interaction of the different tissues during motion. As knee pain is often only experienced during dynamic tasks, the ability to obtain four-dimensional (4D) images of the knee during motion could improve the diagnosis and provide a deeper understanding of the knee joint. In this work, we present a novel approach for dynamic, high-resolution, 4D imaging of the freely moving knee without the need for external triggering. The dominant knee of five healthy volunteers was scanned during a flexion/extension task. To evaluate the effects of non-uniform motion and poor coordination skills on the quality of the reconstructed images, we performed a comparison between fully free movement and movement instructed by a visual cue. The trigger signal for self-gating was extracted using principal component analysis (PCA), and the images were reconstructed using a parallel imaging and compressed sensing reconstruction pipeline. The reconstructed 4D movies were scored for image quality and used to derive bone kinematics through image registration. Using our method, we were able to obtain 4D high-resolution movies of the knee without the need for external triggering hardware. The movies obtained with and without instruction did not differ significantly in terms of image scoring and quantitative values for tibiofemoral kinematics. Our method showed to be robust for the extraction of the self-gating signal even for uninstructed motion. This can make the technique suitable for patients who, as a result of pain, may find it difficult to comply exactly with instructions. Furthermore, bone kinematics can be derived from accelerated MRI without the need for additional hardware for triggering.

PMID: 28873255 [PubMed - as supplied by publisher]

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A Eutectic Mixture of Natural Fatty Acids Can Serve as the Gating Material for Near-Infrared-Triggered Drug Release.

A Eutectic Mixture of Natural Fatty Acids Can Serve as the Gating Material for Near-Infrared-Triggered Drug Release.

Adv Mater. 2017 Sep 05;:

Authors: Zhu C, Huo D, Chen Q, Xue J, Shen S, Xia Y

Abstract
A smart release system responsive to near-infrared (NIR) light is developed for intracellular drug delivery. The concept is demonstrated by coencapsulating doxorubicin (DOX) (an anticancer drug) and IR780 iodide (IR780) (an NIR-absorbing dye) into nanoparticles made of a eutectic mixture of naturally occurring fatty acids. The eutectic mixture has a well-defined melting point at 39 °C, and can be used as a biocompatible phase-change material for NIR-triggered drug release. The resultant nanoparticles exhibit prominent photothermal effect and quick drug release in response to NIR irradiation. Fluorescence microscopy analysis indicates that the DOX trapped in the nanoparticles can be efficiently released into the cytosol under NIR irradiation, resulting in enhanced anticancer activity. A new platform is thus offered for designing effective intracellular drug-release systems, holding great promise for future cancer therapy.

PMID: 28873241 [PubMed - as supplied by publisher]

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Effect of pore size on performance of monolithic tube chromatography of large biomolecules.

Effect of pore size on performance of monolithic tube chromatography of large biomolecules.

Electrophoresis. 2017 Sep 05;:

Authors: Podgornik A, Hamachi M, Isakari Y, Yoshimoto N, Yamamoto S

Abstract
Effect of pore size on the performance of ion-exchange monolith tube chromatography of large biomolecules was investigated. Radial flow 1 mL polymer based monolith tubes of different pore sizes (1.5, 2 and 6 μm) were tested with model samples such as 20mer poly T DNA, basic proteins and acidic proteins (molecular weight 14000-670000). Pressure drop, pH transient, the number of binding site, dynamic binding capacity and peak width were examined. Pressure drop-flow rate curves and dynamic binding capacity values were well correlated with the nominal pore size. While duration of the pH transient curves depends on the pore size, it was found that pH duration normalized on estimated surface area was constant, indicating that the ligand density is the same. This was also confirmed by the constant number of binding site values being independent on pore size. The peak width values were similar to those for axial flow monolith chromatography. These results showed that it is easy to scale up axial flow monolith chromatography to radial flow monolith tube chromatography by choosing the right pore size in terms of the pressure drop and capacity. This article is protected by copyright. All rights reserved.

PMID: 28873229 [PubMed - as supplied by publisher]

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Analysis of head impacts during sub-elite hurling practice sessions.

Analysis of head impacts during sub-elite hurling practice sessions.

J Sports Sci. 2017 Sep 05;:1-6

Authors: O'Sullivan D, Roe M, Blake C

Abstract
The reported incidence of head and neck injuries in hurling is 0.12 per 1000 hours, but no previous research has quantified head impact characteristics in this sport. Here, a wireless accelerometer and gyroscope captured head impacts, in 20 senior club level hurling players. Peak linear and rotational acceleration and impact location were recorded during three hurling training sessions, each player participating once. A mean of 27.9 impacts (linear acceleration >10g) per player, per session were recorded; 1314 impacts during a total exposure time of 247 minutes. Only 2.6% impacts had peak linear acceleration of >70g and 6.2% had peak rotational acceleration >7900 rad/s(2). There were significant differences in the number and magnitude of impacts, quantified by the accelerometer, between three training sessions of differing intensity (ŋ2 0.03-0.09, p < 0.001). This study represents a first step in quantifying head impacts during hurling, demonstrating the feasibility of this technology in the field. The sensors were able to discriminate between sessions of varying intensity. These data can be used to develop athlete monitoring protocols and may be useful in developing innovative helmet-testing standards for hurling. The potential for this technology to provide feedback has clinical utility for team medical personnel.

PMID: 28873025 [PubMed - as supplied by publisher]

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Digital therapy in diabetes.

Digital therapy in diabetes.

J Diabetes. 2017 Sep 05;:

Authors: Cahn A, Akirov A, Raz I

Abstract
Diabetes care is largely dependent on patient self-management and empowerment, given that patients with diabetes must make numerous daily decisions of what to eat, when to exercise, and determine their insulin dose and timing if required. Additionally, patients and providers are generating vast amounts of data from many sources including electronic medical records, insulin pumps, sensors, glucometers, other wearables, as well as evolving genomic, proteomic, metabolomic and microbiomic data. Multiple digital tools and apps have been developed to assist patients to choose wisely, as well as enhance their compliance by employing motivational tools and incorporating incentives from social media and gaming techniques. The health care teams and health administrators benefit from digital developments which sift through the enormous amounts of patient generated data. Data is acquired, integrated, analyzed, and presented in a self-explanatory manner, highlighting important trends and items which require attention. Employment of decision support systems may propose data-driven actions which, for the most, require final approval by the patient or physician before execution, and once implemented may improve patient outcomes. The digital diabetes clinic aims to incorporate all digital patient data and provide individually tailored virtual or face-to-face visits to those persons who need them most. Digital diabetes care has demonstrated only modest HbA1c reduction in multiple studies, and borderline cost-effectiveness, although patient satisfaction appears to be increased. Better understanding of the barriers to digital diabetes care and identification of unmet needs may yield improved utilization of this evolving technology in a safe, effective and cost-saving manner.

PMID: 28872765 [PubMed - as supplied by publisher]

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Communicating risk with aneuploidy screening: things are never as simple as they appear to be.

Communicating risk with aneuploidy screening: things are never as simple as they appear to be.

BJOG. 2017 Sep 05;:

Authors: Robinson J, Wilkins-Haug L

Abstract
The introduction of a new technology, such as an aneuploidy screening test, is an opportunity for advancement, but it is also a risk for misuse and harm. The enthusiasm of researchers, prospective parents, and the biomedical industry should be balanced with a measured approach. Optimal counseling for a particular screening or prenatal diagnostic test to be chosen, or declined, involves a comprehensive understanding of the available tests, the conditions to be screened for, time, and good communication skills. This article is protected by copyright. All rights reserved.

PMID: 28872762 [PubMed - as supplied by publisher]

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Fructus Ligustri Lucidi in Osteoporosis: A Review of its Pharmacology, Phytochemistry, Pharmacokinetics and Safety.

Fructus Ligustri Lucidi in Osteoporosis: A Review of its Pharmacology, Phytochemistry, Pharmacokinetics and Safety.

Molecules. 2017 Sep 05;22(9):

Authors: Chen B, Wang L, Li L, Zhu R, Liu H, Liu C, Ma R, Jia Q, Zhao D, Niu J, Fu M, Gao S, Zhang D

Abstract
Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, pharmacokinetics, pharmacology in bone improving effect, and safety. Materials and Methods: Several databases, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science were consulted to locate publications pertaining to FLL. The initial inquiry was conducted for the presence of the following keywords combinations in the abstracts: Fructus Ligustri Lucidi, osteoporosis, phytochemistry, pharmacokinetics, pharmacology, osteoblasts, osteoclasts, salidroside. About 150 research papers and reviews were consulted. Results: FLL is assumed to exhibit anti-osteoporotic effects by improving liver and kidney deficiencies and reducing lower back soreness in Traditional Chinese Medicine (TCM). The data from animal and cell experiments demonstrate that FLL is able to improve bone metabolism and bone quality in ovariectomized, growing, aged and diabetic rats through the regulation of PTH/FGF-23/1,25-(OH)₂D₃/CaSR, Nox4/ROS/NF-κB, and OPG/RANKL/cathepsin K signaling pathways. More than 100 individual compounds have been isolated from this plant. Oleanolic acid, ursolic acid, salidroside, and nuzhenide have been reported to exhibit the anti-osteoporosis effect. The pharmacokinetics data reveals that salidroside is one of the active constituents, and that tyrosol is hard to detect under physiological conditions. Acute and subacute toxicity studies show that FLL is well tolerated and presents no safety concerns. Conclusions: FLL provides a new option for the prevention and treatment of osteoporosis, which attracts rising interests in identifying potential anti-osteoporotic compounds and fractions from this plant. Further scientific evidences are expected from well-designed clinical trials on its bone protective effects and safety.

