The 8th Yonsei-Nagoya University
Research Exchange Meeting on Health Sciences & Nursing
1st~3rd November, 2017

Yonsei University Wonju Campus
Wonju, Republic of Korea-1-

Table of Contents

1. Preface …………………………………………………………………………..….…………3
2. Welcoming remarks ………………………………………………………..….……….4
3. Schedule …………………………………………………………………………..…….……5
4. Organizing committee ………………………………………………………..….…...6
5. Abstract
A.

Physical Therapy ……………………………………………………………...7B.

Occupational Therapy ……………………………………………………21

C.

Radiological Technology ………………………………………………..39

D.

Biomedical Laboratory Science ……………………………………..59

E.

Nursing …………………………………………………………………………..81

6. List of participants…………………………………………………….……………….96-2-

Preface
As Dean of College of Health Sciences, it is my utmost pleasure to host 2017 Yonsei-Nagoya
University Research Exchange Meeting in Health Sciences (November 1-3rd, 2017) at the Yonsei
University Wonju Campus. On behalf of the Yonsei University Wonju Campus, I would like toextend my heartfelt welcome to the delegates from Nagoya University who take part in thisresearch exchange meeting. I believe that this meeting will be a unique forum to exchange ideas,
discuss not only the results of their research work but also matters of mutual interest andconcerns, and share experiences among professors and students between the two universities.

This is the 8th meeting jointly held by the two institutions, since the 1st meeting was held in
Nagoya University in 2010. I hope that this meeting is still useful for each other, and continue our
joint efforts in the future. Even if we don’t make any wonderful research output until now, thestudents have had wonderful experiences by this program. I hope to see continuously what wewill be able to produce and accomplish through this joint meeting.
As you know, Yonsei University is the best private university in Korea, since 1885 year. We havethe 132th anniversary at this year. And Wonju campus is the one of the three campuses of Yonsei
University (Shincho, Songdo and Wonju). The Wonju campus is focused on Health science fields.
The College of health science in Wonju campus is the first and best college among any otheruniversities in Korea.
I also hope that your visit to our campus will provide you with a great opportunity to get toknow Korea and the Korean people as well as experience Korean culture in a fragrant fallatmosphere. Now is the best time to see the very best and most beautiful autumn foliage. I once
again welcome all of you who are visiting Yonsei University Wonju Campus and I believe that yourvisit to our campus ensure for our bilateral cooperation and partnership between the two
institutions to closely work together in the years to come.

Thank you.

Haejong Lee, PhD
Dean, College of Health Sciences
Yonsei University-3-

Welcoming remarks
On behalf of the Yonsei University Wonju College of Medicine, I would like to extend a
warm-hearted welcome to you for taking the time to be here with us in this exchange
program.

It has been 5 years since the University of Nagoya and the Yonsei University agreed on acollaboration that would include our professors as well as our graduate students inresearch. I strongly believe that the students who had a chance to take part in our
exchange program could develop the skills and knowledge though academic, cultural,and research exchanges.

Nursing is the protection, promotion, and optimization of health and abilities, preventionof illness and injury, facilitation of healing, alleviation of suffering through the diagnosis
and treatment of human response, and advocacy in the care of individuals, families,
groups, communities, and populations. One of the goals of this program is to provide
students the global experience opportunities and be able to enhance the health ofindividuals as well as the local and global communities.

I look forward to seeing more students to be involved in this academic exchange andinternational exposure, which will help them to advance in their careers and pursue
academic ambitions in their chosen field.

I wish your stay in Wonju will be a pleasant and enriching experience and return homewith new insights and vigor.

Thank you very much.

Kang Hyun Lee, M.D., Ph.D.
Dean, Yonsei University Wonju College of Medicine-4-Schedule
November 2nd, 2017
Time

Schedule

10:00~10:45

Opening

Place
Mirae-hall #443

Ceremony
11:00~12:00

Presentation

Physical Therapy: Univ. Headquarters #223
Occupational Therapy: Baekun-hall #103
Radiological Sci. & Tech: Baekun-hall #534
Biological Lab. Sci.: Miae-hall #325

12:00~13:50

Lunch/ Executive

Meeting at Baekun-hall 4th FL, iBMW room

Committee
Meeting

14:00~17:00

Presentation

Physical Therapy: Univ. Headquarters #223
Occupational Therapy: Baekun-hall #103
Radiological Sci. & Tech: Baekun-hall #534
Biological Lab. Sci.: Miae-hall #325
Nursing: Jinri-hall #421 (College of Medicine
campus)Dinnerarranged by each dept.

-5-

Organizing Committee
Dean
Hae-Jong LEE
Vice Dean
Yong-Hyun CHUNG
Contact person
Sang-Hyun CHO

Dept. of Physical Therapy
Woo-Chol CHOI
Dept. of Occupational Therapy
Hae-Yean PARK
Dept. of Radiological Science and Technology
Chul-Hee MIN
Dept. of Biomedical Science and Laboratory
Ki-Jong RHEE
Dept. of Nursing
Ji-Hae CHOI

SponsorInstitute of Health Science
Yonsei University Wonju Campus-6-Abstract

Physical Therapy

-7-

-8-

2017 Yonsei-Nagoya University Joint Symposium on Physical Therapy
Date: November 2nd, 201711:00 – 11:05

Location: Univ. Headquarters #223

Opening remarks
Dr. H. S. Jeon (Yonsei Univ)

11:05 – 11:45

Session I

11:05 – 11:45

The effect of short foot exercise with different ankle position

Chair: Dr. H. S. Jeonon the EMG and medial longitudinal arch angle
H. B. Yoon (Yonsei Univ)
12:00 – 14:00

Lunch/Executive meeting

14:00 – 15:20

Session II

14:00 – 14:40

The relationship between six-minute walk distance and serum

Chair: Dr. Y. Uchiyama

amino acids in elderly people aged 75 or over: A crosssectional study
Y. Ishimaru (Nagoya Univ)
14:40 – 15:20

Physical function and self-perceived ability related to life
space mobility in community-dwelling older people
Y. Tsuchida (Nagoya Univ)
Break

15:30 – 16:50

Session III

15:30 – 16:10

Relationship between body function and structure and activity

Chair: Dr. S. H. Kim

based on ICF model with children with cerebral palsy
J. S. Hwang (Yonsei Univ)
16:10 – 16:50

Comparison of shoulder strength in males with and without
myofascial trigger points in the upper trapezius
H. A. Kim (Yonsei Univ)

16:50 – 16:55

Closing remarks
Dr. Y. Uchiyama (Nagoya Univ)

16:55 – 17:00

Commemorative photographing

17:00 -

Dinner at WoonChae (747-1993)*20 min presentation, followed by 20 min discussion for each speaker-9-Comparison of the Foot Muscle EMG and Medial Longitudinal Arch Angle during
Short Foot Exercises at Different Ankle Position
Hyeo-Bin Yoon, BPT, PT1), Ji-Hyun Kim, BPT, PT1), Joo-Hee Park, Msc, PT1), Hye-Seon Jeon, Ph.D, PT2)
1) Department of Physical Therapy, The Graduate School, Yonsei University2) Department of Physical Therapy, College of Health Science, Yonsei University
Introduction
The medial longitudinal arch (MLA), which is consisted ofseveral tarsal and metatarsal bones, functions that distributing
body weight and absorbing shock during walking (Franco,1987). It has been generally known that the height of MLA is
supported by both abductor hallucis (ABH) and extrinsic
muscles (Murley, Menz, & Landorf, 2009; O’Connor &Hamill, 2004; Jung et al., 2011). Insufficient muscular support
could lower the MLA when the body weight was applied tofoot.
Previous studies revealed that the short foot exercise (SFE) is
effective for the people with pronated foot by increasing theheight of MLA (Jung et al., 2011). Most of the research
related to short foot exercise simply evaluated the efficiency
of SFE using the enhanced ABH electromyography (EMG)
activation. However, Murley et al. (2009) reported that thepeople with pronated foot had increased activation of tibialis
anterior (TA) and decreased activation of peroneus longus(PL). Since the TA, PL and ABH are all involved insupporting MLA, the new experiment design examined the
EMG of selected muscles during SFE should be conducted forclarify the effect of SFE.
Therefore, we examined a modified short foot exercise(MSFE) with three different ankle joint angles to optimize theinvolvement of the foot extrinsic muscles together with ABH.
The purpose of this study was to clarify the effect of MSFE on
MLA angle and activation of both intrinsic and extrinsic
muscles, and to determine the best condition for a pronatedfoot.

angle of MLA between resting position and during SFE
position compared among the ankle position.
Data analysis: within subject one-way repeated ANOVA
was used to analyze the collected EMG data and angle of
MLA.

Figure 1. MSFE in three different ankle positions
Results
The root-mean square EMG activity of the ABH and TA wassignificantly greater in the DF position than in the NE and the
PF positions (p<0.01). The PL was most highly activated in
the DF position, but no statistical significance was detected(Figure 2.) The activation ratio of TA compared with ABH
was lowest in PF position (p<0.01), and highest in DF
position (not statistically significant). The activation ratio of
PL compared with ABH was highest in NE position andlowest in PF position (not statistically significant) (Figure 3.).
The subtracting value in angle of MLA tend to decreasesignificantly during the SFE in DF position, but this finding
doesn’t have statistical significance (Table 1.)

Materials and methods
Study design: This study was an experimental study tocompare the influence of different ankle position to theactivation of arch support muscles and the angle of MLA.
Participants: In this study, twenty healthy subjects (8 males;
12 females; age=22.3, height=167.8, mass=61.4, passive DF
ROM=35.12, passive PF ROM=47.89) with normal feet wererecruited from the local University.
Measurement: We used the Surface EMG (Noraxon
TeleMyo DTS, Noraxon Inc., Scottsdale, AZ, USA) to collectmuscle activation data of TA, PL, and ABH. The EMG data
were analyzed using the Noraxon MyoResearch 1.06 software(Noraxon Inc., Scottsdale, AXZ, USA). While conducting
SFE, the alternation of MLA angle was recorded by the
personal camera (Sony a500, Sony Korea, Seoul, South
Korea), and calculated using ImageJ software. Myo U6 wasused to clarify the location of ABH not for measurement.
Procedure: The subjects performed MSFE in sitting at threedifferent ankle positions [neutral (NL), dorsiflexion (DF) at
30º, and plantar flexion (PF) at 30º] (Figure 1.). During each
MSFE, we measured the activity of the TA, PL and ABH andthe angle of MLA. The three reflective markers were attachedon navicular tuberosity, the medial aspect of the firstmetatarsal head, and the medial side of the calcaneal bone.
When conducting SFE, the height of middle marker increased
and the distance between markers located in both ends
decreased, so the increased height of MLA had the common
mean with the decreased angle of MLA. Subtracting values in\- 10 -

arch angle during toe curl and short foot exercises. Physical
Therapy in Sport, 12(1), 30-35[3] Murley, G. S., Menz, H. B., & Landorf, K.B. (2009). Footposture influences the electromyographic activity of selected
lower limb muscles during gait. Journal of Foot and Ankle
Research, 2(1), 35.
[4] O’Connor, K. M., & Hamill, J. (2004). The role of selected
extrinsic foot muscles during running. Clinical Biomechanics,
19(1), 71–77.

Figure 2. The average activation of TA, PL and ABH
during MSFE in three different ankle positions

Figure 3. The ratio of extrinsic muscles compared with
ABH

Table 1. the angle of MLA during MSFE.
Discussion
The activation of ABH was highest in MSFE in ankle DF
condition, so this result could be interpreted as that SFE in DF
condition is the most effective exercise among the three
conditions including traditional exercise (e.g., SFE in a neutral
ankle joint). However, in terms of the ratio between extrinsic
and intrinsic muscle, the MSFE in PF condition could makeup for the pronated foot with altered muscle activation,
especially TA and PL effectively. Further longitudinalintervention studies are required
References[1] Franco, a H. (1987). Pes cavus and pes planus. Analyses
and treatment. Physical Therapy, 67(5), 688-694[2] Jung, D. Y., Kim, M. H., Koh, E. K., Kwon, O. Y., Cynn,
H. S., &Lee, W. H. (2011). A comparison in the muscle
activity of the abductor hallucis and the medial longitudinal- 11 -

The relationship between six-minute walk distance and serum amino acids in elderly
people aged 75 or over: A cross-sectional study
Yo Ishimaru1), Hironobu Ashikawa1), Takuji Adachi1), Shota Urano1), Yuko Ueda2), Jun Ueyama2), Sumio. Yamada3)
1. Department of Physical and Occupational Therapy, Graduate School of Medicine, Nagoya University, Nagoya, Japan
2. Department of Pathophysiological Laboratory Sciences, Graduate School of Medicine, Nagoya University, Nagoya, Japan
3. Department Rehabilitation Science, Graduate School of Medicine, Nagoya University, Nagoya, Japan
Introduction
Exercise capacity (EC), defined as maximum amount ofphysical exertion that a patient can sustain, is a well-known
prognostic factor in cardiac patients. EC, expressed asoxygen uptake, is determined mainly by cardiovascularperformance and skeletal muscle metabolism. In particular,
EC is reduced in patients with heart failure (HF) due toskeletal muscle abnormalities such as impaired energy
metabolism, fiber type transition and atrophy, as well as
cardiovascular dysfunction.
Numerous studies have demonstrated the effect of aminoacid (AA) supplement on improved EC, although theevidence in HF has not been well established. An anabolic
effect is considered as a major mechanism of this favorable
effect of AA. Moreover, AA also plays a key role in energy
production as substrates of citric acid cycle1. The citric acidcycle produces adenosine triphosphate by using various AAs
in addition to branched chain amino acids. Yet, previous
studies to address the effect of AA have mainly focused onbranched chain amino acid because of its close relationshipwith protein synthesis. Therefore, there is a lack of evidence
on the relationship between EC and detailed AA profile.
We hypothesized that AA profile is related to EC in HF
patients via energy metabolism, as well as muscle protein
synthesis. In this preliminary study, we examined therelationship between EC and AA profile in healthy
community-dwelling elderly people aged 75 or over using
metabolome analysis.
Methods
Study design and subjects
This cross-sectional study was performed as a secondary
study of a prospective cohort study undertaken by ourlaboratory. The inclusion criterion of the main cohort study iscommunity-dwelling elderly people aged 75 or over. The
study protocol was approved by the Ethics Committee of the
School of Health Sciences, Nagoya University (approval
number: 2012-0131). This secondary study was also
approved by the Ethics Committee of the School of Health
Sciences, Nagoya University (approval number: 16-509).
The subjects who participated in follow-up survey in 2015
were enrolled into the present study. The subjects with somemissing data were excluded.
Measurement of six-minute walk distance
We assessed six-minute walk distance (6MWD) as anindicator of EC. Preparations and procedures were conductedin accordance with the guidelines of American Thoracic
Society. Participants were asked to walk as long as possible
in six minutes. Walking aids were used if the participants
normally required these for daily walking.
Measurement of serum amino acids
Blood samples were collected to measure the AA(essential amino acid; EAA, non- essential amino acid;
NEAA, and other amino acids); 250µL was drawn from theserum obtained by centrifugation, and stored at -80℃ until
analysis.

Measurement of the AA was performed using liquid
chromatography–mass spectrometry (LC-MS) coupled withamino acid mixture standard solution type AN-Ⅱ and type B.
LC-MS analysis was run on an Agilent 1200 infinity LC
coupled with an Agilent 6430 Triple Quadrupole LC/MS
System (Agilent Technologies, Inc., Santa Clara, CA, USA).
Figure 1 shows the example of the result of AA measurement
using LC-MS. The detected AA is illustrated as the peak area
(Figure 1.A). The area under the peak is calculated, and then theserum concentration of the AA is estimated according to thecalibration line that corresponds to each AA (Figure 1.B).

Figure 1. Example of the estimation of serum concentrationof AA by using LC-MS.
Sample preparation procedure
Before analyzing serum sample, serum sample preparation
was performed as follows; Twenty ml of distilled water and 1.2
grams of sulfosalicylic acid dihydrate were pipetted into a test
tube, and then 6% sulfosalicylic acid dihydrate were made. Twohundred µl of 6% sulfosalicylic acid dihydrate were added into
the serum samples. After gentle shaking, the serum samples
were incubated at 4℃ for 5 minutes. Five µl of the serumsamples supernatant were thawed and filtered through a syringe
driven filter unit, and then the syringe was injected into LC-MS.
Statistical analysis
Continuous variables were expressed as mean ± standard
deviation (SD). Correlation between 6MWD and each AA wereassessed using Spearman’s correlation coefficient. All statisticalanalyses were performed Stata/SE13 (Stata Corp LP, College- 12 -

Station, TX, USA), and P value <0.05 was regarded asstatistically significant.
Results
Characteristics of the study subjects were shown in Table
1. Of 160 subjects who participated in the follow-up survey
in 2015, 63 subjects were analyzed. The mean age was 80±5
years old and most subjects were female (56 women and 7
men).
Correlation between variables and each AA were shown in
Table 2. Aspartate (r=0.29, P<0.01), monoethanolamine(r=0.34, P< 0.01), and taurine (r=0.29, P<0.02) aresignificantly correlated with 6MWD.
Table 1. Subject characteristics
VariablesAge [years old]
Men [n (%)]
Body mass index [kg/m2]
6-minute walk distance [m]Mean±SD or n (%)
80.3 ± 3.9
7 (11.1)
22.2 ± 3.6
469.1 ± 84.7

Table 2. Correlation between AA and 6MWD
Amino acids
Essential amino acids
ValineLeucine & Isoleucine
Threonine
Phenylalanine
Methionine
Non-essential amino acids
Arginine
Cysteine
Aspartate
SerineGlycineSerineProline
Homocysteine
Asparagine
Glutamate
Other types of amino acids
γ-aminobutyric acid
Monoethanolamine
1-methyl hystidine
3-methyl histidine
Hydroxylysine
Hydroxyproline
α-aminoadipic acid
Ornithine
Citrulline
α-aminobutyric acid
Taurineβ-alanine
Phosphoethanolamine
Cystathionine
5-aminolevulinic acidr

P value

0.02
0.22
0.002
0.13
0.18

0.91
0.24
0.99
0.30
0.16

-0.16
0.05
0.29
-0.005
0.04
-0.13
-0.15
-0.15
0.20
0.14

0.20
0.69
<0.05
0.97
0.73
0.29
0.26
0.26
0.11
0.28

0.24
0.34
0.08
0.08
0.002
-0.05
-0.14
-0.02
-0.1
-0.014
0.29
0.18
0.04
-0.17
0.12

0.06
<0.01
0.56
0.54
0.99
0.73
0.28
0.89
0.45
0.28
<0.05
0.15
0.78
0.19
0.33

Discussion
In this study, we performed a metabolome analysis of AA
profile in community-dwelling elderly people aged 75 orover, and examined the relationship between 6MWD and AA
profile. As the result,taurine, aspartate andmonoethanolamine were significantly correlated with 6MWD.

A previous study2 demonstrated that taurine transporter
knockout rats showed lower production of adenosine
triphosphate in cardiac muscle compared to control group*. In
this study, significant correlation was observed between taurine
and 6MWD. Although the relationship between taurine andenergy metabolism cannot be discussed from our data, taurine
might contribute to energy production during the testing of
6MWD in elderly subjects.
As well as taurine, aspartate and asparagine also play animportant role in myocardial energy metabolism. A previous
study3 reported that asparagine-administered rats showed longer
time to exhaustion with lower blood lactate concentration
during exercise with intensity above aerobic threshold thancontrol group*. Therefore, the fatigue tolerance during exercise
may be an underlying mechanism of the relationship between
aspartates and 6MWD.
There are few studies to address the role ofmonoethanolamine during exercise. Monoethanolamine
concentration in HF patients is negatively correlated with liverfunction and also with left ventricular ejection fraction4.
Another study5 reported that monoethanolamine inhibited
mitochondrial function of liver in vitro*. Considering theseevidence, monoethanolamine was likely to be negatively
associated with EC. In contrast, however, our data showed thepositive correlation between monoethanolamine concentration
and 6MWD. There may be unknown confounding factors, andfurther studies are needed to understand this relationship.
We should describe potential limitations of the present study.
First, the cross-sectional study cannot address the causal
relationship between EC and serum AA profile. Second, twoessential amino acids (histidine and tryptophan) and three nonessential amino acids (alanine, glutamine and tyrosine) were notanalyzed because the reagent used in this study was not applied
to the analysis of these five AAs. Accordingly, measurement
protocol is required to be improved to analyze whole AA profile.
Third, we provided the data in men participants from a small
sample. Finally, we did not assess liver function that may work
as a confounding factor.
Conclusion
In this preliminary study, taurine, aspartate, andmonoethanolamine was correlated with 6MWD in healthyelderly subjects aged 75 years or over. Considering theprevious evidence, these AAs are likely to relate to EC via
energy metabolism. Our subsequent study in HF patients will
examine the relationship between EC and AA profile, and theirusefulness in the clinical setting.
References
1. Carubelli V, Castrini AI, Lazzarini V, Gheorghiade M, Metra
M, Lombardi C. Amino acids and derivatives, a newtreatment of chronic heart failure?. Heart Fail Rev.
2015;20(1):39-51.
2. Schaffer SW, Shimada- takaura K, Jong CJ, et al. Impairedenergy metabolism of the taurine deficient heart. Amino
Acids. 48(2):549-58, 2016.
3. Marquezi ML, Roschel HA, Dos santa costa A, et al. Effectof aspartate and asparagine supplementation on fatigue
determinants in intense exercise. Int J Sport Nutr Exerc
Metab. 13(1):65-75, 2003.
4. Hakuno D, Hamba Y, Toya T, et al. Plasma amino acidprofiling identifies specific amino acid associations withcardiovascular function in patients with systolic heart failure.
PLoS ONE. 10(2): e0117325, 2015
5. Kelly RF, Lamont KT, Somers S, et al. Ethanolamine is a
novel STAT-3 dependent cardioprotective agent. Basic Res
Cardiol. 2010;105(6):763-70.

- 13 -

Physical Function and Self-Perceived Ability
Related to Life Space Mobility in Community-Dwelling Older People
Y. Tsuchida1）, S. Nakashima1）, T. Ito2）, Y. Uchiyama1）1）1) Department of Physical Therapy, School of Health Sciences, Nagoya University, Nagoya, Japan
2）General Center of Rehabilitation in Syutaikai Hospital, Mie, Japan

Introduction
Life space mobility is the important conception as older
people to maintain and expand activity. It may represents
physical function, cognition, psychological function, physicalactibity and participation. It is known that Life Space
Assessment(LSA) is an one of the validitive index for theolder people[1]. Scores on the LSA range from 0 to 120, withhigher scores reflecting greater life-space. Researchers ask
subjects frequency of movement (how many days within aweek) and necessity of any aid, equipment or help from otherpeople during the 4 weeks prior to assessment for fivedifferent life-space levels. Recentry several studies haveshowed relationships between LSA and kinds of risks:
Alzheimer disease[2], frailty[3], mortality[4] and otherproblems. Futhermore, the correlation between LSA and a lotof functions such as cognition, depression, muscle strength,
gait speed and other functions have been reported[1][5].
In addition, it is known that not only actual physicalfunction but also self-perceived ability decline for aging. The
difference value between actual physical function and selfperceived ability is called estimation errors. Robinovitch andCronin reported a tendency for older people to over-estimate,and young people to under-estimate their reaching ability[6].
Fujimoto et al showed the relationship between fall and overestimation of their step ability[7]. The same result wasreported on step-over ability by Sakurai et al[8]. It is
important for actibities and participations of older people tointervene in not only actual physical function but also
estimation errors.
The purpose of this study was to investigate factors of life
space mobility in community-dwelling older people in termsof physical function and self-perceived ability.

Results
A mean age of subjects was 76.7±8.0. There were 22 men and17 women. The number of subjects who had the certification of
long-term care needs were 19. A mean score of LSA was 74.4
±26.3(min~Max:12~120). The propotion of Independence ineach space of LSA was shown in Figure 1.
100%
no activity
75%
use aids or equipment andneed help from other person
50%
need help from other person
25%
use aids or equipments0%
out of town

town

neighborhood

yerd

home

Materials and Methods
Subjects: The total number of subjects were 39 communitydwelling older people. We included older people received thecertificate of long-term care needs. Long-term care wasformal insurance system in Japan. Some care services wereavailable for insured people. We excepted a parson who wasunder 65 years old, long-term care level 4&5 andhospitalized patient.
Measurements: Life space mobility was measured using
Life Space Assessment(LSA). We conducted 4 performance
tests: Obstacle Single Leg Forward Step test (OSFS), 2 steps
test, Functional Reach test(FRT) and 30s Chair Stand test
(CST). In OSFS, subjects stepped forward while stepping
over an obstacle which the height was 10cm and returned tooriginal place while stepping over an obstacle and repeatedthis process five times, as fast as possible. We measured total
time. In 2 steps test, subjects took two steps as large as
possible. In FRT, subjects performed maximum reach. In
CST, we measured the times subjects were enabled to standup from a chair for 30 seconds. These perforamnce tests wereused to assess actual physical function and self-perceived
ability. The ratio of self-estimated to actual was used for data

analysis as a measurement of estimation errors. Other
measurements included Mini-Mental State
Examination(MMSE), Fall Efficacy Scale(FES), Short Form ofGeriatric Depression Scale(GDS-5）, the 25-question GeriatricLocomotive Function Scale(locomo25) and fall experiences.
Statistics analysis: We conducted analysis for extracting
factors of LSA. Simple bivariate correlation coefficients wereused to examine the relationships between LSA scores and all
variables. This analysis was first unadjusted and subsequentry
adjusted for age. Multiple regression by forced entry was used
to determine which physical ability was important for LSA.
We also investigated the characteristics of estimation errors ofphysical function related to LSA. We defineded exactry
perception as the ratio of self-estimated to actual was within 97103%. And we defineded over-estimation as the ratio was>103% and under-estimation as the ratio was <97%(only in
OSFS, this definision was reversed). Chi-squared goodness of
fit test was used to analize the deviation of the number ofexactry perception, over-estimation, under-estimation. Simple
bivariate correlation coefficients were used to examine therelationships between actual physical function and estimation
errors. A probability of 0.05 was considerd statisticallysignificant.

independence

Fig1. The propotion of Independence in each space of LSA- 14 -

LSA was siginificant correlated with OSFS(r=-0.473), 2
steps test(0.577), FRT(0.523), CST(0.328), MMSE(0.502),
FES(0.531), GDS-5(-0.341) and locomo25(-0.747) (P<0.05).
When it was caluclated with adjust of age, LSA wassignificant correlated with OSFS(r=-0.419), 2steps
test(0.390), FRT(0.354), MMSE(0.366), FES(0.545), GDS5(-0.473), locomo25(-0.564)(P<0.05). Multiple regression
analysis suggested significant associations between LSA and
OSFS and 2 steps test(table1).
Table1. Multiple regression analysis of LSA
Variableβ

P value

VIF

OSFS(s)

-.389

.045

2.06

2 steps

.409

.042

2.21

FRT(cm)

.329

.060

1.70

CST(times)

-.320

.106

2.20

VIF: Variance Inflation Factor, R2=0.532, P<0.05
In terms of estimation errors, more subjects over-estimatedtheir own abilities of OSFS(69.7%; P<0.05)(table2). And
only OSFS in 4 physical function measurements had asignificant correlation between actual physical function andthe ratio of self-estimated to actual physical function(r=0.404, P<0.05).
Table2. The number of people who Over-estimated,
Under-estimated and perceived exactly
OSFS*

2stepsFRT

30s CST

Over-estimation

23

10

13

21

Under-estimation

9

20

22

14

1

9

4

4

Exactly perception

Chi-squared goodness of fit test, * P<0.05
Discussions
We investigeted relationships between life space mobility ofcommunity dwelling older people and physical functions. We
also determined the charactrestic of estimation errors ofphysical function related to LSA.
First, we found that OSFS and 2 steps test were more
related with LSA than FRT and 30s CST. Watanabe et alreported older people who rarely go outside per week
declined the gait speed with obstacle avoidance comparedwith older people who often go outside[9]. From our results
and this study, it can be said that the dynamic ability which
includes balances and muschle strengthes is more importantfor mobility of community-dwelling older people.
Second, we found that over-estimated subjects were morethan under-estimated subjects in OSFS. And we also found asignificant correlation between actual physical function andestimation error of OSFS. This correlation indicated the moreactual ability of OSFS was lower, the more self-estimation
was over-estimated. This chracteristic corresponded previous
studies[6][7]. From these results, it can be said that it isdifficult to recognize the decrement of ability of obstacle
avoidance such as OSFS. Therefore, it is important forcommunity-dwelling older people to intervene in actual
function of stepping and obstacle avoidance and estimation
errors of the ability in order to expand life space mobility.

Conclusions
Life space mobility of community dwelling older people wasrelated to step and obstacle avoidance ability especially. In
OSFS, more subjects over-estimated their ability and there wasa significant relationship between actual physical function andestimation errors. These results indicated needs of interventions
not for only actual physical function, but also estimation errors
to expand life space mobility.
References[1] Baker PS, Bodner EV, Allman RM. Measuring life-space
mobility in community-dwelling older adults. J Am Geriatr Soc.
2003, 51:1610–4[2] James BD, Boyle PA, Buchman AS, et al. Life space andrisk of Alzheimer disease, mild cignitive impairment, andcoginitive decline in old age. Am J Geriatr Psychiatry. 2011,19(11):961-969[3] Portegijs E, Rantakokko M, Viljanen A, et al. Is frailty
associated with life-space mobility and perceived autonomy inparticipation outdoors? A longitudinal study. Age and Ageing.
2016, 45:550-553[4] Kennedy RE, Sawyer P, Williams CP, et al. Life-space
mobility change predicts 6-month mortality. J Am Geriatr Soc.
2017, 65: 833-838[5] Peel C, Sawyer Baker P, Roth DL et al. Assessing mobility
in older adults: The UAB Study of Aging Life-Space
Assessment. Phys Ther. 2005, 85:1008– 1119.
[6] Robinovitch SN and Cronin T. Perception of postural limits
in elderly nursing home and day care participants. J Gerontol A
Bio Sci Med Sci. 1999, 54:124-130[7] Fujimoto A, Hori H, Tamura T, et al. Relationships between
estimation errors and falls in healthy aged dwellers.
Gerontology. 2015, 61:109-115[8] Sakurai R, Fujiwara Y, Ishihara M, et al. Age-related selfoverestimation of step-over ability in healthy older adults andits relationship to fall risk. BMC Geriatrics, 2013, 13:44-53[9] Watanabe M, Tanimoto Y, Kono R, et al. Objective
assessment of walking in housebound elderly who are able to goout alone. Nihon Ronen Igakkai Zasshi. 2011, 48(2):170-175
Author address
Email: tsuchida.yoshiki@d.mbox.nagoya-u.ac.jp- 15 -

Relationship between body function and structure and activity based on ICF
model with children with cerebral palsy
Jongseok. Hwnag, MS, PT 1), Jung-A Lee, PhD2), Joshua H. You, PhD, PT3)
SportsMovement Artificial-intelligence Robotics Technology(SMART) Institute, Department of Physical Therapy,
Yonsei University, Wonju, Republic of Korea.
2)
Department of Motor & Cognitive Rehabilitation, Korea National Rehabilitation Research Institute, Seoul, Republic ofKorea.
3)
Sports Movement Artificial-intelligence Robotics Technology(SMART) Institute, Department of Physical Therapy, The
Graduate School, Yonsei University, Wonju, Republic of Korea
1)Introduction
The World Health Organization (WHO) has developed theInternational Classification of Functioning, Disability and
Health (ICF) model for a theoretical foundation of physicaltherapy diagnosis and intervention (1). The ICF model iscomprised of four categories : body structures, body, activities
and participation , and environment (Figure 1) (1), which
provides a direct framework and guideline for outcome
measurements. ICF is renowned but dearth of relationshipinformation for verify real world. The absence of the clear
understanding of directional relationships among ICF
component outcome measures variables can challenge aninternal validity to adopt the ICF framework for outcome
assessment, goal planning and intervention (ref). The purposeof present study was to examine the multidirectional
relationships between the body structure/function domain
variables (e.g., spasticity and movement kinematics) andactivity domain variables (reaching, grasping, folding, andlifting abilities) using the WMFT.

Figure 1 ICF model
MethodStudy Design: This design is a correlational research design.
Participants: 19 children diagnosed with cerebral palsy (CP)were recruited from a major rehabilitation center. 10 of themwere hemiplegic CP and 9 of them were quadriplegic(Table 1)
Measurements: Standardized clinical tests included Tardieu
scale and WMFT, which primarily measure the bodystructure/function domain (e.g., spasticity) and activity
domain (reaching, grasping, folding, and lifting abilities). An
eight infrared motion capture system (VICON, Oxford, UK)
was used to analyze kinematics data, measuring the bodystructure/function domain.
Data analysis: Statistical tests included non-parametric
Spearman rank correlation coefficient was conducted to
identify correlation among the variables via SPSS software(version 23.0).
Results
The major findings are twofold:1)

The relationship between kinematic data and WMFT
ranged from fair to strong correlation (Table 3).

2)

No significant correlation was observed between Tardieu
score and kinematics data or between Tardieu score and
WMFT.

Variablecharacteristics

Sex(Male /Female)

10/9

Average of age

8.8 ± 1.8 years

Height125.4 ± 12.1 Cm

Weight24.2 ± 7.1 Kg

Cerebral palsy type
Hemiplegia

10

Quadriplegia

9
Table 1. Demographic Summary

Acron
ym
MT
MV

Full term

Quantification

Movement time
Maximal velocity

Movement speed
Force production

MAV

Mean angular velocity

Torqueproduction
NJS
Normalized jerk score
Movementsmoothness
Table 2. Explanation of the kinematic variables (bodyfunction/structure domain) in Reaching

Tests

WMF
T scores

WMFT
time

MV in U/E at comfortable speed (rs)-.556*.704**MV in U/E at comfortable speed (rs)*NJS in U/E at comfortable speed (rs).479-.522*-.462*.714**NJS in shoulder at comfortable speed (rs)

NS†

.565*

NJS in elbow at comfortable speed (rs)

NS†

.472*

MT in U/E at fast speed (rs)-.462*.627**MV in U/E at fast speed (rs)

.462

*

-.529*NJS in U/E at fast speed (rs)-.523*.671**NJS in shoulder at fast speed (rs)

N/S

.485*

NJS in elbow at fast speed (rs)-.609**.701**NJS in wrist at fast speed (rs)

NS†

.531*

*Significant correlation p<0.05, ** Significant correlation p<0.01.
†NS, Non-significant correlation. (rs )Spearman’s rank correlation.
MT, movement time; MV, maximal velocity; MAV, mean angularvelocity; NJS, normalized jerk score; WMFT, wolf motor function
test.. U/E: upper extremity.

Table 3. Relation between kinematic data and WMFT
Results- 16 -

Conclusions
The present study demonstrated the multidirectional
relationships between the body structure/function domain
variables (Tardieu spasticity and Kinematic data) and activity
domain variables. Our results revealed a fair to strong
relationship between the body structure/function domain
variables (11 out of 18 kinematic data) and activity domain
variables (WMFT). The present findings suggest that the bodystructure/function domain variables (Kinematic data) areclosely associated with activity domain variables (WMFT).
However, the body structure/function domain variables within
Tardieu spasticity and kinematic data variables were notassociated each other, nor between Tardieu spasticity andactivity domain variables (WMFT), indicating that Tardieu
spasticity function variable does not account for or reflect
active movement or functional activity measures in WFMT.
This finding provide an important clinical insight whendeveloping a comprehensive assessment tool, which
successfully addressing both body structure/function domain
and activity domain variables.
Reference- 17 -

Comparison of shoulder strength in males with and without myofascial
trigger points in the upper trapezius
Hyun-a Kim, MS, PT1), Ui-jae Hwang, PhD, PT1), Sung-hoon Jung, BPT, PT1),, Sun-hee Ahn , MS, PT1), Jun-hee Kim ,BPT, PT1), Oh-yun Kwon, PhD, PT 2)
2)1) Dept. of Physical Therapy, The Graduate School, Yonsei University
Department of Physical Therapy, College of Health Science, Laboratory of Kinetic Ergocise Based on Movement
Analysis, Yonsei University

Introduction
Overuse of the upper trapezius (UT) muscle during shoulder
movements can interfere with scapular alignment and the
movement pattern can lead to specific errors in choosing anappropriate movement strategy (Arlotta et al., 2011).
Pain and tenderness in the UT due to increased muscle
tension cause complaints in individuals with chronic neck andshoulder problems (Leong et al., 2013). It may lead to
involuntary shortening, insufficient nutrient supply, andmetabolic demand on local tissues (Gerwin et al., 2004; RuizSáez et al., 2007).
There are many studies about causes of UT pain. Ge, et al.
(2014) demonstrated that intermuscular muscle activity oflatent MTPs increased significantly in the UT muscle comparedwith non-MTPs during 90° shoulder abduction and at rest due
to overloading of the UT muscle (Ge et al., 2014).
However, Naef et al. (2014) demonstrated that subjects withchronic shoulder pain showed no difference from healthy
subjects in arm abduction maximal strength or recruitment
patterns of the serratus anterior, middle deltoid, and UT (Naefet al., 2015). However, no reported study has demonstrated
maximum isometric shoulder abductor without synergistic
action.
The aim of this study was to compare scapular elevator andshoulder abductor strength with and without restricted scapularelevation in male subjects with and without UT pain.
Materials and methods
Study design: This study was an experimental study tocompare the strength of scapular elevator and shoulder
abductor with and without restricted scapular elevation
between male subjects with and without myofascial trigger
points in the upper trapezius .
Participants: In total, 15 subjects with MTP in UT and 15
age- and weight-matched subjects without MTP in UT wereenrolled.
Measurements: Two load cell Smart KEMA strength
measurement systems (Factorial Inc., Seoul, Korea) were used
to measure isometric shoulder strength and to control scapularelevation by 3 kgf. Isometric strength measurements were
performed twice for 5 s under three conditions: (1) scapularelevation, (2) shoulder abduction, and (3) shoulder abduction
with restricted scapular elevation. (Figure 1)
Data analysis: Independent t-tests were used to compare
shoulder strength values between the MTP and non-MTP
groups.

