Статті в журналах: "MC3D"

1

Green, Thomas D., David C. Montefiori, and Ted M. Ross. "Enhancement of Antibodies to the Human Immunodeficiency Virus Type 1 Envelope by Using the Molecular Adjuvant C3d." Journal of Virology 77, no. 3 (February 1, 2003): 2046–55. http://dx.doi.org/10.1128/jvi.77.3.2046-2055.2003.

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ABSTRACT DNA vaccines expressing the envelope (Env) protein of the human immunodeficiency virus have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, the murine and human homologues of the complement component, C3d, were used in a DNA vaccine to enhance the titers of antibody to Env. Initially, plasmids expressing a secreted form of Env (sgp120) fused to one, two, or three copies of the murine homologue of C3d (mC3d) were constructed. Mice were inoculated with four vaccinations of DNA or two DNA vaccinations, followed by two boosts of affinity-purified gp120 protein. Analyses of titers demonstrated that multiple copies of mC3d coupled to sgp120 induced long-lasting, high-titer anti-Env antibody. Priming mice with sgp120-mC3d-DNA, followed by inoculation of purified gp120 protein, elicited the strongest antibody titers; however, the avidity maturation of the antibody was accelerated in the mice inoculated with sgp120-mC3d3-DNA. In addition, DNAs expressing sgp120 fused to three copies of the human homologue of C3d (hC3d3) efficiently enhanced the anti-Env antibody in rabbits. Lastly, antisera from both mice and rabbits vaccinated with DNA expressing sgp120-C3d3 elicited higher titers of neutralizing antibody than did nonfused forms of Env. These results indicate that C3d, conjugated to sgp120, enhances the antibody responses to Env compared to non-C3d fused forms of Env, and this approach may be one way to overcome the poor ability of DNA vaccines to generate antibodies to Env.

2

Jian, Feng Xu, Pooya Hadian, Stephen Doyle, Simon Molyneux, and Hongfeng Wu. "Major geological surfaces of the Exmouth Plateau from the new Broadband PreSDM reprocessed 3D seismic data with full waveform inversion." APPEA Journal 62, no. 2 (May 13, 2022): S442—S448. http://dx.doi.org/10.1071/aj21049.

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The Barrow Sub-basin and Exmouth Plateau, of Australia’s North West Shelf, contain Australia’s largest gas reserves, underpinning the three major LNG facilities, including Gorgon, Wheatstone and Pluto. In addition, there remains significant near-field exploration potential such as the Sasanof prospect. While there is full 3D seismic coverage in the basin, the existing 3D surveys are of different vintages covering only parts of the basin with diverse acquisition and processing parameters. Multi-Client Resources has produced an extensive 3D seismic reprocessing project (BEX-MC3D) incorporating 23 legacy 3D surveys to provide a seamless 25 570 km2 3D dataset. The BEX-MC3D was processed from field tape through DUG Technology’s advanced Broadband PreSDM processing sequence with Full Waveform Inversion (FWI) imaging. The BEX-MC3D provides one continuous superlative 3D dataset covering almost the entire Barrow Sub-basin and the Exmouth Plateau. Major geological surfaces corresponding to key tectonic events from overburden to reservoirs have been interpreted from the BEX-MC3D Priority area in the current study. These high-fidelity imaged surfaces form a basin-wide framework for: (1) rapid exploration lead and prospect identification through the creation of trap and reservoir visualisations; (2) improved reservoir connectivity analysis and modelling of producing and discovered fields to support better reservoir management and field development decisions; and (3) improved understanding of basin-burial history for reservoir quality and geo-mechanical property prediction. This paper will present and discuss major geological surfaces in the context of future exploration lead/prospect identification, reservoir characterisation for field development and management, and improving overall understanding of the basin history.

3

Bower, Joseph F., Xinzhen Yang, Joseph Sodroski, and Ted M. Ross. "Elicitation of Neutralizing Antibodies with DNA Vaccines Expressing Soluble Stabilized Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers Conjugated to C3d." Journal of Virology 78, no. 9 (May 1, 2004): 4710–19. http://dx.doi.org/10.1128/jvi.78.9.4710-4719.2004.

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ABSTRACT DNA vaccines expressing the envelope (Env) of human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating high-titer, long-lasting immune responses. Oligomeric or trimeric (gp140) forms of Env that more closely mimic the native proteins on the virion are often more effective immunogens than monomeric (gp120) envelopes. In this study, several forms of Env constructed from the HIV-1 isolate YU-2 (HIV-1YU-2) were tested for their immunogenic potential: a trimeric form of uncleaved (−) Env stabilized with a synthetic trimer motif isolated from the fibritin (FT) protein of the T4 bacteriophage, sgp140YU-2(−/FT), was compared to sgp140YU-2(−) without a synthetic trimerization domain, as well as to monomeric gp120YU-2. DNA plasmids were constructed to express Env alone or fused to various copies of murine C3d (mC3d). BALB/c mice were vaccinated (day 1 and week 4) with DNA expressing a codon-optimized envelope gene insert, alone or fused to mC3d. Mice were subsequently boosted (week 8) with the DNA or recombinant Env protein. All mice had high anti-Env antibody titers regardless of the use of mC3d. Sera from mice vaccinated with DNA expressing non-C3d-fused trimers elicited neutralizing antibodies against homologous HIV-1YU-2 virus infection in vitro. In contrast, sera from mice inoculated with DNA expressing Env-C3d protein trimers elicited antibody that neutralized both homologous HIV-1YU-2 and heterologous HIV-1ADA, albeit at low titers. Therefore, DNA vaccines expressing trimeric envelopes coupled to mC3d, expressed in vivo from codon-optimized sequences, elicit low titers of neutralizing antibodies against primary isolates of HIV-1.

4

Wolf, S. "MC3D–3D continuum radiative transfer, Version 2." Computer Physics Communications 150, no. 2 (February 2003): 99–115. http://dx.doi.org/10.1016/s0010-4655(02)00675-6.

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5

Molyneux, Simon, and Stephen Doyle. "Salt in the Vulcan sub-basin, NW Australia: observations from high-quality 3D seismic data and implications for palaeogeography." APPEA Journal 61, no. 2 (2021): 684. http://dx.doi.org/10.1071/aj20068.

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The Vulcan sub-basin is one of the few places in Australia where tectonic features (i.e. diapirs) associated with a mobile substrate can be found. In this presentation one of these features, the Paqualin diapir, and its environs will be described and discussed using the new regional NOVAR MC3D prestack depth migrated seismic dataset. The extent of the NOVAR MC3D seismic dataset makes it possible, for the first time, to integrate the observation of c. 600m of interbedded halite and anhydrite in the Paqualin-1 well, local fault geometries indicative of the movement of a mobile layer and regional tectonic features consistent with the presence of a mobile substrate. In this presentation the observations will be integrated with global analogues, regional palaeogeographic interpretations to refine models for the origin and spatiotemporal distribution of mobile layers in the Vulcan sub-basin.

6

Raverdy, Bruno, Renaud Meignen, Libuse Piar, Stephane Picchi, and Tanguy Janin. "Capabilities of MC3D to investigate the coolability of corium debris beds." Nuclear Engineering and Design 319 (August 2017): 48–60. http://dx.doi.org/10.1016/j.nucengdes.2017.04.005.

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7

Berthoud, G. "Models and validation of particulate debris coolability with the code MC3D-REPO." Nuclear Engineering and Design 236, no. 19-21 (October 2006): 2135–43. http://dx.doi.org/10.1016/j.nucengdes.2006.03.060.

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8

Kokalj, Janez, Mitja Uršič, Matjaž Leskovar, Libuse Piar, and Renaud Meignen. "Modelling of debris bed reflooding in PEARL experimental facility with MC3D code." Nuclear Engineering and Design 330 (April 2018): 450–62. http://dx.doi.org/10.1016/j.nucengdes.2018.02.016.

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9

Meignen, Renaud, and Tanguy Janin. "On the Analysis and Evaluation of Direct Containment Heating with the Multidimensional Multiphase Flow Code MC3D." Science and Technology of Nuclear Installations 2010 (2010): 1–13. http://dx.doi.org/10.1155/2010/289792.