PMID: 28872612 [PubMed - in process]

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Evaluation of VIIRS Land Aerosol Model Selection with AERONET Measurements.

Evaluation of VIIRS Land Aerosol Model Selection with AERONET Measurements.

Int J Environ Res Public Health. 2017 Sep 05;14(9):

Authors: Wang W, Pan Z, Mao F, Gong W, Shen L

Abstract
The Visible Infrared Imaging Radiometer Suite (VIIRS) is a next-generation polar-orbiting operational environmental sensor with a capability for global aerosol observations. Identifying land aerosol types is important because aerosol types are a basic input in retrieving aerosol optical properties for VIIRS. The VIIRS algorithm can automatically select the optimal land aerosol model by minimizing the residual between the derived and expected spectral surface reflectance. In this study, these selected VIIRS aerosol types are evaluated using collocated aerosol types obtained from the Aerosol Robotic Network (AERONET) level 1.5 from 23 January 2013 to 28 February 2017. The spatial distribution of VIIRS aerosol types and the aerosol optical depth bias (VIIRS minus AERONET) demonstrate that misidentifying VIIRS aerosol types may lead to VIIRS retrieval being overestimated over the Eastern United States and the developed regions of East Asia, as well as underestimated over Southern Africa, India, and Northeastern China. Approximately 22.33% of VIIRS aerosol types are coincident with that of AERONET. The agreements between VIIRS and AERONET for fine non-absorbing and absorbing aerosol types are approximately 36% and 57%, respectively. However, the agreement between VIIRS and AERONET is extremely low (only 3.51%). The low agreement for coarse absorbing dust may contribute to the poor performance of VIIRS retrieval under the aerosol model (R = 0.61). Results also show that an appropriate aerosol model can improve the retrieval performance of VIIRS over land, particularly for dust type (R increases from 0.61 to 0.72).

PMID: 28872609 [PubMed - in process]

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The Opportunity Awaits to Lead Orthopaedic Telehealth Innovation: AOA Critical Issues.

The Opportunity Awaits to Lead Orthopaedic Telehealth Innovation: AOA Critical Issues.

J Bone Joint Surg Am. 2017 Sep 06;99(17):e93

Authors: Wongworawat MD, Capistrant G, Stephenson JM

Abstract
Telehealth is a way to provide health-care services to a patient from a provider who is at another location. The most common methods include a live interactive visit with the patient, interpretation of imaging, and monitoring of patient progress. Principally, telehealth is a way of providing a service rather than a type of service. It is about patient care, not data care.Examples of orthopaedic applications include conducting patient examinations, interpreting imaging studies, and providing postoperative care. Teleconsultation has been shown to be cost-effective. Other examples in orthopaedic research include the application of telemedicine when measuring patient-reported outcomes. Especially in cases when the patient lives far away from the provider, telehealth reduces time, produces good patient satisfaction, and costs less than hands-on care. As in everyday life, consumers have learned to demand convenience, ease of use, choice, control, and direct access. The ubiquity of telecommunications, combined with consumer technology savviness, drives the demand for telehealth. Unfortunately, the nation's largest payer for health services is one of the most restrictive for telehealth coverage. Medicare's restrictions are mostly the work of the U.S. Congress under Part B law. Video visits are very narrowly covered. Another major policy barrier is that interstate telehealth requires multiple state licenses for the physician, who must be licensed in the jurisdiction of each patient as well as the provider's physical locations. As Medicare shifts toward capitated payment and other value-based methods, there are opportunities to remove such restrictions.Despite these challenges, some states have been proactive in implementing telehealth systems. Arkansas is one of these states, and being a rural state with 2 main population centers, specialty care is relatively sparse. Implemented in 2014, the hand trauma program has been a partnership between the University of Arkansas for Medical Sciences (UAMS) and the Arkansas Trauma Communications Center (ATCC). This program has been very successful in decreasing the rate of hand trauma transfer, allowing patients to be treated closer to home while having coordinated access to fellowship-trained hand surgeons when necessary.More widespread innovation of orthopaedic applications for telehealth requires physician buy-in and health-systems partnerships. The regulatory environment will need streamlining. Ultimately, consumer demand will drive the implementation of technology to make care more accessible, convenient, and cost-effective.

PMID: 28872535 [PubMed - in process]

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New Records in Human Power.

New Records in Human Power.

Int J Sports Physiol Perform. 2017 Sep 05;:1-27

Authors: Haugen T, Paulsen G, Seiler S, Sandbakk Ø

Abstract
Maximal aerobic and anaerobic power are crucial performance determinants in most sports disciplines. Numerous studies have published power data from elite athletes over the years, particularly in runners, cyclists, rowers and cross-country skiers. In this invited review, we define the current "world records" in human upper limits of aerobic and anaerobic power. Currently, V̇O2max values of ~7.5 and 7.0 L·min(-1) in male cross-country (XC) skiers and rowers, respectively, and/or ~90 ml·kg(-1)·min(-1) in XC skiers, cyclists and runners can be described as upper human limits for aerobic power. Corresponding values for women are slightly below 5.0 L.min(-1) in rowers and XC skiers and ~80 ml·kg·min(-1) obtained in XC skiers and runners. Extremely powerful male athletes may reach ~85 W·kg(-1) in countermovement jump (CMJ) (peak vertical power) and ~36 W·kg(-1) in sprint running (peak horizontal power), cycling (instantaneous power during force-velocity testing from a standing position) and rowing (instantaneous power). Similarly, their female counterparts may reach ~70 W·kg(-1) in CMJ and ~30 W·kg(-1) in sprint running, cycling and rowing. The presented values can serve as reference values for practitioners and scientists working with elite athletes. However, several methodological considerations should be taken into account when interpreting the results. For example, calibrated apparatus and strict procedures are required to ensure high measurement validity and reliability, and the sampling rate for anaerobic power assessments must be strictly predetermined and carefully measured. Doping is also a potential confounding factor when interpreting the human upper limits of aerobic and anaerobic power.

PMID: 28872385 [PubMed - as supplied by publisher]

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Optimizing Heat Acclimation for Endurance Athletes: High- vs Low-Intensity Training.

Optimizing Heat Acclimation for Endurance Athletes: High- vs Low-Intensity Training.

Int J Sports Physiol Perform. 2017 Sep 05;:1-24

Authors: Schmit C, Duffield R, Hausswirth C, Brisswalter J, Le Meur Y

Abstract
PURPOSE: We sought to determine the effect of high- vs. low-intensity training in the heat and ensuing taper period in the heat on endurance performance.
METHODS: Nineteen well-trained triathletes undertook 5 days of normal training and a 1-week taper, including either low- (HA-L, n=10) or high-intensity (HA-H, n=9) training sessions in the heat (30°C, 50% of relative humidity). A control group (n=10) reproduced their usual training in thermoneutral conditions. Indoor twenty-kilometre cycling time-trials (35°C, 50% RH) were performed before (Pre) and after the main heat exposure (Mid) and after the taper (Post).
RESULTS: Power output remained stable in the control group from Pre to Mid (ES: -0.10 ± 0.26) and increased from Mid to Post (0.18 ± 0.22). The HA-L group demonstrated a progressive increase in performance from Pre to Mid (0.62 ± 0.33) and from Mid to Post (0.53 ± 0.30), alongside typical physiological signs of HA (reduced core temperature and heart rate, increased body mass loss). While the HA-H group presented similar adaptations, increased perceived fatigue and decreased performance at Mid (-0.35 ± 0.26) were evidenced and reversed at Post (0.50 ± 0.20). No difference in power output was reported at Post between the HA-H and the control groups.
CONCLUSION: HA-H can quickly induce F-OR in non-acclimatized endurance athletes. Since it was associated with a weak subsequent performance supercompensation, coaches and athletes should pay particular attention to training monitoring during a final preparation in the heat and reduce training intensity when early signs of F-OR are identified.

PMID: 28872380 [PubMed - as supplied by publisher]

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The Specificity of Rugby Union Training Sessions in Preparation for Match Demands.

The Specificity of Rugby Union Training Sessions in Preparation for Match Demands.