Figure 1. Resting position (a), scapular elevation (b), shoulder
abduction (c), and shoulder abduction with restricted scapularelevation(d).
Results
Shoulder strength measures showed good to high intra-rater
reliability (range = 0.85 [95% CI = 0.54–0.95] to 0.98 [95% CI= 0.94–0.99]) (Table 1). Intra-rater SEM% was acceptable(<10%) for most tests except the condition of shoulder
abduction with restricted scapular elevation in the MTP group(SEM% = 10.10%) (Holt et al., 2016)
Table 1. Intra-rater reliability of Smart KEMA strength
sensor.
Group

MTP group

Non-MTP
group

Position

ICC

SEM%

0.90

SEM
(kgf)
2.17

SE
ABD

0.89

1.62

9.04

ABDR

0.98

0.57

10.10

SE

0.89

2.97

9.99

ABD

0.85

1.77

9.87

ABDR

0.90

0.99

8.30

8.27

ICC: intraclass correlation coefficient, CI: confidence interval, SEM:
standard error of the mean; SEM%: SEM divided by mean result, SE:
scapular elevation, ABD: shoulder abduction, ABDR: shoulder
abduction with restricted scapular elevation.

The main results of the research were as follows.
1) Scapular elevator strength was 26.24kgf in the MTP
group and 29.71kgf in the non-MTP group. Shoulder
abductor strength was 17.88kgf in the MTP group and17.95kgf in the non-MTP group. There was no
significant difference between groups in scapularelevation or shoulder abduction (t = 1.274, p > 0.05 andt = 0.048, p > 0.05, respectively; Table 2)- 18 -

2)

However, the results showed that shoulder abductor
strength in the group with MTP (5.64 kgf) was
significantly lower than in the group without MTP(11.96 kgf) when scapular elevation was restricted (p <0.05; Table 2).

the case where people have complaints or pain in the UT despite
having strong muscles. It is important to teach patients tocontrol delicate movements by conscious effort rather than byincreasing their muscle bulk (Sahrmann, 2002). The results ofthis study showed that weakness of shoulder abductor withrestricted scapular elevation may be one cause of MTPs in the
UT.

Table 2. Shoulder strengths in three conditions (n=30)
MTP

Non

Parameter

t

p

1.274

0.213

group

MTP group

26.24(6.42)

29.71(8.38)

ABD

17.88(4.53)

17.95(4.22)

0.048

0.962

ABDR

5.64
(3.99)

11.96(3.02)

4.894

0.000*SE

Conclusion
In conclusion, we demonstrated that there was no difference
in strength of the scapular elevator and shoulder abductor
between males with and without MTPs in the UT. However,when scapular elevation was restricted, shoulder abductor
strength was significantly lower in the MTP group than in the
non-MTP group. We suggest that overuse of the UT can cause
MTP by compensatory movements in shoulder abduction.
Clinicians should evaluate strength of the shoulder abductor
with restricted scapular elevation and apply interventions toadjust individuals’ exercises by conscious effort rather thanintervention to increase muscle volume when assessing
individuals with MTPs.

Values are means (SD), MTP: group with myofascial trigger points,
Non-MTP group: group without myofascial trigger points, SE:
scapular elevator, ABD: shoulder abductor, ABDS: shoulder abductor
with restricted scapular elevation. *Significant difference at p<0.05.

Discussion
The main finding of this study was that there was no
significant difference in strength of the scapular elevator andshoulder abductor without restricted scapular elevation
between males with and without MTPs in the UT. However,shoulder abductor strength was significantly lower in the MTP
group than in the non-MTP group when scapular elevation wasrestricted.
Many studies have investigated shoulder strength and the UT.
However, few studies have compared the strength of thescapular elevator between individuals with and without MTPs
in the UT. Thus, we measured the strength of scapular elevators
between groups with and without MTPs to determine the effecton UT strength of MTPs in the UT. However, we found no
significant difference between the groups (MTP: 26.24kgf;
non-MTP: 29.71kgf). Thus, we postulated that UT strength
does not directly cause MTP.
Many studies have used a convenient and lightweight handheld dynamometer (HHD) to measure the strength of thescapular elevator and shoulder abductor (Michener et al., 2005).
However, previous studies also determined that above 120 N,
the force measured with a HHD could be affected by tester
strength and that the intraexaminer reliability of HHDs was not
acceptable for shoulder measurement (Schrama et al., 2014).
Thus, we measured scapular elevator and shoulder abductor
strength using a convenient and lightweight Smart KEMA
measurement strength system that can measure the subjects’
own strength by Make tests (ICC > 0.85).
Shoulder abductor strength was measured to compare
strength between individuals with and without UT pain. Whensubjects performed maximal isometric shoulder abduction
without restricted scapular movement, both groups had similar
strength values (MTP = 17.88kgf; non-MTP = 17.95kgf);
however, the strength values of the shoulder abduction weresignificantly lower in the MTP group (5.64kgf) than in the nonMTP group (11.96kgf) with restricted scapular movement. It
was shown that prime mover strength in shoulder abduction
was lower in the MTP group than in the non-MTP group when
the synergistic muscle was restricted.
Sharrman (2002) explained the dominance of the UT bymodular element impairment in the nervous system. This isReferences[1] Arlotta M, LoVasc, G, McLea L, Selective recruitment of
the lower fibers of the trapezius muscle. Journal of
Electromyography and Kinesiology. 2011; 21(3), 403410.
[2] Ge HY, Monterde S, Graven-Nielsen T, et al. Latent
myofascial trigger points are associated with an increased
intramuscular electromyographic activity duringsynergistic muscle activation. The journal of pain. 2014;15(2), 181-187.
[3] Gerwin RD, Dommerholt J, Shah JP. An expansion ofSimons’ integrated hypothesis of trigger point formation.
Current pain and headache reports. 2004; 8(6), 468-475.
[4] Holt KL, Raper DP, Boettcher CE, et al. Hand-helddynamometry strength measures for internal and externalrotation demonstrate superior reliability, lower minimal
detectable change and higher correlation to isokinetic
dynamometry than externally-fixed dynamometry of theshoulder. Physical Therapy in Sport. 2016. 21, 75-81.
[5] Leong HT, Ng GY, Leung VY, Fu SN. Quantitative
estimation of muscle shear elastic modulus of the upper
trapezius with supersonic shear imaging during arm
positioning. PLoS One. 2013.8(6), e67199.
[6] Michener LA, Boardman ND, Pidcoe PE, et al. Scapular
muscle tests in subjects with shoulder pain and functional
loss: reliability and construct validity. Physical therapy.
2005. 85(11), 1128-1138.
[7] Naef F, Grace S, Crowley-McHattan Z, et al. The effectof chronic shoulder pain on maximal force of shoulder
abduction. Journal of bodywork and movement therapies.
2015. 19(3), 410-416.
[8] Ruiz-Sáez M1, Fernández-de-las-Peñas C, Blanco CR, et
al. Changes in pressure pain sensitivity in latent
myofascial trigger points in the upper trapezius muscle
after a cervical spine manipulation in pain-free subjects.
Journal of manipulative and physiological therapeutics.
2007; 30(8), 578-583.
[9] Sahrmann S. Diagnosis and treatment of movement
impairment syndromes. Elsevier Health Sciences. 2002.
[10] Stratford PW, Balsor BE. A comparison of make andbreak tests using a hand-held dynamometer and the KinCom. Journal of Orthopaedic & Sports Physical Therapy.
1994. 19(1), 28-32.

- 19 -

- 20 -

Abstract

Occupational Therapy- 21 -

- 22 -

2017' Yonsei-Nagoya University Joint Symposium on
Occupational Therapy(2017/11/02 on Thursday), Baekun Hall #103

11:00~12:00

Campus tour

12:00~13:00

Lunch

13:00~14:00

Laboratory tour

14:00~15:00

Session I

14:00~14:20

Review on Concept and Measurement of Occupational Balance:

Chair: Prof. Junichi Uemura (Nagoya Univ.)

Trend and Therapeutic Prospects
Presenter: Sangmi Park, Ji-Hyuk Park (Yonsei Univ.)
14:20~14:40

A Study of the Ways of Holding Chopsticks and the Respective
Functions of Children with Autistic Spectrum Disorder and Children
Suspected Autistic Spectrum Disorder
Presenter: Takuto Sakuma, Chieko Karashima (Nagoya Univ.)

14:40~15:00

A systematic review of randomized controlled trials(RCTs) with
community-based intervention for patients with dementia
Presenter: Ga-in Shin, Ye-Shin Woo, Hae Yean Park (Yonsei Univ.)

15:00~15:15

Coffee break

15:15~16:35

Session II

15:15~15:35

The effect of cross-cultural exchange program for occupational

Chair: Prof. Arum Han (Yonsei Univ.)

therapy students: A preliminary study
Presenter: Hyun Jung Kim, Min-Ye Jung, PhD, (Yonsei Univ.)
15:35~15:55

The study of the brain functional connectivity during somatosensory
image execution
Presenter: Ryosuke Suzuki, Jun-ichi Uemura (Nagoya Univ.)

15:55~16:15

A systematic review of effects of cognitive rehabilitation therapy for- 23 -

community dwelling adults with early dementia or mild cognitive
impairment
Presenter: Sangmi Park, Ji-Sun Lee, Kyu-Won Lee, Won-Seuk Choi, JungRan Kim (Yonsei Univ.)
16:15~16:35

Study on the production of lightweight customized wrist splint using
3d modeling and 3d printerPresenter: Won-Seuk Choi, Jong-Bae Kim (Yonsei Univ.)

16:35~16:40

Closing Remark

16:40~17:00

Group Photos

Prof. Aiko Hoshino (Nagoya Univ.)※ 15 minutes presentation and 5 minutes Q&A- 24 -

Review on Concept and Measurement of Occupational Balance: Trend andTherapeutic Prospects
Sangmi Park, BHSc, OT1), Hae Yean Park, PhD, OT2), Ji-Hyuk Park, PhD, OT2)
1) Dept. of Occupational Therapy, The Graduate School, Yonsei University2) Dept. of Occupational Therapy, College of Health Science, Yonsei University

Introduction
People are satisfied with their life patterns when they are incertain point of balance. The status is called as occupationalbalance in occupational therapy or occupational science[1]. The
concept of occupational balance is complex but it is known thatoccupational balance is related to health, wellbeing andsatisfaction[2].
Although occupational balance has been considered
important concept in occupational therapy for a long time, asingle definition of occupational balance doesn’t exist yet[3].
There are several definitions of occupational balance byscholars for example,‘A balance among different kinds ofdaily occupations[4]’, ‘A balance of engagement in occupationthat leads to wellbeing[5], ‘the condition of proper distribution
on time, areas of occupations and energy[6]’, ‘subjective
perception of having the right amount and variation ofoccupations[7]’, ‘a personally satisfying pattern of daily
occupations[1]’.
Giving chances to participate in meaningful occupations forclients is the most important part of occupational therapy for
their health, wellbeing, and quality of life[8]. And it is possible
when the therapists understand clients’ life patterns and how
much they are satisfied with their life patterns[9].
The first aim of this study was to understand the trend ofresearch on occupational balance by analyzing the studies aboutoccupational balance. And then, attributes of occupationalbalance were analyzed to find considerations for improving
clients’ occupational balance. Finally, confirming thecorrelation between concept of occupational balance and healthor health related factors.

Records identified through database searching (n=223)∙National Digital Science Library(NDSL): 64∙Riss: 31∙Pubmed: 61∙Google Scholar: 67

Materials and methods
Searchingstrategy:
National
DigitalScience
Library(NDSL), Riss, Pubmed, and Google Scholar were used
to search the articles published from October 2007 to

5 articles without full text were excluded

September 2016 and ‘occupational balance’ OR ‘작업균형’were used as search terms. Inclusion criterion were articles 1)
published in peer-reviewed journals, 2) contained results ofmeasuring occupational balance and reported quantitatively, 3)
published in Korean or English, 4) had at least one author who
was an occupational therapist. Exclusion criterion were articles
1) about occupational balance referring to occupation as ameaning of job or balance as a meaning of physical balance or
postural balance, 2) we cannot access to full text, 3) aboutdeveloping occupational balance measurement.
Data collecting process: As shown in Figure 1, 10 articles
were finally selected for analysis among 223 articles.
Results
General Trend of Research on Occupational balance:
Results of analyzed studies about overall trend from 10 articles
were summarized in table 1.
Measurements and attributes of occupational balance:
There were two ways of measuring occupational balance. One
was using self-reported questionnaires and the other was using
the result of reassessed primary materials like self-record sheet
about time use or activity frequency.

Records excluded by titles (n=157)∙Duplicates or other language: 70∙Occupation as a job or balance as a physicalbalance or postural balance: 84∙Developing occupational balance measurement:
3
screened 66 abstracts
Records excluded by abstracts (n=51)∙Articles not in peer reviewed journals : 28
∙Without any OT authors: 1∙Developing occupational balance measurement:
4∙Qualitative research or studies without
quantitative results of occupational balance: 18

10 articles were selected
Figure 1. Flow diagram for study selection process
Table 1. Summary of overall trend in studies
Study Design
PurposeParticipantsDiseaseAge
GenderYear of the studies
published
Nationsof
thestudies examined

Results
Survey researches all
Measuring participants’ occupationalbalance or analyzing correlation
between occupational balance andother variables
Wide from disease group to healthypeopleAdults, Elderly
More women than men
7 studies were published in recent 5
years out of 10 studies
Republic of Korea, Sweden, Canada,
Israel, United States

Self-reported questionnaires were used in 6 articles to assessclients’ occupational balance. The questionnaires were
Personal Project Analysis(PPA), Intergoal Relations- 25 -

Questionnaire(IRQ),
Occupational
Balance
Questionnaire(OBQ) and Life Balance Inventory(LBI). And acouple of questions developed by the authors were also used asa self-reported questionnaire.
Temporal attribute was measured to assess occupationalbalance in 9 articles. Other attributes to assess occupationalbalance were abilities, achievement of occupations,interrelationship like harmony or conflictions amongoccupations, variety of occupations, congruence between
desired and actual time use.
Measurements with proved validity or reliability were foundin 6 articles and they were PPA, IRQ, OBQ and LBI.
Assessment tools used in Korean studies were not verified byvalidity or reliability test.
Correlation between occupational balance and healthrelated variables: Variables measured to see correlation withoccupational balance were health, wellbeing, participation,
stress, life satisfaction, and leisure. Forhan and Backman[10]revealed that performance, time use, and achievement are three
dimension of occupational balance and health condition waspredictor of these three aspects. Wagman and Håkansson[11]confirmed positive correlation between occupational balanceand health condition. Negative correlation between
occupational imbalance and wellbeing was found in the studyof Anaby et al.[12] and Bejerholm[13] revealed occupationalbalance group showed significantly higher level ofparticipation, wellbeing, stress management and healthmanagement compared to occupational imbalance group.
Discussion
All of 10 selected articles for analysis were survey
researches. Various types of subjects were participated in thestudies and this could mean measuring and improving
occupational balance may have a positive effect not only on
disease group but also general healthy people. In other words,
the clinical fields of occupational therapists are getting wider
toward general people.
Attributes measured to figure out the concept ofoccupational balance were time use, abilities, achievement ofoccupations, interrelationship like harmony or conflictions
among occupations, variety of occupations, congruence
between desired and actual time use. This could be interpreted
as a concept of occupational balance has multidimensional
properties.
The reason we have several definitions of occupationalbalance is areas or kinds of occupations supposed to bebalanced could be changed by the client’s age or roles. Also it
could be difficult for scholars to have a consensus about
definition of occupational balance because each individual
person has different idea about the question ‘what is balanced
life?’
Regarding to correlations between occupational balance andquality of life, wellbeing, participation, stress, life satisfaction,and leisure, the concept of occupational balance could be apply
to occupational therapy intervention for health promotion.
Conclusion
The results of this systematic review were as in the following.
First, studies on occupational balance tended to be
conducted actively during the last 5 years, compared to studies
published within recent 10 years and the participants were
adults and older adults with or without disabilities.
Second, attributes of occupational balance were time use,
abilities, achievement of occupations, interrelationship likeharmony or conflictions among occupations, variety ofoccupations, congruence between desired and actual time use.
Third, occupational balance has a significant correlation
with health related factors like wellbeing, participation, stress.

Interventions for finding or recovering clients’ occupationalbalance could be applicable to improve their wellbeing,
participation or health promotion.
Measuring occupational balance is the first step to improvethe clients’ health, participation, leisure, and quality of life byrestoring their occupational balance. This is possible when themeasurements could assess various properties of occupationalbalance. It is needed to develop measurements for assessing
occupational balance which could show the result ofoccupational composition and satisfaction about theoccupational composition regardless of age, level of education,or cultural influence.
References[1] Christiansen C. (1996). Three perspectives on balance inoccupation. In Zemke, R., Clark, F., Editiors. Occupational
science: the evolving discipline. Philadelphia (PA): F.A.
Davis Company.
[2] Wagman P, Håkansson C, Björklund A. Occupationalbalance as used in occupational therapy: A concept analysis.
Scandinavian Journal of Occupational Therapy.
2012;19(4):322-327.
[3] Dür M, Unger J, Stoffer M, et al. Definitions of occupationalbalance and their coverage by instruments. British Journalof Occupational Therapy. 2015;78(1): 4-15.
[4] Meyer, A. The philosophy of occupation therapy. American
Journal of Occupational Therapy. 1977;31:639-642;(reprinted from Archives of Occupational Therapy. 1922;
1:1-10).
[5] Wilcock A. (2006). An occupational perspective of health(2nd ed.). Thorofare, NJ: Slack.
[6] Kim C, Park C, Sohn YM, et al. The conceptual
understanding on ‘work-life balance’ and its effectiveness.
Journal of leisure studies. 2005;2(3):29-48.
[7] Wagman P, Håkansson C, Jacobsson C, et al. What is
considered important for life balance? Similarities anddifferences among some working adults. Scandinavian
Journal of Occupational Therapy. 2012;19(4):377-384.
[8] Pizzi MA, Richards LG. Guest editorial- Promoting health,well-being, and quality of life in occupational therapy; A
commitment to a paradigm shift for the next 100 years.
AmericanJournalofOccupational
Therapy.
2017;71(4):7104170010p1-7104170010p5.
[9] Law M, Baum C, Dunn W. (Eds). (2017). Measuring
occupational performance: Supporting best practice inoccupational therapy (3rd ed.). Thoropare: NJ: SLACK
Incorporated.
[10] Forhan M, Backman C. Exploring occupational balance inadults with rheumatoid arthrities. OTJR: Occupation,
Participation and Health. 2010;30(3):133-141.
[11] Wagman P, Håkansson C. Exploring occupational balancein adults in Sweden. Scandinavian Journal of Occupational
Therapy. 2014; 21:415-420.
[12] Anaby DR, Backman CL, Jarus T. Measuring occupationalbalance: A theoretical exploration of two approaches.
Canadian
JournalofOccupational
Therapy.
2010;77(5):280-288.
[13] Bejerholm U. Occupational balance in people withschizophrenia. Occupational Therapy in Mental Health.
2010;26(1):1-17.
Author address
E-Mail: hi.sangmipark@gmail.com- 26 -

A Study of the Ways of Holding Chopsticks and the Respective Functions of Children with
Autistic Spectrum Disorder and Children Suspected Autistic Spectrum Disorder.
Takuto Sakuma*, Chieko Karashima
Department of Occupational Therapy, Graduate School of Medicine, Nagoya University, Japan

Introduction
DSM-5 defined Autistic Spectrum Disorder (ASD) as
having persistent deficits in social communication and social
interaction across contexts and restricted, repetitive patterns of
behavior, interests, or activities. Previous studies reported thatchildren with ASD had a lower motor function as comparedwith typically developing children[1], especialy in their writing
ability and the ability to throw a ball [2][3]. For this reason,
occupational therapists suspect that chldren with ASD havedyspraxia, and make an approach to their activities of dailyliving (ADL) in perspective of dyspraxia and sensory
modulation dysfunction [4]. In particular, dyspraxia makes it
difficult to perform ADL well because of the impairment in
performance of movement such as ideation, planning andexecution of motion. Occupational therapists often take anintervention for children with ASD using chopsticks. In Japan,
there is a way of holding chopsticks called "traditional type".
Parents of children with ASD become anxious when theirchidren do not hold the chopsticks in traditional type and theysuspect that it is due to ASD. In the previous studies, it was notclear regarding the relationship between ASD and not being
able to use chopsticks in traditional type. On the other hand,
there were many studies showing that traditional type was themost functional and most kinematically advanced compared toother ways of holding chopsticks among typically developingchildren[5]. The purposes of this study were as follows, I) to
explore the ways of holding chopsticks, and II) to examine thefunctionality of each way of holding chopsticks respectively
among children with ASD. Study I explored the ways ofholding chopsticks among children with ASD and typicallydeveloping children, and then, compared between eachgroup.Study II examined the functionality of each type ofholding chopsticks of children with ASD, and compared theresults with those of typically developing children.
Significance of the study
This study can allow occupational therapists to provide
more effective and evidence based interventions by using themost functional type of holding chopsticks as a model forchildren with ASD in response to the parents’ anxiety about
their children's ability.
Materials and Methods【study I】

Participants: The participants were 102 typically developingchildren and 33 children with ASD or with suspected ASD whowent to both kindergarten and child development support
center(from 5 to 6 years old). For the data of typicallydeveloping children, we used existing data collected by ourlaboratory in 2016 for the study “The ways of holding
chopsticks and the respective functions in typically developingchildren”(the study of typically developing children).
Method: The children in this study picked up and carriedsoybeans and rice to the container at a height of the mouth(15cm) and we videotaped their performances.
Data analysis: Images of their children’s holding
chopsticks were edited from the video and classified into 5
types of holding chopsticks according to the classification
found by the study of typically developing children (Figure1).
In addition, the rate of the number of children in each type wascompared with that of typically developing children.
The classification of the way of holding chopsticks: In thisclassification, the fingers which hold a moving chopstick anda fixed chopstick and the positions of the fingers touching
chopsticks were focused on. The ways of holding chopsticks
were categorized into 5types (Figure1).
【study II】
Participants: The participants were 72 typically developingchildren and 33 children with ASD or with suspected ASD whowent to both kindergarten and child development support
center (from 5 to 6 years old). The data of typically developingchildren were used from the existing data collected by the studyof typically developing children.
Method: The following functions were measured; “pick up
and carry” soybeans, tofu and rice by opening and closing
chopsticks and “separate” fish by holding fish with a fixedchopstick and by opening and closing a moving chopstick
successively for 30 seconds. These performances wererecorded on videotape.
Data analysis: Each average amount of work performed by
the children with ASD was compared by using multiple
comparison analysis tests as follows.
① Comparisons between the average amount of work in eachtype by children with ASD and that by typicallydeveloping children.
② Comparisons of the average amounts of work by each type
among children with ASD.

a moving
chopsticka fixedchopsticktraditional type

type Ⅰ

type Ⅱ

type Ⅲtype Ⅳ

Holding a fixed chopstickby thumb and third finger
and a moving chopstickby thumb, first finger andsecond finger.

Holding chopsticks bysame fingers as
traditional type. The
only difference is the
position of the fingers.

Holding a moving
chopstick by same
fingers as traditional
type.

Holding a fixedchopstick by same
fingers as traditional
type.

It is totally different fromtraditional type. Five
different holding ways ofchopsticks different fromthis image are found.

Figure1: The classification of the way of holding chopsticks had been faund by the study of typically developing children ,2016.

- 27 -

Results【study I】The data of 102 typically developing children and
33 children with ASD were analyzed. The number of children
in each type were as follows.
[typically developing children] traditional type 17(17%),
typeI 37(36%),typeII 28(27%), typeIII 3(3%), typeIV 17(17%)[children with ASD] traditional type 5(15%), typeI 12(37%),
typeII 8(24%), typeIII 0(0%), typeIV8(24%)
There was no significant difference among the rate of thenumber of children in each type between typically developingchildren and children with ASD (p>.05). No statistical
calculations was given to type III because there was no children
with ASD using type III.
【study II】The data of 72 typically developing children and
33 children with ASD were analyzed.
① Comparisons between the average amount of work ineach type by children with ASD and that by typicallydeveloping children.
As for traditional type, there was no significant differenceof the average amount of work between children with ASD andtypically developing children (p>.05). As for type I, theaverage amount of work in fish among children with ASD wassignificantly lower than that among typically developingchildren (p<.05). As for type II, the average amounts of workin using soybeans and fish among children with ASD weresignificantly lower than those among typically developingchildren (p<.05). As for type IV, the average amounts ofwork in using soybeans and fish among children with ASD
were significantly lower than those among typically developingchildren (p<.05).
② Comparisons of the average amounts of work by eachtype among children with ASD.
As for using soybeans, the average amount of work for
traditional type was significantly higher than that for type II
and type IV, and the average amount of work for type I was
significantly higher than that for type IV (p<.05). As for using
tofu, there was no significant difference among the averageamounts of work in each type (p>.05). As for using rice, theaverage amount of work for traditional type was significantly
higher than that for type II and type IV (p<.05). As for using
fish, the average amount of work for traditional type wassignificantly higher than that for type IV (p<.05). And then, as
for all ingredients in this study, there was no significant
difference between the average amount of work for traditional
type and that for type I.
Discussion【 study I 】 We assumed that children with ASD had
difficulties in holding chopsticks in traditional way comparedwith typically developing children because of dyspraxia.
However, there was no significant difference of distribution
ratio; traditional type, type I and IV. Participants of this study
were children with ASD who went to kindergarten. Therefore,
although no evidence was presented, there might be apossibility that the same experiences and education for children
with ASD as typically developing children affected this result.
Thus, our results showed a new perspective of hand skills ofchildren with ASD.
【study II】The functionality of traditional type was similar
between children with ASD and typically developing children
in all ingredients. Therefore when children with ASD
kinematically acquired the skill of using traditional type whichis considered as an advanced way of holding chopsticks, it
seems that their functionality has already matured as well as
typically developing children.
Except for tofu, traditional type using other ingredients wasmore functional compared to type IV which has no functional

elements of traditional type. When people hold the chopsticks
in traditional type, it is considered that they can open a moving
chopstick steadily without moving a fixed chopstick. In
contrast, when people hold chopsticks by type IV, it is
impossible to move only a moving chopstick. Thus, traditional
type had higher functionality than type IV. The reason why
there was no significant difference between the average amountof work in using tofu in traditional type and type IV was thatthe tofu was firm and cubes. This made it easy to handle thetofu in any type.
Among children with ASD, typeI, which is similar to
traditional type, had the same functionality as traditional type,while typeII, which is also similar to traditional type, had lower
functionality than traditional type in soybeans and rice. Type I
uses the same fingers to hold a moving chopstick and a fixedchopstick as traditional type. The only difference is the positionof the fingers. Therefore, type I had the same function to movethe chopsticks without needing to move a fixed chopstick as
traditional type. On the other hand, TypeII uses same fingers tohold a moving chopstick as traditional type but uses different
fingers to hold a fixed chopstick. Because of this, typeII was
considered to have more instability of the fixed chopsticks, andas a result, the functionality became lowered.
Conclusion
This study was designed to explore the ways of holding
chopsticks and examine the functionality of each type ofholding chopsticks among children with ASD and typicallydeveloping children (from 5 to 6 years old).
There was no significant difference among the rate of thenumber of children in each type between typically developingchildren and children with ASD.
The functionality of traditional type was similar amongchildren with ASD and typically developing children.
Among children with ASD, the functionality of traditional
type was higher than the other type which had no similarelements to traditional type. The type which held a moving
chopstick and a fixed chopstick in the same way as traditional
type had higher functionality than other type which was similar
to traditional type.
References[1] L. Kerri, G. Reid. Fundamental movement skills and autism
spectrum disorders. J Autism Dev Disord. 2015; 40: 209-217.
[2] N. Grace, P. G. Enticott, B. P. Johnson. N. J. Rinehart, Do
handwriting difficulties correlate with core symptomology,
motor proficiency and attentional behaviours?. J Autism Dev
Disord. 2016; 44: 1006-1017.
[3] S. Hirata, Y. Ikeda, M. Kokubunn. Relationship between
skillfulness of fingers and ability to adjust forces in autistic
spectrum children. Tokyo gakugei college. 2013; 27: 81-88.
[4] C. Smith, J. Arbesman. Evidence-based review ofinterventions for autism used in or of relevance tooccupational therapy. American Journal of Occupational
Therapy. 2008; 62(4): 416-429.
[5] T. Ooka, J. Kuroishi, M. Mukai. Developmental changes ofchopstick operation method and capture function in earlychildhood. The Japanese Journal of Pediatric Dentistry.
2006; 44: 713-719.
Author address- 28 -

E-Mail: sakuma.takuto@d.mbox.nagoya-u.ac.jp

A systematic review of randomized controlled thrials (RCTs) with
community-based intervention for patients with dementia
Ga-in, Shin, B.H.Sc., OT1), Ye-Shin, Woo, B.H.Sc., OT 1), Hae Yean, Park, PhD, OT 2)
1) Dept. of Occupational Therapy, The Graduate School, Yonsei University2) Dept. of Occupational Therapy, College of Health Science, Yonsei University
Introduction
Population aging is progressing in the world now, and aging isfast progressing in Korea[1] . The aging of this population
naturally accompanies the increase of elderly people withchronic diseases and health problems. One of the chronic
diseases is dementia. Currently, dementia is one of the diseases
that puts burdens on caregivers and spouses[2]. The majority ofdementia patients in Korea live in communities rather than in
facilities, and are usually cared for by family members [3] Thus,
families and caregivers are an important resource in the careand support of patients with dementia [4].
Therefore, caregivers who live with dementia suffer fromdepression, physical illness, bankruptcy, social isolation,
anxiety, and so on. And caregivers are sometimes referred to as'second patients' or 'hidden patients[5]. In order to resolve thesocial burden, it is most important to have a therapeutic
approach to social participation and independent living indemented elderly[6]. In addition, the need for rehabilitation
utilizing the community is emerging in order to lessen the social
burden of the caregiver. Thus, Community-based interventions
have emerged in which people with disabilities themselves,
their families, and local communities participate incommunities to reduce costs and manpower while making themost of local amenities and resources[7]. Community-based
interventions are strategies within the community forrehabilitation, equal opportunity, and social integration for all
people with disabilities[8]. Community-based therapies aretreated and performed by a team of occupational therapists,
physical therapists, language therapists, and nurses. Of these,
occupational therapists play an important role in providing
treatment programs for independent daily living, evaluation andremodeling of the family environment, and necessary
supporting tools[9]. The purpose of visiting occupational
therapy for dementia patients and caregivers residing in thecommunity is to maintain and promote independent daily life,
to improve the quality of life by increasing social participation.
So occupational therapy uses a variety of strategic methods toimprove the quality of life and reduce the burden on
caregivers[10]. Korea is lacking in evidence and research about
the quality of community-based and doesn’t have a high level
qualitative intervention experimental research. Therefore, thisstudy aims to provide a basis for the effectiveness ofcommunity based intervention for patients with dementia
through systematic review using only high quality research.
Materials and methods
Methods to obtain data: As shown Figure 1. The literaturesearch focused on Level I studies published journals from2007 to 2017. The following keywords were used{“Dementia” OR “Alzheimer” OR “Dwelling adult”} AND{“Home-based” OR “Home-based intervention” OR“Community-based” OR “Community-based intervention”}
AND {“RCT” OR “Randomized”}. A total of 375 articles
were found through several database searches. After careful
review, only 9 articles were included for this analysis.
Analytical methods / analysis: The 9 studies were analyzed
using the hierarchy of levels of evidence for evidence-based
practice. The qualitative evaluation of the study used the
Physiotherapy Evidence Database(PEDro) scale[11]. The

details of each study were classified and analyzed based on thetype of intervention, the evaluation tool, the evaluation area,
and the experts who performed the intervention. Selected
articles were systematically organized in PICO frame[12].

Results
Qualitative level of research evidence: The qualitative levelof the articles were all 1 level in the study level 5 stepclassification because all nine articles analyzed the randomized
control study.
Subject of the articles: The results of analysis of the subjects
using community based intervention showed that 5 subjects(55.5%) had the highest number of studies on dementia (orAlzheimer 's and the elderly people), 3 subjects (33.3% ). One
study (11.2%) was conducted for dementia patients and theirspouses.
Analysis of frequency and result of use of intervention: The
most frequently used intervention was the exercise
program(33.4%) and the single domain intervention was
higher than complex domain intervention(77.6%).
Analysis of dependent variables area: The most frequent
dependent variables in the 9 articles included dementia elderly
subjects were the physical domains(55.2%). And the mostfrequent dependent variables in the 3 articles included caregiveror spouse were the quality of life domain(20.0%).
Analysis of the experts who performed the intervention: A
total of five types of expert of in 9 articles, including physicaltherapists, occupational therapists, nurses, medical
practitioners, and others not mentioned. The most frequently
experts were the physical therapist(33.2%) and occupational
therapist and nurse were second most frequent(26.7%).
Discussion
This study shows that the quality of the articles is highbecause only the RCTs that quality of the level is the Level 1
are selected. The results of the nine articles analyzed in thisstudy showed the effects of physical, cognitive, quality of life,
ADL, and community-based interventions in various domains.
This indicates that community-based intervention ismeaningful for patients with dementia. The limitations of thisstudy are that the intervention may not be appropriate to thedomestic situation because of the cultural difference in that the- 29 -

intervention is local rather than domestic. In addition, among
the papers analyzed, there are two papers in which theoccupational therapist plays a role of mediator. In addition,
most of the dementia residents in the community are mild andmoderate, but because this study do not search the level ofdementia and there is no systematic protocol for theeffectiveness of the study, it is difficult to interpret the effect of
the intervention. Therefore, it will be necessary to develop a
protocol on intervention effects and research on community
intervention based on dementia level.

Author address
E-Mail: cohandi2003@gmail.com

Conclusion
When the number of dementia patients increases and manyelderly people live in the community due to social cost burden,community based intervention will be more emphasized in the
future. Therefore, occupational therapists should be aware of
the importance of community participation, quality of life ofdementia patients and their caregivers, and appropriate
intervention methods, frequency and duration of intervention
should be studied in Korea. This study suggests that
community-based intervention may have a positive effect onpatients with dementia. Based on this, we can use various
community-based interventions toincrease patientparticipation in the community, You should be able to present
it.
References[1] Choi, S. H., Lee, J., Kim, S. J., Choi, J. Y., Kwon, J. W.,
Yoon, B. N., ... Jeong, J. H. (2014). Driving in patients withdementia: A CREDOS (clinical research center for dementia
of south Korea) Study. Dementia and Neurocognitive
Disorders, 13, 83-88.
[2] Han, Y. S. (2011). A study on the welfare service
improvement of the old with dementia [dissertation]. Seoul:
Hanyang Univ.
[3] Jo, Y. Y. (2008). A study of the caregiver appraisal infamily caregivers of patients with dementia. (Master’s
thesis), Yonsei University, Seoul.
[4] Cantor, M. H., & Brennan, M. (2000). Social care of theelderly: The effects of ethnicity, class and culture. Springer
Publishing Company.
[5] Schulz, R., & Beach, S. R. (1999). Caregiving as a risk
factor for mortality: The caregiver health effects study.
Jama, 282, 2215-2219.
[6] Park, C.S., Jung, W.M., Oh, H.C. (2010). Analysis ofcaregiver needs for home-based occupational therapy
programs for elderly community dwellers with dementia
based on symptom level and caregiver burden. Journal of
Korean Academy of Occupational Therapy, 18(4), 51-62.
[7] Won, J. I. (2008). Necessity of community-based
rehabilitation system after stroke. Journal of the Korea
Contents Association, 8(1), 16-26.
[8] World Health Organization. (1994). Community-based
rehabilitation for and with people with disabilities: 1994 joint
position paper.
[9] Wood, V. A., & Hewer, R. L. (1996). The prevention andmanagement of stroke. Journal of Public Health, 18, 423-431.
[10] Gitlin, L. N., Winter, L., Dennis, M. P., Hodgson, N., &Hauck, W. W. (2010). A biobehavioral home-based
intervention and the well-being of patients with dementia andtheir caregivers: The cope randomized trial.
[11] Tooth, L., McCluskey, A., Hoffmann, T., McKenna, K., &Lovarini, M. (2005). Appraising the quality of randomized
controlled trials: Inter‐rater reliability for the OTseeker
evidence database. Journal of Evaluation in Clinical Practice,11(6), 547-555.
[12] Cozzolino, M. (2009). A review of evidence-based
rehabilitation: A guide to practice, 2nd edition.

- 30 -

The effect of cross-cultural exchange program for occupational therapy students:
A preliminary study
Hyun Jung Kim, OT1), Min-Ye Jung, PhD, OT2)
1) Dept. of Occupational Therapy, The Graduate School, Yonsei University2) Dept. of Occupational Therapy, College of Health Science, Yonsei University
Introduction
With the growing trend of globalization, occupational
therapy students need to be culturally competent to become askillful healthcare professional [6]. Proficient occupational
therapist will be able to deliver a high quality of effective carewhen culturally relevant meaningful interventions arethoughtfully selected [4]. In order to be able to selectmeaningful occupations for a diverse population of clients as
an occupational therapist in the future, it is important toinvestigate possible opportunities of becoming culturallycompetent for the current students [1]. Students at Yonsei
University, South Korea, are immersed in one of four(American, Chinese, Japanese, or Vietnamese) culture for one
to two weeks. The purpose of this study is to examine the effectof cross-cultural programs for the students through acomprehensive survey.
Methods
Subjects: Participants who participated in the occupational
therapy international exchange program offered at universities
or centers located in the U.S.A., Japan, China, and/or Vietnam.
Instrumentation and experimental procedure: The survey,
consisting of four parts were sent to students who haveparticipated in the international exchange program [2].
Participants were to provide basic information regarding theiracademic year, previous participation of the international
exchange program, duration of the program, language used, andcompetence level of the languages used.
In the second part, students were to explain academic,
clinical, and cultural experiences in detail. Questions regarding
academic components included possible opportunities ofmeeting with professors and/or students, when it took place,possibility of auditing a class, and overall feedback on theexperience. For the clinical components, students were asked
to specifically describe the experience of site visits and possible
interactions they had with the occupational therapists. In
clinical components, students were to describe confronting
cultural differences, how they overcame the differences, andapplication of cultural differences to the field of occupational
therapy [3]. Students were asked to weigh the proportions ofacademic, clinical, and cultural components to reflect thecomponents of their exchange program.
Questionnaires on cost-effectiveness were dealt in the thirdpart. Students were to disclose approximate funding received toparticipate in the exchange program as well as the proportionof the funding in relation to the overall financial expenditure.
The degree of the burden on personal expense throughout thewhole span of the program was rated from one (maximum
burden) to 5 (minimal burden). In addition, possible advantages
students may have felt compared to financial expenditure wasalso rated in a 5-point Likert scale.
For the last part, students were expected to rate eachcomponent in a 5-point scale regarding changes in certain
aspects of professional qualifications before and afterparticipation in the program [5]. Questionnaires ranged fromassurance and satisfaction with studying in the field ofoccupational therapy to six professional qualities, such as
autonomy, creativity, problem solving, cultural sensitivity,
competence, and collaboration.