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In the course of a postulated severe accident in an NPP, Direct Containment Heating (DCH) may occur after an eventual failure of the vessel. DCH is related to dynamical, thermal, and chemical phenomena involved by the eventual fine fragmentation and dispersal of the corium melt out of the vessel pit. It may threaten the integrity of the containment by pressurization of its atmosphere. Several simplified modellings have been proposed in the past but they require a very strong fitting which renders any extrapolation regarding geometry, material, and scales rather doubtful. With the development of multidimensional multiphase flow computer codes, it is now possible to investigate the phenomenon numerically with more details. We present an analysis of the potential of the MC3D code to support the analysis of this phenomenon, restricting our discussion to the dynamical processes. The analysis is applied to the case of French 1300 MWe PWR reactors for which we derive a correlation for the corium dispersal rate for application in a Probabilistic Safety Analysis (PSA) level 2 study.

10

Meilland, Antony, Sameer Kanaan, Marcelo Borges Fernandes, Olivier Chesneau, Florentin Millour, Philippe Stee, and Bruno Lopez. "Resolving the dusty circumstellar environment of the A[e] supergiant HD 62623 with the VLTI/MIDI." Proceedings of the International Astronomical Union 6, S272 (July 2010): 406–7. http://dx.doi.org/10.1017/s1743921311010945.

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AbstractHD 62623 is one of the very few A-type supergiants showing the B[e] phenomenon. We studied the geometry of its circumstellar envelope in the mid-infrared using the VLTI/MIDI instrument. Using the radiative transfer code MC3D, we managed to model it as a dusty disk with an inner radius of 3.85 AU, an inclination angle of 60°, and a mass of 2 × 10−7M⊙. It is the first time that the dusty disk inner rim of a supergiant star exhibiting the B[e] phenomenon is significantly constrained. The inner gaseous envelope likely contributes up to 20% to the total N band flux and acts like a reprocessing disk. Finally, the hypothesis of a stellar wind deceleration by the companion gravitational effect remains the most probable case since the bi-stability mechanism is not efficient for this star.

11

Boulard, P., J.-C. Jaboulay, J.-M. Martinez, and A. Zoia. "CONTRIBUTION OF THERMAL-HYDRAULICS SIMULATION TO CRITICALITY ANALYSIS OF A DEBRIS BED NUMERICAL MOCK-UP." EPJ Web of Conferences 247 (2021): 06010. http://dx.doi.org/10.1051/epjconf/202124706010.

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In this work, we evaluate the impact of simulating the thermal-hydraulics feedback in criticality risk assessment in a benchmark configuration corresponding to a simplified debris bed. We have recently discussed the coupling of the multi-phase thermal-hydraulics code MC3D with a reactivity evaluation scheme based on multi-point kinetics, which paves the way towards the assessment of the system behavior in terms of energy release. In this work, we analyze the system reactivity as a function of the thermal-hydraulics state of the system. For our investigation, we have considered a simplified cylindrical region and assumed that the fuel particles in the mixture consist of spheres of small diameter. The power has been adjusted to be representative of nuclear decay heat. For most of the examined configurations, the maximum reactivity lies below zero, which shows that the occurrence of a criticality event is likely to be excluded, thanks to the contribution of the decay heat of the fuel.

12

Uršič, Mitja, and Matjaž Leskovar. "Analysis of TROI-13 Steam Explosion Experiment." Science and Technology of Nuclear Installations 2008 (2008): 1–9. http://dx.doi.org/10.1155/2008/852047.

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The prediction of steam explosion inducing loads in nuclear power plants must be based on results of experimental research programmes and on simulations using validated fuel-coolant interaction codes. In this work, the TROI-13 steam explosion experiment was analysed with the fuel-coolant interaction MC3D computer code. The TROI-13 experiment is one of several experiments performed in the TROI research program and resulted in a spontaneous steam explosion using corium melt. First, the TROI-13 premixing simulations were performed to determine the initial conditions for the steam explosion simulations and to evaluate the melt droplets hydrodynamic fragmentation model. Next, a number of steam explosion simulations were performed, varying the steam explosion triggering position and the melt droplets mass participating in the steam explosion. The simulation results revealed that there is an important influence of the participating melt droplets mass on the calculated pressure loads, whereas the influence of the steam explosion triggering position on the steam explosion development was less expressive.

13

Musa, Hassan-Hussein, Wei-Juan Zhang, Jing Lv, Xiao-Li Duan, Yang Yang, Chun-Hong Zhu, Hui-Fang Li, Kuan-Wei Chen, Xia Meng, and Guo-Qiang Zhu. "The molecular adjuvant mC3d enhances the immunogenicity of FimA from type I fimbriae of Salmonella enterica serovar Enteritidis." Journal of Microbiology, Immunology and Infection 47, no. 1 (February 2014): 57–62. http://dx.doi.org/10.1016/j.jmii.2012.11.004.

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14

Silva-Gonzalez, Patricio, and Jarrad Grahame. "High-quality data from the Eendracht MC3D seismic survey gives insight about the hydrocarbon potential of the Carnarvon Basin." APPEA Journal 53, no. 2 (2013): 486. http://dx.doi.org/10.1071/aj12097.

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The Eendracht 3D multi-client seismic survey covers an area of about 8,000 km2. It is located in the Carnarvon Basin, one of Australia’s most hydrocarbons-prolific basins. The basin is filled with thick Paleozoic, Mesozoic, and Cenozoic sedimentary successions, deposited during multiple phases of extension and following the breakup of Gondwana. The most prominent structural trend is northeast—southwest with basins and sub-basins aligned as a consequence of the rifting event, which occurred during Jurassic to Early Cretaceous. Recent discoveries like Ragnar–1 and Tallaganda–1 show a working petroleum system and the high prospectivity of the Carnarvon Basin. The Eendracht survey covers a relatively less-explored but prolific area of the basin and provides a large volume of high-quality 3D seismic data. New technologies for acquisition and processing such as Fresnel Zone Bining, Interactive Azimuthal Anisotropy Analysis, and Diffracted Noise/Multiple Attenuation have been used. The hydrocarbon generation, migration, and entrapment in the Carnarvon Basin is controlled by Jurassic to Early Cretaceous syn- and post-rift structures, deposition, and Neogene reactivation. The most dominant successions in the Basin are Triassic to Lower Cretaceous sedimentary units. The Triassic Mungaroo Formation is the main reservoir found in the area covered by the Eendracht survey. Northeast–southwest-oriented extensional structures create potential traps for hydrocarbons and structures like horsts, tilted fault blocks, drapes, and fault-over anticlines can now be better visualised and analysed due to the 3D character of the Eendracht survey.

15

Paten, Tom. "The prospectivity of the Late Triassic intervals in the outboard Exmouth Plateau, Western Australia." APPEA Journal 60, no. 2 (2020): 742. http://dx.doi.org/10.1071/aj19173.

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The Exmouth Plateau is a deep-water plateau on the Australian continental margin underlain by 10–15 km of flat-lying, tilted and block-faulted Paleozoic–Mesozoic sedimentary rocks, which were deposited predominantly during periods of extension before continental break-up commenced in the middle Jurassic. The recent acquisition of the Mawson MC3D broadband seismic survey provides a modern, high-quality dataset located ~230 km to the north-west of Dampier, in the outboard Exmouth Plateau, in a relatively under-explored portion of the Northern Carnarvon Basin. The Late Triassic Mungaroo Formation is the primary reservoir target for the majority of the exploration in the Exmouth Plateau to date. A detailed investigation into the reservoir potential and prospectivity of the Mungaroo Formation is possible by utilising this modern dataset. The high-quality data presents a high-resolution view of the Rhaetian carbonate reef platforms and pinnacle reef complexes that are present within the Mawson survey footprint, revealing an under-explored play type within the region. The development of a detailed stratigraphic framework through the Late Triassic–Jurassic, combined with the use of attribute analyses and amplitude versus offset products can help de-risk identified prospects and highlight further prospectivity during the exploration process.