Int J Sports Physiol Perform. 2017 Sep 05;:1-23

Authors: Campbell PG, Peake JM, Minett GM

Abstract
PURPOSE: Investigations into the specificity of rugby union training practices in preparation for competitive demands has predominantly focussed on physical and physiological demands. The evaluation of the contextual variance in perceptual strain or skill requirements between training and matches in rugby union is unclear, yet holistic understanding may assist to optimise training design. This study evaluated the specificity of physical, physiological, perceptual and skill demands of training sessions compared with competitive match-play in pre-professional, elite club rugby union.
METHODS: Global positioning system (GPS) devices, video capture, heart rate (HR), and session ratings of perceived exertion (sRPE) were used to assess movement patterns, skill completions, physiologic, and perceptual responses, respectively. Data were collected across a season (training sessions n=29; matches n=14). Participants (n=32) were grouped in playing positions as: outside backs, centres, halves, loose forwards, lock forwards, and front row forwards.
RESULTS: Greater total distance, low-intensity activity, maximal speed and metres per min were apparent in matches compared to training in all positions (P<0.02; d>0.90). Similarly, match HR, and sRPE responses were higher than those recorded in training (P<0.05; d>0.8). Key skill completions for forwards (i.e., scrums, rucks and lineouts) and backs (i.e., kicks) were greater under match conditions than in training (P<0.001; d>1.50).
CONCLUSION: Considerable disparities exist between the perceptual, physiological, and key skill demands of competitive matches versus training sessions in pre-professional rugby union players. Practitioners should consider the specificity of training tasks for pre-professional rugby players to ensure the best preparation for match demands.

PMID: 28872372 [PubMed - as supplied by publisher]

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Strategies towards rapid generation of forefoot model incorporating realistic geometry of metatarsals encapsulated into lumped soft tissues for personalized finite element analysis.

Strategies towards rapid generation of forefoot model incorporating realistic geometry of metatarsals encapsulated into lumped soft tissues for personalized finite element analysis.

Comput Methods Biomech Biomed Engin. 2017 Sep 05;:1-10

Authors: Chen WM, Lee SJ, Lee PVS

Abstract
Use of finite element (FE) foot model as a clinical diagnostics tool is likely to improve the specificity of foot injury predictions in the diabetic population. Here we proposed a novel workflow for rapid construction of foot FE model incorporating realistic geometry of metatarsals encapsulated into lumped forefoot's soft tissues. Custom algorithms were implemented to perform unsupervised segmentation and mesh generation to directly convert CT data into a usable FE model. The automatically generated model provided higher efficiency and comparable numerical accuracy when compared to the model constructed using a traditional solid-based mesh process. The entire procedure uses MATLAB as the main platform, and makes the present approach attractive for creating personalized foot models to be used in clinical studies.

PMID: 28872350 [PubMed - as supplied by publisher]

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Glowing cancer tool illuminates brain tumours during pituitary surgery

An experimental imaging tool that uses a targeted fluorescent dye successfully lit up the benign brain tumours of patients during removal surgery, allowing surgeons to identify tumour tissue, a new study from researchers at the Perelman School of Medicine...

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Recurrence of prostate cancer could be reduced thanks to exciting new discovery

Ground breaking research could reduce the recurrence of prostate cancer in males, a new study in the journal Nature Communications reports. During this in depth study, an international team of researchers led by British scientists investigated the impact...

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Vaccine to prevent most cervical cancers shows long-term effectiveness

A vaccine that can literally eradicate the majority of cervical cancer cases shows long-term effectiveness in a study published in The Lancet. This study of 14,215 women in 18 countries extends and solidifies the initial phase 3 efficacy and safety trial...

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European Commission approves pembrolizumab for treatment of advanced bladder cancers

The European Commission has approved pembrolizumab, the company's anti-PD-1 therapy, for the treatment of certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer. Specifically, pembrolizumab is approved for...

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X-Linked Hypohidrotic Ectodermal Dysplasia: New Features and a Novel EDA Gene Mutation

We described a 5-year-old male with hypodontia, hypohidrosis, and facial dysmorphisms characterized by a depressed nasal bridge, maxillary hypoplasia, and protuberant lips. Chromosomal analysis revealed a normal 46,XY male karyotype. Due to the presence of clinical features of hypohidrotic ectodermal dysplasia (HED), the EDA gene, located at Xq12q13.1, of the patient and his family was sequenced. Analysis of the proband's sequence revealed a missense mutation (T to A transversion) in hemizygosity state at nucleotide position 158 in exon 1 of the EDA gene, which changes codon 53 from leucine to histidine, while heterozygosity at this position was detected in the slightly affected mother; moreover, this mutation was not found in the publically available Human Gene Mutation Database. To date, our findings indicate that a novel mutation in EDA is associated with X-linked HED, adding it to the repertoire of EDA mutations.
Cytogenet Genome Res

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Evaluation of tracheobronchial branching abnormalities in patients with microtia using chest computed tomography

Publication date: November 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): Chuan Li, Haiyue Jiang, Jingning Chen, Rongwei Wu, Ye Bi, Meirong Yang, Ye Zhang, Bo Pan
BackgroundThe objective of this study was to identify the characteristics and incidence of Tracheobronchial branching abnormalities in patients with microtia and to evaluate the risk of anesthesia.MethodsA total of 204 consecutive microtia patients and 465 nose cosmetic patients without microtia received a preoperative chest computed tomography. A retrospective study was performed with the clinical and imaging data from July 2016 to April 2017.ResultsWith the chest computed tomography images, a total of 7 cases were documented with Tracheobronchial branching abnormalities, including 6 cases among the microtia patients and 1 case among the cosmetic patients without microtia. The incidence of Tracheobronchial branching abnormalities was higher in microtia patients than the cosmetic patients without microtia (2.94% versus 0.22%, P < 0.01).ConclusionsThe incidence of Tracheobronchial branching abnormalities was high in patients with microtia. Preoperative diagnosis of tracheal bronchus can help anesthesiologists avoid complications. Microtia with Tracheobronchial branching abnormalities may involve a new syndrome previously undiscovered or just another extension with the very wide spectrum of microtia.



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Variations in electrode impedance during and after cochlear implantation: Round window versus extended round window insertions

Publication date: November 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): Jun Wang, Jiaqiang Sun, Jingwu Sun, Jianwen Chen
ObjectivesTo assess differences in intra- and postoperative electrode impedances following cochlear implantation between round window insertions (RWI) and extended round window insertions (ERWI).MethodsFifty patients with congenital hearing loss received unilateral hearing implants (Sonata Ti100, Med-El GmbH, Innsbruck, Austria) with standard electrode arrays. The patients were divided into two groups according to the surgical technique used. Thirty-five procedures were performed with RWI (group A) and 15 with ERWI (group B). Electrode impedance was measured and analysed during the operation, and one week and one month postoperatively.ResultsThere were no statistically significant differences (i.e., P > 0.05) in electrode impedance between groups A and B intraoperatively, or at one week or one month postoperatively. Electrode impedance at one month postoperatively was higher than the intraoperative and postoperative one week values in group A (P < 0.05), with similar results in group B.ConclusionThere was no significant difference between RWI and ERWI in operative duration or complications of cochlear implantation. Moreover, no significant differences in postoperative electrode impedance values were found between the two surgical routes.



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Variations in electrode impedance during and after cochlear implantation: Round window versus extended round window insertions

Publication date: November 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): Jun Wang, Jiaqiang Sun, Jingwu Sun, Jianwen Chen
ObjectivesTo assess differences in intra- and postoperative electrode impedances following cochlear implantation between round window insertions (RWI) and extended round window insertions (ERWI).MethodsFifty patients with congenital hearing loss received unilateral hearing implants (Sonata Ti100, Med-El GmbH, Innsbruck, Austria) with standard electrode arrays. The patients were divided into two groups according to the surgical technique used. Thirty-five procedures were performed with RWI (group A) and 15 with ERWI (group B). Electrode impedance was measured and analysed during the operation, and one week and one month postoperatively.ResultsThere were no statistically significant differences (i.e., P > 0.05) in electrode impedance between groups A and B intraoperatively, or at one week or one month postoperatively. Electrode impedance at one month postoperatively was higher than the intraoperative and postoperative one week values in group A (P < 0.05), with similar results in group B.ConclusionThere was no significant difference between RWI and ERWI in operative duration or complications of cochlear implantation. Moreover, no significant differences in postoperative electrode impedance values were found between the two surgical routes.



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Sixty seconds on . . . the private finance initiative

PFI—how very 1990s! Didn't it go out of the window with New Labour and Cool Britannia?It's definitely "still a thing," to use a catchphrase that probably didn't exist when Tony Blair lived at Downing...

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Child admissions for lower respiratory tract infections fall after smoking ban

Hospital admissions of children with lower respiratory tract infections have fallen by 18.5% since the public smoking ban and 9.8% fewer children have attended hospital for severe asthma...