Results
According to the data collected, most of the programs werein English regardless of where the program took place. The
level of English proficiency did not have direct effect to thequality of the program, although some students anticipatedhigher English proficiency to contribute to richer experiences.
All of the students were able to experience academic, clinical,
and cultural components in the program. The ratio of thecomponents varied with the programs which reflected the focusof each program. The questionnaires on cost-effectivenessrevealed a high degree of burden on personal expense for many
students. However, despite the burden, most recognized theadvantages of the exchange program. For the last part, of thesix professional qualities, most of the students had the highest
positive change in autonomy, cultural sensitivity, andcollaboration, which is distinctive of exchange programs [8].
Discussion
The data provided an exhaustive information on how the four
exchange programs panned out. Descriptive statistics were used
to analyze the change in the factors. According to how the
program distributed the academic, clinical, and culturalexperiences, the degree of change in personal and professional
growth were observed [9].
Conclusions
Since the exchange programs guide students to build
interpersonal and intrapersonal skills, necessary to endeavor in
professional health care settings, it is essential to understand thedetails and expand the beneficial components [7].

References[1] Cameron, D., Cockburn, L., Nixon, S., Parnes, P., Garcia,
L., Leotaud, J., . . . Williams, T. (2013). Global Partnerships
for International Fieldwork in Occupational Therapy:
Reflection and Innovation. Occupational Therapy
International, 20(2), 88-96. doi:10.1002/oti.1352[2] Cheung, Y., Shah, S., & Muncer, S. (2002). An Exploratory
Investigation of Undergraduate Students Perceptions ofCultural Awareness. British Journal of Occupational
Therapy,
65(12),
543-550.
doi:10.1177/030802260206501203[3] Committee Opinion No. 493: Cultural Sensitivity andAwareness in the Delivery of Health Care. (2011).
Obstetrics&
Gynecology,
117(5),
1258-1261.
doi:10.1097/aog.0b013e31821d7db0[4] Gat, S., & Ratzon, N. Z. (2014). Comparison of
Occupational Therapy Students Perceived Skills After
Traditional and Nontraditional Fieldwork. American
JournalofOccupational
Therapy,68(2).
doi:10.5014/ajot.2014.007732[5] Ku, I., Jung, M., Yoo, E., Park, J., Lee, J., & Lee, H.
(2015). Development of Competency Indicators for Korean
Occupational Therapists (K-CIOT). Korean Society ofOccupational Therapy, 23(1), 137-149.
[6] Murden, R., Norman, A., Ross, J., Sturdivant, E., Kedia, M.,& Shah, S. (2008). Occupational therapy students- 31 -

perceptions of their cultural awareness and competency.
Occupational Therapy International, 15(3), 191-203.
doi:10.1002/oti.253[7] Rasmussen, T. M., Lloyd, C., & Wielandt, T. (2005).
Cultural awareness among Queensland undergraduate
occupational therapy students. Australian Occupational
Therapy Journal, 52(4), 302-310. doi:10.1111/j.14401630.2005.00508.x[8] Sood, D., Cepa, D., Dsouza, S. A., Saha, S., Aikat, R., &Tuuk, A. (2014). Impact of International Collaborative
Project on Cultural Competence among Occupational
Therapy Students. The Open Journal of Occupational
Therapy, 2(3). doi:10.15453/2168-6408.1111[9] Whiteford, G., & St-Clair, V. W. (2002). Being Preparedfor Diversity in Practice: Occupational Therapy Students
Perceptions of Valuable Intercultural Learning Experiences.
British Journal of Occupational Therapy, 65(3), 129-137.
doi:10.1177/030802260206500305
Author address
E-mail: hjurbana@hotmail.com- 32 -

The study of the brain functional connectivity
during somatosensory image execution
Ryosuke Suzuki, OT1)*, Jun-ichi Uemura, OT2)
1)2)

Dept. of Physical and Occupational Therapy, Graduate School of Medicine, Nagoya University, JAPAN.
Master’s program student.
Dept. of Physical and Occupational Therapy, Graduate School of Medicine, Nagoya University, JAPAN.
Associate professor

1. Introduction
Recently, rehabilitation therapies for stroke survivor withsensory loss have been developed, e.g. transcranial direct
current stimulation [1]. Previous study using a questionnaire to
the occupational and physical therapists showed that anintervention to stroke survivor with sensory loss was often
based on therapist’s experience [2]. There is a gap between thescientific evidence and the actual conditions in clinical setting.
It is difficult for therapist to prepare the instruments within
limited time and expense in the clinical setting. There is a needfor development of a simpler evidence-based method that canbe applied in clinical settings.
The effectiveness of motor imagery on the rehabilitation formotor impairment has been clarified by both basic and clinicalresearch [3]. In the sensory processing, the performing thesensory imagery task activated the somatosensory related areas[4]. Now, application of somatosensory imagery task is
discussing now [5]. Somatosensory imagery task is to image atactile sense without actual sensory stimulation, e.g. imagine
rubbing your wrist with a brush. Somatosensory imagery task is
not the image of moving brush, but the image of the sense thatrubbed by the brush. Understanding the brain foundation of
sensory imagery is important to clarify the brain nerve changes
by rehabilitation with sensory imagery. These understanding
can lead to find the effective interventions to sensory loss
patients. The foundation of the brain activity during sensory
imagery is not well understood at this moment. Therefore, thepurpose of this study is to clarify the functional connectivity
between primary and secondary somatosensory area duringperforming the somatosensory imagery task.
2. Methodology
2.1 Subjects
Thirteen healthy volunteers (age range 20-23years, 4 males)
participated in the present study. All participants gave informed
consents about the purpose of this study before experiment.
The study was approved by the Ethical Committee of Nagoya
University, school of Health Science.
2.2 MEG recording
The brain neuromagnetic responses were recorded by wholehead magnetoencephalography (MEG) with 160-ch (PQ1160C,
Yokogawa Electric Corporation) in magnetically shielded room.
All participants were instructed to lie on the bed in supine
position with their head inside the whole-head MEG system andnot to move their own bodies and less blink during recording.
Before the MEG recording, participant’s head shape wasmeasured by 3D digitizer with five coils attached to thesubject’s forehead and both ears for making subject’s
reorganized anatomical data from default template. At the
beginning of each recording, subject’s head position wasmeasured. At the same time, two electrodes for measuring each
eye movement and electrocardiographic artefacts were attachedin the vicinity of the right eye and two in the both sides lower
clavicle.
2.3 Experimental conditions

This study constructed by three experimental conditions.
First, we made two different movies; one was the movie
brushing one’s right hand thenar (brushing movie) (BRUSH),
the other was not brushing (non-brushing movie) (NONbrush)(Fig. 1). They were the first-person viewpoint movies. Bothmovies consisted of the same components, i.e. right hand thenarand moving brush. The difference between both movies werewhether there is stimulation by the brush or not. Participants
watched each movie for 60 seconds during the MEG recoding.
Additionally, during watching the brushing movie, participants
performed the somatosensory imagery task which was just to
image a sense evoked by brushing their right hand thenar
without actual stimulation (“Image” condition). All participants
practiced the somatosensory imagery task before themeasurement. During recordings, participants were requested
to concentrate on the task, not to think anything. The order ofconditions was counterbalanced among individual and sessions.
Participants performed each trial with short time interval for the
rest. The instructions about each condition were informed toparticipant from the outside of the magnetically shielded room
via the speaker microphone. Participants watched movies
projected from outside the magnetically shielded MEG room ona translucent screen.

Fig. 1. Two different Movies used in experiments.
The left image is a part of the “brushing movie”. The rightimage is a part of the “non-brushing movie”. Non-brushingmeans moving the upwards brush not hitting to the hand. The
rubbing frequency was about two strokes per second in bothmovies. Both movies have same components i.e. the hand not
moving, moving brush, same rubbing frequency. The only
difference between “brushing movie” and “non-brushingmovie” is whether there is stimulation by the brush or not.
2.4 Data analysis
Eleven clear MEG data were analyzed using the“Brainstorm” software. Excluded data was due to drowsinessduring measurements. Coherence value was calculated as anindex for functional connectivity between somatosensory
regions. The coherence value is a measure of the degree ofrelationship between two signals. It’s represented by a numberof 0 to 1, zero mean there is no correlation and closer to 1
indicates a correlation. .In preparation for calculating coherence
value by brainstorm, the artifacts (electrooculogram: EOG,
electrocardiogram: ECG) rejection were applied to measured
data. From the participant’s anatomical head information
measured by 3D digitizer, individual structural template was- 33 -

created. The channel data collected from MEG recording
projected on the individual structural template to make source
data. Coherence value was calculated from source data. We set
the region of interest (ROI) on the left primary somatosensory
area (SI), left secondary somatosensory area (cSII), and right
SII (iSII). Coherence value calculated between SI - cSII, SI iSII and analysis each frequency band; alpha (8-12Hz), low beta
(13-21Hz), high beta (22-30Hz), low gamma (31-42Hz) andhigh gamma (43-60Hz).
2.5 Statistical analysis
One outlier data was excluded and statistical processing was
performed with ten participants’ data. One-way repeatedmeasurements analysis of variance (ANOVA), with Bonferroni
test were employed for statistical analysis. P value set to lessthan 0.05.
3. Results
There were significant differences in the beta frequency band
between NONbrush and Image conditions. The averaged
coherence value in Image condition was significantly lower
than that in NONbrush (Fig. 2). There was no significant
difference in alpha and gamma frequency band nor that in SIiSII.

Fig. 2. The averaged coherence value in three conditions
between SI and cSII at the beta frequency band.
This figure shows the averaged coherence and SD in eachcondition. There were significant differences between
NONbrush and Image conditions, respectively. The averaged
coherence value in Image was lower than that in NONbrush.
(＊: p < 0.05).
4. Discussion
The coherence in beta frequency band between SI and cSII
was decreased in Image condition compared to NONbrush.
First, I discuss about the significant difference between
NONbrush and Image conditions. There are two differences incomponents between these conditions. Image condition hascomponents of brushing and somatosensory image, but
NONbrush condition does not have. I considered that thesedifferences have influenced on the coherence value between SI
and cSII. The somatosensory imagery task activates
somatosensory area (SI, SII) [4]. Similarly, watching the movie
in which the somatosensory stimulation is presented enhances
the activity of the somatosensory area [6]. Both of those twocomponents could drive the somatosensory information
processing, which is similar to processing for actual stimulation.
This somatosensory processing has influenced on the functional
connectivity among somatosensory areas. On the other hand,
there is no significant difference between NONbrush and
BRUSH, BRUSH and Image conditions. I thought thatwatching the somatosensory stimulation alone or somatosensory
imagery task execution alone cannot induce the significant
activation in somatosensory area.
The coherence in only beta frequency band showedsignificant change. While information processing in thesomatosensory cortex is performing, the activity in the sensorymotor field (SI and primary motor cortex) declines in the 10 to
20 Hz band including the beta band [7]. Image condition taskneeds somatosensory information processing. Thus, only in beta
frequency band, there is significant difference.
The coherence value decreased in the Image condition.
As described above, the local oscillation attenuation
phenomenon occurs in the SI during sensory information
processing. It is considered that the coherence value decreasedin Image condition. These local oscillation attenuations arethought to promote necessary information processing in thesomatosensory area, and these phenomena are caused bywatching movie and performing the somatosensory imagery
task. It should be noted here that the coherence value does notindicate a degree of significant activity.
4. Conclusion
In the present study, we revealed the changes offunctional connectivity between somatosensory related areas bywatching video of somatosensory stimulus and somatosensory
imagery task. This study provides basic knowledge inconsidering the intervention to sensory disorder bysomatosensory imagery task.

Reference
1.
Fujimoto S, Kon N, Otaka Y, Yamaguchi T, Nkayama T,
Kondo K, Patrick R, Tanaka S. Transcranial direct current
stimulation over the primary and secondary
somatosensory cortices transiently improves tactile spatial
discrimination in stroke patients. Front. Neurosci. 10, 1–9,
2016.
2.
Pumpa, L. U., Cahill, L. S. & Carey, L. M.
Somatosensory assessment and treatment after stroke: An
evidence-practice gap. Aust. Occup. Ther. J. 62, 93–104,
2015.
3.
Oostra, K., Oomen, A., Vanderstraeten, G. & Vingerhoets,
G. Influence of motor imagery training on gait
rehabilitation in sub-acute stroke: A randomized
controlled trial. J. Rehabil. Med. 47, 204–209, 2015.
4.
Yoon, K. J., Lee, Y.-T. T. & Han, T. R. Mechanism offunctional recovery after repetitive transcranial magnetic
stimulation (rTMS) in the subacute cerebral ischemic rat
model: neural plasticity or anti-apoptosis? Exp. Brain Res.
214, 549–556, 2011.
5.
Garrison, K. A. et al. Real-time fMRI links subjective
experience with brain activity during focused attention.
Neuroimage 81, 110–118, 2013.
6.
Esther Kuehn, Karsten Mueller, Robert Turner, Simone
Schütz-Bosbach, The functional architecture of S1 during
touch observation described with 7 T fMRI, Brain
Structure and Function, 219(1):119-40, 2014.
7.
Stancák A1, Svoboda J, Rachmanová R, Vrána J, Králík J,
Tintera J, Desynchronization of cortical rhythms
following cutaneous stimulation: effects of stimulus
repetition and intensity, and of the size of corpus callosum,
clinical neurophysiology, 114(10):1936-47, 2003.

Author address
E-Mail: suzuki.ryousuk@d,mbox.nagoya-u.ac.jp- 34 -

A systematic review of effects of cognitive rehabilitation therapy for community
dwelling adults with early dementia or mild cognitive impairment.
Sangmi Park, B.H.Sc., O.T1), Ji-Sun Lee, B.H.Sc., O.T1), Kyu-Won Lee, B.H.Sc., O.T1), Won-Seuk Choi, B.H.Sc.,
O.T1), Jung-Ran Kim, Ph.D., O.T 2)
1) Dept. of Occupational Therapy, Graduate School of Yonsei University2) Dept. of Occupational Therapy, College of Health Science, Yonsei University
Introduction
Along with the rapid increase of the elderly population,
the population of dementia is also increasing [1].
According to the data provided by the national institude of
dementia, as of May 2017, the number of elderly people
aged 65 or older in Korea is about 7.1 million, among
which the prevalence of dementia patients is about 10.2%,
Mild Cognitive Impairment (MCI) Patient prevalence wasabout 28%[2]. The prevalence rate of mild cognitive
impairment by age group was about 21% in the aged
between 65 and 74, about 36% in the elderly between 75
and 84 years old, and about 39% in the elderly over 85
years age group. Therefore, it can be confirmed that themild cognitive impairment prevalence increases with age.
It is known that mild cognitive impairment is a normal
stage of cognitive function except memory. However, it is
known that about 10 to 15% of mild cognitive impairment
patients are transitioned to Alzheimer's dementia every
year[3], so management to slow the progression todementia is necessary. Along with the aging of the
population, various studies have been actively conducted
on dementia, which has become one of the major healthproblems of Korean society today. However, a systematic
review of the effects of cognitive rehabilitation on patientswith early dementia and mild cognitive impairment has not
yet been conducted. Therefore, this study aims tocontribute to the effective intervention by analyzing thecharacteristics and effectiveness of cognitive rehabilitationintervention provided for patients with early dementia andmild cognitive impairment. We will also provide basic datafor developing more effective interventions.
The purpose of this study is to analyze the effects ofcognitive rehabilitation treatment on the cognitive functionof patients with early dementia and mild cognitive
impairment in community by analyzing and synthesizing
previous studies with scientific and objective methodology
using systematic review techniques. We also compared thecharacteristics and outcomes of various approaches toimprove cognitive function in patients with early dementia
and mild cognitive impairment.
Materials and methods
The literature search of this study uses NSDL, RISS,KISS, Pubmed, Embase database. The scope of the thesis
was from January 2007 to December 2016. The English
search term was 'community based program' or 'home
based program' and 'early dementia' or 'mild cognitive
impairment' and 'cognitive rehabilitation' or 'cognitive
therapy'. And Korean search term was also the same. The
selection criteria for the study were as follows: a study ofpatients with early dementia or mild cognitive impairment,a study in which intervention was provided in the form ofcommunity or institutional visits, a study that provided a
non-pharmacological approach as a primary intervention,and involving cognitive function as a dependent variable,

study to acquire full-text, and study of adult subjects. We
excluded gray literature, dissertation, articles written inlanguages other than Korean or English, and qualitative
research. After collecting five database search results toselect the articles to be analyzed, duplicate materials andarticles written in languages other than Korean and English
were excluded from the study title review. Secondly, we
excluded studies that were green only through the abstract
review or did not meet the selection criteria. Next, a totalof 12 papers were selected for the final analysis, except for
the research, the degree research, and the gray literature
which did not meet the selection criteria or could notacquire the specialization through the text review. It
consists of 5 articles written in Korean and 7 articles
written in English. The process of deriving the articles tobe analyzed is shown in the following figure1.

The analysis of this study was based on simple descriptive
statistics, and the frequencies and percentages of thesubjects were divided into the subjects, the intervention
methods, and the evaluation tools used. The qualitative
level of the research was also based on the evidence-based
5-step taxonomy developed by Arbesman, Scheer andLieberman (2008)[4].
Results
As a result of analyzing the qualitative level of the 12
domestic and foreign experimental papers, the highest levelof the Ⅰ stage randomized clinical trial design papers was
6, 50.0% of the total. The subjects were diagnosed as mild
cognitive impairment, early dementia, and early
Alzheimer's disease. The average age of participants was- 35 -

between 70 and 75 years. The mean age of theexperimental groups participating in the 12 papers was
70.3 ± 4.85, and the mean age of the control group was
69.2 ± 3.3.82. The male and female ratio was the highest in
male and female sex ratio. The common cognitive level ofthe subjects was less than 1 CDR and MMSE 15 points ormore. The types of intervention are laughter therapy withcognitive enhancement program, cognitive occupational
therapy, cognitive therapy, cognitive intervention program,neuropsychological training, cognitive rehabilitation
program, computerized cognitive training, animal
mediation activities, external memory training, memory
training, and task-oriented training programs, and provided
interventions that incorporate a variety of factors that affectcognitive functioning in most interventions. In order toinvestigate the effect of the intervention, the result
measurement area was classified into the recognition area
and the non - recognition area. In the cognitive domain, thearea with the highest frequency was the overall cognitive
function (37.2%). On the other hand in the non - cognitive
domain, the highest frequency was in the area of dailyliving ability (25.0%). In the case of cognitive function, 9of 12 studies showed significant improvement in theexperimental group after intervention compared to before
intervention. And there were also the 9 out of 12 papers
with significant results in non cognitive function.

[2] National Institude of Dementia. (2017). Detailed viewof dementia status.
https://www.nid.or.kr/info/today_list_test.aspx[3]Kim, S. H., Han, S. H.(2012). Prevalence of Dementia
among the South Korean Population. The Journal of
Korean Diabetes,13(3),124-128.
[4] Arbesman, M., Scheer, J., & Lieberman, D. (2008).

Discussion
This study is meaningful in that it compared and analyzed
the effects and characteristics of various intervention
methods by systematically examining existing studies on
cognitive rehabilitation treatment for patients with early
dementia and mild cognitive impairment. However, insetting the scope of the literature review, only studies on
early dementia and mild cognitive impairment residing in
the community were extracted. Therefore, studies on
subjects living in hospitals and nursing homes were
excluded, There is a limitation that it can not deal with kindand object. Since most of the studies that reported on the
improvement of cognitive function were small groupstudies, a larger sample group should be studied for thegeneralization of treatment effects in the future.
Conclusion
The purpose of this study was to investigate the effects ofcognitive rehabilitation treatment on the improvement ofcognitive function in patients with early onset dementia
and mild cognitive impairment in community and tocompare the characteristics and results of various cognitive
rehabilitation intervention methods. To do this, weanalyzed 12 domestic and international studies through asystematic review study method and found the following
results. In order to increase the accessibility of cognitive
therapy interventions that have proven effective in patientswith early dementia and mild cognitive impairment, it isnecessary to establish and reorganize institutional devices
for quantitative expansion of service provision and quality
fidelity.
References[1] Lee, G. D., Jeon, B. J. (2014). Effects of Home-based
Cognitive Occupational Therapy Applied to Dementia
Patients in the Initial Stages in Gangwon-do. Korean
Society of Community-Based Occupational Therapy,
4(2),75-83.

- 36 -

Using AOTA’s Critically Appraised Topic(CAT) andCritically Appraised Paper(CAP) series to link evidence
to practice. OT Practice, 13(5), 18–22.

Study on the production of lightweight customized wrist splint using
3d modeling and 3d printer
Won-Seuk Choi, B. H. Sc, O.T1), Jong-Bae Kim, Ph.D2),
1) Dept. of Occupational Therapy, Graduate School, Yonsei University2) Dept. of Occupational Therapy, College of Health Science, Yonsei University
Introduction
3D printing technology is a processing technology to
produce the information obtained from 3D scanning / modelingby the lamination method. Recently, many interest and research
activities have been actively performed due to the innovationof the manufacturing industry. 3D printing technology isapplied to various industrial fields such as aviation, automobile,
ship, medical and so on. Especially in medical field, it is used
for manufacturing personalized organ, denture, prosthetic leg,
orthotic support. With the advent of 3D printers, themanufacturing method is gradually changing. Especially, it ispossible to manufacture a patient-customized splint by using asmall quantity production system of various kinds.
The splint is applied to patients with permanent impairment
or temporary impairment of function due to illness or accident,
which gives stability to the function of the joints and theirsurrounding muscles. The design and manufacturing servicesof the customized splint are very important and essential, sothey have to be supplied in a timely manner. 3D printing is
expected to meet this demand.
3D modeling refers to the process of creating a mathematicalmodel that can be reproduced in the 3D space of the computer
graphics world. This modeling is stored in a form that thecomputer can understand. Usually a 3D object is represented by
a 3D line, and it can have a similar feeling and texture to theactual object through the rendering process. Generally, a 3Dmodel is created by constructing a line in space through aconstruction on a 2D plane, connecting drawn lines andarranging them in a space, and setting these lines as faces of apolygon.
Radial nerve palsy is disturbed by musculoskeletal damage
and radial nerve compression causes wrist drop, making it
difficult to lift the wrist up. Carpal tunnel syndrome is the mostcommon cause of compression of the median nerve due tothickened ligaments of the carpal tunnel. It causes pain andsensory abnormality in the lower arm including the wrist,
paralysis, Symptoms may appear (Figure 1).
A cock-up splint is used to treat this. The wrist splint limits theflexion of the wrist to provide rest and protects the wrist (Figure
2).
Therefore, the present study is to reduce the weight andvolume through 3D modeling and 3D printing technology,
lightweight wrist splint manufacturing practices utilizing andsolving the hygiene and cleanliness issues. In addition, we will
examine the possibility of using the leading technology of the
4th Industrial Revolution in clinical application.

Figure 1. Wrist injury (left: wrist drop, right:
carpal tunnel syndrome)

Figure 2. Wrist splint (Cock-up splint))
Methods
Subjects: This study was performed on a healthy male withnormal wrist joint at Y university. The age of the subject was
27 years old. Height was 172cm and weight was 62.8kg. The
palm width of the left upper limb was 8.5cm, the wrist
circumference was 15.5cm, the wrist and wrinkle were 16cm
below the proximal 2/3 of the lower arm and 24cm below thearm.
Research process: Cock-up splint was designed after the left
upper limb of the subject was fixed on the A3 paper and thelower arm, wrist and hand were drawn along the shape with aballpoint pen. The design of the wrist splint designed on A3
paper was reversed by drawing and 3D design was done in
CAD software. For the basic A type and light weight, a B typewrist splint with a polygon pattern was designed in 3D. The
wrist splint was designed to have dimensions of 144mm (width)* 200mm (height) and 2mm (thickness) (Figure 3).

Figure 3. 3D model (left: A type, right: B type)Research tools
1) CAD software
AutoCAD is a CAD solution developed by Auto desk company.
It is a design solution which is widely used in the world. It canrealize design ideas in 2D and 3D, as well as realizing theconcept of an innovative concept by visualizing and shaping
objects.
2) 3D printers
We used Cubicon's 3DP-310F (single plus) and made the Cockup splint layered by FDM.
3) Material
PLA (PolyLactic Acid) is an eco-friendly resin, a- 37 -

biodegradable resin made from the fermentation sugar of plants.
It is a material with a high degree of preference due to its low
toxicity. It has a low degree of shrinkage in ABS coarse
processing and a low incidence of residue. In addition, since
bubbles are not generated, the result of the product ishomogeneous.
Analysis method: The weight and area values of the B type wrist
orthosis with polygon pattern were obtained by using thestructural analysis function provided by AutoCAD, and theoutput time was confirmed by the 3D printer in terms of theoutput completion time.
Research result
The two types of wrist aids were compared in terms of
production time, material savings due to light weight, andventilation due to decrease in the outer area of the splint (Figure.
4).

3D printer improves, it is expected that the lightweight splint
will be produced quickly by replacing the existing
manufacturing method. In addition, since most of the
production time occurs during the 3D printing output process,the therapist can spend less time on production. If the 3D printermanufacturing process is applied clinically, the satisfaction of
the therapist and the patient will be increased, which is expected
to bring great benefits.
Conclusion
The purpose of this study was to develop a lightweight wrist
splint by using 3D modeling and 3D printing for a healthy malewith normal wrist joints and to propose a new method forcomparison with existing wrist splint. The results of thelightweight wrist splint using 3D modeling and 3D printing are
as follows. At the production time, the lightweight wrist brace
took about 30 minutes, but the weight and area were reduced
compared to the existing wrist aids, thus saving material andbreathability.
In the future study, it will be necessary to study the design
method suitable for the damaged characteristics by making thelightweight wrist support for the patients with damaged wrist
joints.
References[1] C. S. Pak, J. H. Park, H. J. Lee, N. K. Lee, S. H. Park andK. H. Na, 2016, "Topology optimization and 3D printing
manufacturing for the personalized hand orthosis,"한국생산제조학회 학술발표대회 논문집, , pp. 125~125.
[2] C. S. Pak, J. H. Park, H. J. Lee and K. H. Na, 2016, "Designand Manufacturing of the hand orthosis using 3D printing,"한국생산제조학회 학술발표대회 논문집, , pp. 188~188.
[3] B. G. Choi, S. Y. Heo, K. T. Son, S. Y. Lee, D. Y. Na andK. M. Rhee, 2015, "3D printing-based Fabrication of
Orthotic Devices Using 3D Computer-Aided Design and
Rapid Prototyping," Journal of Rehabilitation Welfare
Engineering & Assistive Technology, Vol. 9, No. 2, pp.
145~151.
[4] D. Palousek. , 2014 , Pilot study of the wrist orthosis design
process , Rapid Prototyping Journal 20 (1) : 27 ~ 32
[5] L. Mount. , 1992 , Splint Classification system , American
Society of Hand Therapists[6] Se-Hwan Park and Yong-Soo Choi, 2013, "3D Printing
Technology and Market Analysis," 대한전자공학회

Figure 4. Wrist splint(Cock-up splint)
It was confirmed that B type increased by about 30 minutes
in case of production time, and B type was lightened by 17.09g,
which resulted in a material saving of about 39.7% and an area
reduction of 50796 mm². (Table 1).
Table 1. Comparison of wrist splint
Time
Weight(hour : min)(g)
A type02:16
43.03
B type

02:47

25.94

Area
(mm2)

11458763791

Discussion
The purpose of this study is to provide a basic basis forclinical use of 3D prototyping by using 3D modeling and 3D
printing. As a result, the wrist splint with a polygon pattern has
a longer production time than the basic wrist splint but theweight, material and area are reduced. This improves theconvenience of use, secures materials and ventilation, And skindamage can be prevented. Therefore, if the performance of the학술대회, , pp. 809~812.
[7] J. H. Lee, M. N. Choi, S. B. Yim and G. M. Rhee, 2010,"Case Study on Design, Manufacture and Application ofcustomized Assistive Device for the ADL of Person with
Brain Lesions," Journal of Rehabilitation Welfare
Engineering & Assistive Technology, Vol. 4, No. 1, pp.
81~86.
[8] Sungwoo CHO, 2015, "Application of 3D printing into thesurgical field," The Korean Society of Endoscopic &Laparoscopic Surgeons, pp. 185~186.
[9]Auth Yong-Suk Jang, Sun-Tae Chung, Boo-Gyoun Kim andSeongwon Cho, 2008, "3D Face Modeling based on 3D
Morphable Shape Model," JOURNAL OF THE KOREACONTENTS ASSOCIATION, Vol. 8, No. 1, pp.
212~227.or address
E-Mail: wonseuk@yonsei.ac.kr- 38 -

Abstract

Radiological Science andTechnology- 39 -

- 40 -

Exchange Meeting* Date: 2017.11.02.
* Place: Baekun Hall 534

11:00~11:10

Opening Session

11:10~12:10

Session I

11:10~11:25

Prof.

Chul-Hee Min (Yonsei Univ.)

Chair: Prof. Masataka Komori and Chul Hee Min

Development of SiPM based Scintillation Detector for Energy
Selective X-ray Imaging
C. W. Park, K. B. Kim, H. K. Song, I. S. Kang, and Y. H. Chung (Yonsei
Univ.)

11:25~11:40

Quantification of in vivo 1H Spectrum Using an Experimentallymeasured basis-set at 9.4 T
C. S. Yoon, Y. H. Hwang, M. H. Lee, Areum Min, H. M. Baek, B. S. Han,
and D. Y. Kim (Yonsei Univ.)

11:40~11:55

A Method to Detect Arterial Thrombosis Using 3D cine Phase
Contrast Magnetic Resonance Imaging
T. Mizuno, H. Lsoda, S, Tajima, R. Perera, T. Izumi, T. Tsukada, S.
Naganawa (Nagoya Univ.)

11:55~12:10

Development of the Accurate Skin Dose Evaluation Techniques Using
Tetrahedral-Mesh-Based Computational Human Phantom
B. W. Cheon, D. H. Yoo, H. J. Choi, H. J. Park, J. I. Park, C. H.Min (Yonsei
Univ.)

12:30~14:00

Lunch- 41 -

14:00~15:00
14:00~14:15

Session II Chair: Prof. Masataka Komori and Chul Hee Min
SingleProjection-BasedNew

Software

Schemefor

Scatter

Correction
K. S. Kim, S. Y. Kang, W. S. Kim, H. S. Cho (Yonsei Univ.)
14:15~14:30

Estimation of Optical

Artifacts in Luminescence Imaging of Water

during Proton-Beam Irradiations
T. Yabe, M. Komori, R. Horita, H. Oguchi, T. Toshito, and S. Yamamoto(Nagoya Univ.)
14:30~14:45

Beam-Quality Factor Evaluation for Passive Scattering Proton
Therapy with Farmer Type Ionization Chamber Using Monte Carlo
MethodJ. W. Jang, W. G. Shin, and C. H. Min (Yonsei Univ.)

14:45~15:00

Breast-Dedicated PET System with a Personalized Gantry
I. S. Kang, C. W. Park, H. K. Song, K. B. Kim, Y. H. Chung (Yonsei
Univ.)

15:00~15:10

Closing Remark

15:10~15:20

Group Photos※ 12 minutes presentation and 3 minutes

Prof. Masataka Komori

Q&A- 42 -(Nagoya Univ.)Development of SiPM based Scintillation Detector for Energy Selective X-ray Imaging
Chan Woo Park1), Kyu-Bum Kim1), HanKyeol Song1), In-Soo Kang1), Yong-Hyun Chung1.*)
1.*) Department of Radiation Convergence Engineering, Yonsei University, Wonju, Republic of Korea
Introduction
Scintillation detector is one of the most widely used detector
for the radiation detection in the fields of nuclear physics, spaceand medical applications. Scintillation detector is composed ofscintillation crystals and photon detector such as
photomultiplier tube(PMT), avalanche photodiodes (APD), andsilicon photomultiplier(SiPM:MPPC). Comparing to otherscintillation detector, SiPM scintillation detector has a good
performance due to relatively low operating voltages, wide
dynamic range, good energy resolution and compact structure.
In addition, selective counting of a specified energy photon ispossible by measuring and analyzing x-ray energy spectrum.
Energy selective x-ray imaging can improve the signal-to-noise
ratio (SNR), the image contrast compared to conventional
detector systems and can distinguish the composed materialusing material decomposition.
In this study, a detector based on a scintillation crystal and a
SiPM has been developed and tested for energy selective x-ray
imaging.
Materials and methods
GATE simulation study: The number of X-ray photons
generated in the X-ray tube is excessive and scintillation
detector has a maximum count rate limit, which is characteristicof the photon counting system. The count rate was measured toconfirm the feasibility of x-ray scintillation detector.
The Geant4 Application for Tomographic Emission (GATE)
code was used to simulate the x-ray detection system. Figure 1
shows the simulated x-ray system and water phantom. The
distance between the source and detector was 750 mm, and thephantom was located in the center between the source anddetector. The x-ray source was 83 kVp, 1 mA, which wasfiltered with 2.8 mmAl filter. The collimator was composed of
50 mm thickness Pb (lead). The beam size of the collimator was
27 X 27 mm2, and the fan-beam angle was 1.1º. The water
phantom size was 200 X 200 X 200 mm3. The x-ray
scintillation detector consisted of one module, and the module
consisted of a GAGG crystal that was 3 X 20 X 3 mm3 in GATE.

reflector material (reflective coefficient, RC 0.98). Crystal was
optically coupled to SiPM (ArrayJ-30035-64P, SensL) with
optical grease. Optical grease (BC-630, refractive index of
1.465) had same area as crystal and 0.1 mm thickness (Figure
2).

Figure 2. Simulation geometry using DETECT
The light photon had energy of 30 keV, which was meanenergy of 83 kVp x-ray). The position of generated light photon
was 5 point within 4 X 1 pixel and z-axis position had 0.1 mm
offset (Figure 3).

Figure 3. The position of generated light photon
Experimental study: X-ray spectrum and image wereobtained using GAGG and SiPM based on the results of GATE
and DETECT simulations.
The x-ray source was 83 kVp, 20 mA, which was filteredwith 0.8 mmAl inherent filter and 2.0 mmAl samarium k-edge
filter (40 keV k-edge). Scintillation detector was composed ofa GAGG crystal of 3 X 20 X 3 mm3 and a SiPM (ArrayJ-3003564P, SensL). The SiPM was 8 X 8 array, whose pixel size was
3 X 3 mm2 with a 27 X 27 mm2 sensor area (Figure 4).

Figure 4. Detector module design
Figure 1. Simulation geometry using GATEDETECT simulation study: DETECT simulation was used
to measure transition of light distribution along the source
position in order to image using Anger logic.
GAGG (refractive index of 1.9) with a size of 3 X 20 X 3
mm3 was modeled. The upper and side surface were treatedwith a paint representing the surface painted with the diffuser

The data acquisition system used for the experiments was
described in Figure 5. SiPM signals were amplified by a preamplifier (AB4L-ARRAYJ64P-2X1-S Anger logic board, AiT)and routed to an anger logic circuit generating four anger
signals. The amplifier, constant faction discriminator (CFD),
Gate & Delay module were used as NIM module. The signals
were acquired by a DAQ (PCI-6132, NI). The energy spectrum- 43 -

was extracted from the signals and image was obtained using
Anger logic (Figure 5).

Figure 5. Electronics scheme
Results
GATE simulation study: The GATE simulation results
demonstrated that X-ray can be detected using scintillation
detector with water phantom since photon flux is sufficiently
reduced.

Figure 8. Experimental result(a) : 83 kVp x-ray spectrum using GAGG and samarium filter(b) : 83 kVp x-ray image using GAGG and samarium filter
Discussion & Conclusion
The feasibility of x-ray scintillation detector using GAGG
crystal and SiPM was verified using GATE, DETECT
simulation and experimental study.
In additions, Material decomposition can be performed
through selective counting of low-energy and high-energy
photon using scintillation detector. In further study, we plan to
use the monolithic crystal with the same size as Sensl, SiPM
(27 X 27 mm2) for measuring spectrum and imaging.

Figure 6. GATE simulation result(a) : Comparesion of the count rate with or without water
phantom(b) : 83 kVp x-ray image using GATE simulation
DETECT simulation study: It is possible to image using
anger logic since the transition of light distribution along thesource position within the same pixel is observed.

References[1] James Wear, et al., CZT detector for dual-energy x-ray
absorptiometry, Proceedings of SPIE Vol. 4142 (2000).
[2] Wei Zhao, Goran Ristic, J. A. Rowlands, X-ray imaging
performance of structured
Author address
E-Mail: cksdn9432@gmail.com

Figure 7. DETECT simulation result
Experimental study: In experimental result using GAGG
crystal and SiPM, 83 kVp x-ray spectrum with samarium filter(k-edge filter(40 keV)) was obtained. Due to the K-edge, lowenergy and high-energy regions can be distinguished and eachenergy peak was measured at 38 keV, 65 keV.

- 44 -

Quantification of in vivo 1H Spectrum Using an Experimentally Measured
Basis-Set at 9.4 T
1)Chang-Soo Yun , Yoon Ho Hwang2), Min-Hee Lee2), Areum Min2), Hyeon-Man Baek3),
Bong Soo Han1.*), and Dong Youn Kim2.*)
1.*) Department of Radiation Convergence Engineering, Yonsei University, Wonju, Republic of Korea
2.*) Department of Biomedical Engineering, Yonsei University, Wonju, Republic of Korea,
3) Department of Basic Medical Sciences, Gachon University, Incheon, Republic of Korea,
4) Department of Radiological Science, Yonsei University, Wonju, Republic of Korea.

