Cyclical Stretching Induces Excess Intracellular Ca2+ Influx in Human Keloid-Derived Fibroblasts In Vitro.

BACKGROUND: The incidence of keloids is higher in the case of darker skin. It is more common in the parts exposed to stretching (thorax, abdomen, and joints). Cyclical stretching reportedly induced each Ca2+ spike through differential mechanosensitive channels in human synovial and dermal fibroblasts. Therefore, the authors hypothesized that cyclical stretching also induces a specific Ca2+ spike in keloid-derived fibroblasts. METHODS: This in vitro study compared the intracellular calcium dynamics induced by cyclical stretching between control (human dermal fibroblasts) and keloid (human keloid-derived fibroblasts) groups. Each group was exposed to two-dimensional stretch using an originally developed stretch microdevice. Intracellular Ca2+ was observed for 5 minutes, including 30 seconds of baseline, under a fluorescent confocal laser microscope. The intracellular Ca2+ concentration was evaluated every 0.5 second using the fluorescence intensity ratio. A positive cellular response was defined as a rise of the ratio by greater than or equal to 20%. The normal response cutoff value was determined by receiver operating characteristic analysis. RESULTS: The keloid groups were significantly more responsive than the control groups (15.7% versus 8.2%; P = 0.029). In the cellular response-positive cells, the keloid groups reached significantly higher intracellular Ca2+ concentration peaks than the control groups (2.20 versus 1.26; P = 0.0022). The cutoff value was 1.77, and 10.4% of the keloid-derived fibroblasts exhibited a hyper-Ca2+ spike above the normal range. CONCLUSIONS: Keloid-derived fibroblasts with a hyper-Ca2+ spike might constitute a keloid-specific subpopulation. Hereafter, the authors will study whether the normalization of excessive intracellular Ca2+ concentration leads to keloid treatment in vivo. CLINICAL RELEVANCE STATEMENT: This study result provided a clue to the onset mechanism of keloids, which the authors hope will lead to the development of new therapy in the future.

SIZE-SPECIFIC DOSE ESTIMATES IN FETAL COMPUTED TOMOGRAPHY.

During fetal computed tomography (CT) imaging, because of differences in the pregnancy period and scanning conditions, different doses of radiation are absorbed by the fetus. We propose a correction coefficient for determining the fetal size-specific dose estimate (SSDE) from the CT dose index (CTDI) displayed on the console at tube voltages of 80-135 kVp. The CTDIs corresponding to pregnant women and fetuses were evaluated using a Monte Carlo (MC) simulation, and the ratio of these CTDIs was defined as the Fetus-factor. When the effective diameter of a fetus was approximately 10 cm, the Fetus-factor was 1.0. The estimated pregnant SSDE was multiplied by the Fetus-factor to estimate the fetal SSDE, which was compared with the fetal dose obtained by the MC simulation of the image of the fetal CT examination. The fetal dose could be estimated with an error of 31.5% in fetal examinations conducted using helical CT.

Evaluation of exposure dose in fetal computed tomography using organ-effective modulation.

Organ-effective modulation (OEM) is a computed tomography scanning technique that reduces the exposure dose to organs at risk. Ultrasonography is commonly used for prenatal imaging, but its reliability is reported to be limited. Radiography and computed tomography (CT) are reliable but pose risk of radiation exposure to the pregnant woman and her fetus. Although there are many reports on the exposure dose associated with fetal CT scans, no reports exist on OEM use in fetal CT scans. We measured the basic characteristics of organ-effective modulation (X-ray output modulation angle, maximum X-ray output modulation rate, total X-ray output modulation rate, and noise modulation) and used them in a Monte Carlo simulation to evaluate the effect of this technique on fetal CT scans in terms of image quality and exposure dose to the pregnant woman and fetus. Using ImPACT MC software, Monte Carlo simulations of OEMON and OEMOFF were run on 8 cases involving fetal CT scans. We confirmed that the organ-effective modulation X-ray output modulation angle was 160°; the X-ray output modulation rate increased with increasing tube current; and no modulation occurred at tube currents of 80 mA or below. Our findings suggest that OEM has only a minimal effect in reducing organ exposure in pregnant women; therefore, it should be used on the anterior side (OEMON,front) to reduce the exposure dose to the fetus.

VOLUME CT DOSE INDEX AND DOSE-LENGTH PRODUCT VALUES ACCORDING TO FACILITY SIZE IN JAPAN.

The aim of this study was to investigate differences in volume computed tomography dose index (CTDIvol) and dose-length product (DLP) values according to facility size in Japan. A questionnaire survey was sent to 3000 facilities throughout Japan. Data from each facility were collected including bed number, computed tomography (CT) scan parameters employed and the CTDIvol and/or DLP values displayed on the CT scanner during each examination. The CTDIvol and DLP for 11 adult and 6 paediatric CT examinations were surveyed. Comparison of CTDIvol and DLP values of each examination according to facility size revealed key differences in CT dose between small and large facilities. This study highlights the importance of lowering the dose of coronary artery examination with contrast agent in smaller facilities and of lowering the dose of adult and paediatric head CT without contrast agent in larger facilities. The results of this study are valid in Japan.