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The environmental impacts of one of the largest tailing dam failures worldwide

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Proteomic analysis on roots of Oenothera glazioviana under copper-stress conditions

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Maximum extent and decay of the Laurentide Ice Sheet in Western Baffin Bay during the Last glacial episode

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Pleomorphic bacteria-like structures in human blood represent non-living membrane vesicles and protein particles

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Improving understanding of the functional diversity of fisheries by exploring the influence of global catch reconstruction

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Different spatial patterns of nitrogen and phosphorus resorption efficiencies in China’s forests

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Community-like genome in single cells of the sulfur bacterium Achromatium oxaliferum

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Effects of biochar, waste water irrigation and fertilization on soil properties in West African urban agriculture

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Growth of the northeastern margin of the Tibetan Plateau by squeezing up of the crust at the boundaries

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Tillage and nitrogen fertilization enhanced belowground carbon allocation and plant nitrogen uptake in a semi-arid canola crop–soil system

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Investigations on the dose–response relationship of combined exposure to low doses of three anti-androgens in Wistar rats

Abstract

The current investigation examines whether combined exposure to three anti-androgens (flutamide, prochloraz, vinclozolin) result in interference with endocrine homeostasis when applied at very low dose levels, and whether the results of combined exposure are more pronounced than to the individual compounds. A pre–post-natal in vivo study design was chosen with more parameters than regulatory testing protocols require (additional endpoints addressing hormone levels, morphology and histopathological examinations). Dose levels were chosen to represent the lowest observed adverse effect level (LOAEL), the no observed adverse effect level (NOAEL), and the acceptable daily intake for each individual substance. Anti-androgenic changes were observable at the effect level (LOAEL) but not at lower exposures. Nipple/areola counts appeared to be a sensitive measure of effect, in addition to male sex organ weights at sexual maturation, and finally gross findings. The results indicate the absence of evidence for effects at low or very low dose levels. No (adverse) effects were seen at the NOAEL dose. A non-monotonic dose–response relationship was not evident. Combined exposure at LOAEL level resulted in enhanced responses for anogenital index, number of areolas/nipples, delayed preputial separation and reduced ventral prostate weight in comparison to the individual compounds.

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Effects of non-nutritive (artificial vs natural) sweeteners on 24-h glucose profiles

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Effects of supplementation with quercetin on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials

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Milk-cereal and whole-grain dietary patterns protect against low bone mineral density among male adolescents and young adults

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Gut microbiota composition in relation to the metabolic response to 12-week combined polyphenol supplementation in overweight men and women

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Vitamin B12 status in pregnant women and their infants in South India

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Impact of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring neurodevelopment: 5-year follow-up of a randomized controlled trial

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Association studies of genetic scores of serum vitamin B12 and folate levels with symptoms of depression and anxiety in two danish population studies

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The importance of nuance in statements about methods for human energy expenditure estimation that use motion sensors

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Quantification of whole-body and segmental skeletal muscle mass using phase-sensitive 8-electrode medical bioelectrical impedance devices

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Human milk insulin is related to maternal plasma insulin and BMI: but other components of human milk do not differ by BMI

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Intra-abdominal and subcutaneous abdominal fat as predictors of cardiometabolic risk in a sample of Mexican children

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Infant milk fat droplet size and coating affect postprandial responses in healthy adult men: a proof-of-concept study

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Forearm to fingertip skin temperature gradients in the thermoneutral zone were significantly related to resting metabolic rate: potential implications for nutrition research

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Nutrient intake and contribution of home enteral nutrition to meeting nutritional requirements after oesophagectomy and total gastrectomy

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Central adiposity-induced plasma-free amino acid alterations are associated with increased insulin resistance in healthy Singaporean adults

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A decrease in blood cholesterol after gastrostomy could impact survival in ALS

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Chocolate intake and diabetes risk in postmenopausal American women

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Response to ‘The importance of nuance in statements about methods for human energy expenditure estimation that use motion sensors’

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Tryptone-stabilized gold nanoparticles target tubulin and inhibit cell viability by inducing an unusual form of cell cycle arrest

Publication date: Available online 5 September 2017
Source:Experimental Cell Research
Author(s): Tejashree Mahaddalkar, Sourabh Mehta, Sanith Cheriyamundath, Harries Muthurajan, Manu Lopus
Gold nanoparticles have been investigated extensively for their molecular mechanisms of action and anticancer potential. We report a novel, tubulin-targeted antiproliferative mechanism of action of tryptone-stabilized gold nanoparticles (TsAuNPs). TsAuNPs, synthesized using HAuCl4.3H2O and tryptone and characterized by a variety of spectroscopic methods and transmission electron microscopy, were found to be inhibitory to viability of human pancreatic (PANC-1), cervical (HeLa), and breast (MDA-MB-231) cancer cell lines in a concentration-dependent manner, with highest efficacy against PANC-1 cells. The particles strongly inhibited the clonogenic propagation of PANC-1 cells. TsAuNPs-mediated inhibition of cell viability involved an unusual mode of cell cycle arrest (arrest at both G0-G1 phase and S-phase) followed by apoptosis. In vitro, TsAuNPs bound purified tubulin, competitively inhibited anilinonaphthalene sulfonate binding to tubulin, and suppressed tubulin assembly. In cells, tubulin-TsAuNPs interactions were manifested as a disrupted microtubule network, defective reassembly of cold-disassembled microtubules, and induction of tubulin acetylation. Our data indicate that TsAuNPs inhibit cell viability by inducing differential cell cycle arrest possibly through disrupted dynamicity of cellular microtubules.

Graphical abstract

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The Impact of Frailty on Morbidity and Mortality following Open Emergent Colectomies

Background. Elderly and frail patients undergo open emergency colectomies and are at greater risk for complications. The relationship between frailty and open emergent colectomies is yet unexplored. Objective. The purpose of this study was to evaluate the relationship between frailty and outcomes after open emergent colorectal surgery. Design. Using the American College of Surgeons National Quality Improvement Program database, a validated modified frailty index was used, along with logistic regression, to assess the relationship between frailty and outcomes. Main Outcome Measures. Outcomes included mortality (primary), Clavien-Dindo Complication Grade >3, reintubation, ventilator >48 hours, and reoperation (secondary). Results. The rates for 30-day mortality, Clavien-Dindo Grade >3, reintubation, ventilator > 48 hours, and reoperation in our cohort were 16.6%, 36.9%, 8.6%, 23.9%, and 15.0%, respectively. There was a statistically significant increase in prevalence of all outcomes with increasing frailty. Limitations. A causal relationship between frailty and complications cannot be established in a retrospective analysis. Also, extrapolation of our data to reflect outcomes beyond 30 days must be done with caution. Conclusions. Frailty is a statistically significant predictor of mortality and morbidity after open emergent colectomies and can be used in an acute care setting.

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Advanced In Situ I-V Measurements Used in the Study of Porous Structures Growth on Silicon

The rate of oxide formation during growth of pores structures on silicon was investigated by in situ I-V measurements. The measurements were designed to get two I-V curves in a short time (total time for the two measurements was 300 seconds) taking into account the gap (in mA/cm2) for each corresponding voltage. The in situ I-V measurements were made at different pore depth/time, at the electrolyte-pore tip interface, while etching takes place based on p-type Si. The results showed increasing, decreasing, and constant I-V gap in time, for macropores, nanopores, and electropolishing regimes, respectively. This was related to the expected diffusion limitation of oxide forming (H2O) molecules reaching the electrolyte-pore tip and the anodizing current, while etching takes place. The method can be developed further and has the potential to be applied in other electrochemically etched porous semiconductor materials.

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A New Terrain Classification Framework Using Proprioceptive Sensors for Mobile Robots

Mobile robots that operate in real-world environments interact with the surroundings to generate complex acoustics and vibration signals, which carry rich information about the terrain. This paper presents a new terrain classification framework that utilizes both acoustics and vibration signals resulting from the robot-terrain interaction. As an alternative to handcrafted domain-specific feature extraction, a two-stage feature selection method combining ReliefF and mRMR algorithms was developed to select optimal feature subsets that carry more discriminative information. As different data sources can provide complementary information, a multiclassifier combination method was proposed by considering a priori knowledge and fusing predictions from five data sources: one acoustic data source and four vibration data sources. In this study, four conceptually different classifiers were employed to perform the classification, each with a different number of optimal features. Signals were collected using a tracked robot moving at three different speeds on six different terrains. The new framework successfully improved classification performance of different classifiers using the newly developed optimal feature subsets. The greater improvement was observed for robot traversing at lower speeds.

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Bayesian Methods for Predicting the Shape of Chinese Yam in Terms of Key Diameters

This paper proposes Bayesian methods for the shape estimation of Chinese yam (Dioscorea opposita) using a few key diameters of yam. Shape prediction of yam is applicable to determining optimal cutoff positions of a yam for producing seed yams. Our Bayesian method, which is a combination of Bayesian estimation model and predictive model, enables automatic, rapid, and low-cost processing of yam. After the construction of the proposed models using a sample data set in Japan, the models provide whole shape prediction of yam based on only a few key diameters. The Bayesian method performed well on the shape prediction in terms of minimizing the mean squared error between measured shape and the prediction. In particular, a multiple regression method with key diameters at two fixed positions attained the highest performance for shape prediction. We have developed automatic, rapid, and low-cost yam-processing machines based on the Bayesian estimation model and predictive model. Development of such shape prediction approaches, including our Bayesian method, can be a valuable aid in reducing the cost and time in food processing.

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Discoloration Effects of High-Dose γ-Irradiation and Long-Term Thermal Aging of (U)HMW-PE

Two polyethylene types with ultra-high (UHMW-PE) and high molecular weight (HMW-PE) used as neutron radiation shielding materials in casks for radioactive waste were irradiated with doses up to 600 kGy using a 60Co gamma source. Subsequently, thermal aging at 125°C was applied for up to one year. Degradation effects in the materials were characterized using colorimetry, UV-Vis spectroscopy, IR spectroscopy, and DSC. Both materials exhibited a yellowing upon irradiation. The discoloration of UHMW-PE disappeared again after thermal aging. Therefore, the yellowing is assumed to originate from annealable color centers in the form of free radicals that are trapped in the crystalline regions of the polymer and recombine at elevated temperatures. For the antioxidant-containing HMW-PE, yellowing was observed after both irradiation and thermal aging. The color change was correlated mainly to decomposition products of the antioxidant in addition to trapped radicals as in UHMW-PE. Additionally, black spots appeared after thermal aging of HMW-PE.