16

Yan, H., M. M. El Gomati, D. P. Chu, M. G. Dowsett, M. Prutton, and D. K. Wilkinson. "Mc3D: A three-dimensional Monte Carlo system simulating image contrast in surface analytical scanning electron microscopy I-Object-oriented software design and tests." Scanning 20, no. 6 (December 6, 2006): 465–84. http://dx.doi.org/10.1002/sca.1998.4950200607.

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17

Parker, Scott L., and Matthew J. McGirt. "Determination of the Minimum Improvement in Pain, Disability, and Health State Associated With Cost-Effectiveness." Neurosurgery 71, no. 6 (September 14, 2012): 1149–55. http://dx.doi.org/10.1227/neu.0b013e318271ebde.

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ABSTRACT BACKGROUND: Minimum clinical important difference (MCID) has been adopted as the smallest improvement in patient-reported outcome needed to achieve a level of improvement thought to be meaningful to patients. OBJECTIVE: To use a common MCID calculation method with a cost-utility threshold anchor to introduce the concept of minimum cost-effective difference (MCED). METHODS: Forty-five patients undergoing transforaminal lumbar interbody fusion for degenerative spondylolisthesis were included. Outcome questionnaires were administered before and 2 years after surgery. Total cost per quality-adjusted life-year (QALY) gained was calculated for each patient. MCED was determined from receiver-operating characteristic curve analysis with a cost-effective anchor of < $50 000/QALY and < $75 000/QALY. MCID was determined with the health transition item as the anchor. RESULTS: Significant improvement was observed 2 years after transforaminal lumbar interbody fusion for all outcome measures. Mean total cost per QALY gained at 2 years was $42 854. MCED was greater than MCID for each outcome measure, meaning that a greater improvement was required to represent cost-effectiveness than a clinically meaningful improvement to patients. The area under the receiver-operating characteristic curve was consistently ≥ 0.70 with both cost-effective anchors, suggesting that outcome change scores were accurate predictors of cost-effectiveness. Mean cost per QALY gained was significantly lower for patients achieving compared with those not achieving an MCED in visual analog scale for leg pain ($43 560 vs $112 087), visual analog scale for back pain ($41 280 vs $129 440), Oswestry Disability Index ($30 954 vs $121 750), and EuroQol 5D ($35 800 vs $189 412). CONCLUSION: MCED serves as the smallest improvement in an outcome instrument that is associated with a cost-effective response to surgery. With the use of cost-effective anchor of < $50 000/QALY, MCED after transforaminal lumbar interbody fusion was 4 points for visual analog scale for low back pain, 3 points for visual analog scale for leg pain, 22 points for Oswestry Disability Index, and 0.31 QALYs for EuroQol 5D.

18

Yoon, Jung A., Mun Jang, Jai Won Chang, and Eun Kyoung Lee. "Minimal Change in Nephrotic Syndrome Associated with Mixed Connective Tissue Disease." Korean Journal of Medicine 95, no. 6 (December 1, 2020): 409–12. http://dx.doi.org/10.3904/kjm.2020.95.6.409.

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Mixed connective tissue disease (MCTD) is a rheumatologic disorder that has combined features of systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis with the anti-U1 ribonucleoprotein (RNP) antibody. Although renal involvement is not included in any of the diagnostic criteria, it has been observed in 20% of MCTD patients. The most common renal disease is immune complex nephropathy, histologically classified as membranous glomerulonephritis, but minimal change disease (MCD) is very rare and has only been reported once previously. A previously healthy 33-year-old woman presented with generalized edema, puffy hands, arthralgia, and Raynaud’s phenomenon. We diagnosed MCD with proteinuria (> 9 g/day) and hypoalbuminemia (< 1.0 g/dL) by renal biopsy, and MCTD with a simultaneously high titer of the anti-U1 RNP antibody. The patient was treated with 200 mg/day cyclosporine and 30 mg/day prednisolone. The proteinuria and hypoalbuminemia normalized 2 months later. We report a patient with severe MCD associated with MCTD.

19

Bunch, Mark, Ric Daniel, Mark Lawrence, Greg Browne, Saju Menacherry, Tess Dance, and Malcolm Arnot. "Multi-scale characterisation of the Paaratte Formation, Otway Basin, for CO2 injection and storage." APPEA Journal 52, no. 2 (2012): 664. http://dx.doi.org/10.1071/aj11078.

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A resurgent interest in the gas potential of the Gulf of Papua has been enhanced by the recent announcement of developing new LNG facilities in Port Moresby. Petroleum Geo-Services (PGS) has recently acquired a 6,000-km2Multi-Client 3D (MC3D) survey in the gulf. Although most of the discoveries in PNG are from the highland areas, the gulf is a proven hydrocarbon province with gas/condensate accumulations previously discovered in several reef build-ups. It is thought that sediments from the Papuan Fold Belt produced clastic dominated deltas in the Gulf area. Although this play is untested offshore, there is evidence these sandy facies exist and could contain hydrocarbons. On the first phase of acquisition/interpretation, an efficient screening workflow called Prospect Scanner, developed to highlight areas of AVO effects in large 3D seismic datasets, was tested. It uses pre-stack seismic time migrated (PSTM) gathers to extract AVO attributes that are then inverted to derive relative acoustic and shear impedance volumes. Using idealised cross-plots, the relationship between Vp/Vs ratio and the Ip values gives a good indication of the fluid and lithology of the tested interval. The results are loaded into a conventional interpretation package for interpretation/visualisation. Prospect Scanner has highlighted previously undrilled turbidite and basin floor fan prospects in the region. The Vp/Vs versus Ip cross-plot shows clustering ofthe sand anomaly and good separation from the majority of the plot. These points correspond to the idealised location for a gas sand. Past concerns about lateral prediction of reservoir presence and quality associated with the basin floor fans can be addressed through this workflow.

20

Harrington, Amanda, Cyrille Reiser, Bob Burmaz, and Rod Reed. "Amplitude-versus-offset (AVO) screening in frontier basins: an example from the Gulf of Papua, Papua New Guinea." APPEA Journal 52, no. 2 (2012): 701. http://dx.doi.org/10.1071/aj11115.

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A resurgent interest in the gas potential of the Gulf of Papua has been enhanced by the recent announcement of developing new LNG facilities in Port Moresby. Petroleum Geo-Services (PGS) has recently acquired a 6,000-km2 Multi-Client 3D (MC3D) survey in the gulf. Although most of the discoveries in PNG are from the highland areas, the gulf is a proven hydrocarbon province with gas/condensate accumulations previously discovered in several reef build-ups. It is thought that sediments from the Papuan Fold Belt produced clastic dominated deltas in the Gulf area. Although this play is untested offshore, there is evidence these sandy facies exist and could contain hydrocarbons. On the first phase of acquisition/interpretation, an efficient screening workflow called Prospect Scanner, developed to highlight areas of AVO effects in large 3D seismic datasets, was tested. It uses pre-stack seismic time migrated (PSTM) gathers to extract AVO attributes that are then inverted to derive relative acoustic and shear impedance volumes. Using idealised cross-plots, the relationship between Vp/Vs ratio and the Ip values gives a good indication of the fluid and lithology of the tested interval. The results are loaded into a conventional interpretation package for interpretation/visualisation. Prospect Scanner has highlighted previously undrilled turbidite and basin floor fan prospects in the region. The Vp/Vs versus Ip cross-plot shows clustering of the sand anomaly and good separation from the majority of the plot. These points correspond to the idealised location for a gas sand. Past concerns about lateral prediction of reservoir presence and quality associated with the basin floor fans can be addressed through this workflow.

21

Patruno, Rosa, Ilaria Marech, Nicola Zizzo, Michele Ammendola, Patrizia Nardulli, Claudia Gadaleta, Marcello Introna, et al. "C-Kit Expression, Angiogenesis, and Grading in Canine Mast Cell Tumour: A Unique Model to Study C-Kit Driven Human Malignancies." BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/730246.