Introduction
Proton magnetic resonance spectroscopy (1H-MRS) is a
non-invasive technique that allows quantifying brain
metabolites. Our purpose is to measure experimentally basisset of brain metabolites using 1H-MRS and quantify in vivo 1H
spectrum in a mouse brain based on the basis-set.
Materials and methods
We made phantoms of 17 brain metabolites maintaining thecondition that were in the physiological pH (7.0 ~ 7.2) and low
temperature (0 ~ 4°). All spectra of the phantoms wereacquired at 9.4 T MRI scanner (Agilent) using point resolved
spectroscopy (PRESS) sequence with following acquisition
parameters: repetition time (TR): 10000 ms, echo time (TE): 15
ms, the number of scans (NS): 128, volume of interest (VOI):
27 μL. The measured spectra of brain metabolites were used tomake the basis-set using LCModel. We used the basis-set to fit
in vivo 1H spectrum in a C57BL/6 mouse brain. We set the VOIof 3.6 μL in hippocampus of the mouse brain. In vivo 1H
spectrum was also measured at same scanner using PRESS
sequence (TR: 6000 ms, TE: 15 ms, NS: 384).
Results
We experimentally measured basis-set of the 17 brain
metabolites and quantified 12 brain metabolites inhippocampus of the mouse brain.

Figure 1. (a) T2-weighted axial image with the interest ofvoxel (VOI, 3.6 μL) in hippocampus of mouse brain. (b) In
vivo 1H spectrum (black line) in mouse brain and the result(red line) with LCModel analysis.

Table 1. Absolute concentration (Conc.) and Cramer Raolower bounds (CRLB) of the brain metabolites detected with
LCModel analysis.
Cr

Gln

Glu

GPC

GSH

m-Ins

Conc.

9.086

5.681

4.373

0.984

2.324

2.961

CRLB

3%

10%

7%

6%

8%

8%

NAA

PCho

Tau

NAA +
NAAG

Cr + PCr

Glu+Gln

Conc.

10.35

0.628

7.865

10.35

9.086

10.054

CRLB

5%

11%

3%

5%

3%

6%

Conclusion
In this study, we attempted to make basis-set from phantom
spectra and then quantified in vivo 1H spectrum of brain
metabolites in a mouse. We determined the basis-set of thebrain metabolites. From these basis-set, we quantified 12 brain
metabolites in the mouse. In our future study, we could quantify
the change of the brain metabolites, which may result from thebrain disease, can be periodically monitored.
References[1] Govindaraju V, Young K, Maudsley AA. Proton NMR
chemical shifts and coupling constants for brain metabolites.
NMR in Biomedicine. 2000, 13(3), 129-153.
[2] Provencher SW. Estimation of metabolite concentrations
from localized in vivo proton NMR spectra. Magnetic
Resonance in medicine. 1993, 30, 672-679.
[3] Provencher SW. Automatic quantitation of localized in vivo
1H spectra with LCModel. NMR in Biomedicine. 2001, 14,
260-264.
[4] Cudalbu C, Cavassila S, Rabeson H, et al. Influence ofmeasured and simulated basis sets on metabolite
concentration estimates. NMR in Biomedicine. 2008, 21(6),627-636.
Author address
E-Mail: exylis79@gmail.com- 45 -A Method to Detect Arterial Thrombosis Using 3D cine Phase Contrast Magnetic ResonanceImaging
Takashi Mizuno 1), Haruo Isoda 2),1), Syunsuke Tajima 1), Roshani Perera 1), Takashi Izumi 3), Tetsuya Tsukada 4), 3),
Shinji Naganawa 5)1) Department of Radiological and Medical Laboratory Science, Nagoya University Graduate School of Medicine,
2) Brain & Mind Research Center, Nagoya University3) Department of Neurosurgery, Nagoya University4) Department of Neurosurgery, Nagoya University Graduate School of Medicine
5) Department of Radiology, Nagoya University Graduate School of Medicine
1.
Introduction
Intracranial aneurysm rupture rate is reported to be
0.95 % per year in Japan [1]. One out of three ruptured
aneurysm cases are found to be mortal while anotherone third undergo severe secondary injuries. Therefore,
it is important to predict the rupture of aneurysms.
Hemodynamics in and around the aneurysm could
affect the rupture of intracranial aneurysms [2].
Magnetic resonance fluid dynamics (MRFD) using
3D cine phase contrast (PC) MR has been researched
as a method to analyze hemodynamics [3]. This MR
sequence is the technique utilized to image the motionof proton, which provides blood flow velocity andvessel information (Fig 1)

Fig 1 Schema of 3D cine PC MR,
VENC, velocity encoding
Phase image and rephased image can be obtained from
3D cine PC MR. The pixel values of phase images
provide us the blood velocity components in the x, y, z
direction. By summing the three directional velocities,
three dimensional velocity can be calculated. Rephased
image is a kind of bright blood image in which signalof artery is high.
In MRFD, phase image of 3D cine PC MR provide
blood velocity data while rephased images provide
vascular shape.
Thrombosis inside of giant aneurysm, which may benatural or triggered by treatment, plays a vital role inboth diagnosis and treatment of intracranial aneurysms.
In MRFD, it is important to distinguish the thrombosis
and the aneurysm wall. However, it is difficult todistinct aneurysm wall in existing MR imaging
because the signal intensity of thrombosis changes by
the T1 and T2 value reflecting the history ofthrombosis [4]. This signal intensity fluctuation reduces
the accuracy of MRFD.
The phase image of 3D cine PC MR does notdepend on T1 and T2 value. Thus, we hypothesizedthat the phase images could be utilized to distinguishcomparatively stationary thrombosed region and themoving blood in the artery. The purpose of this study

was to investigate a method to detect arterial thrombosis
apart from artery using phase image of 3D cine PC MR.
2.
Materials and Methods
This study was approved by the institutional review boardof Nagoya University Graduate School of Medicine.
2-1. Subject
We selected a patient who had been treated intracranial
aneurysm with flow diverter stent in Nagoya University
Hospital. In this case, post treatment thrombosis had been
identified and reported from cone beam CT.
2-2. MR Imaging
MR imaging was performed by a 3.0 T MR scanner (Verio,
Siemens, Germany) and 12-channel coil. (Head Matrix Coil,
Siemens, Germany). Imaging parameters of 3D cine PC
MR were as follows: slab orientation, transaxial; repetition
time (TR)/ echo time (TE), 31 ms /3.18 ms; matrix size,
160x160x30 (320x320x30 with zero-filled interpolation
processing [ZIP]); voxel size, 1.0x1.0x1.0 mm3,
(0.5x0.5x1.0 mm3 with ZIP); velocity encoding (VENC),
120 cm/s; number of phases, 24; acquisition time, 33 min
48 s.
2-3. Analysis Methods
The slices in which arterial thrombosis were well displayed
were selected from phase images in the direction of x, y,
and z. Using image analysis software (Image J, National
institutes of Health, USA), the pixel values of phase images
were obtained from the slices over cardiac phases (Fig 2).

Fig 2 Selection of slice and cardiac phase from phase
imagesThe pixel values were loaded to Excel (Microsoft
Corporation, USA) corresponding the location of pixel tocell of Excel. Then, velocity V (cm/s) in the each direction
could be expressed as𝑉𝑉 =𝑃𝑃× 𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉 − 𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉 (1)2048

where P shows pixel value. Net velocity magnitude (𝑁𝑁𝑁𝑁𝑁𝑁)
which was sum of each velocity components in the x, y, z
direction was calculated by the following equation;- 46 -

𝑁𝑁𝑁𝑁𝑁𝑁𝑘𝑘,𝑖𝑖𝑖𝑖 = �(𝑉𝑉𝑥𝑥,𝑘𝑘,𝑖𝑖𝑖𝑖 )2 + (𝑉𝑉𝑦𝑦,𝑘𝑘,𝑖𝑖𝑖𝑖 )2 + (𝑉𝑉𝑧𝑧,𝑘𝑘,𝑖𝑖𝑖𝑖 )2 (2)where k shows the cardiac phase (= 1, 2, ⋯ , n) , i
shows the x coordinate of the 𝑁𝑁𝑁𝑁𝑁𝑁𝑘𝑘 (= 1, 2, ⋯ , 320),
and j shows the y coordinate of the 𝑁𝑁𝑁𝑁𝑁𝑁𝑘𝑘 (=1, 2, ⋯ , 320). Time averaged velocity (𝑇𝑇𝑇𝑇𝑇𝑇 𝑖𝑖𝑖𝑖 ) in eachpixels was calculated by the following equation;∑𝑛𝑛𝑘𝑘=1(𝑁𝑁𝑁𝑁𝑁𝑁𝑘𝑘 ) 𝑖𝑖𝑖𝑖
(3)
𝑇𝑇𝑇𝑇𝑇𝑇 𝑖𝑖𝑖𝑖 =𝑛𝑛Standard deviation of time averaged velocity(𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑖𝑖𝑖𝑖 ) was calculated by the following equation;2���������
∑𝑛𝑛𝑘𝑘=1(𝑁𝑁𝑁𝑁𝑁𝑁
𝚤𝚤𝚤𝚤 − 𝑁𝑁𝑁𝑁𝑁𝑁𝑘𝑘,𝑖𝑖𝑖𝑖 )𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝑖𝑖𝑖𝑖 = �(4)𝑛𝑛
From the results of calculation, histograms werecreated and 𝑇𝑇𝑇𝑇𝑇𝑇 images and 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 images werecolor-coded according to the threshold created fromthe histograms. Distributions of calculated values ofthrombosis, arteries, and parenchyma were obtained.

3.
Results
Fig 3 illustrates the results obtained for the analyzed
case.

obtained by Fig 3 are shown in Table1 and 2.
Table 1 𝑇𝑇𝑇𝑇𝑇𝑇 values of thrombosis and surrounding tissue inthe selected slice

𝑇𝑇𝑇𝑇𝑇𝑇 , time averaged velocity; Rt, right; Lt left; ICA internal
carotid artery; BA, basilar artery

Table 2 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 values of thrombosis and surrounding
tissue in the selected slice

𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 ; standard deviation of time averaged velocity; Rt,
right; Lt, left; ICA, internal carotid artery; BA, basilar
artery4.
Conclusions
In this case, arterial thrombosis, arteries and parenchyma
could be distinguished in 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 image. In the future, it
might be possible to increase the accuracy of MRFD forpartially thrombosed aneurysms by this method.
5.
References[1]. UCAS Japan Investigators, Morita A, et al. N Engl
JMed. 2012 Jun 28; 366: 2474-82.
[2]. Meng H, et al. Stroke. 2007 Jun; 38 (6): 1924-31.
[3]. Isoda H, et al. Neuroradiology. 2010 Oct; 52 (10):921-8.
[4]. Saindane AM, et al. AJR Am J Roentgenol. 2013 Jul;
201 (1): 162-9.
6.
Author address
E-Mail: mizuno.takashi@c.mbox.nagoya-u.ac.jp

Fig 3 Comparison among rephased image, 𝑇𝑇𝑇𝑇𝑇𝑇 image
and 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 image(a) Rephased image of 3D cine PC MR(b) 𝑇𝑇𝑇𝑇𝑇𝑇 image. 𝑇𝑇𝑇𝑇𝑇𝑇 image range; blue cell<5cm/s,
5cm/s<white cell<20cm/s, 20cm/s<red cell(c) 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 image. 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 image range; blue
cell<10cm/s, 10cm/s<white cell<70cm/s, 70cm/s<red
cell,
Rt, right; Lt, left; ICA, internal carotid artery; BA,basilar arteryAs shown in Fig 3b, arteries are detected. However,structure of thrombosis is vague in the 𝑇𝑇𝑇𝑇𝑇𝑇 image
because analyzed values of the thrombosis were almost
equal to those of parenchyma. As shown in Fig 3c,arterial thrombosis is distinct in 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 image. The
analyzed values based on anatomical information- 47 -

Development of the Accurate Skin Dose Evaluation Techniques Using TetrahedralMesh-Based Computational Human Phantom
1)

Bo Wee Cheon , Do Hyeon Yoo1), Hyun Joon Choi1), Hyo Jun Park1), Jung In Kim2) and Chul Hee Min1,*)1,*) Department of Radiation Convergence Engineering, Yonsei University, Republic of Korea
2) Department of Radiation Oncology, Seoul National University Hospital, Republic of Korea
Introduction
Treatment Planning System (TPS) is widely used to deliveraccurate dose to the patient and to anticipate the patient dose
distribution in advance. Since the quality of the treatment
affects the quality of patient’s life, it is important to accurately
evaluate the patient dose. Especially, accurate prediction of
the skin dose is required because of the incorrect skin dose
prediction in radiation therapy can occur the skin side effects
such as inflammation, necrosis, and desquamation (skin target
layer). According to the International Commission on
Radiological Protection (ICRP), the skin dose should bemeasured at 50-100 um depth from the skin surface between
the epidermis and the dermis. However, the current TPS dose
calculation algorithm based on the patient CT images (morethan 600 um voxel size) cannot define the skin target (50 um
from the skin surface and 50 um thick). Recently, newly
computational human phantom was developed to accurately
evaluate the dose from the radiation to the human body(polygon mesh and tetrahedral mesh based phantom). By
using these phantoms, it is possible to precisely define a thinskin target layer and to accurately evaluate the skin dose at that
position.
The purpose of this study is to develop the accurate skin dose
evaluation technique by modeling very skin target layer on thepatient CT based tetrahedral mesh phantom.
Materials and methods
In this study, the Varian Clinac 2300 IX 6 MV linear
accelerator was modeled by using Geant4 Monte Carlo toolkits to simulate the treatment plan and to assess the patient skindose.
In-house developed algorithm was used to extract patient CT
data and to simulate treatment plan from the DICOM offeredby Seoul National University Hospital (SNUH). We
constructed the patient-specific phantom based on thecontouring data from the DICOM file. The patient CT, which
consists of voxels, was converted to polygon-mesh phantom
and the treatment plan was simulated with the phantom.
Through the patient CT images, the patient-CT-based polygon
mesh based computational phantom was modeled include thethin skin layer, such as the epidermis, the basal layer and thedermis.
Finally, the polygon mesh phantom was converted totetrahedral-mesh phantom for fast MC simulation.
Treatment plan of the patient who underwent brain cancer was
employed to evaluate the skin dose using patient-specificphantom. In the treatment, 10 x 10 cm2 6 MV therapeutic beam
was delivered to the patient with the source-to-axis distance(SAD) of 100 cm.
In this study, the skin dose was separately calculated for 50
um basal layer and for 2,000 um whole skin layer, respectively.
The dose distribution and the dose-volume histogram (DVH)
for the skin were obtained to evaluate the dose delivery to theskin layer and the basal layer.

Figure 1. CT image based patient specific phantom with a thinskin layers.

Figure 2. 3-dimensional distribution of absorbed skin dose
(Left) and its transvers view wit Planning Tumor Volume(Right).
Results
Figure 3 shows the simulation of the treatment plan employedin this study. The dose to each tetrahedral was calculated
separately and integrated for assessing the skin and organ dose.
Figure 2 indicates the 3D view of the dose distribution inside
the patient body. The PTV was illustrated with yellow solid on
the right in figure 2. Since sufficient dose was delivered to the
PTV, we regarded the dose distribution as reliable.
The skin dose has been evaluated by being averaged for thewhole skin volume in TPS. However, we suggest that the dosebe assessed in local area, which is indicated as beam path likefigure 4. So, we compared the DVHs of skin dose averaged by
local skin volume and whole skin volume as represented infigure 4.
Figure 5 shows the local DVHs for the skin layer with 2,000
um thickness and 50 um thickness. These result shows that
there is significant difference between the dose to the basal
layer and the entire skin.
Discussion
The dose to the skin was assessed by using patient-specifictetrahedral phantom in this study. In the figure 4, the DVH ofthe local skin area showed significant dose difference comparedto that of the entire skin. The result infers that the skin dose
could be underestimated when it is averaged by the entire skinvolume. With this regard, we suggest that the skin dose shouldbe evaluated in local skin area.
The doses to the entire skin and the basal layer were comparedto evaluate the feasibility of the suggestion in this study. Figure- 48 -

5 shows that dose evaluated with 2,000 um voxels has notabledifference from the dose with 50 um. However, this study did
not consider the patient specific factors such as HU value andthe individual skin thickness. Since there are variations in thosefactors, study on the consideration of these factors in the skindose calculation is required.

[1] Olsen, Deborah Lee, et al. "The effect of aloe vera gel/mild
soap versus mild soap alone in preventing skin reactions inpatients undergoing radiation therapy." Oncology nursing
forum. Vol. 28. No. 3. 2001.
[2] Petoussi-Henss, N., et al. "Conversion coefficients forradiological protection quantities for external radiation
exposures." Annals of the ICRP 40.2-5 (2010): 1-257.
[3] Kim, Chan Hyeong, et al. "A polygon-surface reference
Korean male phantom (PSRK-Man) and its direct
implementation in Geant4 Monte Carlo simulation." Physics
in medicine and biology 56.10 (2011): 3137.
[4] Yeom, Yeon Soo, et al. "Tetrahedral-mesh-based
computational human phantom for fast Monte Carlo dose
calculations." Physics in medicine and biology 59.12 (2014):
3173.
Author address
E-Mail: chmin@yonsei.ac.kr

Figure 3. Tetrahedral mesh based patient specific phantom(Left) and dose calculation simulation of 3D-CRT process(Right).

Figure 4. Dose Volume Histogram (DVH) of whole skin andlocal skin on the basal layer.

Figure 5. Local DVH of according to each layers.
Conclusion
We assessed the patient skin dose by using patient-specifictetrahedral phantom and in-house developed algorithm. The
results showed that the skin dose should be evaluated moreexquisitely with volumes measuring smaller than 50 um, which
the TPS algorithm is not available. Since the factors such as HU
value of the CT image and the individual skin thickness were
not considered in this study, study on the consideration of thesefactors in skin dose calculation will be carried out in the future.
References- 49 -

Single Projection-Based New Software Scheme For Scatter Correction
Kyuseok Kim1), Seokyoon Kang1), Woosung Kim1), and Hyosung Cho1.*)1.*) Department of Radiation Convergence Engineering, Yonsei University, Wonju, Republic of Korea
Introduction
In conventional radiography, image contrast often suffersfrom radiation scatter, which decreases the quantitative
usefulness of radiographic images. Many scatter suppression
methods have been proposed in attempt to overcome these
difficulties, most of which are based on hardware means of
scatter rejection (e.g., antiscatter grid and air-gap techniques)
and software means of scatter correction [1,2]. Several scatter
estimation methods by measurement (e.g., beam-stopmeasurement behind the object of interest to characterize thescatter kernel), mathematical and physical modelling (asanalytical and Monte-Carlo models), or combination of bothhave extensively been investigated in the literature [3-5].
Convolution-based methods by incorporating a thicknessdependent scatter kernel are typically one such algorithm of
scatter correction [6,7]. Nevertheless, those methods demand
extra work to measure the scatter components and theirexperimental validation has not yet been done. In this work,
we propose a new software algorithm for the scatter correction
using a single projection which directly estimates the scatter
intensity using the weighted l1-norm based contextual
regularization framework. We implemented the proposed
algorithm and performed an experiment to demonstrate its
viability.
Materials and Methods
In radiography, the intensity obseved at a detector pixel at(x,y), I(x,y), is simply described by Eqs. (1) and (2):I ( x, y ) = I p ( x, y ) + S ( x, y ) ,(1)

S ( x, y ) = I p ( x, y ) ⊗ sPSF ( x, y ),(2)

where Ip is the primary, S is the scatter component, sPSF is thescatter point-spread function, and the operator ⊗ represents
two-dimensional (2D) convolution. Thus the primary image
can be recovered by simply subtracting the scatter component
from the observed image, if the scatter image is properly
estimated. In this study, we propose a new software scheme of
scatter correction from a single projection based on a Eq. (1).
However, the proposed scheme has difficulty to derive ascatter-corrrected image from the single projection, which ishighly underconstrained. Tarel et al. proposed an effective
constraint imposed on S, considering the heuristic
characteristic of scattering signal that it is spatially diffused inradiography and should be smooth except the edges of theobject structure [8]. Optimal scatter component, S*, can benormally found by minimizing the following objectivefunction, f(s(k)), with the weighted l1-norm based contextual
regularization framework [9], described as in Eq. (3):( )

 I ( x )- I ( y ) 2 ,S * = arg min f S (k ) , W = exp −2
2σS ( k )∈w
( ) 2λ S ( ) − M + W  (D ⊗ S ( ) ) ,f S (k ) =

k

2

k

(3)

Figure 1. Simplified flowchart of the proposed scatter-correction
algorithm in conventional radiography.
where w is the set of feasible S(k), 𝜆𝜆 is the regularization
parameter for balancing the two terms, D is the differential
operator,  represents the elementwise multiplication operator,
W is the weighting function which is related to the squared
difference between the two neighboring pixels of the medianfiltered image M(x,y), and σ is a prescribed parameter. The
optimization problem described in Eq. (3) can be solved
efficiently by using the alternating-direction method ofmultipliers (ADMM) [10].
Figure 1 shows the simplified flowchart of the proposed
algorithm. In brief, as illustrated in Fig. 1, an observed image isacquired from the x-ray imaging system and the corresponding
constraint map M(x,y) is determined by using the median of
median filtering method which was proposed by Tarel et al. And
then, using the predetermined weighting function W and M, f(s(k))
is calculated by the optimization strategy for the next updated
scatter component. Finally, the optimal scatter component S* iscomputed and then directly subtracted from the observed image
to recover a scatter-corrected image.
Based upon the above descriptions, we implemented the
proposed software scheme of scatter correction by using the
MATLABTM (ver. 8.3) programming language and performed anexperiment. Figure 2 shows (a) an anthropomorphic chest
phantom (No. 602, CIRS) and (b) an acrylic step phantom(thicknesses: 8-14 cm) used in the experiment. The radiographysystem (VIDIX-U, JW Medical Corp.) used in the experimentconsists of an amorphous selenium (a-Se) flat-panel detector(dimension: 2560 × 2560, pixel size: 168 µm) and an x-ray tubeof 100 kVp and 320 mA. X-ray images were also acquired withan antiscatter grid (strip density: 200 lines/inch) for comparisonof the image performance.
Results
Figure 3 shows complete sets of the observed images without
and with grid, the scatter image (estimated), and the scattercorrected image of the anthropomorphic chest phantom. Figure 4
shows the enlarged images indicated by the box A in Fig. 3.

2- 50 -

(a)(b)
Figure 2. (a) An anthropomorphic chest phantom and (b) an
acrylic step phantom used in the experiment.
Figure 5 shows complete sets of the observed images
without and with grid, the scatter image (estimated), and thescatter-corrected image of the acrylic step phantom having
thicknesses of 8, 10, 12, and 14 cm. Note that all of the images
were negatively converted.
Figure 6 shows the intensity profiles measured along theline segments of AB indicated in Fig. 5 for the observed
images without and with grid and the scatter-corrected imageof the acrylic step phantom. The exposure dose was about 112µGy for the observed image (without grid), about 48.7
percentage decrease rather than that for the scatter-rejection
image using the grid; its dose was about 230 µGy.

Figure 5. Complete sets of the experiment study for thequantitative evaluation of the scatter correction using the acrylic
step phantom.
1.0

Intensity (normalized)

0.8

0.6

0.4

0.2
Observed image (without grid)
Observed image (with grid)
Scatter-corrected image

0.0
0

500

1000

1500

Position (pixels)

Figure 6. Intensity profiles measured along the line segments
AB indicated in Fig. 5
Figure 3. Complete sets of the performed experiment study
using the anthropomorphic chest phantom.

Figure 4. The enlarged images indicated by the red box A in
Fig. 3.

Discussion
As indicated in Figs. 3 and 4, the structure of the chest
phantom is more clearly visible in the scatter-corrected image
than in both the observed images without and even with grid.
According to Fig. 6, the intensity profile of the scatter-corrected
image follows the exact profile more closely than that of thescatter-corrupted image, which demonstrates the viability of the
proposed software scheme for scatter correction in radiography.
Conclusions
We propose a new software scheme of scatter correction
based on a simple radiographic scattering model in which theintensity of x-ray scatter is directly estimated from a single
projection using the weighted l1-norm based contextual
regularization framework. We implemented the proposed
software scheme and performed an experiment to demonstrate its
viability. According to our results, the proposed software scheme
seems very promising for scatter correction in radiography. The
structure of the examined object was much more clearly visible
in the scatter-corrected image than in both the observed images
without and with grid.

- 51 -

References[1] U. Neitzel. Grids or air gaps for scatter reduction in digitalradiography: A model calculation. Med. Phys. 1992; 19(2):475-481.
[2] Seibert J. A., and Boone J. M. X-ray scatter removal bydeconvolution, Med. Phys. 1988; 15(4): 567-575.
[3] Nykänen, K., and Samuli S. X‐ray scattering in full‐field
digital mammography. Med. Phys. 2003; 30(7): 1864-1873.
[4] W. Zbijewski and F. J. Beekman. Efficient Monte Carlobased scatter artifact reduction in cone-beam micro-CT
IEEE Trans. Med. Imaging. 2006;25(7):817-827.
[5] J. L. Ducote and S. Molloi. Scatter correction in digital
mammography based on image deconvolution. Phys. Med.
Biol. 2010;55(5):1295-1309.
[6] Ahn, S. K., G. Cho, and H. Jeon. A scatter correction using
thickness iteration in dual-energy radiography. IEEE Trans.
Nucl. Sci. 2006;53(1):133-138.
[7] Diaz, O., Dance, D. R., Young, K. C., Elangovan, P., Bakic,
P. R., and Wells, K. Estimation of scattered radiation indigital breast tomosynthesis. Phys. Med. Biol.
2014;59(15):4375-4390.
[8] J. Tarel and N. Hautière. Fast visibility restoration from asingle color or gray level image. Proc. of IEEE 12th
International Conference on Computer Vision, Kyoto,
Japan, Sep. 2009;2201-2208.
[9] G. Meng, Y. Wang, J. Duan, S. Xiang, and C. Pan.
Efficient Image Dehazing with Boundary Constraint andContextual Regularization. In Proc. IEEE International
Conference on Computer Vision (ICCV), Sydney,
Australia, Dec. 2013.
[10] S. Boyd, N. Parikh, E. Chu, B. Peleato, and J. Eckstein.
Distributed Optimization and Statistical Learning via theAlternating Direction Method of Multipliers. Foundations
and Trends in Machine Learning 2011;3(1):1-122.
Author address

E-Mail: seokkyu502@yonsei.ac.kr- 52 -

Estimation of Optical Artifacts in Luminescence Imaging of Water
during Proton-Beam Irradiations
T. Yabe1), M. Komori1), R. Horita1) H. Oguchi1), T. Toshito2) and S. Yamamoto1)
1) Department of Radiological Sciencies, Nagoya University Graduate School of Medicine, Nagoya, Japan
2) Nagoya Proton Therapy Center, Nagoya, Japan
Introduction
We have previously reported that the luminescenceimaging of water using a cooled charged-couple device(CCD) camera with the irradiated energies of proton beam
below the Cerenkov light threshold (Fig.1(A)). The
luminescence imaging was effective method for range
estimation in proton therapy [1]. In comparison with depth
dose profile measured by an ionization chamber, a height of
the Bragg peak of the luminescence imaging was smaller
than that of the ionization chamber and there was an offset
region beyond the Bragg peak (Fig.1 (B)). This phenomenon
was probably caused by optical artifacts. The possible
aretifacts are 1) parallax errors of the CCD camera, 2)
reflected luminescence by a water phantom’s wall and 3)
scattered luminescence in water.
The purpose of this study was to estimate the levels ofthese artifacts affecting on the luminescence image of water.

(A)(B)
Fig.1 Luminescence image of water during proton beamirradiations for 100 MeV-energy (A), and comparison of
depth profile of luminescence image and depth-dose
distribution measured by ionization chamber (B).
Materials and Methods
The measurement was performed at the spot scanning roomof the Nagoya Proton Therapy Center. Fig.2 shows theexperimental setup for the luminescence imaging during
proton-beam irradiations. A phantom of transparent container
was filled with tap-water up to 2 cm from the top of thephantom. The water phantom was placed on a couch in the
spot scanning treatment room (Hitachi, Japan). The CCD
camera (BITRAN BS-40L, Japan) operating at 3°C with Cmount F-1.4 lens (Computar, Japan) was set ~ 40 cm fromthe phantom surface. Then, we measured the luminescence
image during proton-beam irradiation using the CCD camera
for three minutes. We also measured an optical photo of thephantom and a blank image (image without irradiating protonbeam). The former was used to measure the absolute size ofthe phantom, while the latter was used to correct thebackground offset and the non-uniformity of the CCD
camera for the measurement.
The measured images were analyzed using public domain
software (ImageJ). The depth profiles of the luminescence
image were measured by setting a profile with 30 pixels on
the luminescence part of water.
(1) Parallax errors
To evaluate the effect of the parallax errors, we measured
the luminescence images for the difference positions of the
optical axis of the CCD camera by using a lab jack. (Fig.2).

The lab jack was moved from the depth of the Bragg peak in beam
direction.
(2) Reflection of luminescence
In our previous study, a phantom of transparent container wasused to measure the luminescence image. However, theluminescence images include the effect of the reflected
luminescence by the phantom’s wall. Therefore, we measured theluminescence images using a phantom with black painted wall andevaluated the effect of the reflected luminescence.
(3) Scatter of luminescence in water
To remove the scattered luminescence in water, a profile of thescattered luminescence was measured on the outside of theluminescence part of water and subtracted from the luminescencepart.

Fig.2 Experimental setup for luminescence imaging of water
during proton-beam irradiations.
Results and Discussion(1) Parallax errors
Fig. 3 shows the luminescence images when the position of the
optical axis matched to the depth of the water surface (A),matched to the Bragg peak (B) and depth profiles derived fromthese images (C) measured for the proton energy of 73 MeV.

(A)

(B)

(C)
Fig.3 Luminescence images with position of optical axis matched
to depth of water surface (A), matched to Bragg peak (B) and
depth profiles derived from these images (C) measured for protonenergy of 73 MeV.

- 53 -

Fig. 4 shows the maximum intensity (Bragg peak’s height)of 73 MeV protons for the different distance from the opticalaxis to the Bragg peak position. When the position of the
optical axis matched to the depth of the Bragg peak, themaximum intensity in the images (Bragg peak’s height) was
the highest.
We found that the parallax errors reduced the height of the
Bragg peak. The accuracy of the luminescence in Bragg peak
was improved by matching the optical axis to the depth of the
Bragg peak.

depth profiles derived from these images (C).
Fig. 6(D) shows a comparison of depth profiles for proton beamof 100 MeV with and without the removal of the scatteredluminescence. After the removal of the scattered luminescence, theBragg peak’s height showed higher than that without the removal.

(A)

Fig.4 Maximum intensity in the images (Bragg peak’s
height) of proton energy of 73 MeV for different distancefrom optical axis to Bragg peak position.
(2) Reflection of luminescence
Comparisons of the depth profile with transparent phantom
and black painted phantom for the proton energy of 71 MeV,
100 MeV and 139 MeV are shown in Fig. 5(A), (B), and (C),respectively. The effect of the reflected luminescence seemed
to be slightly contributed to depth profile.
By using the phantom with the black painted wall, theheights of the depth profiles were slightly smaller than thosewith the transparent phantom, especially obvious for that of
139 MeV protons as shown in Fig 5 (C).

(A)

(B)

(C)
Fig.5 Comparisons of depth profile with transparent phantom
and black painted phantom for proton energy of 71 MeV (A),
100 MeV (B) and 139 MeV(C).
(3) Scatter of luminescence in water
Fig.6 shows a position of the profile set to the luminescencepart of water (A) and that set to the scattered part (B) and

(B)

(C)
(D)
Fig.6 Luminescence image and position of profile set toluminescence part of water (A), that set to scattered part (B),profiles derived from these two (C), comparison of depth profile
with and without removal of scattered luminescence (D).
As shown in Fig.7, in comparison with the ionization chamber,the Bragg peak’s height of the luminescence approached to that of
the ionization chamber. However, the Bragg peak’s height of theluminescence was still lower than that of the ionization chamber.
This phenomenon may caused by other mechanism not measured
by the ionization chamber.

Fig.7 Comparison of depth profile with removal of scatteredluminescence and that measured by ionization chamber.
Conclusion
In this study, we estimated the optical artifacts which affected on
the luminescence images of water. The parallax error and thereflection of the luminescence affected on the height of the Bragg
peak and the shapes of depth profiles of the luminescence. By theremoval of the scattered luminescence, the Bragg peak’s height ofthe depth profile almost approached to that measured by ionizationchamber.
References[1] S Yamamoto et al. Luminescence imaging of water during
proton-beamirradiation
for
range
estimation.
Med.
Phys.42(11),6498-6506 (2015)
Author address
E-Mail: yabe.takuya@d.mbox.nagoya-u.ac.jp- 54 -

Beam-Quality Factor Evalution For Passive Scattering Proton TherapyWith Farmer Type Ionization Chamber Using Monte Carlo Method
Ji Won Jang1), Wook-Geun Shin1), and Chul Hee Min1.*)1.*) Department of Radiation Convergence Engineering, Yonsei University, Wonju, Republic of Korea
Introduction
The primary objective of radiation therapy is to deliver thedose from ionizing radiation to the target while minimizing thedose to the healthy tissue. In order to describe and predict withhigh accuracy, it is important to correctly understand theabsolute dose of the radiation field and its effect on the target
volume. Ionization chambers are widely used in radiotherapy
to measure the absorbed dose, however, the calibration between
ion pairs in chamber and absolute dose should be performed.
Secondary Standard Laboratory (SSDL) provides therelationship between absolute dose and ion pairs respectively
measured by calorimeter and ionization chamber. However, it
is very hard to measure the absolute dose with user beam suchas LINAC and proton beam due to the limitation of calorimeter.
Because of above reason, SSDL provides the calibration datawith 60Co beam, and users calculate the beam quality correction
factor with Monte Carlo (MC) method, or employ the beam
quality correction factor provided by TRS-398 and ICRU-78
protocol based on EGS-nrc MC code [1,2]. However, it is toocomplex to use MC method for various ionization chamber andmachine-specific beam condition. Moreover, EGS-nrc cantransport only photon and electron.
The purpose of this study is to develop an automated MC
system for ionization chamber simulation using Geant4 MC
toolkit, and to evaluate beam quality factor for therapeutic
beam of passive scattering proton therapy machine installed at
National Cancer Center Korea (KNCC) with PTW-30013
Farmer-type ionization chamber.
Materials and methods
Farmer-type ionization chamber modeling in Geant4: It is ahuge burden to model ionization chamber of every
manufacturer, type, and use. In this study, the automatic system
for MC modeling of Farmer-type chamber was developed.
in this study, we use the parameters to model the PTW-30013
ionization chamber in Geant4 MC tool with the ionizationchamber modeling system. User can easily find the parametersin TRS-398 or product sheet. PTW-30013 (PTW, Freiburg,
Germany) consisted of an air cavity, a graphite and PMMA
wall, aluminum stem, and electrode.
Perturbation factor calculation for MC commissioning: The
dose in an air cavity Dair is related to the absorbed dose to water
Dw by applying Spencer-Attix stopping power ratio [3] between
water and air sw,air. However, perturbations caused by the finite
volume of the detector and its construction with atomic
composition and density should be considered. With the factorsof perturbation, the absorbed dose to water Dw is:
𝐷𝐷𝑤𝑤 = 𝐷𝐷𝑎𝑎𝑎𝑎𝑎𝑎 (𝑝𝑝𝑐𝑐𝑐𝑐𝑐𝑐 𝑝𝑝𝑤𝑤𝑤𝑤𝑤𝑤𝑤𝑤 𝑝𝑝𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑝𝑝𝑑𝑑𝑑𝑑𝑑𝑑 𝑝𝑝𝑐𝑐𝑐𝑐𝑐𝑐 )𝑠𝑠𝑤𝑤,𝑎𝑎𝑎𝑎𝑎𝑎(1)where pcel, pwall, pstem, pdis, and pcav indicate the perturbation
factors of central electrode, wall, stem, displacement, andcavity, respectively. To validate the MC system of theionization chamber simulation, the perturbation factors were
calculated with reference beam condition.
Phase space file of 60Co beam provided by IAEA wasemployed with reference condition recommended by TRS-398[5]. Both of the MC simulations use variance reduction
techniques (VRT) of cross section enhancement (CSE) andrange rejection, Russian Roulette, intermediate phase-spacestorage (IPSS) in EGS-nrc, and range rejection, particle
splitting in Geant4 to reduce calculation time [6].

Figure 1. MC simulations for the calculation of perturbation
factors. The various perturbation factors are calculated by theratio of the dose in a water (1) and the cavity of ionizationchamber (2-5).
Figure 1 shows a schematic procedure for calculation of theperturbation factors [4]. The ratio of the doses in the cavity (orwater volume) with a component of ionization chamber was
defined as a perturbation correction factor of the component.
Based on the perturbation factors calculated in the above
procedure, the overall perturbation factor pQ is obtained by:
𝑝𝑝𝑄𝑄 = 𝑝𝑝𝑤𝑤𝑤𝑤𝑤𝑤𝑤𝑤 𝑝𝑝𝑐𝑐𝑐𝑐𝑐𝑐 𝑝𝑝𝑑𝑑𝑑𝑑𝑑𝑑 𝑝𝑝𝑐𝑐𝑐𝑐𝑐𝑐 𝑝𝑝𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 =𝐷𝐷1
𝑠𝑠
𝐷𝐷5 𝑤𝑤,𝑎𝑎𝑎𝑎𝑎𝑎(2)

The perturbation factors calculated by developed system werecompared with perturbation factors calculated by EGS-nrc andrecommendation of TRS-398.
Beam quality factor of therapeutic proton beam: The beam
quality correction factor is the ratio of the stopping power ratio
multiplying overall perturbation factors between user beam andreference beam with the general assumption of (Wair)Q=(Wair)Q0.
𝐷𝐷
� 1�
𝐷𝐷5 𝑄𝑄
𝑘𝑘𝑄𝑄 ≈=𝐷𝐷�𝑝𝑝𝑄𝑄 𝑠𝑠𝑤𝑤,𝑎𝑎𝑎𝑎𝑎𝑎 �60Co
� 1�
𝐷𝐷5 60Co
�𝑝𝑝𝑄𝑄 𝑠𝑠𝑤𝑤,𝑎𝑎𝑎𝑎𝑎𝑎 �𝑄𝑄(3)where Q is the therapeutic proton beam in this study, and the�𝑝𝑝𝑄𝑄 𝑠𝑠𝑤𝑤,𝑎𝑎𝑎𝑎𝑎𝑎 �60Co calculated in previous section was used. To
obtain therapeutic proton beam, the beam nozzle codedeveloped in previous study was employed [7]. The calculated
beam quality factors according to the residual range (𝑅𝑅𝑟𝑟𝑟𝑟𝑟𝑟 ) at
the middle of spread-out Bragg peak (SOBP) representing
beam quality were compared with the recommendation of TRS398.