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Isolation and characterization of the compounds responsible for the antimutagenic activity of Combretum microphyllum (Combretaceae) leaf extracts

Mutations play a major role in the pathogenesis and development of several chronic degenerative diseases including cancer. It follows, therefore that antimutagenic compound may inhibit the pathological process...

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Effects of Mollugo pentaphylla extract on monosodium urate crystal-induced gouty arthritis in mice

Gout is an inflammatory condition induced by the deposition of monosodium urate (MSU) crystals in joints and soft tissues, and it can lead to acute or chronic arthritis. MSU are pro-inflammatory stimuli that c...

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Oral administration of taheebo (Tabebuia avellanedae Lorentz ex Griseb.) water extract prevents DSS-induced colitis in mice by up-regulating type II T helper immune responses

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders that are mediated by pathogenic Th1 and Th17 cells. Previous studies have demonstrated that taheebo water extract (TWE) derived from Tabebuia ...

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Gypenosides ameliorate memory deficits in MPTP-lesioned mouse model of Parkinson’s disease treated with L-DOPA

Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The pres...

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Subchronic toxicity of herbal compound “Jiedu Huayu” granules in rats

"Jiedu Huayu" (JDHY) granules are traditional Chinese herbal compounds that have been used to treat severe liver injury for many years. The purpose of the current study is to evaluate the safety of JDHY granules.

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Phase I study of axitinib and everolimus in metastatic solid tumours and extension to metastatic renal cell carcinoma: Results of EVAX study

Publication date: November 2017
Source:European Journal of Cancer, Volume 85
Author(s): Alain Ravaud, Carlos Gomez-Roca, Marie-Quitterie Picat, Laurence Digue, Christine Chevreau, Anne Gimbert, Emmanuelle Chauzit, Rémi Sitta, François Cornelis, Julien Asselineau, Richard Aziza, Amaury Daste, Cathy Quemener, Jessica Baud, Andréas Bikfalvi, Delphine Pedenon–Périchout, Adelaïde Doussau, Mathieu Molimard, Jean-Pierre Delord
PurposeAnti-angiogenic and mammalian target of rapamycin inhibitors have shown efficacy in solid tumours. Reported combination of both drugs was deemed to be too toxic. Due to a potential favourable safety profile of axitinib (AX), a phase I study combining everolimus (EV) and AX for solid tumours was explored.Experimental designPatients (pts) with advanced cancers were enrolled in an escalation phase I study to investigate the safety of the combination. Pharmacokinetic profile and functional vascular imaging were performed. An extension to pts with naive metastatic renal cell carcinoma (MRCC) was explored.Results15 pts were included over three different dose levels (DLs); DL 0: AX 3 mg BID (twice daily)/EV 5 mg OD (once daily); DL 1: AX 5 mg BID/EV 5 mg OD and DL 2: AX 5 mg BID/EV 10 mg OD for 28 d. One dose-limiting toxicity (DLT) was reported at DL 0: grade (Gr) III diarrhoea and one DLT at DL 2: Gr III asthenia. Three severe adverse events (AEs) in two pts were unexpected: jaw osteonecrosis, recurrent renal failure and cardiomyopathy. Maximum tolerated dose (MTD) was level 2. After 1st cycle, Gr III or Gr II AEs of interest were mainly asthenia, diarrhoea and anorexia. All pts but one showed tumour shrinkage. Partial responses (PRs) were seen in one pt with bladder carcinoma and in one pt in 1st line MRCC in the escalating phase. In the extension phase in naive MRCC treated at MTD, five pts had a PR and one pt had a prolonged stable disease.ConclusionThe recommended dose for phase II is AX 5 mg BID/EV 10 mg OD.



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The Center for Epidemiologic Studies Depression Scale is an adequate screening instrument for depression and anxiety disorder in adults with congential heart disease

The Center for Epidemiological Studies Depression Scale (CES-D) is an instrument that is commonly used to screen for depression in patients with chronic disease, but the characteristics of the CES-D in adults ...

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French raise alarm over smoldering blanket in PET/MRI

French researchers are alerting radiology facilities to an incident that occurred...

Read more on AuntMinnieEurope.com

Related Reading:

MRI provider calls for urgent action on patient safety

MRI accident leads to loss of thumb for French boy

Europe plays catch-up on MRI safety

Improve MRI safety in Europe, urge medical physicists

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Interview: "Es gibt keine Marktgottheit".

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Development and external validation of nomograms to predict the risk of skeletal metastasis at the time of diagnosis and skeletal metastasis-free survival in nasopharyngeal carcinoma

The skeletal system is the most common site of distant metastasis in nasopharyngeal carcinoma (NPC); various prognostic factors have been reported for skeletal metastasis, though most studies have focused on a...

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Circadian disruption promotes tumor growth by anabolic host metabolism; experimental evidence in a rat model

Light at night creates a conflicting signal to the biological clock and disrupts circadian physiology. In rodents, light at night increases the risk to develop mood disorders, overweight, disrupted energy meta...

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The association between smoking and breast cancer characteristics and outcome

Smoking is associated with an increased incidence of hormone receptor positive breast cancer. Data regarding worse breast cancer outcome in smokers are accumulating. Current literature regarding the impact of ...

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ERp29 controls invasion and metastasis of gastric carcinoma by inhibition of epithelial-mesenchymal transition via PI3K/Aktsignaling pathway

Gastric cancer (GC) accounts for the fourth most occurring malignancy and the third major cause of cancer death. Identifying novel molecular signaling pathways participating in gastric tumorigenesis and progre...

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The values of neutrophil-lymphocyte ratio and/or prostate-specific antigen in discriminating real Gleason score ≥ 7 prostate cancer from group of biopsy-based Gleason score ≤ 6

The discrepant concordance between biopsy and radical prostatectomy (RP) specimen are well reported. To validate the clinical usefulness of neutrophil-lymphocyte ratio (NLR) in discriminating real GS ≥ 7 PCa f...

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Implantierbare Hörsysteme

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The dosimetric effects of limited elective nodal irradiation in volumetric modulated arc therapy treatment planning for locally advanced non-small cell lung cancer

Abstract

Objective

Contemporary radiotherapy guidelines for locally advanced non-small cell lung carcinoma (LA-NSCLC) recommend omitting elective nodal irradiation, despite the fact that evidence supporting this came primarily from older reports assessing comprehensive nodal coverage using 3D conformal techniques. Herein, we evaluated the dosimetric implications of the addition of limited elective nodal irradiation (LENI) to standard involved field irradiation (IFI) using volumetric modulated arc therapy (VMAT) planning.

Method

Target volumes and organs-at-risk (OARs) were delineated on CT simulation images of 20 patients with LA-NSCLC. Two VMAT plans (IFI and LENI) were generated for each patient. Involved sites were treated to 60 Gy in 30 fractions for both IFI and LENI plans. Adjacent uninvolved nodal regions, considered high risk based on the primary tumor site and extent of nodal involvement, were treated to 51 Gy in 30 fractions in LENI plans using a simultaneous integrated boost approach.

Results

All planning objectives for PTVs and OARs were achieved for both IFI and LENI plans. LENI resulted in significantly higher esophagus D _mean (15.3 vs. 22.5 Gy, p < 0.01), spinal cord D _max (34.9 vs. 42.4 Gy, p = 0.02) and lung D _mean (13.5 vs. 15.9 Gy, p = 0.02), V ₂₀ (23.0 vs. 27.9%, p = 0.03), and V ₅ (52.6 vs. 59.4%, p = 0.02). No differences were observed in heart parameters. On average, only 32.2% of the high-risk nodal volume received an incidental dose of 51 Gy when untargeted in IFI plans.

Conclusion

The addition of LENI to VMAT plans for LA-NSCLC is feasible, with only modestly increased doses to OARs and marginal expected increase in associated toxicity.

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Rehabilitation bei Fazialisparese und Schwindel bei Patienten mit Vestibularisschwannom

Zusammenfassung

Hintergrund

Fazialisparese und Schwindel als Symptom eines Vestibularisschwannoms (VS) oder als Folge der Therapie beeinträchtigen die Lebensqualität der Patienten erheblich.

Fragestellung

Die Arbeit analysierte die aktuelle Literatur zum Thema und gibt darauf basierend Handlungsempfehlungen.

Material und Methode

Es handelt sich um eine PubMed-basierte Literaturrecherche der letzten 10 Jahre.