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Canine cutaneous mast cell tumour (CMCT) is a c-Kit driven tumour sharing similar c-Kit aberrations found in human gastrointestinal stromal tumour. CMCT is classified into three forms: well- (G1), intermediately (G2) (more benign diseases), and poorly (G3) differentiated (malignant) forms. We assess a correlation between c-Kit status, grading, and angiogenesis in CMCTs to explore their potential significance in humans. C-Kit receptor (c-KitR) expression, microvascular density (MVD), and mast cell granulated and degranulated status density (MCGD and MCDD, resp.) were analyzed in 97 CMCTs, by means of histochemistry, immunohistochemistry double staining, and image analysis system. Data showed that predominantly diffuse cytoplasmic- and predominantly focal paranuclear- (Golgi-like) c-Kit protein (PDC-c-Kit and PFP-c-Kit, resp.) expression correlate with high MVD, G3 histopathological grade, and MCDD. Moreover, predominant cell membrane-c-KitR (PCM-c-KitR) expression status correlates with low MVD, G1-G2 histopathological grade, and MCGD. These findings underline the key role of c-Kit in the biopathology of canine MCTs, indicating a link between aberrant c-Kit expression, increased angiogenesis, and higher histopathological grade. CMCT seems to be a model to study contributions of c-Kit activated MCs in tumour angiogenesis and to evaluate the inhibition of MCs activation by means of c-Kit tyrosine kinase inhibitors, currently translated in humans.

22

Abouyahya, I., S. Liem, Z. Amoura, J. E. Fonseca, B. Chaigne, M. Cutolo, A. Doria, et al. "AB0675 Health related quality of life in patients with mixed connective tissue disease: A comparison with matched systemic sclerosis patients." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1465.2–1465. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2359.

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BackgroundMixed connective tissue disease (MCTD) is a systemic auto-immune disorder, being probably the least common among the connective tissue diseases. Symptoms can be severe and could affect health-related quality of life (HRQoL). Identification of the burden of MCTD patients is of key importance to provide appropriate pharmacological and non-pharmacological care. No reports on HRQoL have been published in adult patients with MCTD.ObjectivesTo perform an explorative study to evaluate HRQoL and its main determinants in MCTD patients, and compare HRQoL between MCTD and matched systemic sclerosis (SSc) patients.MethodsMCTD patients fulfilling the Kahn criteria and participating in the MCTD prospective follow-up cohort of the Leiden University Medical Center were included. In addition, SSc patients matched for age, gender and disease duration were included for comparison. Data on disease characteristics, functional disability and HRQoL were collected annually for both disease groups. HRQoL was evaluated using the 36-Item Short Form Health Survey (SF36) and EuroQol (EQ5D). At baseline, HRQoL, as reflected by SF36 mental component score (MCS), SF 36 physical component score (PCS) and EQ5D were compared between MCTD and SSc patients. For MCTD patients, factors associated with HRQoL at baseline were identified using linear regression and change in HRQoL over 3 years was evaluated using linear mixed models. In addition, characteristics of MCTD patients who showed worsening of MCS and/or had PCS superior to the minimal clinical important difference of three points were identified.ResultsThirty-four MCTD patients (121 visits; 82% female, mean age 42 years, median disease duration 45 months) and 102 SSc patients (424 visits; 82% female, mean age 45 years, median disease duration 49 months) were included. At baseline, MCTD-patients more often had ILD (47% vs. 34%, p=0.027), cardiac involvement (30% vs. 2%, p<0.001), synovitis (26% vs. 11%, p=0.004) and myositis (15% vs. 1%, p=0.001) compared to SSc patients, whereas SSc patients more often used immunosuppressive treatments except for hydroxychloroquine (MCTD:18% vs. SSc:7%, p=0.007).Baseline HRQoL in MCTD was comparable to HRQoL in SSc, with mean SF36-PCS of 40.2 (SD:9.1) and mean SF36-MCS of 44.9 (SD:9.9), which is (nearly) one standard deviation lower than the general Dutch population. The SF36 subscore “general health perception” was the most impacted in both groups (MCTD: 38.5 [SD:7.0], SSc: 39.9 [SD:8.9]). The median EQ5DNL was 0.38 (IQR:0.14 – 0.54) and comparable between SSc and MCTD.At baseline, in MCTD, ILD was significantly associated with SF36-PCS (β:6.98, 95% CI: 1.10 to 12.86) and SF36-MCS (β:-8.10, 95% CI:-14.93 to -1.26). Sclerodactyly was significantly associated with EQ5DNL (β:0.006; 95% CI:0.002 to 0.010) and SF36-PCS (β:0.12, 95% CI:0.03 to 0.21). No other significant associations were identified.Over time, in MCTD, both the SF36-MCS and SF36-PCS improved significantly (MCS: β:2.35/year [95% CI:0.58 to 4.13], PCS: β:1.34/year [95% CI:0.03 to 2.65), whereas EQ5DNL was stable. Explorative analyses did not reveal a specific clinical characteristic with significant impact on the change of HRQoL over time. With an MCID of 3 points on the MCS and PCS, 7 MCTD-patients worsened on the MCS and 3 on the PCS. Patients who showed worsening of MCS over time tended to be older, more often had ILD, sclerodactyly and GI complaints, and had worse exercise tolerance. All these differences did not reach statistical significance. The patients who decreased PCS more often had ILD (100% vs. 41%, p=0.015), and used glucocorticoids more often (33% vs. 0%, p=0.046), were slightly older and had a worse exercise tolerance as compared to those who showed a stable/improving PCS over time.ConclusionLike in SSc, HRQoL is significantly impaired in MCTD, especially the general health perception of patients. Cardiac involvement, ILD, age and worse functional disability might specifically impact HRQoL in MCTD. However, these associations need further evaluations in larger cohorts.Disclosure of InterestsNone declared

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Bianco, Lucas, James May, and Alan Nasypany. "Novel Approach to Treating Acute Hamstring Injury- Effects of Primal Reflex Release Technique." Clinical Practice in Athletic Training 2, no. 1 (March 5, 2019): 19–31. http://dx.doi.org/10.31622/2019/0001.5.

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Hamstring injuries have an occurrence rate of 3.05 per 1000 athlete exposures in intercollegiate athletics. Current clinical practice recommendations for rehabilitation of hamstring injuries are based on pathoanatomical muscle tissue healing timeframes. The purpose of this study was to examine the effects of modulating the nervous system with Primal Reflex Release Technique (PRRT) in patients clinically diagnosed with functional neuromuscular hamstring muscle-related disorder (FNHD). In this a priori case series , PRRT was utilized in four patients participating in intercollegiate, National Collegiate Athletic Association Division II, athletics to evaluate Numeric Pain Rating Scale (NRS) for current pain, Disablement of the Physically Active (DPA) scale, modified Patient Specific Functional Scale (PSFS), and Active Knee Extension Test (AKET). The initial pre-treatment to post-treatment average difference for NRS (3.25±2.5 points) and AKET (11±2.16°) improved by an amount that satisfied MCID and MCD respectively. The pre-treatment to one-week follow-up average difference for NRS (5.5±2.3 points), PSFS (4.75±2.5 points), and AKET (20.5±14°) improved by an amount that satisfied MCID or MCD. The average timeline for discharge to full unrestricted activity was 2.75 days. In the four patients classified with a functional neuromuscular muscle disorder, PRRT was utilized as the only manual therapy intervention. Through modulation of the nervous system, the outcomes reported by the patients were both meaningful and clinically significant. Based on the results and the current standard of care for similar patients , the need for further research into this paradigm is warranted. Hamstring injuries continue to be a significant clinical injury in the athletic patient population. A thorough evaluation and appropriate classification of muscle injury can help clinicians decided an effective treatment for the patient. Clinicians seeking to improve patient outcomes may benefit from considering a paradigm that modifies the neural allostatic loads.

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Nantavithya, Chonnipa, Kitwadee Saksornchai, Puntiwa Oonsiri, and Kanjana Shotelersuk. "Dosimetric study of three-dimensional conformal radiotherapy, electronic compensator technique, intensity-modulated radiation therapy and volumetric-modulated arc therapy in whole breast irradiation." Journal of Radiotherapy in Practice 16, no. 4 (May 9, 2017): 431–43. http://dx.doi.org/10.1017/s1460396917000243.