OPTIMISATION OF SWALLOWING CT EXAMINATION: DOSE REDUCTION AND IMAGE QUALITY.

This study sought to optimise the swallowing computed tomography (SCT) scan protocol for use with the new wide-area detector-row CT (ADCT) scanner and to estimate patient dose in terms of the organ-absorbed dose and the effective dose. The conventional ADCT (ADCTViSION) and the new ADCT (ADCTGENESIS) scanner were compared using: (1) the organ-absorbed dose and the effective dose, with a phantom study, (2) the detailed organ-absorbed doses of the neck region, using a Monte Carlo simulation and (3) a relative visual quality analysis. The effective energy differed significantly between the ADCTViSION (50 keV) and the ADCTGENESIS (57 keV). The effective doses were 2.9 and 1.9 mSv, respectively. Compared with the ADCTViSION, the absorbed dose was reduced by 34% with the ADCTGENESIS. With the ADCTGENESIS, the tube current could be reduced from 40 to 30 mA. With the optimised scan protocol, a further 25% dose reduction can be achieved.

Diagnostic reference levels and achievable doses for common computed tomography examinations: Results from the Japanese nationwide dose survey.

OBJECTIVE:: To propose a new set of Japanese diagnostic reference levels (DRLs) and achievable doses (ADs) for 2017 and to verify the usefulness of Japanese DRLs (DRLs 2015) for CT, by investigating changes in the volume CT dose index (CTDIvol) from 2014 to 2017. METHODS:: Detailed information on the CT scan parameters used throughout Japan were obtained by questionnaire survey. The CTDIvol and dose-length product for the 11 commonest adult and 6 commonest paediatric CT examinations were surveyed and compared with 2014 data and DRLs 2015. RESULTS:: Evaluations of adult head (helical), and abdomen and pelvis without contrast agent, paediatric chest without contrast agent, and abdomen and pelvis without contrast agent showed a slightly lower mean CTDIvol in 2017 than in 2014 (t-test, p < 0.05). The interquartile range of CTDIvol for all 2017 examinations was lower than in 2014. CONCLUSIONS:: This study verified the lower mean, 75th percentile, and interquartile range by investigating changes in the CTDIvol from 2014 to 2017. The DRLs 2015 contributed to CT radiation dose reduction. ADVANCES IN KNOWLEDGE:: The widespread implementation of iterative reconstruction algorithms and low-tube voltage in CT scanners is likely to facilitate further reduction in the CT radiation dose used in Japan. Although radiological technologists may require further education on appropriate CTDIvol and DLP usage, the DRLs 2015 greatly contributed to the reduction of the CT radiation dose used in Japan.

SWALLOWING COMPUTED TOMOGRAPHY: DOSE ESTIMATION IN A PHANTOM STUDY CONDUCTED AT VARIOUS PATIENT RECLINING ANGLES.

Swallowing computed tomography (SCT) is a relatively new technique for the morphological and kinematic analyses of swallowing. However, no optimal scan protocols are available till date. We conducted the present SCT study to estimate the patient dose at various patient reclining positions. A RANDO phantom with a thermoluminescent dosemeter was placed on a hard Table board in a semi-reclining position at the centre and off-centre. According to predetermined scan protocols, irradiation was performed to acquire scanograms at reclining angles of 55° and 65°. The effective dose was the lowest at the centre 45° (3.8 mSv) reclining angle. Comparison between the off-centre (4.6 mSv at 55°, 6.8 mSv at 65°) and centre (4.5 mSv, 5.8 mSv) values suggested that the off-centre position is undesirable with regard to the patient dose. Accordingly, we believe that SCT methods must be revised on the basis of these factors.

PATIENT EXPOSURE DURING PLAIN RADIOGRAPHY AND MAMMOGRAPHY IN JAPAN IN 1974-2014.

We investigated changes in the entrance skin dose (ESD) and the mean glandular dose (MGD) during plain radiography or mammography in Japan from 1974 to 2014. Surveys regarding the conditions used for plain radiography and mammography were performed throughout Japan in 1974, 1979, 1989, 1993, 1997, 2001, 2003, 2007, 2011 and 2014. The anatomical regions considered were categorised as follows: skull anteroposterior (AP), lumbar AP, lumbar lateral (LAT), pelvis (AP), ankle, chest posteroanterior (PA), Guthmann (lateral pelviography for pregnant women), infant hip joint and mammography. The doses for all anatomical regions decreased from 1974 to 1993. The MGD for mammography remained low from 1993 to 2014, and the ESDs for chest (PA) radiography trended upward. After the 2000s, the use of digital imaging increased in Japan. This is the first long-term study to examine changes in ESDs and MGDs in Japan.

[Analysis of Scattered Radiation in an Irradiated Body by Means of the Monte Carlo Simulation: Back-scatter Factors of Diagnostic X-rays in the Incident Surface Which is Not Flat].