Ergebnisse

Zur Behandlung der akuten postoperativen Fazialisparese nach VS-Operation gibt es keine evidenzbasierte medikamentöse Therapie. Für die chirurgische Therapie gibt es etablierte Verfahren zur Nervenrekonstruktion, zum Muskeltransfer und zu statischen Maßnahmen. Eine physiotherapeutische Bewegungstherapie, am besten mit Biofeedback, verbessert möglicherweise die Fazialisfunktion bei Patienten mit Defektheilung. Botulinumtoxin ist Therapie der Wahl zur Behandlung von Synkinesien. Gegen akuten und chronischen Schwindel bei Patienten mit VS werden dieselben Antivertiginosa wie bei anderen Schwindelpatienten eingesetzt. Bei noch erhaltener Vestibularisfunktion ist die präoperative intratympanale Gentamycinausschaltung und ein Kompensationstraining eine vielversprechende Therapiestrategie, um postoperativen Schwindel zu verringern. Eine gute Vestibularisrehabilitation umfasst ein intensives und regelmäßiges Bewegungstraining, am besten mit Echtzeitfeedback und Therapiekontrolle.

Schlussfolgerungen

Es gibt eine Vielzahl durch Studien belegte konservative, chirurgische oder kombiniert konservativ-chirurgische Behandlungsoptionen zur individuellen Fazialisrehabilitation bei VS-Patienten. Bei akutem Schwindel ist eine Pharmakotherapie angezeigt. Sowohl bei akutem als auch bei belastendem chronischem Schwindel lindert eine intensive Bewegungstherapie die Beschwerden.

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Vestibularisschwannome – Teil 2

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Implantierbare Hörsysteme

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Multidrug Resistant Enteric Bacterial Pathogens in a Psychiatric Hospital in Ghana: Implications for Control of Nosocomial Infections

Enteric bacteria are commonly implicated in hospital-acquired or nosocomial infections. In Ghana, these infections constitute an important public health problem but little is known about their contribution to antibiotic resistance. The aim of the study was to determine the extent and pattern of antibiotic resistance of enteric bacteria isolated from patients and environmental sources at the Accra Psychiatric Hospital. A total of 265 samples were collected from the study site including 142 stool and 82 urine samples from patients, 7 swab samples of door handle, and 3 samples of drinking water. Enteric bacteria were isolated using standard microbiological methods. Antibiograms of the isolates were determined using the disc diffusion method. Overall, 232 enteric bacteria were isolated. Escherichia coli was the most common (38.3%), followed by Proteus (19.8%), Klebsiella (17.7%), Citrobacter (14.7%), Morganella (8.2%), and Pseudomonas (1.3%). All isolates were resistant to ampicillin but sensitive to cefotaxime. The resistance ranged from 15.5% to 84.5%. Multidrug resistance was most prevalent (100%) among isolates of Proteus and Morganella and least prevalent among isolates of Pseudomonas (33.3%). Multidrug resistance among enteric bacteria at the study hospital is high and hence there is a need for screening before therapy to ensure prudent use of antibiotics.

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Experimental Investigation of Seismic-Induced Hydrodynamic Pressures on a Vertical Wall under Conditions of Wave Resonance

The distribution of hydrodynamic pressure acting on the structural face of a dam significantly influences the stability of the dam. The present study investigates the development of the hydrodynamic pressure acting on the surface of a dam at different heights with respect to time during earthquakes with different dominant frequencies using a shaking table. The results demonstrate that the variation in the hydrodynamic pressure significantly follows the seismically accelerated wave motion in the absence of resonance. However, under conditions of resonance, the fluctuations in the hydrodynamic pressure exhibit similarities with a sine wave, and the positive peak values present some hysteresis. The experimental pressure values in the absence of resonance present parabolic distributions with respect to the water height that are in good agreement with the corresponding hydrodynamic pressures determined by Westergaard's equation, while conditions of wave resonance produce a uniform distribution of hydrodynamic pressures with greater values and much longer periods of increased hydrodynamic pressure than the case of nonresonance. In addition, the seismic frequency, fundamental frequency of the reservoir, maximum peak seismic acceleration, and initial water depth are treated as variables. An empirical equation is derived to predict the maximum hydrodynamic pressure in conjunction with wave resonance conditions.

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The herbicides trifluralin and tebuthiuron have no genotoxic or mutagenic potential as evidenced by genetic tests

Abstract

Brazil has been the largest world consumer of pesticides since 2008, followed by the USA. The herbicides trifluralin and tebuthiuron have been widely applied in agriculture. These herbicides are selective for some plant species, and their use brings various benefits. However, the genotoxic and mutagenic effects of tebuthiuron on non-target organisms are poorly known, and in addition, the effects of trifluralin must be better investigated. Therefore, this study employed genetic tests including the comet assay and micronucleus test to evaluate the genotoxic effects of trifluralin and tebuthiuron on HepG2 cells. In addition, we have used the Ames test to assess the mutagenic effects of the herbicides on the TA97a, TA98, TA100, and TA1535 strains of Salmonella typhimurium. On the basis of the comet assay and the micronucleus test, trifluralin did not cause genetic damage to HepG2 cells. In addition, trifluralin did not impact the tested S. typhimurium strains. Regarding tebuthiuron, literature has shown that this herbicide damaged DNA in Oreochromis niloticus. Nevertheless, we have found that tebuthiuron was not genotoxic to either HepG2 cells or the S. typhimurium strains. Therefore, neither trifluralin nor tebuthiuron exerted genotoxic or mutagenic potential at the tested conditions.

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Thread like calcifications in mesenteric phlebosclerosis

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Prenatal congenital vertical talus (rocker bottom foot): a marker for multisystem anomalies

Abstract

Background

Congenital vertical talus is a rare foot anomaly characterized by a prominent calcaneus and rigid forefoot dorsiflexion. While congenital vertical talus has been associated with anomalies such as trisomy 18, myelomeningocele and arthrogryposis, postnatal series have reported cases of isolated congenital vertical talus.

Objective

The purpose of our study was to determine the incidence of isolated congenital vertical talus prenatally and identify the most common anomalies associated with this finding.

Materials and methods

A retrospective review was performed of congenital vertical talus cases identified in our fetal center from 2006 to 2015. The prenatal US and MR imaging appearance of congenital vertical talus was evaluated and differentiation from congenital talipes equinovarus was assessed. Studies were evaluated for additional abnormalities affecting the central nervous system, face, limbs, viscera, growth and amniotic fluid. Imaging findings were recorded and correlated with outcomes when available.

Results

Twenty-four cases of congenital vertical talus were identified prenatally (gestational age: 19–36 weeks). All 24 had prenatal US and 21 also underwent fetal MRI on the same day. There were no isolated cases of congenital vertical talus in this series; all 24 had additional anomalies identified prenatally. Sixteen cases had bilateral congenital vertical talus (67%). Additional anomalies were identified in the brain (15), spine (11), face (6), abdominal wall (3), heart (8) and other limbs (12). Chromosomal abnormalities were identified in 6 of 20 patients who underwent genetic testing. Overall, US held some advantage in detecting the abnormality: in 10 cases, US depicted congenital vertical talus more clearly than MRI; in 8 cases, US and MRI were equal in detection and in 3 cases, MRI was superior. In 9/15 cases with intracranial abnormalities, MRI was superior to US in demonstrating structural anomalies. Outcomes included termination (11), intrauterine fetal demise (1), stillbirth or immediate neonatal demise (5), lost to follow-up (1), and 6 survivors with postnatal follow-up.

Conclusion

In our series, there were no cases of isolated congenital vertical talus, with additional anomalies variably affecting multiple systems including the brain, spine, face, viscera and limbs. When congenital vertical talus is identified prenatally, a thorough search for additional anomalies is indicated. Fetal MRI can be a useful adjunct in confirming the diagnosis and further delineating additional anomalies, particularly in the brain and spine.

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Real-Time Clustered Multiple Signal Classification (RTC-MUSIC)

Abstract

Magnetoencephalography (MEG) and electroencephalography provide a high temporal resolution, which allows estimation of the detailed time courses of neuronal activity. However, in real-time analysis of these data two major challenges must be handled: the low signal-to-noise ratio (SNR) and the limited time available for computations. In this work, we present real-time clustered multiple signal classification (RTC-MUSIC) a real-time source localization algorithm, which can handle low SNRs and can reduce the computational effort. It provides correlation information together with sparse source estimation results, which can, e.g., be used to identify evoked responses with high sensitivity. RTC-MUSIC clusters the forward solution based on an anatomical brain atlas and optimizes the scanning process inherent to MUSIC approaches. We evaluated RTC-MUSIC by analyzing MEG auditory and somatosensory data. The results demonstrate that the proposed method localizes sources reliably. For the auditory experiment the most dominant correlated source pair was located bilaterally in the superior temporal gyri. The highest activation in the somatosensory experiment was found in the contra-lateral primary somatosensory cortex.

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Clinical grade manufacturing of genetically modified, CAR-expressing NK-92 cells for the treatment of ErbB2-positive malignancies

Abstract

Background

The NK-92/5.28.z cell line (also referred to as HER2.taNK) represents a stable, lentiviral-transduced clone of ErbB2 (HER2)-specific, second-generation CAR-expressing derivative of clinically applicable NK-92 cells. This study addresses manufacturing-related issues and aimed to develop a GMP-compliant protocol for the generation of NK-92/5.28.z therapeutic doses starting from a well-characterized GMP-compliant master cell bank.