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AbstractBackgroundWhole breast irradiation is an essential treatment after breast-conserving surgery (BCS). However, there are some adverse effects from inhomogeneity and dose to adjacent normal tissues.ObjectiveAim of this study was to compare dosimetry among standard technique, three-dimensional conformal radiotherapy (3D-CRT), and advanced techniques, electronic compensator (ECOMP), inverse intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT).MethodsWhole breast irradiation treatment plans of patients who had underwent BCS and whole breast irradiation were re-planned with all four techniques. Clinical target volume was contoured according to the Radiation Therapy Oncology Group atlas for breast only in patients who had negative node or ductal carcinoma in situ and breast with chest wall for patients with positive node. Planning target volume was non-uniformly expanded. Dose prescription was 50 Gy in 25 fractions with 6 MV photon energy.ResultsIn total, 25 patients underwent whole breast irradiation with computed tomography simulation from November 2013 to November 2014 were included. Six patients with positive nodes were re-planned for breast with chest wall irradiation and 19 patients with negative nodes were re-planned for breast only irradiation. Primary outcome, radical dose homogeneity index (HI) of 3D-CRT, ECOMP, IMRT and VMAT were 0·865, 0·889, 0·890 and 0·866, respectively. ECOMP and IMRT showed significant higher HI than 3D-CRT (p-value<0·001). Secondary outcome, conformity index (CI) of advanced technique were significantly better than 3D-CRT. Lung V20, mean ipsilateral lung dose (MILD), mean heart dose (MHD), heart V25, heart V30 of advanced techniques were also lower than 3D-CRT. ECOMP had better mean lung dose (MLD), mean contralateral lung dose (MCLD) and mean contralateral breast dose (MCBD) when compared with 3D-CRT. Monitor units of advanced techniques were significantly higher than 3D-CRT.ConclusionsHI of ECOMP and IMRT were significantly higher than 3D-CRT technique. All advanced techniques showed statistically better in CI. Lung V20, MILD, heart V25 and heart V30 of advanced techniques were lower than 3D-CRT. However, only ECOMP showed decreased MLD, MHD, MCLD and MCBD when compared with 3D-CRT.

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Stauff, Anna, Ellen Schneider, and Frank Heckel. "2-MCPD, 3-MCPD and fatty acid esters of 2-MCPD, 3-MCPD and glycidol in fine bakery wares." European Food Research and Technology 246, no. 10 (July 1, 2020): 1945–53. http://dx.doi.org/10.1007/s00217-020-03546-4.

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Chong, C. L. G., Faizah Othman, and Farida Hussan. "Vascular Protective Effects of Morinda citrifolia Leaf Extract on Postmenopausal Rats Fed with Thermoxidized Palm Oil Diet: Evidence at Microscopic Level." International Journal of Vascular Medicine 2018 (September 5, 2018): 1–10. http://dx.doi.org/10.1155/2018/6317434.

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Atherosclerosis is now well understood as an inflammatory disease instead of lipid storage disorder; however, the conventional treatment is not targeted on treating the inflammation. Morinda citrifolia L. (Rubiaceae) leaf or noni leaf, which is a medicinal food (ulam) used in Traditional Malay Medicine to prevent chronic diseases, may have the potential to be formulated into a functional antiatherosclerotic agent. This study aimed to investigate the effectiveness of Morinda citrifolia leaf extract (MCLE) treatment at histological and ultrastructural level, comparing it with Simvastatin. Thirty-eight female Sprague Dawley rats were divided into five groups: Sham (Sham), ovariectomized (OVX), ovariectomized with Simvastatin 10 mg/kg (OVX+ST), ovariectomized with low dose MC 500 mg/kg (OVX+MCLD), and ovariectomized with high dose MC 1000 mg/kg (OVX+MCHD). Atherosclerosis was induced by producing oestrogen deficiency through ovariectomy and feeding with thermoxidized palm oil (TPO) diet for 12 weeks along with the treatment. The results revealed significantly (P<0.05) lower systolic blood pressure (SBP) in the group treated with MCHD compared to the untreated OVX, whereas the diastolic blood pressure (DBP) was significantly higher in the untreated OVX group compared to the Sham group. Treatment with MCHD also significantly lowered the total cholesterol (TC) level compared to the OVX. The OVX group showed significantly lower high-density lipoprotein (HDL) level compared to the Sham group. The untreated OVX group showed evident histological and ultrastructural features of vascular inflammation such as blood cells accumulation in the lumen, vacuolation of the endothelial cells, subendothelial space widening, elastic fibres disruption, increased intima media thickness (IMT), smooth muscle cells fragmentation, and perivascular adipose tissue (PVAT) deposition. All these pathological changes were less seen in the groups treated with MCLE. In conclusion, we reported the mechanism of antiatherosclerotic property of MCLE through lipids elimination and anti-inflammatory activity. In addition, we do not recommend the use of statin in the absence of dyslipidemia as it causes PVAT deposition.

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in ’t Veld, C. J. "MCAD-deficiëntie." Bijblijven 32, no. 8-9 (October 25, 2016): 533–34. http://dx.doi.org/10.1007/s12414-016-0180-z.

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MIKULÍKOVÁ, Renata, Zdeněk SVOBODA, Karolína BENEŠOVÁ, and Sylvie BĚLÁKOVÁ. "3-MCPD Process Contaminant in Malt." Kvasny Prumysl 64, no. 1 (February 15, 2018): 6–9. http://dx.doi.org/10.18832/kp201802.

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Haustein, Uwe-Frithjof. "MCTD - Mixed Connective Tissue Disease. MCTD - Mixed Connective Tissue Disease." Journal der Deutschen Dermatologischen Gesellschaft 3, no. 2 (February 2005): 97–104. http://dx.doi.org/10.1111/j.1610-0378.2005.04089.x.

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Pervadchuk, V., D. Vladimirova, D. Dektiarev, and A. Pesterev. "DESIGNING OF OPTIMAL STABILIZING REGULATOR IN THE MCVD PROCESS." Applied Photonics 4, no. 3 (September 29, 2017): 212–21. http://dx.doi.org/10.15593/2411-4367/2017.03.04.

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Bognár, Erzsébet, Gabriella Hellner, Andrea Radnóti, László Somogyi, and Zsolt Kemény. "Effect of Different Chlorine Sources on the Formation of 3-Monochloro-1,2-Propanediol and 2-Monochloro-1,3-Propanediol Fatty Acid Esters during Frying." Periodica Polytechnica Chemical Engineering 64, no. 4 (September 19, 2019): 523–29. http://dx.doi.org/10.3311/ppch.14137.

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Several studies indicated that chlorine salts provoke 3-monochloro-1,2-propanediol fatty acid esters (3-MCPD-FE) and 2-monochloro-1,3- propanediol fatty acid esters (2-MCPD-FE) formation in oils during frying. The amount of MCPD strongly depends on the type and the amount of chlorine salt. Food raw materials, additives themselves may contain several chlorine compounds, providing precursors for 2- and 3-MCPD-FE formation during frying. Then, the fat uptake can cause measurable concentrations in the fried food as well. This paper aims at screening chlorine compounds occurring in food industry. Influence of sodium chloride (NaCl), potassium chloride (KCl), calcium chloride (CaCl2), ferric chloride (FeCl3) and ammonium chloride (NH4Cl) on the formation of MCPD-FE was investigated, mimicking frying conditions (175-180 °C, atmospheric pressure), applying high oleic sunflower oil as frying medium. 2-MCPD-FE and 3-MCPD-FE were determined by using an indirect method based on alkaline-catalyzed transesterification and GC-MS analysis. As expected, the reference sample without using any chlorine salt resulted only slight increase in 3-MCPD-FE concentration, and no increase in 2-MCPD-FE concentration. In case of the stable salts minor formation was observed. At as high as 3 % dosage of NaCl and KCl 1.6 and 2.4 mg/kg 3-MCPD-FE generated, respectively. Adding CaCl2, NH4Cl and FeCl3 resulted in very strong MCPD-FE formation by both isomers (2- and 3-MCPD-FE) in this increasing order. 0.1 % FeCl3 generated 70 mg/kg 2-MCPD-FE and 238 mg/kg 3-MCPD-FE by the end of 8-hour heating.