- 55 -

Results and Discussion

Figure 2. Perturbation factors about displacement, wall, central
electrode, and overall factor proposed by TRS-398 (blacksquare), calculated by EGS-nrc (red circle) and Geant4 (bluetriangle)
Figure 2 shows the perturbation factors recommended by TRS398 protocol, and calculated in this study with Geant4 and
EGS-nrc. The calculation time was 6,000 and 60 CPU-hours inGeant4 with 2X1010 and EGS-nrc with 2X109 particles,
respectively. Due to the VRT, the standard deviation of
perturbation calculated by Geant4 is more than the otherperturbation factors. However, the differences of perturbation
factors of three methods are negligible. This results reflected
the accuracy of the chamber modeling and MC simulations.

commissioning, the perturbation factors of PTW-30013
proposed by TRS-398 were well-matched with perturbation
factors calculated by EGS-nrc and Geant4 MC tool, and thebeam quality factor for therapeutic proton beam of KNCC also
identical. However, the calculation time of 10 times the EGSnrc is a limitation. The MC system developed in this study canbe used for cross-calibration of ionization chamber employedin each instruments, moreover, validation of absolute dose in
SSDL is possible. In further study, VRT for the reduction of
calculation time would be applied, and the beam quality factors
for pencil beam scanning with parallel-plate type chamber will
be evaluated.
References[1] Andreo, P., et al. "IAEA TRS-398–Absorbed Dose
Determination in External Beam Radiotherapy: An
International Code of Practice for Dosimetry based onStandards of Absorbed Dose to Water." International
Atomic Energy Agency (2000)[2] ICRP, 1997. Individual Monitoring for Internal Exposure ofWorkers (preface and glossary missing). ICRP Publication
78. Ann. ICRP 27 (3-4)[3] Spencer LV and Attix FH. A theory of cavity ionization.
Radiat. Research 1955;3:239-254[4] Wulff J. Clinical dosimetry in photon radiotherapy –aMonte Carlo based investigation. University of Marburg
2010[5] Capote R., et. al. Phase-space database for external beam
radiotherapy. Nucl. Data Sec. INDC (NDC)-0484 2006
[6] Wulff J. Efficiency improvements for ion chamber
calculations in high energy photon beams. Med. Phys.
2008;35;1328-1336[7] Shin WG, Shin JI, Jeong JH, Lee SB, Min CH. A Monte
Carlo study of the relationship between the time structuresof prompt gammas and the in-vivo radiation dose in proton
therapy. J Korean Phys Soc. 2015;67(1):248-253
Author address
E-Mail: jwjang1911@yonsei.ac.kr

Figure 3. Beam quality correction factor 𝑘𝑘𝑄𝑄 proposed by
TRS-398 (black square) and calculated by Geant4 (red circle)
according to the residual range at the middle of SOBP
representing proton beam quality.
Figure 3 shows the beam quality factors according to theresidual range 𝑅𝑅𝑟𝑟𝑟𝑟𝑟𝑟 at the middle of SOBP calculated byGeant4 simulation, and proposed by TRS-398. The simulation
for calculation of beam quality factor took 30-400 CPU-hours
according to the beam quality index 𝑅𝑅𝑟𝑟𝑟𝑟𝑟𝑟 . The beam code cangenerate therapeutic proton beam of 4.51-28.42 g/cm2. To
obtain the beam range below 4.51 g/cm2, PMMA range shifter
was employed, the 𝑅𝑅𝑟𝑟𝑟𝑟𝑟𝑟 is up to 10 g/cm2. The difference
between the two values is within 1 σ, so that the validity of thecurrently used 𝑘𝑘𝑄𝑄 values can be confirmed.

Conclusion
We developed an automated MC system for ionizationchamber simulation using Geant4 MC toolkit. In the MC- 56 -

Breast-Dedicated PET System with a Personalized Gantry
In-Soo Kang1), Chan-Woo Park1), HanKyeol Song1), Kyu-Bom Kim1), Yong-Hyun Chung1.*)
1.*) Dept. of Radiation Convergence Engineering, Yonsei University, Wonju, Republic Korea
Introduction
Breast cancer is one of the most prevalent cancer in women
worldwide. The early detection of breast cancer can increase
the survival rates. Breast PET image is widely used for clinicalresearch because it can be non-invasively quantify biologicalprocesses at the molecular levels. But the conventional PET has
weakness for detecting a small lesion due to limited spatial
resolution and sensitivity. We designed a new breast-dedicatedPET system with a transformable gantry which can be fitted toindividual breast shape.
Materials and methods
Detector modules: The detector module consisted of 24 × 12
array of LSO crystals with a pixel size of 2 × 2 × 10 𝑚𝑚𝑚𝑚3 . The
scanner was composed of 4 rings and each ring was arranged inpolygonal shapes. The ring shape can be transformed from 12square to 10-square, 9-square, 8-square and 6-square shapeswith a radius of 9.95 cm, 8.35 cm, 7.55 cm, 6.75 cm and 5.15
cm, respectively.

set by 450 keV to 650 keV. Also, 1D profile data was measured
in 1.25 mm diameter hot rod.
Results
There were sensitivity differences following source location.
At the center of axial position, sensitivity of design 1 gantry
was reduced. Excluding center position, a sensitivity of new
gantry design was higher than conventional gantry. Figure 3
illustrated performance of sensitivity.

Figure 3. Sensitivity as a function of axial and radial position,energy window: 450-650 keV.
The results of profile analysis were similar with sensitivity
measurements. New gantry designs have a higher count rates
than the conventional gantry excluding center position.

Figure 1. Three type of gantry designs: (a) Conventional
gantry: cylindrical shape gantry, (b) Design 1: 12, 10, 9 and 6
modules per ring, (c) Design 2: 12, 10, 9 and 8 modules per
ring
Source information: In order to evaluate the effect of gantry
size on the system sensitivity, total coincidence count rates
were simulated with 5 MBq Na-22 source by GATE code. The
gamma source was located at axial offset ± 1.2, 2.4, 3.6 and 0
cm, respectively and at radial offset ± 0.1cm, 0.2 and 0 cm,
respectively.
Design of simulation phantom: The derenzo phantom wasdesigned for profile analysis. Figure 1 illustrated the diameterof derenzo phantom. Each hot rod had 100 kBq Na-22 source.
It was located at axial offset + 1.2cm, + 2.4 cm and + 3.6 cm.

Figure 2. Diameter of derenzo phantom and hot rods. A
height of phantom was 0.5 mm.
Personalized gantry system concept: Figure 4 illustrates how
the gantry shape can be transformed. When the center module
moves backward, other modules move frontward. The 12
modules per ring can be reduced to 10, 9, 8 and 6 modules per
ring.
Performance of sensitivity: Sensitivity was measured byaxial and radial location of the source and energy window was

Figure 4. Plots of profiles for 1.25 mm diameter hot rod.
Discussion
The simulation results demonstrated that the transformablegantries have higher sensitivity than the convention al gantry.
Design 1 gantry has sensitivity loss in the center. It can becaused by empty space between the gantries. In terms ofsensitivity, Design 2 gantry is superior to conventional gantry.
Conclusion
We designed a new breast-dedicated PET system. The
proposed PET system has a better sensitivity than theconventional PET. The proposed PET system will be expected
to detect small breast cancer, where early diagnosis is importantcompared to the conventional PET.
References[1] L.Moliner, A.J.González, A.Soriano, F.Sánchez, et al.
Design and evaluation of the MAMMI dedicated breast PET.
Med. Phys. 39 (9), September 2012.
[2] Masafumi Furuta, Keishi Kitamura, Junichi Ohi, Hiromichi
Tonami, et al. Basic Evaluation of a C-Shaped Breast PET
Scanner. IEEE 2009:2548-2552.
[3] Richard Freifelder, Chris Cardi, Joel S. Karp. Fi rs t results of a dedi cat ed breas t PET im ager,
BP ET, using NaI(Tl) Curve P lat e det ect ors. IEEE 2002.
1241-1245.
[4] Raymond R. Raylman, Stan Majewski, Randy Wojcik,
Andrew G. Weisenberger, et al. The potential role of positronemission mammography for detectionof breast cancer. A phantom study, Med. Phys. 27, August 2000.

- 57 -

[5] FanzhenMeng, Xu Cao, Xuezhou Cao, Jianxun Wang, etal. Influence of Rotation Increments on Imaging Performancefor a Rotatory Dual-Head PET System, BioMed ResearchInternational, Volume 2017, Article ID 8615086, 11 pages
Author address
E-Mail: iskang@yonsei.ac.kr- 58 -

Abstract

Biomedical Laboratory
Science- 59 -

- 60 -

2017 Yonsei-Nagoya University Joint Symposium in Biomedical Laboratory Science
Miare-Hall #325
11:00 ~ 11:05

Opening Session

Prof. Ki-Jong Rhee (Yonsei Univ.)

11:05 ~ 11:55

Session I

Chair: Korea (Yonsei Univ.)

11:05 ~ 11:30

Diagnostic and clinicopathological value of ΔNp63 in cervical cancer and cervicalintraepithelial neoplasia

11:30 ~ 11:55(Suji Lee – Yonsei Univ)

Assessment of F9 mutation associated with inhibitor development in Japanesehemophilia B patients (Hiroto Sakane – Nagoya Univ)

12:00 ~ 14:00

Lunch

14:00 ~ 15:15

Session II

14:00 ~ 14:25

Plumbagin inhibits expression of virulence factor and growth of Helicobacter

Chair: Prof. Jun (Nagoya Univ.)

pylori (Hye Jin Kwon – Yonsei Univ)
14:25 ~ 14:50

Development of diagnostic assay against for Chikungunya fever (Monoldorova
Sezim-Yonsei Univ)

14:50 ~ 15:15

Highly sensitive and simultaneous determination of urinary metabolites ofpyrethroids using gas chromatography-tandem mass spectrometry (Yuko Ueda –Nagoya Univ)

15:15 ~ 15:30

Coffee Break

15:30 ~ 16:45

Session III

15:30 ~ 15:55

Improved colitis-associated cancer model using ETBF (Soonjae Hwang – Yonsei

Chair: Korea (Yonsei Univ.)

Univ)
15:55 ~ 16:20

Development of anti-EGFR lipid micellar nanoparticles co-encapsulating
quantum dots and paclitaxel for tumor-specific theranosis (Seong Jae Kang –- 61 -

Yonsei Univ)
16:20 ~ 16:45

Amplification of distinct α-synuclein fibril conformers using protein misfolding
cyclic amplification (Byung Chul Jung – Yonsei Univ)

16:45 ~ 17:00

Closing Remarks and Group photo

18:00 ~ 20:00

Dinner- 62 -

Prof. Ki-Jong Rhee (Yonsei Univ.)Diagnostic value of ΔNp63 expression in cervical cancer and cervicalintraepithelial neoplasia
Suji Lee1), Sunyoung Park1), Kwang Hwa Park2)*, Hyeyoung Lee1)*1) Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University,2) Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju College of Medicine*corresponding authors
Introduction
Cervical cancer is the third most common cancer in women
worldwide [1]. In developed countries, effective treatment
strategies for cervical cancer have decreased the morbidity
and mortality [2]. Although most patients with cervicalcancer respond relatively well to standard treatment, sometumors are biologically more aggressive or are shown
recurrence after the treatment [3]. Therefore theidentification of new markers to develop an optimaltreatment strategy for individual patients is important goal
[4]. The p63 is a member of the p53 family of transcription
factors, involved in tumor suppressive activities to induce
transcriptional target genes to induce apoptosis and anothertumor suppressive mechanism. Unlike p53, p63 does nothave frequent mutations in human cancer. The lack ofmutation in p63 in human cancer and their anti-tumorigenic
activities make them attractive for therapeutic marker [5]. In
the study, we performed real-time PCR targeting p63 mRNAin cervical 165 formalin-fixed paraffin-embedded (FFPE)
tissues. P63 mRNA expression from cervical tissues wasevaluated for selecting appropriate target as cervical cancer
treatment marker.
Materials and Methods
Clinical tissues: A total of 165 FFPE tissue tissues werecollected at the Department of Pathology, Yonsei University
Wonju Severance Christian Hospital between 2010 and2013. This study was approved by the Institutional Ethics
Committee at Yonsei University Wonju College ofMedicine (approval no. CR315052). Cases with available
tissue biopsies were reviewed by two pathologists.
Deparaffinization of FFPE tissue and total RNA
extraction: Three to four pieces of 10 μm thick section of
cervical FFPE tissues were used for total RNA extraction.
For extraction of RNA, Qiagen RNeasy FFPE kits (Qiagen,Hilden, Germany) were utilized according to the
manufacturer’s protocol. The purity and concentration of
total RNA were determined by measuring the ratio of theabsorbance at 260 and 280 nm using a spectrophotometer(Infinite 200, Tecan, Salzburg, Austria). All preparation andhandling procedure were conducted under RNase-free
conditions. Isolated total RNA was stored at -70℃.
cDNA synthesis: Complementary DNA (cDNA) was
synthesized using an M-MLV Reverse Transcriptase kit(Invitrogen, Carlsbad, CA, USA) and random hexamers(Invitrogen).
Reverse transcription-quantitative polymerase chain
reaction: Detection of TAp63 and ΔNp63 mRNA
expressions in cervical specimens was performed byquantitative reverse-transcriptase-PCR (RT-qPCR). The
assay was performed in 10 μL 2× Thunderbird probe qPCT
mix (Toyobo, Osaka, Japan), 3 μL primer and TaqMan probe
mixture, 2 μL template cDNA, and distilled water (DW) to a
final volume of 20 μL per tissue. mRNA levels were
quantified by using a CFX-96 real time PCR system (BioRad, Hercules, CA, USA) for thermal cycling andfluorescence detection. To avoid false negative because ofmRNA degradation, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal control. Gene
expression was assessed using the comparative C T (2-ΔΔCT)
method, which represents the mRNA expression level
relative to the reference gene.
Statistical analysis: Statistical analyses were performed
using GraphPad Prism software version 5.02 (GraphPad, La
Jolla, CA, USA). Student's t-test, 95% confidence interval(CI), and ROC curve were used to determine the statisticalsignificance of data.
Results
A total of 165 cervical cancer FFPE specimens including
52 cancer (31.5%), 39 cervical intraepithelial neoplasia(CIN) 3 (23.6%), 34 CIN 1 (20.6%), and 40 normal (24.2%)
were used in this study (Table 1). For 52 cervical cancer cases,
data on histology, FIGO stage, tumor size, and lymph nodemetastasis were retrospectively reviewed from patientelectrical medical records (EMR). Cervical cancer specimen
information provided histology, FIGO stage, lymph nodemetastasis, tumor size, and Human papillomavirus (HPV)
typing results, respectively. Of 52 cervical cancer specimens,
52 (100%) were histologically diagnosed as SCC, 43 (47.8%)
were FIGO stage IIB abnormalities, and 39 (43.4%) werelymph node metastasis. Thirty-four (37.8%) had a tumor
Table 1. Clinical characteristics of patients.

Cancer(n = 52)
n (%)

CIN 3
(n = 39)
n (%)

CIN 1
(n = 34)n (%)

Normal(n = 40)n (%)< 50 years

19 (36.5)

31 (79.5)

19 (55.9)

25 (62.5)≥ 50 years

33 (63.5)

8 (20.5)

15 (44.1)

14 (35.0)Age

1 (2.5)

Unknown*
Histology
SCC

52 (100.0)

ADC

0 (0.0)FIGO stage< IIB

21 (40.4)≥ IIB

28 (53.8)

Unknown*

3 (5.8)Lymph nodes
Negative

28 (53.8)

Positive

22 (42.3)

Unknown*

2 (3.8)Tumor size
< 4 cm30 (57.7)≥ 4 cm22 (42.3)

HPV DNA
Negative

8 (15.4)

Positive

44 (84.6)

size greater than 4 cm and 44 (84.6%) were infected with
HPV.

- 63 -

***To determine the p63 mRNA expression level incervical cancer, p63 mRNA RT-qPCR assay was performedon 52 cervical cancer tissues and 40 normal tissues. TAp63,
which is known to function as a tumor suppressor, mRNA
expression level was confirmed, and ΔNp63, which is
known to play an oncogenic role, was confirmed. Notably,
ΔNp63 significantly increased in cancer compared tonormal (P = 0.0002), but TAp63 did not have a significant
difference between cancer and normal (Figure 1). As a result,ΔNp63 is related to cancer development of cervical cancer.

**
**

*

ΔNp63 fold change

80***** P<0.0005** P<0.005* P<0.05

60
40
20
0
NormalCIN I

CIN III

Cancer(n=40)(n=34)(n=39)(n=52)

Figure 3. ΔNp63 expression in normal, CIN 1, CIN 3, andcancer FFPE tissues

Figure 1. The relative expression of TAp63 (A) and ΔNp63(B) in cervical cancer and normal tissues
To investigate whether ΔNp63, which was higher incancer than normal tissues, was associated withtumorigenesis of cervical cancer, we analyzed thecorrelation with Ki-67, a proliferation marker. Analysis of
the association between ΔNp63 and Ki-67 in cervical cancer
tissues showed a significant positive correlation between
ΔNp63 and Ki-67 (r = 0.4758, P = 0.0004, figure 2). The
positive correlation with proliferation marker Ki-67
suggests that ΔNp63 may also be associated with cancer
progression in cervical cancer.

Discussion
The expression levels of ΔNp63 in cervical cancer FFPE
specimens were overexpressed compared to that in normal,
but TAp63 showed no difference between normal and cancer.
These results suggest that ΔNp63 is more likely to develop
cervical cancer than TAp63 and ΔNp63 is known to play an
oncogenic role. To confirm the association of ΔNp63 withthe development of cervical cancer, the positive correlation
with proliferation marker Ki-67 was shown. This suggeststhat ΔNp63 may be associated with the proliferation ofcancer cells. Furthermore, we examined the precancerous
lesion and cancer of ΔNp63. The expression level of ΔNp63
in cancer was significantly higher than that in precancerous
lesion. ΔNp63, an isoform associated with the developmentof cervical cancer, was overexpressed in cervical cancer
tissues and was associated with Ki-67, a proliferation marker,
which enabled discrimination of normal, precancerous
lesions, and cancer.
Conclusion
ΔNp63 could be used as a therapeutic target for cervicalcancer, and subsequent studies will be useful as a marker for
cervical cancer treatment.

Figure 2. Correlation between ΔNp63 and Ki-67 insquamous cell carcinoma of the cervix
To determine whether ΔNp63 is indeed associated withthe progression of cancer, the expression levels in normal,
pre-cancerous, and cancerous tumors were compared.
ΔNp63 mRNA RT-qPCR was performed using 40 normal,
34 CIN 1, 39 CIN 3 , and 52 cancer FFPE tissues. As a result,the expression of ΔNp63 in CIN 1, CIN 3, and cancer was
statistically significantly higher than normal (Figure. 3).
Also, when comparing CIN 1 and CIN 3 with cancer tissues,
the expression of ΔNp63 of cancer tissues were significantly
over-expressed than that of CIN 1 and CIN 3.

References[1] World Cancer Report, 2014. World Health Organization(2014. pp. Chapter 5.12. ISBN 9283204298)[2] Safaeian M, Solomon D. Cervical Cancer Prevention –Cervical Screening: Science in Evolution. Obstet Gynecol
Clin North Am. 2007;34(4):739-60[3] Kim YB, Kim GE, Cho NH, Pyo HR, Shim SJ, Chang
SK, Park HC, Suh CO, Park TK, Kim BS. Overexpressionof Cyclooxygenase-2 Is Associated with a Poor Prognosis inPatients with Squamous Cell Carcinoma of the Uterine
Cervix Treated with Radiation and Concurrent
Chemotherapy. Cancer. 2002;95(3):531-9[4] Liu HX, Li N, Wei L, Zhou FX, Ma R, Xiao F, Zhang W,
Zhang Y, Hui Y, Song H, Chen BL. High expression of
Kruppel-like factor 4 as a predictor of poor prognosis for
cervical cancer patient response to radiotherapy. Tumor
Biology. 2017;39(6):1-9.
[5] Venkatanarayan A, Raulji P, Norton W, Flores ER. Noveltherapeutic interventions for p53-altered tumors throughmanipulation of its family members, p63 and p73. Cell
Cycle. 2016;15(2):164-71
Author address
E-Mail: secretlsj@naver.com- 64 -

Assessment of F9 mutation associated with inhibitor development
in Japanese hemophilia B patients
1

1

Hiroto Sakane , Shogo Tamura , Erika Hashimoto1, Akiya Fujioka1, Ayumi Makiyama1, Nami Kawamura1, Sachiko Suzuki1,
Yuki Takagi1,2, Akira Takagi1, Takeshi Kanematsu3, Mayuko Kishimoto3, Mika Ogawa4, Nobuaki Suzuki3, Tadashi
Matsushita3, Koji Yada5, Midori Shima5, Tetsuhito Kojima1, Japan Hemophilia Inhibitor Study
1) Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan
2) Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan
3) Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan
4) Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
5) Department of Pediatrics, Nara Medical University Hospital, Nara,
Working group: Japan Hemophilia Inhibitor Study (J-HIS) group
Introduction
Hemophilia B is an X chromosome-linked hereditary
bleeding disorder, which shows a quantitative or qualitative
reduction of coagulation factor IX (FIX) due to genetic
abnormality of FIX gene (F9). FIX is a vitamin K-dependent
serine protease which plays an important role in intrinsic
blood coagulation pathway. About one in 25,000-30,000
males suffer from hemophilia B, and muscle hemorrhage or
joint bleeding are mainly obserbed as clinical symptoms.
Based on FIX activity (FIX:C), this disease severity can beclassified as severe (<1% of normal), moderate (1-5% ofnormal) and mild (5>-<40% of normal) [1] .
In case of hemophilia B, FIX replacement therapy is
exclusive way to treat hemophiliacs; however, inhibitors
against FIX can neutralize the therapeutic effect of FIX
replacement agents, which is a serious problem in thetreatment of hemophilia B.
The risk factor to develop a FIX inhibitor have beenstudied in Europe and America [2,3]. However, in Asia
including Japan, FIX inhibitor risks in hemophilia B have notbeen investigated on a large scale. To investigate theinhibitor-developing risk factor of hemophilia, Japan
Hemophilia Inhibitor Study (J-HIS) has launched since 2008.
Materials and methods
Patient registration and DNA samples: In this study, 47
hemophilia B patients registered in the J-HIS from Japanesehospitals including Nagoya University Hospital were enroled.
FIX:C and inhibitor development were referred from patient
datasheets in J-HIS database. We classified hemophilia B
severity by the lowest FIX:C. For gene analysis, we obtained
informed consent from all cases and then genomic DNA wasextracted from peripheral blood leukocytes peripheral [4].
The study was approved by the Ethics Committee of Nagoya
University Graduate School of Medicine.
PCR amplification and F9 sequencing: To amplify alleight exons including promoter and exon flanking regions,polymerase chain reaction (PCR) was performed using
F9-specific PCR primer sets [5]. PCR products were
subjected to the Sanger direct-sequencing with BigDye
Terminator Cycle Sequencing Kit and ABI Prism 310
Genetic Analyzer (Applied Biosystems, Foster City, USA).
Detection of DNA breakpoint deleting F9: In case ofsuspected F9 deletion, multiplex ligation-dependent probe
amplification (MLPA) analysis or mapping PCR was carriedout. MLPA is a semi-quantitative assay to investigate exonic
deletion in the gene. Mapping PCR is an exploring method
for identifying region deleted in the X chromosome locus.
Breakpoints were identified by inverse or long-range PCR,
following direct-sequencing of the PCR products [6].

Results
Forty seven hemophilia B patients including 4 inhibitor
positive cases were registered in the J-HIS until 2017. The
severity of hemophilia B was 26 severe, 16 moderate and 5 mildin 47 hemophilia B patients. We detected causative genetic
defects in all hemophilia B patients tested, including 39 point
mutations (24 missense, 5 nonsense, 8 splice-junction and 2
promoter region mutations) and 8 other gene abnormalities (4partial deletions, 2 gross deletions, 1 insertion and 1 complex
genome rearrangement) (Table 1).
The genetic abnormalities other than point mutation aredetailed in below.
Deletion
All deletion cases caused severe hemophilia B.
■ Two cases of small deletion: 2 bp deletion in exon 8(c.1074_1075delAG, p.Arg358Serfs*15); 4 bp deletion inexon 2 (c.185_188delGAGA, p.Arg62Asnfs*41)■Two cases of partial F9 deletion: 11 kb deletion includingexon 5-6; 12 kb deletion including exon 7-8■Two cases of gross deletion of F9 including adjacent genes aspreviously reported [6]Insertion
One novel case of insertion was identified: 2 bp insertion inexon 8 (c.1145_1146insCG, p.Leu383Valfs*44).
Complex genome rearrangement
We identified a large insertion into 5’-flanking site of F9exon 6. The inserted sequence (2.5 kb) was an antisenseorientated SVA-F (SINE-VNTR-Alu subfamily F) element [7].
Inhibitor development
The rate of hemophilia B patients with FIX inhibitor was
8.5% (4/47) in this study. All patients with FIX inhibitor weresevere hemophilia B, in which detected F9 mutations were 2
nonsense mutations (p.Arg75* and p.Ser365*), 1 entire F9
deletion and 1 complexed rearrangement (Figure 1). It wasreported that hemophilia B patient carrying the nonsense
mutation (p.Arg75*) developed inhibitor [8].
Table 1. Type of mutation and hemophilia B severity- 65 -

Figuire 1. Association with type of mutation and inhibitor
development in hemophilia B patients registered in J-HIS.
Left panel shows distribution of type of mutation ininhibitor positive or negative group. Right panel shows
frequency of inhibitor development.
Discussion
The development of an inhibitor is one of the mosttroubling complications of hemophilia B. Population-based
studies indicate that 3.7-24% of hemophilia B patientsdevelop inhibitory antibodies to FIX, which were exclusively
in patients with severe disease [9]. In this study, we
identified causative F9 abnormality in all 47 hemophilia B
patients tested, and found that 4 (8.5%) patients with severe
hemophilia B developed a FIX inhibitor. This was consistent
with the previous reports.
Two F9 point mutations in the case with inhibitor
development were both nonsense mutation causing severe
hemophilia B. In the case of one entire F9 deletion and one
complex genome rearrangement on the X-chromosome, FIX
inhibitors were also developed. On the other hand, in the casewith F9 missense mutations, no inhibitor development wasobserved. These results suggest that “null” mutations
destroying FIX production may be considered as a higher
risk factor to develop FIX inhibitor. This was a cosistent
result with previous reports that large deletions and nonsense
mutations are high risk factors of inhibitor development [9].
Although misssense mutaitons apprear not to associatewith inhibitor development in this study, it has been foundthat several F9 missense mutations are also responsible forthe development of inhibitors [10,11]. In addition, there aremuch less cases of non-severe hemophilia B patientsdeveloping inhibitors than severe hemophilia B [12]. Risk
factors for the inhibitor development have been mainly
analyzed from hemophilia A as compared with hemophilia B.
However, more data to analyze the risk factors ofdevelopment of FIX inhibitor in hemophilia B patients will
be needed to support future care for hemophilia B patients.
Therefore, further studies are necessary to accurately assess
the risk factors for inhibitor development against FIX in
Japanese hemophilia B patients.

References[1] Rallapalli PM, Kemball-Cook G, Tuddenham EG, et al. An
interactive mutation database for human coagulation factor
IX provides novel insights into the phenotypes and geneticsof hemophilia B. J Thromb Haemost 2013; 11(7): 1329-40.
[2] Mårtensson A, Letelier A, Halldén C, et al. Mutation
analysis of Swedish haemophilia B families - highfrequency of unique mutations. Haemophilia 2016; 22(3):440-5.
[3] Li T, Miller CH, Driggers J, et al. Mutation analysis of acohort of US patients with hemophilia B. Am J Hematol
2014; 89(4): 375-9.
[4] Kojima T, Tanimoto M, Kamiya T, et al. Possible absenceof common polymorphisms in coagulation factor IX gene inJapanese subjects. Blood 1987; 69(1): 349-52.
[5] Okumura K, Fujimori Y, Takagi A, et al. Skewed X
chromosome inactivation in fraternal female twins results inmoderately severe and mild haemophilia B. Haemophilia
2008; 14(5): 1088-93.
[6] Nakamura Y, Ando Y, Takagi Y, et al. Distinct X
chromosomal rearrangements in four haemophilia B patientswith entire F9 deletion. Haemophilia 2016; 22(3): 433-9.
[7] Nakamura Y, Murata M, Takagi Y, et al. SVA
retrotransposition in exon 6 of the coagulation factor IX
gene causing severe hemophilia B. Int J Hematol 2015;
102(1): 134-9.
[8] Green PM, Bentley DR, Mibashan RS, et al. Molecularpathology of haemophilia B. EMBO J 1989; 8(4): 1067-72.
[9] Radic CP, Rossetti LC, Abelleyro MM, et al. Assessment of
the F9 genotype-specific FIX inhibitor risks andcharacterisation of 10 novel severe F9 defects in the firstmolecular series of Argentinian patients with haemophilia B.
Thromb Haemost 2013; 109(1): 24-33.
[10] Goodeve AC. Hemophilia B: molecular pathogenesis andmutation analysis. J Thromb Haemost 2015; 13(7): 1184-95.
[11] Zhou J, Ding Q, Chen Z, et al. Risk factors associated with
inhibitor development in Chinese patients with haemophilia
B. Haemophilia 2015; 21(4): e286-93.
[12] Puetz J, Soucie JM, Kempton CL, et al. Prevalent
inhibitors in haemophilia B subjects enrolled in the
Universal Data Collection database. Haemophilia 2014;20(1): 25-31.
Author address

E-mail: sakane.hiroto@b.mbox.nagoya-u.ac.jp

Conclusions
We demonstrated that the null mutation due to nonsense
mutation or deletion of F9 is one of the crucial risk factor for
inhibitor development in Japanese hemophilia B patients.
The genetic diagnosis could contribute to prediction of theinhibitor development in hemophilia B patients.

- 66 -

Plumbagin Inhibits Expression of Virulence Factors and Growth of Helicobacter pylori
Hye Jin Kwon, Min Ho Lee, Hyun Jun Woo, Ji Yeong Yang, Min Ji Yeon, Do Hyun Kim and Jong-Bae Kim*

Department of Biomedical Laboratory Science, College of Health Sciences,
Yonsei University, Wonju, Gangwon-do 26493, Republic of Korea

Introduction
Plumbagin is a naturally occuring compound originatedfrom Plumbaginaceae, Droseraceae and Ebenceae families [1].
Crude extracts of plumbagin have been used to curerheumatoid arthritis, dysmenorrhea, and toothache in the folk
remedy [2].
Helicobacter pylori is a Gram-negative bacterium
possessing its characteristic helical appearance. H. pylori
primarily colonizes on human stomach and it has beenreported to infect approximately half of the world population[3]. Infection of H. pylori on gastric mucosa is associated withvarious gastric disease including inflammation, chronic
gastritis, peptic ulcer and gastric adenocarcinoma [4].
Moreover, because of its involvement in the gastric cancer
development, H. pylori was classified as a group I carcinogenby WHO [5].
The most studied virulence factors of H. pylori arecytotoxin-associated protein A (CagA) and vacuolating
cytotoxin A (VacA). Once injected, CagA proteins arephosphorylated by host cell Src kinases at its EPIYA motif
and subsequently deregulate intracellular signalingtransduction pathways, disrupt epithelial cell junctions, andinduce inflammation [6, 7]. Moreover, VacA increases bcatenin level in the host cells by inhibiting glycogen synthasekinase 3-b and leads to uncontrolled cell growth [8].
In this study, we demonstrated minimal inhibitory
concentration (MIC) of plumbagin on East Asian typereference strain of H. pylori (ATCC 49503) by agar dilution
method and investigated expression of RNA polymerase
subunits as well as various virulence factors after plumbagin
treatment.
Materials and Methods
Materials
H. pylori reference strain was purchased from ATCC
(ATCC49503, VA, USA). Mueller-Hinton broth, MuellerHinton agar and Brucella agar were purchased from BectonDickinson (MA, USA). Plumbagin and protease inhibitor
cocktail were obtained from Sigma-Aldrich (MO, USA).
Antibodies to detect CagA and VacA were purchased fromSanta Cruz Biotechnology (TX, USA) and polyclonal
antibody against whole H. pylori (ATCC 49503) was
produced as previously described [9].
Bacterial culture
H. pylori were grown on the Brucella agar plate
supplemented with 10% bovine serum at 37℃ for 72 h in ahumidified atmosphere with 5% CO 2 . For cultivation in broth,bacterial colonies were collected and suspended in MuellerHinton broth supplemented with 10% bovine serum. The
number of bacterial particles in the H. pylori suspension was
set to McFarland 0.33 and incubated at 37℃ for 72 h in ahumidified atmosphere with 5% CO 2 .

Agar dilution method to determine MIC
H. pylori grown on the Brucella agar plate were collected
and suspended in saline. The number of bacterial particles inthe H. pylori suspension was set to McFarland 4.0. Thirty μlof the bacterial suspension was placed on the Mueller-Hinton
agar supplemented with 10% bovine serum including
indicated concentrations of plumbagin. The bacteria wereincubated for 72 h and MIC was determined based on thelowest concentration at which inhibition of growth wasobserved.
Broth dilution method to determine MIC
H. pylori grown on the Brucella agar plate were collected
and suspended in Mueller-Hinton broth supplemented with 10%
bovine serum. The number of bacterial particles in the H.
pylori suspension was set to McFarland scale 0.5. Various
concentrations of plumbagin (125 nM−4 μM) were treated andthe bacteria were incubated for 72 h and final optical density(600 nm wave length) of the bacterial suspension wasmeasured by spectrophotometry.
RT-PCR (reverse transcription-polymerase chain reaction)
H. pylori was grown in the Mueller-Hinton broth for 72 h.
Cultured H. pylori were washed twice with PBS and total
RNA was extracted using Trizol reagent as described in the
manufacturer’s instructions. cDNA was synthesized byreverse transcription with 2 μg total RNA, 0.25 μg of random
hexamer and 200 U of MMLVRT for 50 min at 37℃ and 15
min at 70℃. Subsequent PCR amplification using 0.2 U of
Taq polymerase was performed in a thermocycler using
specific primers.
Western blotting
Cultured H. pylori were washed twice with PBS and thenlysed with RIPA buffer containing protease inhibitor cocktail.
The cell lysates were sonicated for 1 min and incubated on ice
for 10 min. The cell lysates were then centrifuged and thesupernatants were collected. The proteins were separated by
SDS-polyacrylamide gel electrophoresis and transferred to anitrocellulose membrane. The membrane was incubated with
optimal concentrations of primary antibody at 4℃ overnight
and then incubated with the appropriate secondary antibody(anti-mouse or anti-rabbit) for 1 h at room temperature. The
immune-labeled proteins were visualized using ECL. Anti-H.
pylori antibody was used as an internal control.

- 67 -

Results

Figure 1. Demonstration of minimal inhibitory concentrationof plumbagin against H. pylori(A) Thirty mL of bacterial suspension set to McFarland scale
4.0 (1.2 x 109/ml) was placed on the Mueller-Hinton agar
supplemented with 10% bovine serum and treated withindicated concentrations of plumbagin. (B) H. pylori
suspension was set to McFarland scale 0.5 in Mueller-Hintonbroth supplemented with 10% bovine serum. Indicatedconcentrations of plumbagin (125 nM ~ 4 mM) were treated.
MIC of plumbagin against H. pylori was determined after 72 hof incubation.

Figure 2. Effect of plumbagin on the expression of RNApolymerase subunits in H. pylori
H. pylori suspension set to McFarland scale 0.33 (1 x 108/ml)
was treated with 2 mM of plumbagin for indicated time
periods. RNA was harvested and subjected to RT-PCR toinvestigate the expression of RNA polymerase subunits (rpoA,
rpoB, rpoD, and rpoN). galE were used as an internal control.