Materials and methods

Commercially available GMP-grade culture media and supplements (fresh frozen plasma, platelet lysate) were evaluated for their ability to support expansion of NK-92/5.28.z. Irradiation sensitivity and cytokine release were also investigated.

Results

NK-92/5.28.z cells can be grown to clinically applicable cell doses of 5 × 10⁸ cells/L in a 5-day batch culture without loss of viability and potency. X-Vivo 10 containing recombinant transferrin supplemented with 5% FFP and 500 IU/mL IL-2 in VueLife 750-C1 bags showed the best results. Platelet lysate was less suited to support NK-92/5.28.z proliferation. Irradiation with 10 Gy completely abrogated NK-92/5.28.z proliferation and preserved viability and potency for at least 24 h. NK-92/5.28.z showed higher baseline cytokine release compared to NK-92, which was significantly increased upon encountering ErbB2(+) targets [GZMB (twofold), IFN-γ (fourfold), IL-8 (24-fold) and IL-10 (fivefold)]. IL-6 was not released by NK cells, but was observed in some stimulated targets. Irradiation resulted in upregulation of IL-8 and downregulation of sFasL, while other cytokines were not impacted.

Conclusion

Our concept suggests NK-92/5.28.z maintenance culture from which therapeutic doses up to 5 × 10⁹ cells can be expanded in 10 L within 5 days. This established process is feasible to analyze NK-92/5.28.z in phase I/II trials.

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Iterative hard thresholding for model selection in genome-wide association studies

ABSTRACT

A genome-wide association study (GWAS) correlates marker and trait variation in a study sample. Each subject is genotyped at a multitude of SNPs (single nucleotide polymorphisms) spanning the genome. Here, we assume that subjects are randomly collected unrelateds and that trait values are normally distributed or can be transformed to normality. Over the past decade, geneticists have been remarkably successful in applying GWAS analysis to hundreds of traits. The massive amount of data produced in these studies present unique computational challenges. Penalized regression with the ℓ₁ penalty (LASSO) or minimax concave penalty (MCP) penalties is capable of selecting a handful of associated SNPs from millions of potential SNPs. Unfortunately, model selection can be corrupted by false positives and false negatives, obscuring the genetic underpinning of a trait. Here, we compare LASSO and MCP penalized regression to iterative hard thresholding (IHT). On GWAS regression data, IHT is better at model selection and comparable in speed to both methods of penalized regression. This conclusion holds for both simulated and real GWAS data. IHT fosters parallelization and scales well in problems with large numbers of causal markers. Our parallel implementation of IHT accommodates SNP genotype compression and exploits multiple CPU cores and graphics processing units (GPUs). This allows statistical geneticists to leverage commodity desktop computers in GWAS analysis and to avoid supercomputing. Availability: Source code is freely available at http://ift.tt/2axHkms.

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Iterative hard thresholding for model selection in genome-wide association studies

ABSTRACT

A genome-wide association study (GWAS) correlates marker and trait variation in a study sample. Each subject is genotyped at a multitude of SNPs (single nucleotide polymorphisms) spanning the genome. Here, we assume that subjects are randomly collected unrelateds and that trait values are normally distributed or can be transformed to normality. Over the past decade, geneticists have been remarkably successful in applying GWAS analysis to hundreds of traits. The massive amount of data produced in these studies present unique computational challenges. Penalized regression with the ℓ₁ penalty (LASSO) or minimax concave penalty (MCP) penalties is capable of selecting a handful of associated SNPs from millions of potential SNPs. Unfortunately, model selection can be corrupted by false positives and false negatives, obscuring the genetic underpinning of a trait. Here, we compare LASSO and MCP penalized regression to iterative hard thresholding (IHT). On GWAS regression data, IHT is better at model selection and comparable in speed to both methods of penalized regression. This conclusion holds for both simulated and real GWAS data. IHT fosters parallelization and scales well in problems with large numbers of causal markers. Our parallel implementation of IHT accommodates SNP genotype compression and exploits multiple CPU cores and graphics processing units (GPUs). This allows statistical geneticists to leverage commodity desktop computers in GWAS analysis and to avoid supercomputing. Availability: Source code is freely available at http://ift.tt/2axHkms.

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A Pilot Study of Perceived Mouth Dryness, Perceived Swallowing Effort, and Saliva Substitute Effects in Healthy Adults Across the Age Range

Abstract

Xerostomia, or perceived mouth dryness, increases with advancing age, but its influence on swallowing effort is unknown. This study: (1) quantified relationships among age, perceived sense of swallowing effort, and ratings of perceived mouth dryness, and (2) examined changes in swallowing effort following application of a gel-based saliva substitute in healthy participants. This was a cross-sectional observational study and data were collected from attendees of a community healthy aging fair. Forty-two healthy participants (mean age = 65 years; 20 female) were enrolled. Each participant rated perceived effort with swallowing and perceived mouth dryness on a 10-cm horizontal, undifferentiated line. After participants applied a gel-based saliva substitute (Biotene^® Oral Balance) to their tongue and oral mucosa, they rated perceived effort with swallowing again. Age was associated with greater perceived mouth dryness (r = 0.37, p < 0.03) but not with perceived swallowing effort (r = 0.16, p = 0.32). Perceived mouth dryness was associated with greater perceived swallowing effort (r = 0.62, p < 0.001). Perceived swallowing effort declined following application of the salivary substitute (mean difference = 9.39 mm, p < 0.002). Age was found to be a significant predictor of perceived mouth dryness (p < .02); and perceived mouth dryness was found to significantly predict perceived swallow effort (p < .001). Perceived mouth dryness increased with advancing age, but perceived swallowing effort did not. Regardless of age, participants with higher levels of perceived mouth dryness also reported more perceived effort with swallowing suggesting a role for adequate oral lubrication in this perception. Even in healthy participants, use of a gel-based saliva substitute lowered perceived swallowing effort.

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Analysis of Factors Affecting the Longevity of Voice Prosthesis Following Total Laryngectomy with a Review of Literature

Abstract

Tracheoesophageal voice puncture (TEP) coupled with the use of voice prosthesis has been considered as the gold standard for speech rehabilitation in patients of advanced laryngeal/hypopharyngeal carcinomas, who have undergone a total laryngectomy with or without partial pharyngectomy. Although prosthetic voice rehabilitation is commonly practiced worldwide including India, there is a paucity of published Indian data, more so in the current era of organ conservation. This study included 60 laryngectomized patients with a prosthetic voice rehabilitation at a tertiary cancer center in South India between January 1, 2010 and December 31, 2013. Among the 60 patients, the primary site of cancer was the larynx in 43 patients and hypopharynx in the remaining 17. All patients had undergone a primary TEP insertion, 55 in the upfront setting and five in the salvage (post-radiation/chemo-radiation) setting. The ability to retain a successful trachea-esophageal speech on follow-up (median 15.5 months) in our series was around 82%. The mean device life of voice prosthesis in our patient cohort was 16 months. There was surprisingly no significant difference in the prosthesis device life on correlation with age, co-morbidities, habitat, literacy status, pre-operative tracheostomy, setting of surgery, and the extent of surgery. Our series has successfully demonstrated the safety and feasibility of using primary TEP coupled with the use of voice prosthesis for voice rehabilitation in properly selected and motivated patients of advanced laryngeal and hypopharyngeal carcinomas across all clinical settings. A mean device life of 16 months makes prosthetic voice rehabilitation, an attractive as well as a financially viable option for patients in a resource constrained setting.

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Comparison of Esophageal Function Tests in Chinese Patients with Functional Heartburn and Reflux Hypersensitivity

Objective. To investigate the differences in the results of esophageal function tests for functional heartburn (FH) and reflux hypersensitivity (RH). Methods. Patients with FH and RH and healthy volunteers (HVs) from the Department of Gastroenterology, Beijing Anzhen Hospital and Beijing Chao-Yang hospital, who underwent high-resolution manometry and impedance (HRIM), and 24-hour multichannel intraluminal impedance and pH recording (MII/pH) between 2014 and 2016, were enrolled in this study. Results. 36 HV, 147 FH patients, and 91 RH patients were enrolled. The postreflux swallow-induced peristaltic wave index (PSPW index) and mean nocturnal baseline impedance (MNBI) values were significantly lower in RH than in FH and HV. The ineffective esophageal motility (IEM), fragmented peristalsis rates, total bolus exposure, proximal total reflux events, and distal total reflux events were significantly greater in RH than in FH and HV. Conclusions. Compared to HV and FH patients, RH patients exhibited greater IEM and fragmented peristalsis rates, a greater total bolus exposure, more proximal total and distal total reflux events, and reduced chemical clearance and mucosal integrity. By using the above described parameters, HRIM and MII/pH assays could be used to correctly classify RH and FH and hence allow physicians to provide adequate relief from associated symptoms.

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An Accurate PSO-GA Based Neural Network to Model Growth of Carbon Nanotubes

By combining particle swarm optimization (PSO) and genetic algorithms (GA) this paper offers an innovative algorithm to train artificial neural networks (ANNs) for the purpose of calculating the experimental growth parameters of CNTs. The paper explores experimentally obtaining data to train ANNs, as a method to reduce simulation time while ensuring the precision of formal physics models. The results are compared with conventional particle swarm optimization based neural network (CPSONN) and Levenberg–Marquardt (LM) techniques. The results show that PSOGANN can be successfully utilized for modeling the experimental parameters that are critical for the growth of CNTs.