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Doležal, M., J. Kertisová, Z. Zelinková, and J. Velíšek. "Analysis of Bread Lipids for 3-MCPD Esters." Czech Journal of Food Sciences 27, Special Issue 1 (June 24, 2009): S417—S420. http://dx.doi.org/10.17221/932-cjfs.

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Objective of this work was determination of processing contaminant known as 3-MCPD (3-chloropropane-1,2-diol) in its free and bound form in breads with defined parameters of processing. Selected and analysed were 24 samples, which represented two sets of breads produced in bakeries equipped with a continual line. In all cases determinations were carried out for breadcrumb and crust separately. The first set of samples were wheat-rye breads produced chronologically in ten days in the bakery Michelská pekárna, slightly different in temperatures and times of baking. The second set contained 14 samples of wheat-rye breads with a content of rye flour less than 40% differing in the yeast type and acidity. These breads were produced in the bakery Kontinua. The fat content was determined in all samples by Soxhlet extraction. Free and bound 3-MCPD was determined by gas chromatography–mass spectrometry method. Concentration of free 3-MCPD in samples was at interval < 9–54.5 μg/kg. Concentration of bound 3-MCPD was at interval 1.56–23.60 mg/kg of fat (i.e. 5.7–84.9 μg/kg of sample).

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MAEKAWA, Kazuyo, Yuko HAMADA, Motoyoshi MARUNO, Shigeo NONAKA, Fumio NAGAMINE, and Nobuyuki TAKASU. "MCTD with Pulmonary Hypertension." Nishi Nihon Hifuka 61, no. 4 (1999): 438–42. http://dx.doi.org/10.2336/nishinihonhifu.61.438.

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Dearlove, O. R., and R. Perkins. "MCAD deficiency and anaesthesia." Anaesthesia 50, no. 3 (March 1995): 265. http://dx.doi.org/10.1111/j.1365-2044.1995.tb04584.x.

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Aksenov, V. A., G. A. Ivanov, V. A. Isaev, and M. E. Likhachev. "MCVD of fluorosilicate glass." Inorganic Materials 46, no. 9 (August 29, 2010): 994–97. http://dx.doi.org/10.1134/s002016851009013x.

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Andresen, Brage Storstein, Allan Meldgaard Lund, David Michael Hougaard, Ernst Christensen, Birthe Gahrn, Mette Christensen, Peter Bross, et al. "MCAD deficiency in Denmark." Molecular Genetics and Metabolism 106, no. 2 (June 2012): 175–88. http://dx.doi.org/10.1016/j.ymgme.2012.03.018.

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Cohen, Elaine, Tom Lyche, and Richard F. Riesenfeld. "MCAD: Key historical developments." Computer Methods in Applied Mechanics and Engineering 199, no. 5-8 (January 2010): 224–28. http://dx.doi.org/10.1016/j.cma.2009.08.003.

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Lê Đình, Chi, Thượng Nguyễn Như, Tú Vũ Ngọc, Hồng Hảo Lê Thị та Sơn Trần Cao. "Xác định đồng thời các dạng ester của 3-MCPD và 2-MCPD trong sữa công thức bằng GC-MS/MS". Heavy metals and arsenic concentrations in water, agricultural soil, and rice in Ngan Son district, Bac Kan province, Vietnam 3, № 2 (10 червня 2020): 133–44. http://dx.doi.org/10.47866/2615-9252/vjfc.653.

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Nghiên cứu đã phát triển và thẩm định phương pháp xác định đồng thời các dạng ester của 3-MCPD và 2-MCPD trong sữa công thức bằng GC-MS/MS. Các ester của MCPD được chiết từ mẫu sữa công thức bằng hỗn hợp ethanol/n-hexane/diethyl ether (1/1/1, v/v/v), sau đó được xử lý với acid sulfuric để giải phóng dạng tự do. Các chất 3-MCPD và 2-MCPD dạng tự do và nội chuẩn đồng vị 3-MCPD-d5 and 2-MCPD-d5 được dẫn xuất với acid phenylboronic và sau đó dẫn xuất được phân tích bằng GC-MS/MS ở chế độ MRM. Cột tách được sử dụng là cột mao quản DB-5MS, khí mang là Heli ở tốc độ 1 mL/phút. Chế độ MRM đã được sử dụng để lựa chọn 1 ion mẹ và 2 ion con cho mỗi chất phân tích. Kết quả thẩm định cho thấy phương pháp đáp ứng các yêu cầu theo AOAC SMPR. Phương pháp đã được ứng dụng để xác định các ester của 3-MCPD và 2-MCPD trong các mẫu sữa công thức lấy ở một số tỉnh, thành phố của Việt Nam. Có 38,9% số mẫu phát hiện 3-MCPD ester và 34,7% số mẫu phát hiện 2-MCPD ester.

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LEVI, NOAH J., JOO YUN JUN, TUSHAR P. PATEL, ANDREW J. UHLMAN, ROBIN ROBERSON, and JACK A. YANOVSKI. "Liver-Specific Reactivation of MC3R Partially Reverses the Obesity of MC3R Deficiency." Diabetes 67, Supplement 1 (May 2018): 2017—P. http://dx.doi.org/10.2337/db18-2017-p.

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Doležal, M., P. Calta, and J. Velíšek. "Formation and decomposition of 3-chloropropane-1,2-diol in model systems." Czech Journal of Food Sciences 22, SI - Chem. Reactions in Foods V (January 1, 2004): S263—S266. http://dx.doi.org/10.17221/10677-cjfs.

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Model experiments were carried out using mixtures of 3-chloropropane-1,2-diol (3-MCPD), its precursor glycerol, NaCl, water and an emulsifier. The aim of this study was to simulate formation and decomposition of 3-MCPD at the surface layers of thermally processed foods containing naturally present or intentionally added salt. The formed 3-MCPD levels depend on temperature and reach the maximum value at 230°C. One kg of glycerol gives rise to about 50 mg of 3-MCPD, while about 0.6 mg of 3-MCPD arise at 100°C. The rate constants k1 of 3-MCPD formation from glycerol and constants k2 of 3-MCPD decomposition were calculated employing the first order reaction kinetics. The rate constants k2 of 3-MCPD degradation are higher than the respective constants of its formation. Other kinetic parameters (time of maximum concentration) were also calculated and the achieved results were discussed with respect to levels of 3-MCPD in foods.

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Bedenbaugh, Michelle N., Serena Sweet, Haley Mendoza-Romero, Samantha Brener, Sydney Hawkins, Gina Yu, Jessie Zimmermann, Patrick Sweeney, Roger Cone, and Richard Simerly. "28 Melanocortin 3 Receptor in Neural Circuits Linking Metabolic State with Reproduction and Growth." Journal of Animal Science 101, Supplement_3 (November 6, 2023): 231–32. http://dx.doi.org/10.1093/jas/skad281.280.