To obtain patient entrance surface dose in X-ray photography, a calculation method based on measured exposure or air kerma radiated from X-ray tube is generally used. Two factors are necessary for this calculation: (1) exposure/air kerma to absorb dose conversion factor and (2) back-scatter factor (BSF) based on X-ray quality and on field size. These BSFs are commonly obtained by interpolation from existent data which were given for a water phantom whose entrance surface is flat. Since patient's surface in X-ray photograph is not flat, some error may occur when existent BSF is used in this calculation. In this article, BSF for water phantom with cylindrical surface and elliptic cylinder surface were calculated by means of the Monte Carlo simulation. And these BSFs were compared with BSF for flat surface phantom. As a result (1) radius of curvature of cylindrical phantom or horizontal axis of elliptic cylinder phantom is smaller, (2) half value layer of X-ray is larger, (3) field size is larger, difference of these BSF with that for flat surface phantom tends to be larger. Maximum difference by calculation condition assumed in this article was more than 10%. The cause of this difference is because scattering volume in irradiated body of cylindrical or elliptic cylinder phantom is smaller than flat surface phantom. To obtain patient entrance surface dose more precisely, it is necessary to use BSF respectively calculated for phantom resembling patient's body such as cylindrical or elliptic cylinder phantom by means of the Monte Carlo simulation.

Effective radiation doses of CT examinations in Japan: a nationwide questionnaire-based study.

OBJECTIVE: The aims of this study were to estimate the effective radiation doses from CT examinations of both adults and children in Japan and to study the impact of various scan parameters on the effective doses. METHODS: A questionnaire, which contained detailed questions on the CT scan parameters employed, was distributed to 3000 facilities throughout Japan. For each scanner protocol, the effective doses for head (non-helical and helical), chest and upper abdomen acquisitions were estimated using ImPACT CT Patient Dosimetry Calculator software v. 1.0.4 (St George's Hospital, London, UK). RESULTS: The mean effective doses for chest and abdominal examinations using 80-110 kV were significantly lower than those using 120 kV. However, there was no statistically significant difference in the mean effective doses for head scans between facilities employing 80-110 kV and 120 kV. In chest and abdominal examinations, the mean effective doses using CT scanners from Western manufacturers [Siemens (Forchheim, Germany), Philips (Eindhoven, Netherlands) and GE Medical Systems (Milwaukee, WI)] were significantly lower than those of examinations using Japanese scanners [Hitachi (Kashiwa, Japan) and Toshiba (Otawara, Tochigi, Japan)], except for in paediatric chest examinations. CONCLUSION: The mean effective doses for adult head, chest and abdominal CT examinations were 2.9, 7.7 and 10.0 mSv, respectively, whereas the corresponding mean effective doses for paediatric examinations were 2.6, 7.1 and 7.7 mSv, respectively. ADVANCES IN KNOWLEDGE: Facilities using CT scanners by Western manufacturers commonly adopt low-tube-voltage techniques, and low-tube-voltage CT may be useful for reducing the radiation doses to the patients, particularly for the body region.

Myosin-II-mediated directional migration of Dictyostelium cells in response to cyclic stretching of substratum.

Living cells are constantly subjected to various mechanical stimulations, such as shear flow, osmotic pressure, and hardness of substratum. They must sense the mechanical aspects of their environment and respond appropriately for proper cell function. Cells adhering to substrata must receive and respond to mechanical stimuli from the substrata to decide their shape and/or migrating direction. In response to cyclic stretching of the elastic substratum, intracellular stress fibers in fibroblasts and endothelial, osteosarcoma, and smooth muscle cells are rearranged perpendicular to the stretching direction, and the shape of those cells becomes extended in this new direction. In the case of migrating Dictyostelium cells, cyclic stretching regulates the direction of migration, and not the shape, of the cell. The cells migrate in a direction perpendicular to that of the stretching. However, the molecular mechanisms that induce the directional migration remain unknown. Here, using a microstretching device, we recorded green fluorescent protein (GFP)-myosin-II dynamics in Dictyostelium cells on an elastic substratum under cyclic stretching. Repeated stretching induced myosin II localization equally on both stretching sides in the cells. Although myosin-II-null cells migrated randomly, myosin-II-null cells expressing a variant of myosin II that cannot hydrolyze ATP migrated perpendicular to the stretching. These results indicate that Dictyostelium cells accumulate myosin II at the portion of the cell where a large strain is received and migrate in a direction other than that of the portion where myosin II accumulated. This polarity generation for migration does not require the contraction of actomyosin.

Effects of the surface pressure on the formation of Langmuir-Blodgett monolayer of nanoparticles.

The effects of the surface pressure on the particle arrangement of Langmuir-Blodgett (LB) monolayers of alkanethiol-capped gold nanoparticles were studied. The LB monolayers were prepared from a highly concentrated particle solution, which increases film fabrication efficiency but readily causes small particle voids in the particle array. Overcompressing the LB monolayer to a high surface pressure restructured the particles and eliminated the voids. When the gold particles capped by dodecanethiol were 8.5 nm in diameter, the particle arrangement was vastly improved and a wafer-scale LB monolayer was transferred onto a substrate at the surface pressure of 20 mN/m.