Figure 3. Effect of plumbagin on the expression of H. pylori
virulence factors
H. pylori suspension set to McFarland scale 0.33 (1 x 108/ml)
was treated with 2 mM of plumbagin for indicated time

periods. (A) mRNA expression level of cagA, vacA and secA
after plumbagin treatment. (B) Protein level of CagA and
VacA toxins after plumbagin treatment.
Discussion
In this study, we confirmed inhibitory effect of plumbagin on
East Asian type H. pylori strain (ATCC49503). Although antimicrobial activity of plumbagin has been studied in a few
types of H. pylori strains (ATCC 43504, BCRC 17021, BCRC
17023, BCRC 17026, BCRC 17027 and BCRC 15415), themechanism in which plumbagin inhibits growth of H. pylori
has not been reported yet [10, 11].
To elucidate the inhibitory mechanism, we investigatedexpression of the molecules associated with DNA replication
or transcription in H. pylori after plumbagin treatment.
Transcription is also tightly associated with growth of livingorganisms because it is indispensable for synthesis of proteinin the end. In the investigation on the RNA polymerase
subunits, which are key molecules for transcription, we foundthat mRNA level of α subunit (rpoA) in H. pylori was reducedby plumbagin treatment.
As many virulence factors in H. pylori are associated withsuccessful infection of the bacteria or bacteria induced
pathogenesis, down-regulation of virulence factors may
decrease chance for H. pylori to colonize on the host gastricepithelium as well as reducing pathogenesis by the bacteria.
Among the various virulence factors, we found plumbagin
treatment inhibited expression of cagA, vacA, ureA, and alpA
in H. pylori. CagA and VacA toxins are closely associatedwith tumorigenesis by H. pylori.
Therefore, natural compounds such as plumbagin can bepotentially suggested as an alternative choice for eradicationof H. pylori in the future, although further studies seem to benecessary to completely understand the inhibitory mechanismof plumbagin on H. pylori and to confirm the effectiveness invivo.
Conclusion
We confirmed inhibitory effect of plumbagin on East Asiantype H. pylori strain (ATCC49503) and defined MIC.
Plumbagin inhibits expression of RNA polymerase a subunitin H. pylori. Expressions of major virulence factors (cagA andvacA) were decreased by plumbagin treatment in H. pylori.
Although further studies seem to be necessary, naturalcompounds such as plumbagin can be potentially suggested as
an alternative choice for eradication of H. pylori in the future.
References[1] Khaw AK, Sameni S, Venkatesan S, Kalthur G, andHande MP. 2015. Mutat Res Genet Toxicol Environ Mutagen.
793: 86-95.
[2] Padhye S, Dandawate P, Yusufi M, Ahmad A, andSarkar FH. 2012. Med Res Rev. 32: 1131-1158.
[3] Wiedemann T, Loell E, Mueller S, Stoeckelhuber M,
Stolte M, Haas R, and Rieder G. 2009. PLoS One. 4: e4754.
[4] Cover TL and Blaser MJ. 2009. Gastroenterology. 136:
1863-1873.
[5] IARC Working Group on the Evaluation ofCarcinogenic Risks to Humans. 1994. Schistosomes, liver
flukes and Helicobacter pylori. IARC Monogr Eval Carcinog
Risks Hum. 61: 1-241.
[6] Bornschein J and Malfertheiner P. 2014. Dig Dis. 32:
249-264.
[7] Hatakeyama M. 2004. Nat Rev Cancer. 4: 688-694.
[8] Nakayama M, Hisatsune J, Yamasaki E, Isomoto H,
Kurazono H, Hatakeyama M, et al. 2009. J Biol Chem. 284:
1612-1619.

- 68 -

[9] Kim SH, Park M, Woo H, Tharmalingam N, Lee G,
Rhee KJ, et al. 2012. Int. J. Med. Sci. 9: 838−842.
[10] Park BS, Lee HK, Lee SE, Piao XL, Takeoka GR,
Wong RY, et al. 2006. J. Ethnopharmacol. 105:255−262.
[11] Wang YC, Huang TL. 2005. J. Chromatogr A. 1094:
99−104.

- 69 -

Development of Serological Assay for Chikungunya Virus Infection
Monoldorova Sezim1, Myeong Il Kim2, Minsun Hong2, Bo-Young Jeon 1

1

Department of Biomedical laboratory Science, College of Health Science, Yonesi University, Wonju, Republic of Korea
2
Division of Biological Science and Technology, College of Science and Technology, Wonju, Repulbic of Korea

The CHIKV-positive specimens supplied from ABO
Pharmaceuticals were collected in Colombia; all subjects
were female according to the supplier’s information. In
total, 51 healthy subjects were enrolled in the present
study; the median age of the enrolled subjects was 47
years (range 23–73 years), and 90.2% were female. All
subjects were Korean. The healthy subjects werereported to have no C-reactive protein and erythrocyte

Introduction

Chikungunya virus (CHIKV) is a mosquito-transmitted
RNA virus that causes acute febrile infection associatedwith polyarthalgia in humans. The CHIKV contains a
positive-sense,
singlestranded,non-segmented
ribonucleic acid (RNA) genome of approximately 11.8
kilobases in length, with a virion diameter ofapproximately 70-100nm. The diagnosis of acuteinfections is based on the serological test by systems
detecting specific IgG and IgM antibodies. Anti-CHIKV
IgM antibodies can usually be detected in the patientserum during the acute phase of the disease, whereas
anti-CHIKV IgG are detected after virus clearance andcan persist for several months after infection. The E2
protein is a good candidate for serological diagnosis
since it is the immunodominant antigen during the courseof infection. The present study describes thedevelopment of ELISA (enzyme-linked immunosorbent
assay) using recombinant Chikungunya virus envelope 2
protein, which was expressed using E. coli expression
system. Recombinant CHIKV E2 whole protein was
highly reactive in the CHIKV patients both in the antihuman IgG and in the anti-human IgM. ELISA using
CHIKV E2 proteins would be useful for rapid andaccurate diagnosis of chikungunya virus infection.

sedimentation rates in the normal range.

M

1

75

50
37

20

Materials and methods

Subjects and serum panel
A CHIKV-positive serum panel was purchased fromABO Pharmaceuticals, it consisted of 33 plasma samples,
based on the anti-CHIKV IgM antibody titer and antiCHIKV IgG Antibody titer. As a negative control, serum
samples were collected from 51 healthy subjects who
presented to Wonju Severance Christian Hospital, Wonju,
Republic of Korea. Blood samples were collected fromhealthy subjects using serum vacuum tubes, and serum
samples isolated and stored at –80°C until use.
Cloning and expression of CHIKV E2 protein
The sequence of the CHIKV envelope E2 gene wasconfirmed by Macrogen (data not shown), and the
CHIKV E2 gene after enzyme digestion was subcloned
into the pQE30 expression vector and expressed in E. coli
M15 cells. The purified recombinant protein was
analyzed by sodium dodecyl sulfate-polyacrylamide gelelectrophoresis (SDS-PAGE) with Coomassie blue
staining, and a protein band with an approximate
molecular mass of 44 kDa was observed (Fig. 1).
Anti-CHIKV IgG or IgM indirect enzyme-linked
immunosorbent assay (ELISA)An ELISA was performed to evaluate the reactivity of
the recombinant CHIKV E2 protein to anti-CHIKV or
anti-CHIKV IgM antibodies
Results

Figure 1. SDS PAGE of recombinant CHIKV E2
proteinFigure 2. Reactivity of CHIKV E2 protein for IgM
antibody

The recombinant CHIKV E2 protein showedstrong anti-CHIKV IgG reactivity for CHIKVpositive serum samples, but anti-CHIKV IgG
reactivity was very weak for CHIKV-negative
serum samples. The anti-IgG reactivity of therecombinant CHIKV E2 protein was slightly
higher than that of the ABO Pharmaceuticals- 70 -

specimens for CHIKV-positive serum samples(Fig. 2).

Figure 3. Reactivity of CHIKV E2 protein for IgG
antibody

The reactivity of recombinant CHIKV E2 protein was
also estimated for anti-CHIKV IgM antibodies using a
CHIKV-positive and -negative serum panel. The
recombinant CHIKV E2 protein showed rather highreactivity for anti-CHIKV IgM and was comparable tothat of the ABO Pharmaceuticals specimens (Fig. 3).

[5] Enserink M. Epidemiology. Tropical disease

follows mosquitoes to Europe. Science 2007;
317(5844):1485.
[6] Khan M, Dhanwani R, Kumar JS, Rao PV,
Parida M. Comparative evaluation of thediagnostic potential of recombinant envelope
proteins and native cell culture purified viral
antigens of Chikungunya virus. J Med Virol
2014; 86(7):1169-1175.
[7] Dash PK, Parida MM, Santhosh SR, Verma SK,
Tripathi NK, Ambuj S, et al. East Central South
African genotype as the causative agent inreemergence of Chikungunya outbreak in India.
Vector Borne Zoonotic Dis 2007; 7(4):519-27.
[8] Priya R, Khan M, Rao MK, Parida M. Cloning,
expression and evaluation of diagnostic
potential of recombinant capsid protein based
IgM ELISA for chikungunya virus. J Virol
Methods. 2014; 203:15-22.
Author address
sezima91@gmail.com

Discussion

The recombinant E2 protein was highly effective for thedetection of anti-CHIKV IgG and IgM antibodies fromCHIKV-positive plasma specimens from Colombia, a
CHIKV-endemic country in South America. The
performance of Asian CHIKV E2 protein needs to beevaluated with various panels, which include the diverse
subjects and origins including ECSA strain, Indian
ocean strain, West African strains as well as Asianstrain.
Conclusion
The E2 protein of the Asian genotype CHIKV strain
was expressed via an E. coli expression system, and therecombinant protein was highly reactive to anti-CHIKV
IgG and IgM antibodies in CHIKV-positive patient
specimens from a CHIKV-endemic country in SouthAmerica.
References[1] AbuBakar S, Sam IC, Wong PF, MatRahim N,

Hooi PS, Roslan N. Reemergence of endemic
Chikungunya, Malaysia. Emerg Infect Dis 2007;
13(1):147-9.
[2] Burdino E, Calleri G, Caramello P, Ghisetti V.
Unmet Needs for a Rapid Diagnosis of
Chikungunya Virus Infection. Emerg Infect Dis
2016; 22(10):1837-9.
[3] Cho B, Kim J, Cho JE, Jeon BY, Park S.
Expression of the capsid protein of Chikungunya
virus in a baculovirus for serodiagnosis of
Chikungunya disease. J Virol Methods 2008b;
154(1-2):154-9.
[4] Chikungunya outbreak in India. Vector Borne
Zoonotic Dis 2007; 7(4):519-27.

- 71 -

Highly sensitive and simultaneous determination of urinary metabolites of pyrethroids using
gas chromatography-tandem mass spectrometry
Yuko Ueda1, Jun Ueyama1, Masaya Oda1, Takaaki Kondo1, Isao Saito2, Shinya Wakusawa1
1) Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
2) Food Safety and Quality Research Center, Tokai COOP Federation, Nagakute, Japan
Introduction
Pyrethroids (PYRs) are synthetic chemical insecticides
whose chemical structures have chrysanthemic acid esters,
and are widely used as a pesticide for foliar and seedtreatments in the agro fields, which can significantly increase
crop productivity (hereafter called pesticide-PYR).
According to the Food and Agriculture Organization (FAO)
survey, the usage level of pesticide-PYR ingredients havedecreased gradually from 304 tonne in 2000 to 208 tonne in2014 primarily due to the emergence of insects resistant toconventional pesticides in Japan. PYRs also contribute tomaintain a good hygienic condition. In particular, PYRs arealso most frequently used for controlling indoor and outdoor
insects such as mosquito, a primary vector of dengue,
chikungunya and Zika viruses [1][2]. These PYRs arereferred to as hygiene-PYR.
The primary target of pesticide-PYRs and hygiene-PYRs
is the voltage-dependent sodium channel [3]. Although there
are a lot of PYR compounds, in many case PYR compounds
are used properly as pesticide-PYRs and hygiene-PYRs
depends on physic-chemical characterization of PYR
compounds such as insect toxic specificity, photostability,and volatility. More recently, newly developed hygine-PYR,
which have tetrafluorobenzyl and cyclopropane strictureswith high vapor activity at ambient temperature, are now
playing a key role in controlling insects in our daily life
safely. Typical names of these compounds are metoflthrin,
profluthrin, transfluthrin, and tefluthrin.
It is well known that exposure assessment of chemicals
we use is a key component of human health risk assessment.
Some methodological studies for urinary PYR metabolite
assay have been developed over the past decade [4][5][6],largely because biological monitoring is an effective way toidentify the PYR exposure level in individuals, ensuring thesafety of food, the living environment and occupational
exposure. Consequently, a number of epidemiological studies
on the characterization of urinary PYR metabolite
concentration in each fields [7][8][9], and on effects oflong-term exposure to low-level PYRs on human health[10][11] have been conducted. But these studies havemeasured limited urinary PYR metabolite, 3-phenoxybenzoic
acid (3-PBA) and 3-(2,2-Dichlorovinyl)-2,2dimethylcyclopropane-1-carboxylic acid (DCCA), which aremainly derived from pesticide-PYRs. This might be causedby that only a few study on the determination method ofhygiene-PYR metabolites in urine have been reported. Morerecently, Yoshida has reported the determination method fora part of hygiene-PYR metabolites in urine, which need large
amount of urine sample (10 ml) and labor-intensive andtime-consuming sample procedure [12]. The method for
determination of urinary hygiene- and pesticide- PYR
metabolites needs further development for application toepidemiological study due in part to evaluate the effect ofdaily PYR exposure on human health.
The aim of this study was to develop a simple andhigh-throughput method for simultaneous determination ofurinary PYR metabolites, mainly hygiene-PYR metabolites,
using gas chromatography–tandem mass spectrometry(GC-MS/MS), which is sensitive enough to be adopted not
only in occupational but non-occupational PYR exposure

settings. Figure 1 shows the relationship between urinary
hygiene- and pesticide-PYR metabolites we focused on thisstudy (shaded areas) and their parent compounds.
F

F

O

F

F
HO

O

H 3C

F

F

F

O

F

H 3C

F
F

F

F

F

CH3 -FB-Al

H3C

F

F

F

F

Transfluthrin

FB-Ac
HO

Cl
H3C

OH
CH3

CH3

Permethrin*

DCCA

O

O
O

CH3

OH
F

CH3

O

Cl

O

F

Cl
H 3C

Cl

OH

O
Cl

O

F

Cl

F

O

F

CH3 -FB-Ac

O

FB-Al

OH

H 3C

CH 3

O

F

F

O

F

Profluthrin

OH

H3C

F
CH 3

O

OH

Cl

F

CH3 OCH2 -FB-Al

Metofluthrin
F

F

OH

O

H 3C

CH 3

F

F

F

H 3C

H3C

F

F

HOCH2 -FB-Al
F

F

CH 3

O

OH

H3C

O

CH3

CDCA

CN
O

Cl

COOH

H3C

3-PBA

CH3
O

Cypermethrin*
O

O
O

CH3

H3C

O
H3C

Ethofenprox*

O
H3C

O
CH3

othersCyhalothrin*, Esfenvalerate*
Deltamethrin, Fenpropathrin*

H3C

O
CH3

CH3
CH3

Phenothrin O

H3C

CH3

O

Resmethrin
othersAllethrin*, Imiprothrin
Tetramethrin, Prallethrin

Figure 1. The relationship between pyrethroid and thosemetabolites, and example of insecticide products. DCCA,
3-(2,2-Dichlorovinyl)-2,2dimethylcyclopropane-1-carboxylic acid; 3-PBA: 3-phenoxybenzoic acid;
CDCA, 1R-trans-chrysanthemum dicarboxylic acid; FB-Al, 2,3,5,6tetrafluorobenzyl alcohol; FB-Ac, 2,3,5,6-tetrafluorobenzoic acid;
HOCH2-FB-Al, 4-hydroxymethyl-2,3,5,6-tetrafluorobenzyl alcohol;
CH3-FB-Al, 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol; CH3OCH2-FB-Al,
4-methoxymethyl-2,3,5,6-tetrafluorobenzylalcohol; MCA, 2,2-dimethyl-3(1-propenyl)-cyclopropanecarboxylic acid; CH3-FB-Ac, 4-methyl-2,3,5,6tetrafluorobenzoic acid. *pesticide-insecticide.

Methods
Sample preparation procedue: A flow chart of the procedurefor determining urinary PYR metabolites is shown in Fig. 2.
Two point five milliliters of urine was pipetted into a 24 wellplate (each well volume is 10 ml), and 600 µl deconjugation
reagent (6 mol/l HCl) and 25 µl I.S. solution (0.5 mg/l isotope
labeled HOCH2-FB-Al and 2-PBA) was added. After gentle
shaking, the well plate was sealed with heat resistance thin film,
followed by incubation at 100 oC for 2 hours in thermostat
chamber for deconjugation, and cooled on ice. Then, 3 ml oftert-butyl methyl ether was added to each well, and the mixture
was shaken vigorously for 10 min and centrifuged for 5 min at
2000×g. The organic phase (upper layer) was transferred into a
new 24 well plate. The residue was re-extracted with 2.5 ml
tert-butyl methyl ether, shaken and centrifuged. These
liquid-liquid extractions were performed by applying theautomation system in plate formats Extrahera™ (Biotarge,- 72 -

Uppsala, Sweden) except for the shake and centrifuge. The
organic phase was divided into 2 tubes for further
pretreatment procedures. The resulting extracts were
evaporated at 4 oC (ice block) to dryness in vacuum statechamber.
The residues were dissolved in each
derivatization reagents and incubated for 30 min at room
temperature. Then, sodium hydrogen carbonate solution (1mol/l) and iso-octane were added. The test tubes were shaken
vigorously and centrifuged for 5 min at 2,000×g. Then, 1 µlof the iso-octane phase was injected into GC-MS/MS within
1 week after the derivatization. Iso-octane phase obtained
from Fraction 1 is for HOCH2-FB-Al, CH3OCH2-FB-Al,
CH3-FB-Al, FB-Al, FB-Ac analysis, and Fraction 2 is for
CH3-FB-Ac, 3PBA, CDCA, and DCCA analysis.
2.5 ml urine sample
25 µl 2-PBA (0.5 mg/L)
25 µl isotope labeled HOCH2-FB-Al (0.5 mg/L)
600 µl HCl (6 mol/L)
Heat chamber (106 o C, 2 h )Cool down (chill on ice)
3 ml tert-butyl methyl ether (2.5 ml in second round)
Vigorous Shake (10 min )Centrifuge (2,000 ´ g, 5 min)Extract
aqueousphase again

Transfer organic layer
Mix well and divide into two
3 ml
Fraction 1
10 ml screw-top
glass test tube

2 ml
Fraction 2
2 ml polypropylene
test tube

Evaporate in vacuum chamber (4 oC)
100 µl acetone
50 µl BSTFA-TMCS

125 µl acetonitrile
15 µl HFIP
10 µl DIC

Slightly shake & incubate for 30 min at R/T (derivatization step)
100 µl iso-octane
1 ml NaHCO3 sol.

100 µl iso-octane
500 µl NaHCO3 sol.

Vigorous Shake (10 min) and centrifuge (2,000 ´ g, 5 min)Both iso-octane (upper) phases were analyzed by GC-MS/MS, separately

Figure 2. Analytical procedure for urinary hygiene- andpesticide-PYR metabolites. Fraction 1 is for HOCH2-FB-Al,
CH3OCH2-FB-Al, CH3-FB-Al, FB-Al, FB-Ac, and Fraction 2 is for
CH3-FB-Ac, 3PBA, CDCA, DCCA analysis.

GC-MS/MS analysis: GC-MS/MS analysis was run on an
Agilent 7890 GC coupled with an Agilent 7000B inert mass
spectrometer (Agilent Technologies, Inc. CO, USA). Twotypes of GC columns were adopted in this assay. One is
DB-5ms for Fraction 1 analysis (Agilent, 30 m × 0.25 mm
i.d., 0.25 µm ﬁlm thickness), another one is Rtx-65 for
Fraction 2 analysis (Restek, Bellefonte, PA, USA, 30 m ×
0.25 mm i.d., 0.25 µm film thickness).
Application of methods to field study samples: Our
method was applied to human spot urine obtained inAugust-September of 2012 from children, who attended amunicipal health check program covering three-year-old
children in two suburban areas of Aichi, the central region ofJapan. Collected spot urine samples were transported at -4 oC
to our laboratory within 5 hours, and then stored at -80 oC
until metabolite analyses. The Ethics Committees of the
Nagoya City University Graduate School of Medicine, andthe Ethical Review Committee of the Akita University
Graduate School of Medicine approved the study protocol.
Results and discussion
Percentage of recovery of the analyte frommetabolite-spiked urine at three concentrations ranged from31 (for 1.25 µg/l FB-Al) to 143% (for 0.6 µg/l CDCA). Lower
recoveries of FB-Al might be attributable to its relatively highvolatility. Results from the validation study demonstrated good
within- precisions (less than 13% except for 22% of FB-Al)
with low detection limits (ranging from 0.02 to 0.12 µg/l for
FB-metabolites, and 0.01 to 0.05 µg/l for the other PYR
metabolites. LOD for the other PYR metabolites were lower
than the previously reported values [13]. On the other hand,
LOD for CH3OCH2-FB-Al and CH3-FB-Al approximately fiveand twelve times higher than the previously reported values [13].
This may be caused by volume of urine. More urine may bebetter if it’s necessarily to improve sensitivity.
Preliminary application of the established method tochildren revealed that the detection rate was 80% in bothsummer and winter seasons. The median concentration(maximum value) was 0.13 (4.08) µg/l in summer and 0.06
(0.11) µg/l in winter, suggesting that exposure of metofluthrin
or profluthrin of children was high in summer. Especially, theactivity of mosquitoes and flies becomes active and the use of
insecticides increases in summer. Therefore, the usage of
metofluthrin and profluthrin may be increased. The results
obtained in this study seem to reflect this usage pattern.
Conclusion
This method is sensitive and precise, and has beensuccessfully applied to quantify the concentration ofcomprehensive PYR metabolites in Japanese urine sample.
References[1] Scott, T.W., Chow, E., Strickman, D., Kittayapong, P.,
Wirtz, R.A., Lorenz, L.H., Edman J.D. Journal of Medical
Entomology, 1993, 30(5), 922–7.
[2] Coffey, L.L., Failloux, A-B., Weaver, S.C. Viruses, 2014,
6(11), 4628-4663.
[3] Soderlund, D.M. , Clark, J.M., Sheets, L.P., Mullin, L.S.,
Piccirillo, V.J., Sargent, D., Stevens, J.T., Weiner, M.L.
Toxicology, 2002, 271(1), 3-59.
[4] Olsson, A.O., Baker, S.E., Nguyen, J.V., Romanoff, L.C.,
Udunka, S.O., Walker, R.D., Flemmen, K.L., Barr, D.B.
Analytical Chemistry, 2004, 76, 2453–2461.
[5] Baker, S.E., Olsson, A.P., Barr, D.B. Archives ofEnvironmental Contamination and Toxicology, 2004, 46,
281–288.
[6] Leng, G., Gries, W., Selim, S. Toxicology Letters, 2006, 162,
195–201.
[7] Centers for Disease Control and Prevention (CDC). Fourth
National Report on Human Exposure to Environmental
Chemicals. 2009.
[8] Becker, K., Seiwert, M., Angerer, J., Kolossa-Gehring, M.,
Hoppe, H.W., Ball, M., Schulz, C., Thumulla, J., Seifert, B.
International Journal of Hygiene and Environmental Health,
2006, 209, 221–233.
[9] Ueyama, J., Kimata, A., Kamijima, M., Hamajima, N., Ito,Y., Suzuki, K., Inoue, T., Yamamoto, K., Takagi, K.,
Saito, I., Miyamoto, K., Hasegawa, T., Kondo, T.
Environmental Research, 2009, 109(2), 175-180.
[10] Oulhote, Y., Bouchard, M.F. Environmental Health
Perspectives, 2013, 121(11-12), 1378-1384.
[11] Ding, G., Shi, R., Gao, Y., Zhang, Y., Kamijima, M., Sakai,
K.,Wang, G., Feng, C., Tian, Y. Environmental Science &Technology, 2012, 46, 13480–13487.
[12] Yoshida, T. Journal of Chromatographic Science, 2017,
1-9.
Author address
E-Mail: ueda.yuuko@g.mbox.nagoya-u.ac.jp- 73 -

Improved colitis-associated cancer model using ETBF

Soonjae Hwang1, Chang Gun Lee1, Minjeong Jo1, Chan Oh Park1, Sun-Yeong Gwon1, Hwang, Samnoh1, Yi, Hye Chin1,
So-Yeon Lee2, Yong-Bin Eom2,3, Ki-Jong Rhee1*
1) Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju
2) Department of Medical Science, College of Medical Sciences, Soonchunhyang University3) Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University
Introduction
The colorectal cancer is a major cause of death in developed
countries1. Genetic mutations in epithelial cells are the main
etiological factor for colorectal cancer2. However,environmental factors can greatly influence the pathogenesis ofcolorectal cancer3. Among these factors, inflammation plays apivotal role in enhancing tumor survival and progression
through signal transduction of pro-inflammatory cytokines4.
Numerous studies have supported a link between microbialinduced inflammation and cancer5,6. Examples include
Helicobacter pylori-induced gastritis, Hepatitis B virusinduced hepatitis and human papillomavirus-induced cervicitis
which promote gastric cancer7, hepatic cancer8 and cervicalcancer9, respectively.
Enterotoxigenic Bacteroides fragilis (ETBF) is a humancolonic commensal associated with juvenile diarrhea as well as
high grade colorectal cancer (ref). The key virulence factor of
ETBF is attributed to BFT, a 20 kDa zinc-dependent
metalloprotease toxin present as three isotypes (BFT-1, BFT-2
and BFT-3). BFT induces E-cadherin cleavage both in vitro andin vivo, resulting in increased intestinal permeability andsubsequent colitis. BFT activates β-catenin, NF-κB and MAPK
pathways with enhanced cellular proliferation and secretion of
IL-8 in HT29/C1 cells.
More importantly, ETBF infection can promote Th17dependant colonic tumorigenesis in MinApc+/− mouse model.
MinApc+/− mice harbor a heterozygous germline mutation in the
APC gene (MinApc+/−) and is an animal model for familial
adenomatous polyposis (FAP). MinApc+/− mice are often used toassess anti-tumor drugs, nutritional risk factors, and to elucidate
mechanisms of colonic tumorigenesis in vivo. However, one
disadvantage of the MinApc+/− mouse model is that the
adenomas arise predominantly in the small intestine and less soin the colon. In addition, maintenance of a large number ofbreeding pairs are necessary, a limitation for small-sizedlaboratories.
Another often used animal model for colon cancer is theazoxymethane (AOM)/dextran sulfate sodium (DSS) mousemodel of colitis-associated cancer (CAC). An advantage of theAOM/DSS system is ease of manipulation and documented
efficacy in wild type mice strains (eg, BALB/c and C57BL/6).
Prolonged AOM/DSS treatment induce progression fromadenomas to adenocarcinomas in a subset of adenoma
depending on the mouse strain and treatment conditions.
Furthermore, all polyps in AOM/DSS-treated mice form in thecolon. One main disadvantage of the AOM/DSS model is thesmall number of polyps that form in the colon. In the current
study, we assessed the tumorigenic potential of ETBF
colonization in AOM/DSS system. We found that ETBF
colonization of wild-type C57BL/6 mice administered with
AOM/DSS rapidly develop a large number of polyps
predominantly in the colorectal region. This protocol describedherein can be readily implemented to study ETBF
tumorigenesis in wild-type mice and provides an experimental
platform for understanding ETBF induced pathogenesis.

Azoxymethane (AOM) and dextran sulfate sodium (DSS).
DSS (36–50 kDa) was purchased from MP Biomedicals. AOM
was purchased from Sigma-Aldrich. Eight-week-old female
Balb/c and C57BL/6 mice (Rionbio, Korea) received a single
i.p. injection of AOM (10 mg/kg) and 7 days later provided
DSS containing water (1%, 2% w/v) 5 days for either 6 (1 roundof DSS cycle) or 12 (3 rounds of DSS cycle) weeks.
Bacterial strains. WT-ETBF strains used are as follows: B.
fragilis VPI 13784 (bft-1), B. fragilis O86-5443-2-2 (bft-2) andB. fragilis Korea 570 (bft-3). The, nontoxigenic wild-type B.
fragilis (WT-NTBF) strain, B. fragilis NCTC 9343, does not
express BFT. WT-NTBF recombinant strains overexpressing
active BFT (rETBF; bft-2) and WT-NTBF overexpressing a
biologically inactive mutated BFT (rNTBF; bft-2 H352Y) werereported previously. Both of rETBF and rNTBF strains have aclindamycin-resistant gene on a plasmid.
Mouse infection. Mice were given water containing
clindamycin (100 mg / liter) and gentamicin (300 mg / liter) topromote colonization of B. fragilis. Antibiotic-containing water
was initiated 5 days prior to bacterial inoculation and continued
for 10 days. Bacteria were grown in brain heart infusion brothand adjusted to 1 x 109 CFU / 200 ul for mouse oral inoculations.
Colonization of bacteria was monitored by serial dilution ofstool and plating on brain heart infusion agar plates containing
gentamicin (50 ug/ml) and clindamycin (6 ug/ml).
Characteristic B. fragilis colonies were enumerated after
anaerobic culture as shown as CFU/g stool.
Tissue harvest and histology. After sacrificing ETBF-based
AOM/DSS-treated mice, isolated large intestines of mice wereseparated into cecum and remaining colon by scissors. To
obtain fine pictures of flat colon with tumors, colonic tissues
were formalin-fixed (10%) for 1 hour. Gross of stiffened large
intestines was pictured by Canon SX510 HS camera in a petri
dish. After getting image of gross of isolated colon, the colonictissues were formalin-fixed (10%) for additional histologic
examination. Paraffin-embedded colon tissues were sectioned(5 um) and stained with hematoxylin and eosin (H&E) andPeriodic acid–Schiff (PAS).
Immunohistochemistry. All immunohistochemistry was
performed on formalin-fixed, paraffin-embedded samples.
Paraffin blocks were sectioned at 4 um thickness. After getting
sectioning, poly-L-lysine-coated slides were used to promoteadhering of paraffin-section to the slides which were then dried.
Images of IHC slides were pictured by optical microscopy(Leica) and rendered using Adobe Photoshop.
Quantitative RT-PCR. Frozen colonic tissues were thawed,
followed by homogenized using autoclaved plastic
homogenizer for 10 min. Total RNA was isolated from large
intestine using TRIzol reagent (Life Technologies, CLD, CA)according to the manufacturer’s instructions. RNA wasconverted to cDNA using the M-MLV Reverse

Materials and methods- 74 -

Statistics. All statistical analyses were performed using theMann-Whitney test (GraphPad Prism). A p value < 0.05 wasregarded as significant.
Study approval. All animal experiments were approved by theInstitutional Animal Care and Use Committee of Yonsei
University at Wonju (YWC-151005-1, YWCI-201612-014-01)
and Institutional Biosafety Committee of Yonsei University at
Wonju (201612-P-014-01).

Figure 1. Balb/c mice were subjected to the standard
ETBF/AOM/DSS (2%) protocol for 12 weeks. Mice were
infected with WT-ETBF (bft-2), rETBF (bft-2), or rNTBF (bft2 H352Y). C, AOM/DSS; E2, WT-ETBF; rE2, rETBF; rN2,
rNTBF. Rectum of mice.

n.s

0.05

References
1 Center, M. M et al. CA Cancer J 59, 366-378 (2009).
2 Fearon, E. R. Annu Rev Pathol 6, 479-507 (2011).
3 Markowitz, S. D. & Bertagnolli, M. M. N Engl J Med 361,
2449-2460 (2009).
4 Grivennikov, S. et al. Cancer Cell 15, 103-113 (2009).
5 Karin, M., Lawrence, T. & Nizet, V. Cell 124, 823-835(2006).
6 Mariathasan, S. & Monack, D. M. Nat Rev Immunol 7, 3140 (2007).
7 Boleij, A. et al. Clin Infect Dis 60, 208-215(2015).
8 Sears, C. L. et al. Clin Infect Dis 47, 797-803 (2008).
9 Sears, C. L. Toxicon 39, 1737-1746 (2001).
Author address
Soonjae Hwang, E-Mail: yoyosong1@naver.com
Ki-Jong Rhee, E-Mail: kjrhee@yonsei.ac.kr

C

+

+

N

0.00

C

N

E3

0.10

+

+

C

C

E2
+

C

C

+

E1

0

***
***

E3

10

***

+

n.s

Acknowledgements
This work was supported by NRF (National Research
Foundation of Korea) Grant funded by the Ministry of
Education(2017R1D1A1A02018088
and
NRF2017R1D1A1B03032960), and NRF-2017-Fostering Core
Leaders of the Future Basic Science Program/Global Ph.D.
Fellowship Program, 2017H1A2A1045727.

C

20

E2

30

***

0.15

E1

40

Conclusion
In this study, we demonstrated that ETBF plays a role inenhancing colonic tumor number and progression in
AOM/DSS-treated Balb/c mice through BFT. Consequently,
Bacteorides fragilis harboring bft gene could be used as a noveland experiemental platform for studying colitis-associatedcancer in wild-type mice.

n.s

0.20

C

**

+

*

C

**

50

C

Polyp number

60

Polyp area (cm 2)

Results
We
determined
whethertumorigenesis
intheETBF/AOM/DSS model requires BFT expression. Balb/c mice
were inoculated with a wild-type strain of ETBF expressing
BFT-2 (WT-ETBF), nontoxigenic B. fragilis strain harboring aplasmid containing the active BFT-2 gene (rETBF), and B.
fragilis secreting catalytically inactive BFT (rNTBF). We
found that mice inoculated with WT-ETBF and rETBF showed
increased polyps, whereas those inoculated with rNTBF
developed polyps comparable to those observed in miceadministered AOM/DSS alone (Fig. 1). Increased spleen
weight and decreased colon length, all indicative of enhanced
inflammation, was observed in WT-ETBF and rETBF mice ascompared with those in rNTBF mice (data not shown).
Cytokine analysis was performed by real-time polymerase
chain reaction (PCR) of distal colonic tissues and cytokine beadarray of serum cytokines.
The strain ETBF is categorized into three types depending on
the secretion of one of the three BFT isotypes. We examined
the tumorigenic potential of three WT-ETBF strains secreting
BFT (i.e., BFT-1, BFT-2, and BFT-3) in the AOM/DSS model.
We found that all three WT-ETBF strains induced comparable
number of colonic polyps, whereas the nontoxigenic B. fragilis
strain (WT-NTBF) that does not secrete BFT showed noincrease in polyp number as compared with that for AOM/DSS
alone (Fig 2).

Discussion
Using developed method to ETBF-promoted CAC, wedemonstrate for the first time that ETBF- CAC model based onwild type inbred mouse model. Also, this method may also
apply to other inbred strains of mouse such as 129S1/S, A/J,
AKR/J, C3H/HeJ and FVB/NJ. Previous study reported that
ICR mouse of outbred strains show strong colonictumorigenesis similar to BALB/c mouse which is sensitive
strain to AOM/DSS among several inbred strains. In addition,
our characterization of the method will facilitate the research toinvestigate not only for ETBF-induced carcinogenesis but also
canonical oncogenesis, followed by reduced the material cost,labor, and time for evaluation of factors to affect ETBF-CAC
model. We envision that ETBF-CAC method will be easily
used an alternative model in wild type mice in place of
MinApc+/− mice-based ETBF model because method of
AOM/DSS added with ETBF has merits such as easily
manipulable system, strong colonic tumorigenesis andenhanced proportion of high grade tumor and cancer.

Figure 2. Balb/c mice were subjected to the standard
ETBF/AOM/DSS (2%) protocol for 12 weeks. Mice were
infected with three different WT-ETBF strains expressing
different BFT isotypes. C, AOM/DSS; E1, WT-ETBF (BFT1); E2, WT-ETBF (BFT-2); E3, WT-ETBF (BFT-3); N, WTNTBF. Polyp number and polyp size distribution (n = 5–7 mice
per group). *P < 0.05, **P < 0.01, ***P < 0.001. ns, nostatistical significance.