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Abstract Metabolic state must be communicated to the brain to regulate behavior, growth, nutrient partitioning and development to meet energetic demands. While it is clearly evident that reproduction and energy balance are closely intertwined, the neural circuits integrating these two processes are poorly understood. Recent functional data suggests the melanocortin 3 receptor (MC3R) mediates the exchange of information between reproductive and metabolic state. Additionally, females exhibit uniquely aberrant metabolic and reproductive phenotypes after deletion of MC3R. In this work, we aimed to characterize the role of MC3R neural circuits in linking metabolic state with reproduction and growth in females. We found that MC3R is expressed in brain regions known to have a role in the control of reproductive and metabolic state, including the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARH). In the ARH of female mice, significant differences in overall levels of Mc3r mRNA were not observed at postnatal day 16 (P16), P28 or P48, nor did the percentage of ARH Kiss1, Esr1, Sst, Pomc or Agrp neurons doubly-labeled for Mc3r appear to change during postnatal development. However, the percentage of ARH Ghrh neurons labeled for Mc3r significantly increased from P16 to P48. Thus, MC3R in the ARH may play a potential role in conveying metabolic signals critical for growth during development. In the AVPV of female mice, overall abundance of Mc3r mRNA was low at P16, but increased significantly by P28, and was further elevated in mature mice (P48). Additionally, the percentage of Kiss1- and Esr1-expressing neurons in the AVPV labeled for Mc3r increased significantly between P16 and P48, suggesting that Mc3r may have an important role in the timing of sexual maturation. In addition to the direct regulatory action of MC3R expressed in KISS1 neurons in the AVPV, the impact of MC3R signaling may also be transmitted transynaptically via direct neural projections from MC3R neurons to KISS1 neurons in the AVPV, or to GnRH neurons in the rostral preoptic area. Clearly labeled MC3R terminals were observed in close apposition to both KISS1 neurons in the AVPV, and GnRH neurons in the rostral medial preoptic area. Although both the GnRH and KISS1 neuronal populations appeared heavily innervated by MC3R neurons, the density of MC3R terminals onto KISS1 neurons appeared to be substantially greater than that onto GnRH neurons, suggesting that inputs to AVPV neurons may be particularly impactful on reproduction. Thus, MC3R may not only regulate the activity of KISS1 neurons in the AVPV directly, but may also function transynaptically as an important neurobiological substrate for coordination of metabolic state with sexual maturation and reproductive function.

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Chambers, Christopher V., William T. Leach, Kaitlyn Davis, and Ronald E. Myers. "Primary Care Provider Receptivity to Multi-Cancer Early Detection Test Use in Cancer Screening." Journal of Personalized Medicine 13, no. 12 (November 29, 2023): 1673. http://dx.doi.org/10.3390/jpm13121673.

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Multi-cancer early detection tests (MCEDs) are blood-based tests that detect biomarkers released or induced by cancer cells. If MCED tests are shown to be safe and effective in cancer screening, they are likely to be ordered and managed in primary care. To understand primary care providers’ support for and concerns about the implementation and management of MCED testing, the research team developed a cross-sectional survey that was sent to 939 primary care providers (physicians, residents/fellows, and advanced practice providers) in a large academic health system in the greater Philadelphia area. The survey included standard items used to assess provider background characteristics and to measure provider awareness of challenges related to MCED test use (7 items), perceived competence in MCED testing (5 items), and receptivity to MCED test use in the future (4 items). A total of 351 (37.4%) primary care providers completed the survey. Among respondents, the awareness of challenges in MCED testing (mean = 3.95, sd = 0.64), perceived competence (3.67, sd = 0.85), and receptivity to MCED use in practice (mean = 3.62, 0.75) were moderately high. Multiple regression was performed to identify factors associated with receptivity to MCED testing. We found that provider number of years in practice (DATA), awareness of challenges related to MCED testing (DATA), and perceived competence in MCED test use (DATA) were positively and significantly associated with receptivity to MCED test use in practice. An exploratory factor analysis extracted two components: receptivity to MCEDs and awareness of challenges. Surprisingly, these factors had a positive correlation (r = 0.124, p = 0.024). Providers’ perceived competence in using MCED tests and providers’ experience level were significantly associated with receptivity to MCED testing. While there was strong agreement with potential challenges to implementing MCEDs, PCPs were generally receptive to using MCEDs in cancer screening. Keeping PCPs updated on the evolving knowledge of MCEDs is likely critical to building receptivity to MCED testing.

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Ji, Ren-Lei, Lu Huang, Yin Wang, Ting Liu, Si-Yu Fan, Min Tao, and Ya-Xiong Tao. "Topmouth culter melanocortin-3 receptor: regulation by two isoforms of melanocortin-2 receptor accessory protein 2." Endocrine Connections 10, no. 11 (November 1, 2021): 1489–501. http://dx.doi.org/10.1530/ec-21-0459.

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Melanocortin-3 receptor (MC3R) is a regulator of energy homeostasis, and interaction of MC3R and melanocortin-2 receptor accessory protein 2 (MRAP2) plays a critical role in MC3R signaling of mammals. However, the physiological roles of MC3R in teleosts are not well understood. In this study, qRT-PCR was used to measure gene expression. Radioligand binding assay was used to study the binding properties of topmouth culter MC3R (caMC3R). Intracellular cAMP generation was determined by RIA, and caMC3R expression was quantified with flow cytometry. We showed that culter mc3r had higher expression in the CNS. All agonists could bind and stimulate caMC3R to increase dose dependently intracellular cAMP accumulation. Compared to human MC3R, culter MC3R showed higher constitutive activity, higher efficacies, and Rmax to alpha-melanocyte-stimulating hormone (α-MSH), des-α-MSH, and adrenocorticotrophic hormone. Both caMRAP2a and caMRAP2b markedly decreased caMC3R basal cAMP production. However, only caMRAP2a significantly decreased cell surface expression, Bmax, and Rmax of caMC3R. Expression analysis suggested that MRAP2a and MRAP2b might be more important in regulating MC3R/MC4R signaling during larval period, and reduced mc3r, mc4r, and pomc expression might be primarily involved in modulation of MC3R/MC4R in adults. These data indicated that the cloned caMC3R was a functional receptor. MRAP2a and MRAP2b had different effects on expression and signaling of caMC3R. In addition, expression analysis suggested that MRAP2s, receptors, and hormones might play different roles in regulating culter development and growth.

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Lippert, Rachel N., Kate L. J. Ellacott, and Roger D. Cone. "Gender-Specific Roles for the Melanocortin-3 Receptor in the Regulation of the Mesolimbic Dopamine System in Mice." Endocrinology 155, no. 5 (May 1, 2014): 1718–27. http://dx.doi.org/10.1210/en.2013-2049.

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The melanocortin-3 receptor (MC3R) and MC4R are known to play critical roles in energy homeostasis. However, the physiological functions of the MC3R remain poorly understood. Earlier reports indicated that the ventral tegmental area (VTA) is one of the highest sites of MC3R expression, and we sought to determine the function of the receptor in this brain region. A MC3R-green-fluorescent protein transgenic mouse and a MC3R knockout mouse strain were used to characterize the neurochemical identity of the MC3R neurons in the VTA and to determine the effects of global MC3R deletion on VTA dopamine (DA) homeostasis. We demonstrate that the MC3R, but not MC4R, is expressed in up to a third of dopaminergic neurons of the VTA. Global deletion of the MC3R increases total dopamine by 42% in the VTA and decreases sucrose intake and preference in female but not male mice. Ovariectomy restores dopamine levels to normal, but aberrant decreased VTA dopamine levels are also observed in prepubertal female mice. Because arcuate Agouti-related peptide/neuropeptide Y neurons are known to innervate and regulate VTA signaling, the MC3R in dopaminergic neurons provides a specific input for communication of nutritional state within the mesolimbic dopamine system. Data provided here suggest that this input may be highly sexually dimorphic, functioning as a specific circuit regulating effects of estrogen on VTA dopamine levels and on sucrose preference. Overall, this data support a sexually dimorphic function of MC3R in regulation of the mesolimbic dopaminergic system and reward.

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Gao, Boyan, Yanfang Li, Guoren Huang, and Liangli Yu. "Fatty Acid Esters of 3-Monochloropropanediol: A Review." Annual Review of Food Science and Technology 10, no. 1 (March 25, 2019): 259–84. http://dx.doi.org/10.1146/annurev-food-032818-121245.

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Fatty acid esters of 3-monochloropropane-1,2-diol (3-MCPD esters) are a new group of processing-induced chemical toxicants with possible nephrotoxicity and testicular toxicity. 3-MCPD esters have been detected in many food categories, including refined edible oils, bread, coffee, and infant formula. 3-MCPD esters have also been detected in human breast milk, indicating their possible absorption and distribution in human organs and tissues. 3-MCPD esters have become a food safety concern, and in 2013 the European Food Safety Authority estimated a tolerable daily value (TDI) of 2 μg/kg body weight (BW) for the amount of free 3-MCPD. This review summarizes the available information on 3-MCPD ester research, including the analytical methods, exposure biomarkers, absorption and metabolism, toxicities, formation mechanisms, and mitigation strategies as well as the occurrence of 3-MCPD esters in human foods. This review may serve as a scientific foundation for advancing our understanding of 3-MCPD esters and their food safety concerns.