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An Adaptive and Time-Efficient ECG R-Peak Detection Algorithm

R-peak detection is crucial in electrocardiogram (ECG) signal analysis. This study proposed an adaptive and time-efficient R-peak detection algorithm for ECG processing. First, wavelet multiresolution analysis was applied to enhance the ECG signal representation. Then, ECG was mirrored to convert large negative R-peaks to positive ones. After that, local maximums were calculated by the first-order forward differential approach and were truncated by the amplitude and time interval thresholds to locate the R-peaks. The algorithm performances, including detection accuracy and time consumption, were tested on the MIT-BIH arrhythmia database and the QT database. Experimental results showed that the proposed algorithm achieved mean sensitivity of 99.39%, positive predictivity of 99.49%, and accuracy of 98.89% on the MIT-BIH arrhythmia database and 99.83%, 99.90%, and 99.73%, respectively, on the QT database. By processing one ECG record, the mean time consumptions were 0.872 s and 0.763 s for the MIT-BIH arrhythmia database and QT database, respectively, yielding 30.6% and 32.9% of time reduction compared to the traditional Pan-Tompkins method.

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Electronic Controlling on Nanotribological Properties of a Textured Surface by Laser Processing

The friction-reducing performance of surfaces with regular nanotextures is a key topic in surface engineering research. This paper presented a simple, easily controlled method for fabricating regular nanotextures on an electrodeposited Ni-Co alloy. The electronic controlling on the friction performance of a nanotexured surface was investigated by AFM. The results showed that the frictional force of a nanotexured surface can be controlled by an external electric field. Before laser processing, the friction initially increased with the bias voltage and then decreased after the bias voltage exceeded 1.0 V. Its friction forces can be changed more than 2 times under the different external electric field. After laser processing, the trend of the frictional force was reversed and its friction forces changed more than 12 times for the laser-processed sample with 0.18 J/cm2 laser power. The results also showed that the friction force decreased when using different nanotextures in an external electric field.

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Low Levels of Usual Physical Activity Are Associated with Higher 24 h Blood Pressure in Type 2 Diabetes Mellitus in a Cross-Sectional Study

The aim of this study is to evaluate the association between usual physical activity and 24 h blood pressure (BP) profile in people with type 2 diabetes mellitus (DM). This is a cross-sectional study of 151 participants with type 2 DM. Usual physical activity was assessed by step counting and self-reported questionnaire. BP was measured in office and by 24 h ambulatory BP monitoring (ABPM; 24 h, daytime and nighttime). Mean participant age was 61.1 ± 8.4 years, 64% was women, and mean duration of diabetes was 14.3 ± 8.5 years. Ninety-two percent of participants had hypertension, and office BP was 138 ± 18/78 ± 10 mmHg. Inverse correlations were observed between step count and 24 h BP (systolic, ; ), daytime BP (systolic, ; ), and nighttime BP (pulse pressure, ; ). People were categorized into tertiles of daily step count, and the 1st tertile had higher 24 h systolic BP, daytime systolic BP, daytime mean BP, and daytime systolic BP load than those in the other tertiles, even after adjusting for age and HbA1c. Participants with type 2 DM and low levels of physical activity exhibit higher 24 h and daytime systolic ambulatory BP values as compared with those who performed more steps per day, even after adjustments for confounding factors.

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High Prevalence of Autoimmune Diabetes and Poor Glycaemic Control among Adults in Madagascar: A Brief Report from a Humanitarian Health Campaign in Ambanja

Madagascar is a geographically isolated country considered a biodiversity hotspot with unique genomics. Both the low-income and the geographical isolation represent risk factors for the development of diabetes. During a humanitarian health campaign conducted in Ambanja, a rural city in the northern part of Madagascar, we identified 42 adult subjects with diabetes and compared their features to 24 randomly enrolled healthy controls. 42.9% () of diabetic subjects showed HbA1c values ≥ 9.0%. Unexpectedly, waist circumference and BMI were similar in people with diabetes and controls. Different from the healthy controls, diabetic subjects showed a low prevalence of obesity (5.7% versus 30%, ). Accordingly, we found a high prevalence of autoimmune diabetes as 12% of people with diabetes showed positivity for the autoantibody against glutamic acid decarboxylase. Diabetic subjects with positive autoantibody had higher HbA1c values (11.3 ± 4.1% versus 8.3 ± 2.6%, ) compared to diabetic subjects with negative autoantibody. In conclusion, here we describe the presence of diabetes and its features in a rural area of Northern Madagascar, documenting poor glycaemic control and a high prevalence of autoimmune diabetes. These data highlight that the diabetes epidemic involves every corner of the world possibly with different patterns and features.

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IJMS, Vol. 18, Pages 1901: The Supramolecular Buildup of Eumelanin: Structures, Mechanisms, Controllability

IJMS, Vol. 18, Pages 1901: The Supramolecular Buildup of Eumelanin: Structures, Mechanisms, Controllability

International Journal of Molecular Sciences doi: 10.3390/ijms18091901

Authors: Anne Büngeler Benjamin Hämisch Oliver Strube

Research on the supramolecular buildup of eumelanin has gained high momentum in the last years. Several new aspects regarding the involved structures and mechanisms have been established, which has led to a better understanding of the entire process. This review intends to provide a clearly laid-out summary of previous and new findings regarding structures, mechanisms, and controllability. With respect to materials applications, the aspect of controllability is of supreme importance. A focus of this review is therefore set on a novel method with high potential for specific synthesis of various, isolated particle morphologies. Finally, open questions and possibilities for their elucidation are discussed.

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IJMS, Vol. 18, Pages 1907: Intestinal and Circulating MicroRNAs in Coeliac Disease

IJMS, Vol. 18, Pages 1907: Intestinal and Circulating MicroRNAs in Coeliac Disease

International Journal of Molecular Sciences doi: 10.3390/ijms18091907

Authors: Cristina Felli Antonella Baldassarre Andrea Masotti

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play a key role in the pathogenesis of autoimmune and gastrointestinal diseases. Previous studies have revealed that miRNAs are dysregulated in intestinal biopsies of patients affected by coeliac disease (CD). Combined bioinformatics analyses of miRNA expression profiles and mRNA target genes as classified by Gene Ontology, are powerful tools to investigate the functional role of miRNAs in coeliac disease. However, little is still known about the function of circulating miRNAs, their expression level compared to tissue miRNAs, and whether the mechanisms of post-transcriptional regulation are the same of tissue miRNAs. In any case, if we assume that a cell-cell communication process has to occur, and that circulating miRNAs are delivered to recipient cells, we can derive useful information by performing target predictions. Interestingly, all of the mRNA targets of dysregulated miRNAs reported in the literature (i.e., miR-31-5p, miR-192, miR-194, miR-449a and miR-638) belong to several important biological processes, such as Wnt signaling, cell proliferation and differentiation, and adherens junction pathways. Although we think that these predictions have to be necessarily confirmed by "wet-lab" data, the miRNAs dysregulated during the development of CD could be potentially involved in the pathogenesis of coeliac disease and their correlation with circulating miRNAs offers new possibilities to use them as disease biomarkers.

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IJMS, Vol. 18, Pages 1908: Dietary Phenethyl Isothiocyanate Protects Mice from Colitis Associated Colon Cancer

IJMS, Vol. 18, Pages 1908: Dietary Phenethyl Isothiocyanate Protects Mice from Colitis Associated Colon Cancer

International Journal of Molecular Sciences doi: 10.3390/ijms18091908

Authors: Yi Liu Moul Dey

We have previously reported alleviation of dextran sodium sulfate (DSS)-induced ulcerative colitis signs in phenethyl isothiocyanate (PEITC)-treated mice. Here we investigated chemoprotective activities of PEITC in mice with Azoxymethane-DSS induced colitis associated colon carcinogenesis. We also examined the molecular mediators associated with the PEITC effects using relevant cell lines. A 0.12% PEITC-enriched mouse-diet reduced mucosal and submucosal inflammation as well as glandular atypia by 12% and the frequency of adenocarcinoma by 17% with a concomitant improvement in overall disease activity indices compared to the diseased control group. Lipopolysaccharide-induced in vitro up-regulation of key mediators of inflammation, immune response, apoptosis, and cell proliferation were attenuated by 10 μM PEITC. Three of these mediators showed concentration-dependent reduction in respective mRNAs. Furthermore, PEITC inhibited Nuclear factor kappa B1 (NFκB1) proteins in a concentration-dependent manner. The NFκB1 mRNA expression inversely correlated (r = −0.940, p = 0.013) with tri-methylation of lysine 27 on histone 3 near its promoter region in a time-dependent manner. These results indicate that PEITC may slow down the development of colon carcinogenesis in an inflammatory intestinal setting which is potentially associated with epigenetic modulation of NFκB1 signaling.

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Absolute quantification of microparticles by flow cytometry in ascites of patients with decompensated cirrhosis: a cohort study

Microparticles (MPs) are small (

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