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Development of anti-EGFR lipid micellar nanoparticles
co-encapsulating quantum dots and paclitaxel
for tumor-specific theranosis
Seong Jae Kang1), Min Woo Kim1), Moon Jung Choi1), In Ho Jeong1), Chan Su Im1), Young Myoung You1), In Ho Song2),
Tae Sup Lee2), Yong Serk Park1)
1) Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea
2) Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Science (KIRAMS),
Seoul, Republic of Korea.
Introduction
Diagnostic therapy, refered as theranosis, has been considered
as a powerful tool that can not only diagnose diseases at an
early stage but also precisely treat diseases in accordance with
monitoring individual responses to therapeutic processes [1]. In
cancer therapy, the heterogenecity of cancer is a major leading
cause of different therapeutic outcomes among patients in spiteof using same treatment regimen [2]. Therefore, theranosis has
been regarded as a useful strategy for personalized medicine tocancer [3]. In general, theranostic technology is nanomedicine
combined with molecular imaging [4]. The theranosis is basedon a concept that anti-cancer molecules and imaging agents are
simultaneously delivered to the target site by using ananocarrier. Aim of this study was to develop tumor-specifictheranostic nanoparticles enabling clinical applications. In thisstudy, we prepared tumor-targeted theranostic nanoparticles
that co-loaded paclitaxel and QDs as an anti-cancer drugs anda molecular imaging agent, respectively. For tumor-specificdelivery of QDs and PTX, anti-EGFR antibodies or aptamers
were decorated to the surface of micelles, respectively. EGFRspecific delivery capacity and therapeutic activities of thetheranostic nanoparticles were assessed in cancer cells andtumor-xenografted mouse models. Biological behavior andtumor accumulation of the theranostic nanoparticles weremonitored by in vivo fluorescence imaging. Furthermore,
efficacies of aptamers as an active targeting ligand werecompared with those of conventional antibodies.
Materials and methods
Materials:1,2-distearoyl-sn-glycero-3phosphoethanolamine-N-[methoxy(polyethylene glycol)2000](DSPE-mPEG2000)
and
1,2-distearoyl-sn-glycero-3phosphoethanolamine-N-[maleimide(polyethylene
glycol)2000] (DSPE-PEG2000-mal) were purchased from
Avanti Polar Lipid, Inc. (Alabaster, AL, USA). CdSe/ZnS High
Quality organic NSQ-dots quantum dots (Q-dot, λemit = 620nm) were purchased from Nanosquare Inc. (Seoul, Korea).
Paclitaxel was purchased from Sigma-Aldrich (St. Louis, MO,
USA). Anti-EGFR antibodies, named as cetuximab, werepurchased from Merck KgaA (Darmstadt, Germany). The antiEGFR aptamers which were functionalized with sulfhydryl
group at 3’-end were purchased from Aptamer Science Inc.
(Pohang, Korea).
Cell lines and culture: LS174T (human colorectal
adenocarcinoma, #10188) cell lines were purchased from
Korean Cell Line Bank (Seoul, Korea). LS174T cells weremaintained in RPMI1640 (Gibco, Carlsbad, CA, USA)supplemented with 10% fetal bovine serum (FBS, Gibco), 100
IU/ml penicillin (Gibco) and 100 μg/ml streptomycin (Gibco)

in a humidified atmosphere of 95% air and 5% CO2 at 37℃.
Preparation of lipidic micelles co-loading paclitaxel and
QDs: Paclitaxel (PTX) and QDs were co-encapsulated in thelipidic micelle cores by thin film methods. Firstly, DSPEmPEG2000 in chloroform and methanol solution (2:1, v/v),

PTX in methanol and QDs in chloroform were mixed by
700:57:1 molar ratio. The organic solvents were evaporated
under a stream of N2 gas. Vacuum desiccation for 1 hr was
performed to remove the residual organic solvents. The dried
film was incubated at 80℃ for 2 hr and was hydrated withHEPES buffer (HEPES 25 mM, NaCl 140 mM, pH 7.5) in 1
mg/ml lipid concentration. QD and PTX aggregates which are
not encapsulated in micelles were removed by using Nuclepore
Track-Etched polycarbonate membrane filter (Whatman Inc.,
Piscataway, NJ, USA) with 100 nm pore size. The QDsencapsulated micelles were called as QDMs. The lipidic
micelles co-loading PTX and QDs were named as PTX-QDMs.
Conjugation of anti-EGFR antibodies to the PTX-QDMs:
For coupling anti-EGFR antibodies to the surface of the PTXQDMs, the primary amines of antibodies in HEPES-EDTA
buffer (25 mM HEPES, 140 mM, NaCl, 2 mM EDTA, pH 8.0)
were thiolated by Traut’s reagents (Thermo Scientific,
Rockford, IL, USA) The thiolated antibodies were added to the
PTX-QDMs-mal at the molar ratio of 0.2:1 (antibody:DSPEPEG2000-mal) for 18 hr at 4℃. The anti-EGFR antibodiesconjugated PTX-QDMs were named as Immuno-PTX-QDMs.
Conjugation of anti-EGFR aptamers to the PTX-QDMs: To
obtain the reduced form of protected aptamers which werecrosslinked each other by disulfide bond, the equal volumes of
20 mM tris-(2-carboxyethyl)phosphine (TCEP, Invitrogen,
Carlsbad, CA, USA) and 100 uM aptamers in HEPES buffer
were mixed for 1 hr at room temperature. The aptamers wereadded to the PTX-QDMs-mal at the molar ratio of 0.2:1(aptamer:DSPE-PEG2000-mal) for 18 hr at room temperature.
The anti-EGFR aptamer-conjugated PTX-QDMs are named as
Aptamo-PTX-QDMs.
LS174T-xenografted mouse model: All animal experiments
were approved by the Institutional Animal Care and Use
Committee (IACUC) of Yonsei University at Wonju (YWCI201608-008-01) and conducted under protocols in accordancewith the school guidelines and regulations. 6-week old female
BALB/c nude mice (Orient Bio, Seongnam, Korea) were
subcutaneously injected with 2×106 cells of LS174T cells in theleft low back of each mouse. Length and width of tumors were
measured by caliper and tumor volumes (mm3) were estimatedas (length×width2)/2.
In vivo fluorescence imaging: When the tumor volume
reached at approximately 500-800 mm3, LS174T-xenografted
mice were randomly divided into 3 groups (n = 3 per group).
The mice in each group were intravenously injected with 800
pmole QDs/mouse of QDMs, Immuno-QDMs and AptamoQDMs, respectively. In vivo fluorescence images wereobtained at 1, 4, 8, 24, 48, and 72 hr post-injection by using a
Maestro 2 in vivo imaging system (λex: 550 nm, λemit: 620 nm,
Caliper Life Sciences, Hopkinton, MA, USA).
In vivo therapeutic activities of Immuno-/Aptamo-PTXQDMs: When the tumor volume reached at approximately 100
mm3, LS174T-xenografted mice were randomly divided into 5groups. The mice in each group were intravenously injected- 76 -

with 1.25 mg/kg PTX per mouse (n = 5 each group) of saline,
PTX, PTX-QDMs, Immuno-PTX-QDMs and Aptamo-PTXQDMs for 3-times with 3 days intervals. The tumor volumes
were measured once every 2 days. When the largest tumor
volume reached to approximately 2000 mm3, all mice weresacrificed.
Statistical analysis: Data were represented as mean ±standard deviation (S.D.). Statistical analysis was performed
with one-way or two-way ANOVA using Prism 7 (GraphPad
Software, Inc.). p < 0.05 was considered statistically significant.

of QDMs, Immuno-QDMs and Aptamo-QDMs. At 1, 4, 8, 24,
48, and 72 hr post-injection, in vivo fluorescence images wereobtained. The tumors were located on the left low back of all
mice.

Results

Figure 1. Schematic illustration of Immuno-/AptamoPTX-QDMs.

Table I. Physicochemical properties of Immuno/Aptamo-PTX-QDMs.

a)Size, PDI and Zeta-potential were measured 3 times with a particle
analyzer.
b)QDs and PTX encapsulation efficiency were estimated with 3 timesrepeated experiments.
c)Size (nm), average size ± S.D.; PDI, average PDI ± S.D.; Zetapotential (mV), average zeta-potential ± S.D.; QDs/PTX encapsulation
efficiency (%), average QDs/PTX encapsulation efficiency ± S.D.

Figure 3. Growth inhibition of tumors using Immuno/Aptamo-PTX-QDMs. LS174T-xenografted mice wereintravenously injected with saline, PTX, PTX-QDMs,
Immuno-PTX-QDMs, and Aptamo-PTX-QDMs (1.25 mg/kg
PTX) at 1, 4, and 7 days. The tumor growth rates were
measured once every two days. Each error bar represented themean ± S.D. for five mice. ***, p < 0.001 vs. QDMs-injectedmouse group.
Discussion
To develop tumor-targeted theranostic nanoparticles, wellcharacterized Immuno-/Aptamo-PTX-QDMs were prepared.
Physicochemical properties of Immuno-/Aptamo-PTX-QDMs
were suitable for tumor accumulation via passive targeting intumor-xenografted mice. Tumor targeting ability of Immuno/Aptamo-PTX-QDMs were about 5-folded higher than that of
non-targeted PTX-QDMs. The high tumor accumulation of
Immuno-/Aptamo-PTX-QDMs led to effective optical imaging
modalities which was specific to target tumors. The LS174T
tumors in mice were significantly treated without side effects
by using the Immuno-/Aptamo-PTX-QDMs at a low dose.
Conclusion
Immuno-/Aptamo-PTX-QDMs could be utilized for tumorspecific theranostic nanoparticles and be a candidate for clinicaluse. Furthermore, aptamers were used as a targeting ligand forcancer theranosis in this study which have provided an example
of expanding the utility of aptamers.
References[1] T. Lammers, S. Aime, W.E. Hennink, G. Storm, F.
Kiessling, Theranostic nanomedicine, Acc Chem Res 44(10)(2011) 1029-38.
[2] R.A. Burrell, N. McGranahan, J. Bartek, C. Swanton, The
causes and consequences of genetic heterogeneity in cancer
evolution, Nature 501(7467) (2013) 338-45.
[3] T. Lammers, L.Y. Rizzo, G. Storm, F. Kiessling,
Personalized nanomedicine, Clin Cancer Res 18(18) (2012)
4889-94.
[4] K.Y. Choi, G. Liu, S. Lee, X. Chen, Theranostic
nanoplatforms for simultaneous cancer imaging and therapy:
current approaches and future perspectives, Nanoscale 4(2)(2012) 330-42.

Figure 2. Representative images on In vivo fluorescenceimaging of Immuno-/Aptamo-QDMs. LS174T-xenografted
mice were intravenously injected with 800 pmole QDs/mouse

Author address
E-Mail: sjkang332@gmail.com- 77 -

Amplification of distinct α-synuclein fibril conformers using Protein Misfolding Cyclic
Amplification
Byung Chul Jung 1,2, Yoon suk Kim2, Seung-Jae Lee1

1) Dept. of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine
2) Dept. of Biomedical Laboratory Science, College of Health Science, Yonsei University
Introduction
Amyloid fibril formation has been implicated in thepathogenesis of neurodegenerative diseases. Fibrillation
generates numerous conformers. Presumably, the conformers
may possess specific biological properties, thus providing abiochemical framework for strains of prions. However, theprecise relationship between various fibril conformers and theirpathogenic functions has not been determined because oflimited accessibility to adequate amounts of fibrils from tissue
samples. α-synuclein is one such protein, and it has been
implicated in Parkinson disease. Using a technique known asprotein misfolding cyclic amplification, originally developed
for amplifying prions, we established a procedure throughwhich the amplification of α-synuclein fibrils is possible. Witha trace amount of seeds, we succeeded in amplifying αsynuclein fibrils. The replication of the seeds was faithful interms of conformation even after multiple rounds of cyclic
amplification. Moreover, two transgenic mouse strains each
representing a distinct synucleinopathy were used to investigate
different conformers by using this technique. The amplified αsynuclein fibrils derived from the tissue extracts of these twostrains led to the production of two different fibril conformers
with distinct proteinase K digestion profiles. Together, ourresults demonstrated that a trace amount of α-synuclein fibrils
in tissue extracts could be amplified with their conformations
conserved. This procedure should be useful in amplifying αsynuclein fibrils from the brains and body fluids of patientsafflicted with synucleinopathies and may serve as a potential
diagnostic tool for Parkinson disease and othersynucleionpathies
Materials and methods
Purification of recombinant α-synuclein: Protein expression
was induced with 0.1 mM IPTG for 3 hours at 37 °C when theabsorbance of the E. coli strain BL21 (DE3) (RBC Korea, Seoul,
Korea) culture reached 0.6 at 600 nm. The cells were pelleted
and resuspended in 20 mM sodium phosphate buffer (pH 7.4)
for sonication and were subsequently boiled at 100 °C for 20
min, then centrifuged at 10,000 × g for 10 min. The supernatant
was subjected to anion-exchange chromatography andSuperdex-200 gel filtration column chromatography for further
purification. The purified α-synuclein was dialyzed against
distilled water and subsequently lyophilized. For monomer
preparation, lyophilized α-synuclein was reconstituted inphosphate-buffered saline (PBS; #CAP08-050, GenDEPOT,
Katy, TX, USA), then subjected to ultrafiltration using a
100,000 molecular weight cut-off centrifugal device (Pall, New
York, USA). For fibrillation, α-synuclein (200 µM in PBS) was
incubated at 37 °C for 19 days with constant shaking at 1,050
rpm in a Thermomixer C (#5382000015, Eppendorf, Hamburg,
Germany). When used as seeds, the fibrils were sonicated for 1
min (Amplitude 30%) before treated to fibrillation reaction.
Mouse strains: (THY1-SNCA*A53T) F53Sud/JA53T +/mice were purchased from Jackson Laboratory (Bar Harbor,
ME). Human α-Synuclein (A53T) transgenic line G2-3 wasproduced and maintained as descried in Lee et al.
Preparation of brain tissues as exogenous seeds: Brain andspinal cord tissues were homogenized with a tissue grinder(#358039, Wheaton, Millville, NJ, USA) to 10%

weight/volume (w/v) solution with homogenizing buffer (1%Triton X-100, 150 mM NaCl, Protease Inhibitor Cocktail). The
protein concentration was determined by using a bicinchoninicacid assay (Pierce, Rockford, IL, USA).
PMCA: The equipment for PMCA, including a microplatehorn (#431MPX), sound enclosure (#432MP) andthermoelectric chiller (#4900), was purchased from Qsonica(Qsonica, Newtown, CT, USA). PMCA was performed using
recombinant α-synuclein monomers as substrates andrecombinant α-synuclein fibrils or tissue homogenates oftransgenic as exogenous seeds. α-synuclein monomers wereprepared to a final concentration of 20 µM in conversion buffer(1% Triton X-100 and 150 mM NaCl), and 100 µL of thissample transferred into siliconized PCR tubes. The samples for
PMCA were subjected to cycles of 20 sec sonication(Amplitude 50%) and 29 min 40 sec incubation at 37 °C for a
day or several days. Exogenous fibril seeds were added to final
concentrations of 0.04%, 0.2% or 1%.
PK digestion: Twenty micromolar α-synuclein samples
were incubated with final concentrations of 10 or 100 µg/ml PK
for 30 min to 2 hours at 37 °C. Subsequently, sodium dodecyl
sulfate (SDS)-PAGE buffer was added to the samples, whichwere then heated for 10 min at 95 °C.
Results
To establish a procedure for cyclic amplification of αsynuclein fibrils, we generated a modified PMCA protocol for
α-synuclein. Western blotting confirmed that SDS-stable
aggregates of α-synuclein were formed during the PMCA
cycles in the seed-added group. The PK digestion assay showedthat the PMCA product with seed exhibited a PK digestion
pattern similar to that of the seed fibril itself, whereas themonomers or PMCA products without seed did not result in
PK-resistant bands. These results suggest that the PMCA of αsynuclein is highly sensitive and accurate in amplifying trace
fibrils with conserved conformations (figure 1). Next, we
attempted to amplify α-synuclein fibrils from tissue samples.
Two different transgenic mouse models were utilized for invivo experiments. PK digestion analysis exhibited different
digestion patterns, thus indicating that the fibrils amplified
from these mouse models were distinct conformers (figure 2).

Figure 1. In vitro α-synuclein fibrils are amplified using
PMCA. Immunoblotting of PMCA product without (left) andwith PK digestion (right). Similar PK-resistant fragments weredetected in fibrils (F, seed itself) and the seed-added PMCA
products, whereas nothing remained in monomers (M) andseed-absent PMCA products.

- 78 -

Figure 2. PMCA generates α-synuclein aggregatesfrom in vivo samples. PK digestion patterns of
PMCA products with different tissue seeds. Note theextra band (black arrow) on seed B-derived PMCA
products. Thy1-A53T mice brain homogenate (seedA) Immunoblotting of mPrP-A53T spinal cord
homogenates (seed B).
Discussion
To date, research exploring various structures of fibrils has
primarily been conducted on in vitro materials derived fromsynthetic peptides or recombinant proteins expressed inbacteria. In vivo-generated fibrils, however, have not beenthoroughly investigated, owing to the scarcity of samples frompatient brain tissues or animal models. In the present study, we
generated and amplified α-synuclein fibrils both in vitro and invivo by implementing a PMCA technique. Experimental
verification indicated that the PMCA products showed the same
conformations as those of the seeds added to the reaction.
Hence, we demonstrated that PMCA can be conducted throughseveral rounds without the alteration of the original seed. These
results suggest that a trace amount of in vivo fibrils can beamplified, and thus their specific structures can be determined.
In the present study, proteinase K digestion patterns were used
to monitor structural diversities among fibrils. Although thismethod has some limitations in specifically identifying distinct
fibril structures, PK digestion has nevertheless been widely andfaithfully used to examine fibril conformers not only for prions
but also for other amyloid fibrils, such as α-synuclein 101,130.
For higher accuracy, high-resolution techniques, such as solidstate nuclear magnetic resonance (ssNMR), may be used todetermine fibril structures.
The PMCA technique was originally developed to amplify
prions from tissues or body fluids. Although this technique has
been used to amplify prions from various sources, it has also
been applied to non-prion amyloid proteins, including Aβ, tau
and α-synuclein. In a previous study, Herva et al. have used invitro-generated α-synuclein fibrils as seeds in α-synuclein
PMCA. This study successfully showed that α-synuclein fibrils
can be rapidly amplified from synthetic seeds and that the
PMCA products “infect” cells and consequently generate
cytoplasmic aggregates. Although this study notably has
demonstrated that PMCA can be applied to α-synuclein, it has
drawbacks in not addressing sensitivity and fidelity. The
novelty of the present study is the amplification of in vivoderived α-synuclein fibrils and the demonstration of highsensitivity and fidelity. In the present study, we demonstrated
that as little as 0.04% monomer can be amplified from trace
seeds using the PMCA procedure. Moreover, we showed theamplification of two distinct α-synuclein fibrils in two different
transgenic mouse models and the production of PK digestion
patterns unique to each model. The products from the initial
PMCA can also be used as seeds in the next successive roundsof amplification and through several rounds, fibril
conformations are faithfully replicated. These results indicatethat α-synuclein fibrils can be amplified from both in vitro andin vivo sources with high sensitivity and fidelity.
There are two notable aspects of the current study. Primarily,
Aβ-PMCA made it possible to concretely determine thestructures of in vivo fibrils. Recently, α-synuclein fibrils havebeen isolated and amplified from two AD patients with distinct
clinical manifestations. The determination of the structures ofthese fibrils through ssNMR has revealed that the fibrils wereindeed distinguishable from each other in terms ofconformations. On the basis of these observations, the authors
have suggested that the different clinical features of the patientsreflected distinct fibrils conformers, thus potentiallyrepresenting two distinct “strains”. To perform structural
studies with such high resolution, large quantities, over several
milligrams, of protein are required. Such quantities, however,are impossible to obtain from several rounds of PMCA. The
products themselves should be further amplified throughconventional seeded fibrillation. In the present study, wedemonstrated the feasibility of attaining a large quantity of  synuclein fibrils through the conventional seeded fibrillation of
α-synuclein-PMCA product without changing the fibril
structure.
Second, the study demonstrated the clinical potential of theamplified α-synuclein fibrils from biological samples, whichmight be strategically used for diagnosing synucleinopathies.
The aggregation of α-synuclein is associated with PD, DLB,MSA and AD. It is difficult to precisely pinpoint eachsynucleinopathy in diagnostics solely on the basis of thesymptoms observed. In prion diseases, PMCA exemplified theprospective diagnostic detection of pathogenic prions frombody fluids. Consequently, we expect that a similar approach
using the PMCA technique can be adapted to synucleinopathies,
thereby bringing the field one step closer to developing
differential diagnostic tools.
Conclusion
Addition of in vivo and in vitro α-synuclein seeds accelerated
PMCA reactions and the PMCA end-products maintain seedcharacters, which suggest PMCA may be utilized for
amplifying human brain and/or CSF α-synuclein and apotential diagnosis tool for PD.
References[1] Iwai A, Masliah E, Yoshimoto M, Ge N, Flanagan L, deSilva HA, Kittel A,Saitoh T: The precursor protein of non-A
beta component of Alzheimer’s disease amyloid is apresynaptic protein of the central nervous system. Neuron 1995,
14:467– 475.
[2] Joaquın Castilla, Rodrigo Morales, Paula Saa, Marcelo
Barria1, Pierluigi, Gambetti and Claudio Soto: Cell-free
propagation of prion strains Embo 2008, 27:2557-2566[3] Maria Eugenia Herva, Shahin Zibaee, Graham Fraser,
Roger A. Barker, Michel Goedert, and Maria Grazia Spillantini :Anti-amyloid Compounds Inhibit α-synuclein Aggregation
Induced by Protein Misfolding Cyclic Amplification (PMCA).
Journal of Biological chemistry 2014, 289:11897-11905[4] Virginia Meyer, Paul D. Dinkel, Emily Rickman Hager, andMartin Margittai: Amplification of Tau Fibrils from Minute
Quantities of Seeds. Biochemistry 2014, 53:5804-5809
Author address
E-Mail: sandbag9@naver.com- 79 -

- 80 -

Abstract

Nursing- 81 -

- 82 -

2017 Yonsei-Nagoya University
Joint Symposium on Department of Nursing
Date: 2017.11.02(Thursday)

Jinri Hall #421

Moderator: Prof. Jihea CHOI
Session I (14:00~15:45)

14:00~14:15

Welcome Remark
Introduction of YUWCM Dept. of Nursing

Prof. Ki Kyong KIM

14:15~14:30

Introduction of Nagoya University

Prof. Yuki TAKAHASHI

14:30~14:45

Introduction of Nagoya University Hospital

Megumi YOKOYAMA

Caregiver Burden In Accordance With Behavioral And
14:45~15:00

Psychological Symptoms Of Dementia(BPSD) In Alzheimer

Bo-kyoung KIM

Dementia Patients
The Association Of Japanese Mothers’ Perineal And
15:00~15:15

Physical Pain After Vaginal Birth With Parental Behavior In

Akiko YAMADA

Early Postpartum: A Literature Review
The Effects Of Communication Competency And Job
15:15~15:30

Embeddedness On Nursing Performance In Small And

In-sun CHEON

Medium-Sized Hospital: Literature Review
15:30~15:45

Coffee BreakSession II (15:45~17:00)

15:45~16:00

16:00~16:15

Association Of Early Skin-To-Skin Contact With MotherInfant Attachment For The First Month
Premenstrual Syndrome in Female Workers: A Literature
Review

Prof. Yuki TAKAHASHI

Ah-reum JEONG

Health-Related QOL In Japanese Patients With GERD And
16:15~16:30

16:30~16:45

Aoi KONO

The Role Of Nursing
Literature Review On Self-Care Behavior Of JapanesePregnant Women

Miki KAMIYA

16:45~17:00

Discussion

Prof. Hee Young SONG

17:00~

Closing Remark & Group Photos

Prof. Ki Kyong KIM- 83 -

Caregiver Burden in Accordance with
Behavioral and Psychological Symptoms of Dementia(BPSD)
in Alzheimer Dementia Patients
BK. Kim
Department of Nursing, Wonju College of Medicine, Yonsei University, Wonju, Korea

Introduction
Along with increasing of the number of dementia
patients [1, 2] caregiver burden due to behavioral andpsychological symptoms of dementia (BPSD) in Alzheimer
dementia (AD) patients also considered as serious problems[3, 4, 5].
The purpose of this study was to examine the BPSD in
AD as well as to verify the factors related with caregiverburden.

Methods
Study Design: The path analysis study based on
situation relating theory was conducted.
Participants: Total 170 study participants, who visited
neurology in tertiary hospital located in Seoul area, wererecruited for this study.
Data Collection: The data were collected from January
2011 to February 2016 through the survey for the caregivers
and the electronic medical record of the patients.
Measurements: The measurement tool included Korean
Neuropsychiatric inventory (NPI), Korean version of Minimental status examination (MMSE), Short form of GeriatricDepression scale (GDpS), Clinical Dementia Rating (CDR),
Korean version of Bathel Activities of Daily Living Index(ADL), and Seoul-Instrumental Activities of Daily Living(IADL).
Data Analysis: For the data analysis, SPSS Win 22.0
and AMOS 22.0 were used.

Results
1) Patients’ BPSD score was 17.68±20.67 and the scoreof caregivers’ burden was 9.65±11.12. The level ofcaregivers’ burden was significantly different according tofamily relationship, CDR, ADL, and IADL.
2) Based on the results by the factor analysis of BPSD,
the identified factors were Hyperactivity (Disinhibition,
Irritability/Lability, Agitation/ Aggression), Psychosis(Hallucination, Anxiety, Elation/ Euphoria, Delusion,
Depression/Dysphoria), Physical behavior (Appetite andeating disorders, Apathy/Indifference, Aberrant motor
behavior, Sleep and nighttime behavior disorders).
3) In terms of the level of patients’ symptoms by thecharacteristics of caregivers and patients, patients’ educationlevel, drinking, CDR, GDpS, ADL, IADL were significant in
hyperactivity symptom cluster; CDR, IADL were significant
in psychosis symptom cluster; and family relationship,patients’ age, MMSE, CDR, ADL, IADL were significant inphysical behavior symptom cluster.
4) Among the factors which affected caregiver burden,
CDR, IADL, hyperactivity, psychosis, physical behavior
showed positive relationship, and MMSE and ADL showednegative rela- tionship.
5) Based on goodness of fit in modified model,
χ2=8.73(p=.189), χ2 /df(1.456), GFI(.985), AGFI(.932),

CFI(.996), NFI(.987), IFI(.996), SRMR(.034), RMSEA(.052)
was selected for final model.
6) Among the 22 paths in the model, 12 paths were
supported. Among the hyperactivity symptom, ADL and IADL
showed direct effect and total effect, and among the psychosis
symptom, CDR and IADL showed direct effect and total effect.
Finally, among the physical behavior symptom, CDR and ADL
showed direct effect and total effect. Among the caregiverburden, hyperactivity symptom, psychotic symptom andphysical behavior symptom showed direct effect and total effect.

Conclusions and Suggestions
To sum, the behavior patterns of Alzheimer dementia
were categorized into hyperactivity, psychosis and physicalbehavior. In accordance with the model, CDR, ADL, IADL
affected caregivers’ burden through hyperactivity, psychosis
and physical behavior. Hyperactivity, psychosis, and physicalbehavior symptom had complete mediating effect.
Thus, in order to alleviate burden in caregivers, intensive
nursing interventions focusing on CDR, ADL, IADL should be
developed and practically applied. Base on the findings of thisstudy, by delaying and preventing BPSD in AD patients,
caregivers’ burden would be alleviated.

References[1] World Health Organization. Dementia. 2016. Retrieved
from http://www.who.int/mediacentre/factsheets/fs362/en/[2] Dementia Center. Annual Report of Dementia Center 2015.
2016. Retrieved fromhttp://www.edementia.or.kr/resource/resourceView?currentPa
ge=&searchKey=&searchValue=&boardClass=01&bid=137&
articleNo=137&seq=1&step=0[3] Cerejeira, J., Lagarto, L., & Mukaetova-Ladinska, E. B.
Behavioral and psychological symptoms of dementia. Front
Neurol. 2012;3(73): 1-21. doi:10.3389/fneur.2012.00073[4] Huang, S.-S., Lee, M.-C., Liao, Y.-C., Wang, W.-F., & Lai,
T.-J. Caregiver burden associated with behavioral andpsychological symptoms of dementia (BPSD) in Taiwaneseelderly. Archives of Gerontology and Geriatrics. 2012;55(1):55-59. doi:10.1016 /j.archger.2011.04.009[5] Song, JA., Park, JW., Kim, HJ. Impact of Behavioral andPsychological Symptoms of Dementia on Caregiver Burden in
Nursing Homes. Journal of Korean Gerontological Nursing.
2013;15(1): 62-74.

Author address
E-Mail: alohabonnie@yonsei.ac.kr- 84 -

The Association of Japanese Mothers’

Perineal and Physical Pain

after Vaginal Birth with Parental Behavior in Early Postpartum: A Literature Review
A. Yamada, M. Kamiya, Y. Takahashi
Department of Nursing, Nagoya University Graduate School of Medicine, Nagoya, Japan

Introduction
The postpartum period is a vital transitional time for awoman, her baby, and her family. Perinatal nurses andmidwives should carefully assess a mother’s physicalrecovery and her psychological adaptation from childbirth toensure positive future mother-infant relationship.
A process of becoming a mother requires extensive
psychological, social, and physical effort [1]. The maternalrole starts during pregnancy and continues to develop for 1
year postpartum, throughout which a mother’s demographic,obstetric, and psychosocial factors determine their parenting
behavior and maternal role [1-3].
Mercer’s theory of becoming a mother [4] wasdeveloped by Rubin’s theory of maternal role attainment [5].
Maternal attachment is the process through which maternallove develops as a result of the satisfying and pleasing
interaction between mother and infants [6] following 4 stages[4]; commitment, attachment, and preparation during
pregnancy; acquaintance, learning, and physical restorationin the first 2 to 6 weeks following birth; moving toward a
new normal between the first 2 weeks and 4 months; and theachievement of maternal identity at around 4 months. Almost
all mothers learn to read their infant’s cues within 1 monthafter birth [5]. To facilitate this process, a mother and her
infant should be together immediately after birth, and theyshould look after the baby by themselves [7] to gain the“parental behavior” experiences such as smiling, touching,kissing, hugging, patting, singing, maintaining eye contact,breastfeeding, sensitivity, and affection [8-10]. As a result,maternal self-confidence and satisfaction with her baby
increases, thus enhancing mother-infant attachment.
However, the mother-infant interaction may be hampered bymother’s physical recovery from childbirth [1].
While mothers are free from labor pain after giving birth,they experience various types of pain such as perineal pain,
posterior pelvic pain, and lower back pain, which may getdelayed attention and prevent mothers from properly looking
after their babies and performing their own daily activities[11-14]. Previous study from Japan has shown that Japanesemothers who were in a poor physical state were less willing
to look after their infants by themselves, and less interested
in their infants compared with mothers who were in a good
physical state 1 month postpartum [15].
Mothers experience various pregnancy and deliveryrelated pain in the early postpartum period that may influence
their daily life activities and prevent them fromunderstanding their baby’s cues and respond on time.
Therefore, this literature review aims to describe how
perineal pain after birth impacts Japanese mothers in their
daily life and how it affects their parental behavior. The

present study specifically focuses on Japanese mothers becauseof the cultural differences in verbal and non-verbal emotional
expression. The objective of this study is to gain a deeper
understanding of maternal adaptation in early postpartum tofacilitate perinatal and midwifery practices.

Materials and Methods
The purpose of the review was to summarize therelationship between a mother’s perineal and physical pain aftervaginal birth and their parental behavior in the early postpartum
period.
The database Ichushi-Web (Japan Medical Abstracts
Society) was used to search for original Japanese research
articles published between 2000 and 2017 that studied humanparticipants. The following inclusion criteria were used: (a)original research, (b) studies that clearly described the changing
perineal pain and the type of pain in early postpartum, (c)studies that indicate how perineal pain influences postnatal
mother’s daily life activity, and (d) studies that identify amother’s needs in early postpartum.
The terms postpartum, perineal pain, and lower back pain
were searched both with and without hyphenation on August 25,
2017. The search yielded 30 studies of perineal pain in
postpartum and 19 studies of lower back pain in postpartum. Six
articles were selected for inclusion in the literature review.

Results
Of the 6 papers selected for review, 3 were research
articles on perineal pain, 3 were research articles on lower back
pain.
1.

1)

Changing perineal pain and how mothers’ perineal andphysical pain after vaginal birth impact their daily life
activities in early postpartum

Perineal pain [16]Perineal pain was evaluated from 0 to 100 (no pain to
worst pain) on the Visual Analogue Scale (VAS). Perinatal pain
was reported in 85.9% of women who felt the strongest pain atdays 0 and 1. The mean and standard deviation of VAS-related
pain in episiotomy were 65.2±19.94 at day 0, 59.4±19.72 at
day 2, and 44.0±22.26 at day 4. Perineal pain on each day was
positively related (r=.57, r=.28, r=.18, respectively). Moreover,perineal pain on each day was positively related with difficultyof daily activities, and strongly associated with difficulty ofsitting position (r=.83), decreasing motivation (r=.60), difficulty- 85 -

of excretion and cleaning their vagina (r=.70) and difficultyof general movement (r=.83).

2)

Lower back pain [12][14][17]Nakazawa et al., [12] conducted research with 253
postpartum mothers, of which 225 (88.9%) gave birthnaturally and the remaining 28 (11.1%) gave birth via
caesarean section. A total of 148 mothers had lower backpain 1 week after birth and 140 mothers (57.9%) reported itafter 1 month. They reported difficulties with daily life
activities such as getting up, bending forward, and sitting forover 30 minutes even a week after birth. Difficulties related
to looking after their baby, such as changing diapers andbreastfeeding were also reported. Kusumi et al., [17] studied
67 postpartum mothers who gave birth to a baby by vaginal
delivery. They found lower back pain in postpartum was
experienced by 31 mothers (46.3%) at day 4, in 35 mothers(52.2%) at day 5, and 32 mothers (47.8%) 1 month after birth.
They also reported a positive relationship between
episiotomy-related perineal pain and difficulty in daily life
activities at day 5 because of lower back pain (r=.41).
Research by Fukuyama et al., [14] on 163 mothers at day 4, 1
month, and 2 months after birth by vaginal delivery foundthat 31.9% of mothers had low back pain at day 4, 23.3% at 1
month, and 24.5% at 2 months after birth. In addition, 8.6%of mothers said the pain had not subsided since pregnancy,
and among those aware of the pain at day 4, 21.5% reported
that the pain persisted until 2 months postpartum. Mothers
who had lower back pain at day 4 also had difficulties intheir daily life activities. Lower back and posterior pelvic
pain was found in 50.6% of women before pregnancy, in
83.0% of women during pregnancy, in 58.5% of women 1
week after delivery, and in 55.3% 1 month after delivery.
[12]
Discussion
The findings of this review showed that perineal pain
and physical pain are negatively related with a mother’s daily
life activities Thus meaning that immediately after birthmothers are in pain whilst caring their baby, andbreastfeeding them. To date, there has been limited research
into the relationship between perineal pain and parental
behavior in early postpartum. Despite existing policies for
hospital discharge, raising awareness about major concerns
such as perineal pain, postpartum complications, newborn
feeding and care should not be routinely practiced in thehospital schedule. A mother’s learning needs and the processof recovery from her birth may differ and change during the
postpartum period. It is common for new mothers to behospitalized for 5 to 7 days after birth in Japan. This length isan advantage for Japanese perinatal nurses and midwives as itenables them to assess a mother’s physical recovery and their
psychological adaptation. Clinical health care providers can also
support mothers to establish breastfeeding. Previous studies
have shown that the first 2 to 3 days is the most painful period
for mothers. We therefore have to examine a mother’s physicalrecovery and identify potential barriers to daily life activities
such as looking after their baby and breastfeeding. It is
important to note however that it is during this time that amother can get used to being with her baby and better
understand how to read her infant’s cues for future motherinfant attachment. Mother-infant interaction is engaged
increasing maternal-confidence related to the baby [1]. Throughinteraction with their babies, mothers gain self-effect, selfesteem, and stability. These successful experiences build up
their identity as becoming a mother. The early postpartum
period is precious and important for initiating actual baby care.
Therefore, we have to reconsider our routine postnatal practices
for positive future mother-infant attachment.

References[1] Mercer RT. Nursing support of the process of becoming amother. J Obstet Gynecol Neonatal Nurs. 2006;35(5):649-51.
[2] Rogan F, Shmied V, Barclay L, Everitt L, Wyllie A.
‘Becoming a mother’ – developing a new theory of earlymotherhood. J Advanced Nursing. 1997; 25: 877-885.
[3] Calışır H, Karaçam Z. Factors associated with parenting
behavior of mothers in the early postpartum period in Turkey.
Nursing and Health Science. 2011;13: 488-494. Çalıs H[4] Mercer RT. Becoming a mother versus maternal roleattainment. J Nursing Scholarship. 2004; 36(3): 226-232.
[5] Rubin R. Attainment of the maternal role. Nursing Research.
1967; 16(3): 237-245.
[6] Mercer RT, Ferketich SL. Predictors of maternal rolecompetence by risk status. Nurs Res. 1994 Jan-Feb;43(1):38-43.
[7] Klaus MH, Jerauld R, Kreger NC, McAlpine W, Steffa M,
Kennel JH. Maternal attachment. Importance of the first postpartum days. N Engl J Med. 1972 Mar 2;286(9):460-3. No
abstract available.