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M Breitling-Utzmann, C., H. Hrenn, N. U Haase, and G. M Unbehend. "Influence of dough ingredients on 3-Mcpd formation in toast." Czech Journal of Food Sciences 22, SI - Chem. Reactions in Foods V (January 1, 2004): S25—S28. http://dx.doi.org/10.17221/10605-cjfs.

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The influences of both traditional dough ingredients like fat and salt and a commercially used baking agent on the formation of 3-chloropropane-1,2-diol (3-MCPD) during toasting of bread were investigated. Whereas varying the fat or salt contents within technologically practicable limits showed negligible effects on 3-MCPD formation, the baking agent turned out to have a crucial impact on generating 3-MCPD in toasted bread slices. We found considerable evidence that the baking agent’s main component saccharose was the major cause for its boosting the 3-MCPD formation. Emulsifiers like mono- and diacylglycerols or lecithin did not have any significant influence. 3-MCPD formation showed good correlation with the degree of browning of the bread slices; their 3-MCPD content increased exponentially towards dark brown coloured toasts. The relative proportions between 3-MCPD and 2-MCPD were an average of 3:1 in all samples. Dichloropropanols like e.g. 1,3-dichloropropan-2-ol could not be detected.

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Sweeney, Patrick, Michelle N. Bedenbaugh, Jose Maldonado, Pauline Pan, Katelyn Fowler, Savannah Y. Williams, Luis E. Gimenez, et al. "The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia." Science Translational Medicine 13, no. 590 (April 21, 2021): eabd6434. http://dx.doi.org/10.1126/scitranslmed.abd6434.

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Ablation of hypothalamic AgRP (Agouti-related protein) neurons is known to lead to fatal anorexia, whereas their activation stimulates voracious feeding and suppresses other motivational states including fear and anxiety. Despite the critical role of AgRP neurons in bidirectionally controlling feeding, there are currently no therapeutics available specifically targeting this circuitry. The melanocortin-3 receptor (MC3R) is expressed in multiple brain regions and exhibits sexual dimorphism of expression in some of those regions in both mice and humans. MC3R deletion produced multiple forms of sexually dimorphic anorexia that resembled aspects of human anorexia nervosa. However, there was no sexual dimorphism in the expression of MC3R in AgRP neurons, 97% of which expressed MC3R. Chemogenetic manipulation of arcuate MC3R neurons and pharmacologic manipulation of MC3R each exerted potent bidirectional regulation over feeding behavior in male and female mice, whereas global ablation of MC3R-expressing cells produced fatal anorexia. Pharmacological effects of MC3R compounds on feeding were dependent on intact AgRP circuitry in the mice. Thus, the dominant effect of MC3R appears to be the regulation of the AgRP circuitry in both male and female mice, with sexually dimorphic sites playing specialized and subordinate roles in feeding behavior. Therefore, MC3R is a potential therapeutic target for disorders characterized by anorexia, as well as a potential target for weight loss therapeutics.

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Park, Jeenah, Neeraj Sharma, and Garry R. Cutting. "Melanocortin 3 Receptor Has a 5′ Exon That Directs Translation of Apically Localized Protein From the Second In-Frame ATG." Molecular Endocrinology 28, no. 9 (September 1, 2014): 1547–57. http://dx.doi.org/10.1210/me.2014-1105.

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Melanocortin-3 receptor (MC3R) is a canonical MSH receptor that plays an essential role in energy homeostasis. Variants in MC3R have been implicated in obesity in humans and mice. However, interpretation of the functional consequences of these variants is challenging because the translational start site of MC3R is unclear. Using 5′ rapid amplification of cDNA ends, we discovered a novel upstream exon that extends the length of the 5′ untranslated region (UTR) in MC3R without changing the open-reading frame. The full-length 5′ UTR directs utilization of an evolutionarily conserved second in-frame ATG as the primary translation start site. MC3R synthesized from the second ATG is localized to apical membranes of polarized Madin-Darby canine kidney cells, consistent with its function as a cell surface mediator of melanocortin signaling. Expression of MC3R causes relocalization of melanocortin receptor accessory protein 2, an accessory factor for melanocortin-2 receptor, to the apical membrane, coincident with the location of MC3R. In contrast, protein synthesized from MC3R cDNAs lacking the 5′ UTR displayed diffuse cytosolic distribution and has no effect on the distribution of melanocortin receptor accessory protein 2. Our findings demonstrate that a previously unannotated 5′ exon directs translation of MC3R protein that localizes to apical membranes of polarized cells. Together, our work provides insight on the structure of human MC3R and reveals a new pathway for regulation of energy metabolism.

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Magouliotis, Dimitrios E., Metaxia Bareka, Arian Arjomandi Rad, Grigorios Christodoulidis, and Thanos Athanasiou. "Demystifying the Value of Minimal Clinically Important Difference in the Cardiothoracic Surgery Context." Life 13, no. 3 (March 6, 2023): 716. http://dx.doi.org/10.3390/life13030716.

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The aim of this review is to describe the different statistical methods used in estimating the minimal clinically important difference (MCID) for the assessment of quality of life (QOL)-related and clinical improvement interventions, along with their implementation in cardiothoracic surgery. A thorough literature search was performed in three databases (PubMed/Medline, Scopus, Google Scholar) for relevant articles from 1980 to 2022. We included articles that implemented and assessed statistical methods used to estimate the concept of MCID in cardiothoracic surgery. MCID has been successfully implemented in several medical specialties. Anchor-based and distribution-based methods are the most common approaches when evaluating the MCID. Nonetheless, we found only five studies investigating the MCID in the context of cardiothoracic surgery. Four of them used anchor-based approaches, and one used both anchor-based and distribution-based methods. MCID values were very variable depending on the methods applied, as was the clinical context of the study. The variables of interest were certain QOL measuring questionnaires, used as anchors. Multiple anchors and methods were applied, leading to different estimations of MCID. Since cardiothoracic surgery is related to important perioperative morbidity, MCID might represent an important and efficient adjunct tool to interpret clinical outcomes. The need for MCID methodology implementation is even higher in patients with heart failure undergoing cardiac surgery. More studies are needed to validate different MCID methods in this context.

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Divínová, V., M. Doležal, and J. Velíšek. "Free and bound 3-chloropropane-1,2-diol in coffee surrogates and malts." Czech Journal of Food Sciences 25, No. 1 (January 7, 2008): 39–47. http://dx.doi.org/10.17221/735-cjfs.

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The levels are reported of the free 3-chloropropane-1,2-diol (3-MCPD), its bound forms, the recognised precursors of 3-MCPD, and the factors influencing its formation in 5 selected coffee surrogates and 18 malts in the Czech Republic. The coffee surrogates had the free 3-MCPD level in the range of < 9.0 to 32 µg/kg while the highest amount was found in roasted barley. In malts, the free 3-MCPD levels were similarly low (< 9.0 to 45 µg/kg) being the highest in roasted malts (16-45 µg/kg). Nevertheless, the values found in either surrogates or malts, calculated after normalisation to 40% dry matter content, did not exceed the European Union limit of 20 µg/kg adopted for soy sauces and acid-HVP. The risk for consumers could arise from the bound 3-MCPD, its elevated levels having been found in both coffee surrogates and malts. In coffee surrogates, the bound 3-MCPD levels varied between 145−1184 µg/kg product; the highest level was found in roasted barley. The bound 3-MCPD levels exceeded the free 3-MCPD levels 32 to 81 times. In malts, the bound 3-MCPD levels ranged from 4.0−650 µg/kg, the highest amount having been found in roasted malts (463−650 µg/kg). The bound 3-MCPD levels exceeded the free 3-MCPD levels 0.4 to 36 times.

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