Author address

E-Mail: yamada.akiko@b.mbox.nagoya-u.ac.jp- 86 -

The Effects of Communication Competency and Job Embeddedness on Nursing
Performance in Small and Medium-sized Hospital: A Literature Review
I.S. Cheon
Department of Nursing, Wonju College of Medicine, Yonsei University, Wonju, Korea
Introduction
Nursing performance shows how effective it is toperform roles and responsibilities related to patient care. In
the hospital setting, patient care and nursing are top priority
tasks [1]. The nurses' workload and intensity of work wereincreased as the demand for quality nursing services increased, and high nursing work performance was also required through professional improvement to increase theproductivity of the hospital [2-3]. In this case, small andmedium hospitals often exceed their working hours due toinsufficient nursing staff compared to large hospitals, thework environment is not good due to relatively low salaries[3]. Due to the difficulty of securing nursing staff nursing
manpower management is also very difficult. Nursing work
performance is an important management factor because of
the low quality of nursing work and low interest in nursing
work performance [4]. The personal dimension that influences the performance of these nursing tasks is the job
embeddedness of the nurse to stay in the organization
without leaving the organization, the ability to communicate, the self-efficacy of self- Leadership, nurse emotional
labor, emotional intelligence resilience, and self-efficacy.
[4, 7, 8-10,15-16,22]. Organizational dimension to improve
productivity and efficiency of hospital organization: nursing organization culture, nursing work environment, transformational leadership of nursing manager, coaching behavior of nursing manager are reported [11-13].
PurposeThe purpose of this study was to investigate the effectof communication competency and job embeddedness ofnurses in small and medium hospitals on nursing performance.
Methods
As a key question in this research, firstly, whether thecommunication ability of the nurse and the job embeddedness are related to the nursing performance. Second,
what is the size of the relationship and what are the factorsthat affect it? The search database was composed of theses
and doctoral dissertations from 2008 to present (2017.8)
and articles published in journals (KoreaMed, PubMed,
RISS, National Assembly Library, Yonsei University Library). A review of selected literature references based on
selection criteria was included in the analysis of 22 studies
that met the selection criteria. The main keywords insearching the database were 'Small hospital nurse', 'Job
embeddedness ', 'Communication ability', 'Nursing performance', and 'Communication ability AND nursing work
performance', ' Job embeddedness 'and' nursing performance '.
Results
The important factors influencing the performance ofnursing work through the searched literature are the resultsof the variables related to the nurses’ communication ability and job embeddedness [1, 4, 8, 14-17, 19-20, 22-23].
Nursing performance is the degree to which nurses
perform their roles in a rational way to improve the qualityof nursing based on their expertise, and thus perform thegoals of the nursing organization efficiently [5]. Improving
the performance of nursing work leads to the improvementof the quality of nursing service and nursing productivity[6].
Communicative competence is the ability to use
communication in interpersonal relationships to the ability
to communicate in an organization refers to how well you
use communication in the course of performing tasks [23].
Nurses have difficulty communicating with patients, caregivers, doctors, or fellow nurses. The difficulty of such
communication causes conflict, anxiety, stress, and eventually decides to leave. Competence nurses have difficultycommunicating with patients, caregivers, doctors or fellow
nurses. This difficulty of communication causes conflict,anxiety, stress, and eventually it is an opportunity to decide
the turnover. Therefore, communication ability is very
important for nurses [14]. Communication skills reduce thepossibility of physical frictions among members in thecourse of job performance and improve the professional
ability of nurses [15]. Communication ability has a positive(+) correlation with communication ability and nursing
work performance. The higher the communication ability,
the higher the nursing work performance. On the other
hand, the lower the communication, Stress was increased[1, 8, 15-16].
In relation to the factors influencing the performanceof nursing work, the job embeddedness is a new conceptthat identifies the factors of organizational stay based on
individual and job relations, so that the individual can stayin the organization without leaving the organization. It is a
web of individual complexity entangled with a new research area that synthesizes psychological events or behaviors that shift and turnover [17,18]. It is an important variable that influences individuals' decision to stay in or leavean organization. It is an intra-job factor that focuses on"why do people stay in the organization?" It is composedof fitness, linkage, and sacrifice as sub-factors [18]. The
higher the nurse's job embeddedness was, the lower theintention to turnover [17, 19-20]. The job embeddedness
had a positive correlation with nursing work performance[22]. In many medical institutions, it is important to increase the job embeddedness and to reduce the turnoverrate of nurses. It is to increase the efficiency of the nursing
work by enhancing the efficiency of the work by having a
lot of competent nurses 7]. This job embeddedness has adirect effect on job performance, and the more hospitals,
organizations, and jobs that nurses work with, the better theindividuals, the more active interaction with relevant departments and colleagues in the hospital, And the higher
the perceived material and mental loss due to leaving the- 87 -

hospital, the higher the performance of nursing work [7, 21,22]. The hospital is the place to treat and nurse the patient,and the best nursing performance is essential. It is important to understand the factors influencing
Conclusions
Literature review results, there are many researches onnurse 's communication ability and nursing work performance, but research on job embeddedness and nursing
work performance is on the one hand and most of them
have studied on job embeddedness as an influence factor
on turnover intention. It is necessary to study the effects ofcommunication ability and job embeddedness of nurses insmall and medium hospitals on the performance of nursing
work and to provide useful basic data for nursing work
improvement and nursing human resource management.
References[1] Son YJ, Lee YA, Sim KN, Kong SS, Park YS. Influence of Communication Competence and Burnout on
Nursing Performance of Intensive Care Units Nurses.
Journal of the Korean Academy of Fundamentals of
Nursing, 2013;20(3): 278-288.
[2] Lee HS. Relationships among Communication Competence, Communication Types, Organizational Commitment of Nurses. Dankook University. 2007. Chunan, Korea.
[3] Kim JK, Kim MJ, Kim SY, Yu M, Lee KA. Effects ofgeneral hospital nurses' work environment on job embeddedness and burnout. Journal of Korean Academyof Nursing Administration, 2014;20(1):69-81.
[4] Lim MY. Effectsof Empowerment, Communication
Ability, and Job Stresson Nursing Service Performanceof Small and Medium-sized Hospital Nurses. Kongju
University. 2016. Choongnam. Korea.
[5] Ko YK, Lee TW, Lim JY. Development of a performance measurement scale for hospital nurses. Journalof Korean Academy of Nursing. 2007;37(3):286-294.
[6] Ha NS, Chol J. An Analysis of Nursing Competency
affecting on Job Satisfaction and Nursing Performance
among Clinical Nurses. Journal of Korean Academy of
Nursing Administration . 2010;16(3): 286-294.
[7] Lee HS. Yom HY. Role of Self-leadership and Social
Support in the Relationship between Job Embeddedness and Job Performance among General Hospital
Nurses, Journal of Korean Academy of Nursing Administration. 2015;21(4):375-385.
[8] Kim YJ. The Effects of Emotional Intelligence andCommunication Competency on Nursing Performanceof Outpatient Nurses. Yonsei University. 2016. Seoul.
Korea.
[9] Lee EJ. University hospital nurse's feelings regarding
the impact on the business performance of nursing labor research. Soonchunhyang University. 2013. Chunan. Korea.
[10] Park SK. The impact of resilience on nursing outcomeof clinical nurses. Hanyang University. 2014. Seoul.
Korea.
[11] Lee YM. A study of correlation between leadershipstyles of head nurses and nursing performance: the regulation effect of nursing organizational culture. Soonchun University. 2015. Jeonnam. Korea.
[12] Kim JK. Structural Model of Hospital Nurses' Turnover Intention : Focusing on Organizational Characteristics, Job Satisfaction, and Job Embeddedness. Journalof Korean academy of nursing administration. 2016;22(3):292-302.
[13] Ryu SY. The relationship between Coaching Behaviors of Nursing Managers, Empowerment and Job Performance of Staff Nurses. Yonsei University,2009,

Seoul, Korea.
[14] Kim SH, Lee MA. Effects of Emotional Labor andCommunication Competence on Turnover Intention in
Nurses. Journal of Korean Academy of Nursing Administration, 2014;20(3): 332-341.
[15] Bae JY. The relationships among the level of communication competence, the types of communication, andthe level of nursing performance. Kosin University.
2008. Busan. Korea.
[16] Choi JH. Relationship between nurse's emotional intelligence, communication competency and organizational commitment. Ajou University. 2010. Kyonggido. Korea.
[17] Kim JH. The effects of job embeddedness on turnover
intention and organizational citizenship behavior in
hospital employees: Focusing on moderating effect of
personality traits. Kyungsung Universit. 2010. Busan.
[18] Mitchell TR, Holtom BC, Lee TW, Sablynski CJ, Erez
M. Why people stay: using job embeddedness to predict voluntary turnover. Academy of Management
Journal. 2001;44(6):1102-1121.
[19] Jeon JH, Yom YH. Roles of empowerment and emotional intelligence in the relationship between job embeddedness and turnover intension among general hospital nurses. Journaal of Korean Academy of Nursing
Administration. 2014;20(3):302-312.
[20] Kim YS. Rhu SA. Influence of Job Embeddedness
Factors on Turnover Intention of Nurses in Small andMedium Sized General Hospitals. Journal of Korean
Academy of Nursing Administration. 2016;22(2):158166.
[21] Halbesleben JRB, Wheeler AR. The relative roles ofengagement and embeddedness in predicting job performance and intention to leave. Work and Stress.
2008;22(3):242-256.
[22] Kwon SB, Pakk MJ, Song HM, Moon JS. Effects of
Job Embeddedness and Emotional Intelligence on Performance of Nurses in Medium and Small sized Hospital. The Korean Journal of Health Service Management.
2017;11(1):55-66.
[23] Papa MJ. Communicator competence and employee
performance with new technology. Southern Communication Journal, 1989;55(1):87-101.

Author address
E-Mail: cis0306@nate.com- 88 -

Association of Early Skin-to-Skin Contact with Mother-Infant Attachment for the First Month
Y. Takahashi, A Yamada, M Kamiya, K. Tamakoshi
Department of Nursing, Nagoya University Graduate School of Medicine, Nagoya, Japan

Introduction
Mother who held their infant skin-to-skin contact (SSC)
after birth were more likely to breastfeed sooner, more
effectively, and for longer durations compared with motherwho did not have SSC [1-5]. After SSC, mother was morecare for their infant with more confidence and to recognize
and respond to their baby’s needs sooner [1, 5-7]. Infant who
had SSC during first hour after birth cried less [1,5,8,9],
stayed warmer [1,4,10,11], had more stable glucose levels
and cardiorespiratory function [5,6,12-14], had lower stresshormone levels [14], were more likely to leave the hospital
having been exclusive breastfed at various intervals during
the first 6 months after birth [1,2]. Despite rich evidences of
SSC for mother and infant, they are often separated without
medical reasons [15]. Mother-infant attachment begins todevelop before a child is born [16] and also the attachment
for fetus is strongly correlated with postnatal attachment.
Klaus and Kennell have shown that a stronger impact ofearly skin-to-skin contact on their attachement [17]. However
few studies have done in full-term mother-infant dyads
compared with preterm dyads.
Thus, the aim of this study is to explorer the relationshipbetween early SSC and mother-infant attachment for the firstmonth.
Materials and Methods
Subjects: This study was part of a larger study conductedin Aichi, Japan, from January to October in 2009[14]. The
subjects were 75 healthy mothers selected according to thecriteria below. Maternal inclusion criteria were vaginal birthof a singleton full-term healthy infant, uncomplicatedpregnancy. Maternal exclusion criteria were past mental
disease of the mothers, signs of fetal distress during labor,
and cesarean section. Infant exclusion criteria were any
congenital anomaly, and obvious birth asphyxia as assessedby either 1 or 5 minute’s APGAR of seven or less. According
to the above-mentioned criteria, we distributed and collected
the questionnaires directly during hospitalization, whereas
one month after birth, the questionnaires were distributed by
mail. Finally, the current analysis was restricted to 56 healthy
dyads. This study protocol was approved by the Ethics
Review Committee of the Nagoya University School of
Medicine, Nagoya, Japan.
Measures: Demographic data were collected frommedical records during hospitalization.
Stein’s Maternity Blues Scale (MBS)[18], MBS is selfrating scale with 13 items, evaluates maternity blues. We
used the Japanese version of the MBS validated by
Yamashita[19]. The sum of the score for each item with arange of 0-26 was provided every day during hospitalization (4or 5 days).
Edinburgh Postnatal Depression Scale (EPDS); a self-rating
scale with 10 items, has been used in screening for postpartum
depression[20]. The EPDS was translated into Japanese andstandardized[21,22]. The questionnaire contains 10 items, andeach item is scored on a four-point scale from 0~3, with theminimum and maximum total scores being 0 and 30 points,
respectively, and the cut-off point was 8/9 in this study for theassessment of postpartum depression. At one month after
delivery, the subjects received the EPDS by mail.
Maternal Attachment Inventory (MAI); MAI is a selfreported questionnaire with 26 items, designed to measurematernal affectionate attachment to infants[23]. The MAI wastranslated into Japanese and was verified for concurrent
validity[24]. Each item is scored on a four-point scale from 1~4,
the minimum and maximum total scores being 26 and 104
points, respectively; a higher score indicates a stronger
attachment to the infant. We asked mothers to fill in at 3 days, 5days, and 1 month after delivery.
Others; we directly asked some questions about feeling andmood regarding pregnancy, childbirth, and their partner on thefirst day after delivery. These questions were the original 8-item
rating scale, which was scored according to a five-step scale of
1: ‘strongly disagree’; 2: ‘somewhat disagree’; 3: ‘neutral’; 4:‘somewhat agree’; and 5: ‘strongly agree. ’ Most respondents
were 5. Therefore, the 5: ‘strongly agree’ category was rescored‘agree overall’ and other categories were combined. In theanalyses mentioned below, they were used as two categoricaldata.
Data analysis: Descriptive statistics were used tosummarize the demographic factors. All continuous variables
are shown as mean ± standard deviation (SD), and categorical
data are presented based on frequency and percentage. The
correlation of MAI, MBS and EPDS with other study variables
is given by Pearson’s correlation coefficients or Spearman’srank-correlation coefficient. Multiple regression analysis byforced entry method was performed to estimate the contributionof study variables to MAI each 3, 5 days and 1 month
postpartum. Each MAI was the dependent variable and thevariables borderline significantly associated with MAI (aprobability value <0.1) were the independent variables. A
probability value <0.05 was considered significant. Data wereanalyzed using SPSS version 23.0 for Windows. Differenceswere considered significant when P<0.05 for the two tails.

- 89 -

Results
Characteristics; the mean age of the mothers who
participated in this study was 31.1±4.1 years, the mean
gestation age was 39.7±1.0 weeks. The mean infant’s birthweight was 3015 ±353 grams in 25 (44.6%) boys and 31 girls(55.4g).
Distribution of MAI, MB, EPDS; the mean of MAI at day
3, day 5 and 1M were 96.4±6.7, 99.0±5.8, 99.6±5.5,respectively. Eight mothers (14.3%) were suspected as
Maternity blues until day 3 postpartum and eleven mothers(19.6%) were also suspected until day 5. At 1 month, 8mothers (14.3%) had an EPDS score of nine or more. All
mother and newborn infant physical conditions were good.
Feeling and mood regarding pregnancy, childbirth, andtheir husbands/partners; the proportion of ‘strongly agree’
was 70-90% for each of the questions except [I tried to dosomething for the baby during my pregnancy].
The associations among each MAI and study variables;
MAI scores were strongly and positively correlated with eachother. MBS until day 3 and each MAI were negatively
correlated with each other, see Table1.
Table 1. Correlation between each MAI, MBS and EPDS
MAI
Day 3
Infant attachment score at 3day

MAI
Day 5

MAI
at 1M

0.86**

0.73**

Infant attachment score at 5day

0.81**

Infant attachment score at 1M
The Maternty blues score until day 3-0.32**-0.37**-0.29**The Maternty blues score until day 5-0.30**-0.33**-0.26

EPDS at 1 M-0.06**P <0.05

A positive association between duration of SSC and MAI
at day 3(r=0.25, p<0.10) and day 5 (r=0.31, p<0.05) wereobserved. Also [I was happy when I felt fetal movement] waspositively correlated with MAI day 3 (r=0.30, p<0.05) andday 5 (r=0.38, p<0.05). [My partner was happy when told of
my pregnancy] (r=0.38, r=0.46, r=0.29, respectively) and[My partner cooperated with me during my pregnancy](r=0.28, r=0.38, r=0.35, respectively) were correlated with
MAI until 1M (p<0.05). [Mother’s age] was marginally andnegatively correlated with MAI at 1M (r=-0.25, p<0.10),[Mother's occupation] (r=-0.24, p<0.10) and [Satogaeribunben] (r=-0.24, p<0.10) were marginally and negatively
correlated with MAI at day 3.
Accosiation between MAI and other variables; By
multiple linear regression analysis, [MBS until day 3],[mother's occupation] and [satogaeri bunben] were wereindependently and inversely associated with MAI score atday 3 and [My partner was happy when told of my pregnancy]
was independently and positively associated with MAI at day
3. [Duration of SSC] was significantly and positively
associated with MAI at day 3 by simple correlation analysis.

[Duration of SSC], [My partner was happy when told of mypregnancy] were independently and positively associated with
MAI at day 5, but MBS until day 5 were independently andinversely associated with MAI score at day 5.
However, any variables did not associated with MAI at 1
month. Only mother's age was significantly and negatively
associated with MAI at 1 month by simple correlation analysis.
Discussion
We found that early SSC lead to the positive mother-infant
attachment in early postpartum.
Klaus and Kennell’s bonding theory recommends thatmother have early SSC contact during the ‘sensitive period’
after birth17). Previous studies have shown that early SSC ispositive, observable differences in maternal-child interaction as
measured a few days after birth18) and by using a standardized
assessment technique 1 year later19). When both mother andinfant are in the sensitive period immediately after birth, SSC
could be positively impacts them respectively. Oxytocin couldemphasis maternal affectionate behavior and to induce bonding
to her infant during SSC and their first breastfeeding20). Thus,
early SSC enhances early postpartum mother-infant attachment.
These results suggest that the effective care and support suitablefor each point postpartum may serve to enhance maternal-infant
attachment in future through the factors related to theattachment change postpartum.
There are two limitations in our study. One limitation wasthat our study was observational. Thus, subjects must be
randomized to confirm our results even enough, though thecharacteristics of SSC groups were almost comparable andmultivariate adjustment was performed. Another limitationarises from the fact that healthy and full-term infants were thesubjects of our study. Hence, our results may not apply topreterm infants and infants with any complication.
Conclusions
1. MAI scores at Day3, Day5, and 1 month postpartum weresignificantly and strongly correlated.
2. At 5 day, the duration of skin-to-skin contact wassignificantly and positively associated with MAI score at 5
day postpartum.
3. The husband’s affirmative feeling, attitude, and behavior
during pregnancy were significantly and positively
associated with MAI scores at 1 month postpartum bysimple correlation analysis.
References[1] Moore ER, Bergman N, Anderson GC, Medley N. Earlyskin-to-skin contact for mothers and their healthy
newborn infants. Cochrane Database Syst Rev. 2016[2] Bramson L1, Lee JW, Moore E, Montgomery S, Neish C,
Bahjri K, Melcher CL. Effect of early skin-to-skinmother--infant contact during the first 3 hours following
birth on exclusive breastfeeding during the maternity
hospital stay. J Hum Lact. 2010;26(2):130-7.
Author address
E-Mail: yukitaka@met.nagoya-u. ac.jp- 90 -

Premenstrual Syndrome in Female Workers: A Literature Review
A.R. Jeong
Department of Nursing, Wonju College of Medicine, Yonsei University, Wonju, Korea

Introduction
Premenstrual syndrome (PMS) refers to physicaland emotional symptoms that occur in the one to two
weeks before a woman's period. Up to 80% of womenreport having some symptoms prior to menstruation. It isreported that main symptoms of female workers having
PMS is fatigue, lack of enthusiasm and emotional burnout
and PMS has relevance to their functional decline ofoccupation. However, most women hardly ever consult thehealth professionals. They primarily take a rest or takemedicine arbitrarily to relieve their symptoms.

PurposeThe purpose of this study was to explore
epidemiology, causes, signs and symptoms andmanagement state of premenstrual syndrome for Korean
female workers.

Methods
Data were extracted from 9 studies found to beeligible. Nine research studies were reviewed in terms ofsamples, outcome measurements.

Results
Premenstrual syndrome(PMS) is a condition inwhich some women experience unpleasant physical andemotional feelings for a few days before their period.
PMS is known to have a great impact on daily life
activities and social functions, and might result insignificantly decreased quality of life. Prevalence rate of
PMS is measured differently depending on measurement
tool. However, almost every women experience at least
one symptom[9] and severity of symptoms is various inaccordance with the individual.
1. Causal factor
Causative factor of PMS would not be regarded as
being clearly unfounded. Many researches have been
conducted to find out factors to aggravate or alleviate
symptoms. It has been reported that, of the physical factor
to degenerate symptoms, it is hypermenorrhea[1] and age[6]and so on. However, age and menstruation history is
misrelated PMS according to other stydy[1]. Also, stressfrom various area is main psychological factor[2, 6, 9] andsome female worker who perform emotional labor theirduties are troubled with severe PMS. Perception femininity
is not related to PMS. In addition to that, low income,
caffeine intake, marriage is relating factor to have an effectsymptoms of PMS
2. Symptoms
Most frequent symptom is fatigue, physicaldiscomfort and water retention[3-6]. Those symptoms giverise to anger-repression[8] and degrade their quality of life.

3.Treatment
To reduce their discomfort, half of women think
medical treatment but only 12.5% of women see a
doctor[3]. They usually take a break in their spare time ortake medicine without doctor’s prescription.
Conclusions
Through a literature review, it has been found thatpremenstrual syndrome is important issue for evaluation ofhealth state and management for female workers.
Individual exertions is required to assess their own signs
and symptoms of PMS and management for relief. Also
further research is need to understand factors associatedwith Premenstrual syndrome in female workers.

References[1]Kim TH, Park HS, Lee HH, Chung SH. Premenstrual
syndrome and dysmenorrhea in the career women atbucheon city. Obstetrics & Gynecology Science,
2011;54(9): 523-528.
[2]Cho JH, Kim DI, Park KB. The correlation analysis offactors related to PMS through survey. The Journal Of
Oriental Gynecology, 2006;19(4):174-204.
[3]Park HE, Jee BC, Ku SY, Suh CS, Kim SH, Choi YM,
Kime JG, Moon SY. A survey on premenstrual syndrome.
Obstetrics & Gynecology Science, 2005;48(2): 401-410.
[4]Park YH, Jeong BS, Kim CY, Lee C. Journal of Korean
Neuropsychiatric Association,, 2001;40(5):832-841.
[5]Kim BM, Song YM, Lee JG, You JH, Jeong JI.
Association of premenstrual syndrome with quality oflife in young women. Korean Journal of Family
Medicine, 2008;29(2):108-113.
[6]Kim SJ, Kim EH.
Pre-menstruation discomforts
experienced by women. Korean journal of women healthnursing, 2001;7(4): 631-641.
[7]Kim KH, Kim EK, Seo SY, Lee SH, Choi TK, Kim MY,
Yook KY. Exploratory study of relationship between
self-perception to feminity and premenstrual symptomsIn nurses who worked for some university hospitals-.
Cognitive Behavior Therapy in Korea, 2008;8(2),63-74.
[8]Seo SY, Kim MY, Lee SH. Anger and alexithymia in
women with Premenstrual Syndrome. Korean journal of
psychosomatic medicine, 2006;14(2):108-115.
[9]Lee SH, Song JA, Hur MH. Effect of emotional laborand stress on premenstrual syndrome among hospitalnurses. Korean Journal of Women Health Nursing,2016;22(1):61-70.

Author address
E-Mail: zzzz.01@daum.net- 91 -

Health-related QOL in Japanesse patients with GERD and the role of Nursing
A.Kono, N.Nakayama
Department of Nursing, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Introduction
Gastroesophageal reflux disease (GERD) is defined as "acondition that develops when the reflux of stomach contents
causes troublesome symptoms and/or complications"[1]. In
addition to a typical symptom, which is called "heartburn",
the patients complain a variety of troublesome/painful
symptoms. The patients’ quality of life (QOL) is regarded asimportant element. As GERD symptoms improve, thepatients’ QOL also become better [2, 3].
Although research on the medical approach to GERD has
been done, no research on nursing for GERD patients wasfounded. Therefore, we analyzed QOL of patients with
GERD through Japanese literature and explored the role ofnursing for GERD.

Table 1. Each sample’s characteristics
article
Ⅰ
Ⅰ
Ⅱ
Ⅱ
Ⅱ
Ⅱ
Ⅲ
Ⅳ
Ⅴ
Ⅴ
Ⅴ
Ⅵ
Ⅵ
Ⅵ
Ⅵ

Materials and Methods
We used a database Igaku Chuo Zasshi (ICHUSHI) web
version, which is established and being updated by the Japan
Medical Abstracts Society (JAMAS). Keywords used for the
search were; "gastroesophageal reflux disease" "GERD""reflux esophagitis" and "QOL." 374 articles were identified.
We screened the articles for eligibility and selected 19
articles. The articles were the research studies which
examined the effect of medical approach on QOL
improvement among adult patients without othergastrointestinal diseases and/or surgeries. Next, we limited
HR-QOL measured by 36-Item Short Form Health Survey(SF-36) or 8-Item Short Form Health Survey (SF-8) in thisstudy. According to the international consensus about
HR-QOL, it has basic three component; "physical function","mental health" and "social life function"[4]. SF-36 and SF-8
can measure both physical and mental aspects of HR-QOL.
We included 6 articles which used SF-36 or SF-8 to measure
HR-QOL in the final review.
SF-36 is a self-administered questionnaire consisting of
8 subscales; physical functioning (PF), role-physical (RP),body pain (BP), general health (GH), vitality (VT), social
function (SF), role-emotional (RE) and mental health (MH).
These 8 subscales can be used to compute physicalcomponent summary (PCS) and mental component summary(MCS) [5]. SF-8 is a short version of SF-36 and contains 8
subscales and 2 summary scales like SF-36. Reliability andvalidity of both scales have been established in Japan [5].

Results
There were 15 samples in the selected 6 studies. Eachsample’s characteristics are shown in Table 1.
First, the QOL scores of the 15 samples before and after
the medical treatment were compared with national standard
values (Table 2). Before the medical treatment, PCS was
lower than the national standard value in all samples.
Especially, PF, RP and BP were remarkably low. After the
medical treatment, almost all samples reached the national
standard values. However, four subscales VT, SF, RE andMH which belongs to MCS were lower than the national
standard values even after the medical treatment.
Next, we examined the change in the QOL score after the
medical treatment (Table 3). BP improved significantly insam ple
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o

n
109
108
92
17
66
10
28
81
63
62
47
47
40
35
20

age
62.1(25-85)
59.4(22-83)
57.5±15.1
65.5±13.3
50.5±17.2
56.2±12.766.3±12.4
55.7±14.0
56.6±15.1
53.4±15.451.3±17.9
57±14
58±14
54±15
58±15

sex, m :f
35:74
28:80
48:44
11:6
26:40
3:7
12:16
43:48
37:26
26:36
17:30
31:16
24:16
21:14
9:11

Table 2. the QOL scores compared with national standard values
subscalessummary
samplePF RP BP GH VT SF RE MH PCS MCS
Before the medical treatment
a
L
L
b
L
L
s
L
L
L
L
L
L
L
L
L
L
d
S
S
L
L
S
S
S
L
L
L
e
L
L
L
L
L
L
L
L
L
L
f
L
L
L
L
L
L
S
L
L
L
g
L
L
S
L
S
L
S
S
L
S
h
L
L
i
L
L
L
L
L
L
L
L
L
L
j+k
L
L
L
L
L
L
L
L
L
L
l
L
L
L
L
L
L
L
L
m
S
S
L
L
L
S
L
L
n
S
L
L
L
L
S
L
L
o
s
L
L
L
L
L
L
L
After the medical treatment
a
L
L
b
L
L
c
L
L
d
S
S
e
L
S
f
S
L
g
L
L
S
L
S
L
S
S
L
S
h
S
S
i
L
L
L
L
L
L
L
L
L
L
j+k
L
L
L
L
L
L
L
L
L
L
l
S
S
S
S
S
L
L
L
m
S
S
S
L
L
S
S
L
n
S
S
S
L
L
L
L
L
o
S
L
S
L
L
S
L
L
L, lower than national standard values
S, same as national standard values-, not statedmany samples. There was no significant improvement in RP. SF
and RE of each sample were declined after the medical
treatment.

- 92 -

Table 3. Changes in the QOL scoressubscales
samplePF RP BP GH VT SF
a
b
c
d
e
f
g
S
S
I
S
I
N
h
i
I
I
I
I
I
I
j
I
N
S
S
S
I
k
I
I
I
I
I
I
l
S
I
S
S
S
I
m
N
N
S
I
I
N
n
N
I
S
N
S
W
o
N
N
S
I
I
I

RE
N
W
I
I
S
I
S
N

summary
MH PCS MCS
S
S
I
I
S
S
S
I
S
S
I
I
N
S
N
S
S
I
I
I
S
I
S
I
I
I
S
N
S
I
-

S, significantly improved
Ｉ, improved not significantly
N, not changed
W, got worse-, not stated

References[1] Vakil N, Zanten SV, Kahrilas P, et al. The Montreal
definition and classification of gastroesophageal reflux
disease: a global evidence-based consensus. Am J
Gastroenterol. 2006; 101: 1900-1920.
[2] Akihito S, Kato T, Ito K, et al. Correlation between
symptomatic improvement and quality of life in patientswith reflux and dyspeptic symptoms. Journal of Clinical
Biochemistry and Nutrition. 2012; 50(3): 205-210.
[3] Hongo M, Miwa H, Kusunol M. Effect of rabeprazole
treatment on health-related quality of life and symptoms inpatients with reflux esophagitis: a prospective multicenter
observational study in Japan. Journal of Gastroenterology.
2011; 46(3): 297-304.
[4] Ikegami N, Fukuhara S, Shimozuma K, Ikeda S. QOL
evaluation handbook for clinical use [in Japanese].
Igakushoin. 2002.
[5] Fukuhara S, Bito S, Green J, Hsiao A, Kurokawa K.
Translation, Adaptation, and Validation of the SF-36 Health
Survey for Use in Japan. J Clin Epidemiol. 1998; 51(11):1037-1044.
[6] World Health Organization. The Ottawa Charter for Health
Promotion. First International Conference on Health
Promotion. 1986.

Discussion
When compared with the national standard values,
GERD patients feel decreased level of health on both
physical and mental aspects before starting medical treatment.
After the medical treatment, HR-QOL of physical aspect isalmost same as healthy people, while patients still feel a
psychosocial burden.
The results imply the role of nurses in caring for GERD
patients include; 1) to approach the patients’ psychosocial
aspects, 2) to support them to continue their medical
approach, and 3) to assist them in adjusting to new lifestyles
and habits. The rationales of these implications are as follows.
Since patients experience psychosocial burden even after
medical treatment, it is necessary to approach psychosocial
aspects. Nurses can educate patients and their family about
selecting or cooking meal, spending time after the meal,
drinking and smoking and so on. it is proposed that nurses
can also regulate work time in liaison with occupational
nurse or introduce peer support group to them. Continuing
appropriate medical approach seems to contribute to theimprovement of HR-QOL. Therefore, we recommend nurse
to support the patients in selecting and continuing suitable
medical approach. Nurses are expected to assist the patients
to change and adjust to the new lifestyles and habits which
can alleviate GERD symptoms.

Conclusions
GERD patients have a variety of symptoms which
compromise body function, mental health and social function.
As a result, HR-QOL of patients with GERD is lower thanthat of healthy people. However, improvement of HR-QOL
in physical function can be achieved by receiving medical
treatment and appropriate control of symptoms. On the other
hand, psychosocial aspects of HR-QOL are not improvement.
The results of this literature review imply that the roleof the nurses in caring for patients with GERD are; 1) toapproach to psychosocial aspects, 2) to support them tocontinue their medical approach, and 3) to assist in adjusting
to lifestyles and habits.
Author address

E-Mail: kouno.aoi@i.mbox.nagoya-u.ac.jp- 93 -

Literature review on self-care behavior of Japanese pregnant women
M. Kamiya, A. Yamada, Y. Takahashi
Department of Nursing, Nagoya University Graduate School of Medicine, Nagoya, Japan

Introduction
Pregnancy is associated with normal physiologicalchanges that assist fetal development as well as preparation
for labor. A woman in the first stage of her pregnancy
usually works toward improving her health or family
situation [1-3]. Thus, perinatal nurses and midwives should
lead pregnant women from the beginning stages to preventand reduce occurrences of a complicated pregnancy and help
them develop a healthy mother-fetus attachment for future
development.
However, pregnancy poses both physical andpsychological health risks because it brings many changes tothe body of the woman, and it may cause abnormal signs andsymptoms for both the woman and the fetus even if thesymptoms are unnoticeable. Thus, to prevent maternal healthproblems during pregnancy and childbirth, healthy self-carebehavior are needed [4].
Human pregnancy comprises three trimesters: 1sttrimester (0~15 gestational weeks), 2nd trimester (16 to 27
gestational weeks), and 3rd trimester (28 gestational weeks ~until birth). Each trimester is accompanied by specifichormonal and physiological changes. The 1st trimester is themost crucial one for fetus development, and women need tomake lifestyle changes such as avoiding smoking or cutting
down on alcohol. During this period, hormonal levels change
dramatically and affect almost every organ system causing
fatigue, morning sickness, headache, and constipation.
Through the 2nd and 3rd trimesters, endocrinal changes areslight, and the pregnant woman begins to develop an
attachment to her unborn baby, a bond that increases
following fetal movement. Both international and Japanesestudies have shown that fetal movement has a strong impact
on developing mother-fetus attachment [1, 2, 5-8]. However,pregnant women may also experience a whole new set ofsymptoms in this stage, such as lower back pain, abdominal
pain, leg cramps, constipation, and heartburn due to theincreasing size of the uterus [9, 10].
Therefore, pregnancy may be an optimal time to informand challenge women to change their daily habits toward
healthy self-care behavior. However previous studies haveshown that self-care during pregnancy is independently
related to demographic characteristics such as knowledge,
perceived benefits, perceived barriers, social support, andself-efficacy [5, 11]. Thus, it may not be easy for pregnant
women to maintain healthy self-care behavior in difficult
circumstances.
Therefore, we would like to clarify the factors andexperiences that act as "motivation" and "intention" to selectappropriate healthy self-care behavior in order to prevent
serious pregnancy complications and develop a “healthy”
mother-infant relationship from the beginning of thepregnancy period. In this study, we also present perinatal andmidwifery practices for effective pregnant education.

Methods
The aim of this review was to summarize the related
factors leading to motivation and intention toward
developing healthy self-care behavior during pregnancy. The
database Ichushi-Web (Japan Medical Abstracts Society) wasused in the search for original Japanese research articles

published from 2000 to 2017 that studied human participants
and were written in Japanese.
The terms pregnancy, self-management, attachment,maternal role were searched both with and without hyphenation
on August 19, 2017. After adding a hand search. We finallyidentified 11 articles to use for this review.

Results
We found that 6 out of the 11 searched papers were studied
by Manabe’s research group, which developed the scales for
self-care behavior and clarified the definition of self-carebehavior. Three studies clarified own definitions of self-carebehavior. Although 2 of the 5 studies used Manabe’s model, one
study did not clarify the definition, as can be seen from Table 1.
Table 1. Definitions of self-care behavior in pregnant womenaccording to each study
Authors
Manabe et al.,（2000）

Terms
Self-Care
Behavior

Uemura et al.,(2011)

Self-Care
Behavior

Takatsu et al.,(2013)

Healthy
Self-Care
Behavior
Self-Care
Behavior

Tachibana etal., (2014)

Soma (2011)

Sasaki (2013）
1.

Definitions
Pregnant women perceive
their own physical andpsychological changes andas a result, adopt practices ofideal daily life behaviors for
growth of the fetus andprepare for delivery andchildrearing
Pregnant women cope withthe physical andpsychological changes that
occur during pregnancy
Pregnant women cope withthe physical changes that
occur during pregnancy
Pregnant women change
their behavior for improving
their obvious symptoms that
occur during pregnancy

Daily life
behavior

Pregnant women change
their life habits for
improving their physicaland psychological health andgrowth of fetus
No identification

Self-care behavior model during pregnancy by Manabe etal. [12] [13]Manabe et al. [13] proposed a practical approach using theconcept of "self-care behavior," which was developed from the
HAPA model. According to their definition of self-carebehavior, “pregnant women perceive their own physical andpsychological changes, practice ideal daily life behaviors for thegrowth of the fetus, and prepare themselves for delivery and- 94 -

childrearing.” Next, they mentioned that self-care behavior
involves, “internal motivation” such as being interested in the“growth of the fetus” or in the “prevention of abnormal
pregnancy.” The second is “external motivation,” such as
obtaining health care providers’ approval for their practices
or “practicing similar behavior or techniques with theirfriends.” They showed that “internal motivation” is strongly
associated with action when compared to “externalmotivation”.
2.

A study on motivation for healthy self-care behavior by
Takas et al. [14]Takatsu et al. used semi-structured interviews of 10
pregnant women between 30 and 34 gestational weeks tounderstand factors that enhanced motivation and difficulties
for self-care behavior among them. They reported motivation
for self-care behavior among women with regard to thefollowing: (a) interest and concern for the infant and for their
daily life during pregnancy, (b) suggestions received from a
medical professional, (c) their husband, or colleagues, (d)their own body and their baby’s health during and after birth,and (e) changes during the course of pregnancy. About theirdifficulties are in; (1) change their dietary habit or life habit,and (2) change working environment.
3.

Factors related to motivation toward self-care behavior
during pregnancy

Manabe et al. [15] conducted a study on 295 Japanesepregnant women from 9 to 38 gestational weeks using the"pregnant women's self-care behavior motivation scale" thatthey developed. They showed that internal motivation was
positively related to positive feelings when they noticed
pregnant, positive fetal attachment, and affection toward theirhusband . Also they showed that primipara had stronger
internal motivation to self-care behavior than multiparas [16].
Only the depressive mode was negatively correlated tomotivation toward self-care behavior. Uemura et al., [17]studied 112 pregnant women who were between 5 and 15
gestational weeks using Manabe’s scales [16]. They
demonstrated that young age, primipara, and a short marriage
period were positively related to motivation to self-carebehavior. Furthermore, motivation to self-care behavior was
positively correlated to a better relationship with the husband,with the mother, positive feeling of pregnancy, and positive
identification with the maternal role. Sasaki [18] studied 70
pregnant women between 20 and 27 gestational weeks using
Manabe’s scales [16]. She reported that motivation to selfcare was not related to pregnancy history. These findings
were different from the original results.
4.

Factors related to intention and implementation of selfcare behavior during pregnancy

Manabe et al., [19] conducted another study among 243
primiparae who were between 16 and 38 gestational weeks to
explore the factors related to intention to self-care behavior.
They found that positive relations between intention to selfcare behavior and positive emotion toward the fetus, selfmanagement skills, wish to have a baby, emotional support,
and state of occupation; they found intention to self-care wasnegatively correlated to depressive mode. Sasaki et al., [18]showed that women with a normal pregnancy showed ahigher score on intention to self-care behavior than womenwith complications during pregnancy. In addition, pregnant

women whose BMI < 25 showed a high score of intention toself-care behavior when compared to those with BMI >25.
Tachibana et al., [20] conducted a survey among 140 pregnant
women (not clear about their gestational weeks) using 20 items
chosen from the Pregnancy Behavior Scale (PBS), which wasdeveloped in 2009. They showed that occupation/income,planned pregnancy, and satogaeri were related to actual
implementation of behavior. Soma et al., [8] examined thisrelation between maternal-fetal attachment and the daily life
behavior in 440 primiparae at the end of pregnancy. They
reported a positive relationship between maternal-fetal
attachment and hopes and plans for pregnancy, feeling ofpregnancy, experiences of childrearing before pregnancy, highself-esteem, changes in dietary habits during pregnancy,
consuming food with higher iron content, sleeping during theday, and exercise habits.

Discussion
The findings of this review suggest that mother-fetus
attachment plays an important role in motivation and intention
toward self-care behavior among pregnant women. However,we were unable to determine whether the pregnant women who
participated in the study maintained their self-care behavior
during pregnancy due to the study design. All reviewed studies
were cross-sectional and analyzed all trimesters together. Whenplanning to offer an effective pregnant education, we need toconsider trimester differences because of the different physicalsymptoms and psychological changes during pregnancy.
Therefore, we hope to find strong evidences for feasible
education during pregnancy for the future health of pregnant
women with sustainable routine postnatal practices, and fordeveloping healthy mother-infant attachment.

References[1] Rubin R. Attainment of the maternal role, Nursing Reserch.
1967;16(3), 237-245.
[2] Mercer RT. Becoming a mother versus maternal roleattainment, J Nursing Scholarship. 2004; 36(3), 226-232.
[3] Stern.D.N/Kitamura F. To become a mother: The birth of anew "me". 2012. Sougensha, Tokyo.
[4] World Health Organization. Self-care in the context ofprimary health care. Report of Regional Consultation. 2009.
[Online] Available:
http://www.searo.who.int/entity/primary_health_care/documents/sea_hsd_320.pdf. Retrieved[5] Müller ME. A questionnaire to measure mother-to- infant
attachment, J Nurs Meas, 1994; 2, 129-141.
[6] Sakae R. The factors influencing development of maternalfetal attachment during pregnancy, J Jpn. Acad. Midwife.
2004;18(1), 49-55. [Japanase][7] Sato S. The Effect Attachment to Pregnant Women’s Fetus
on the Attachment to Their Infant, J.Jpn.Acad Nurs Sci.
2004; 24(3), 72-80. [Japanase][8] Souma M. The relation between maternal-fetal attachment
and behavior in daily life of primigravid women. J.Jpn.Acad,
Midwife. 2011;25(2), 203-214. [Japanase][9] J.joseph, Corinne H. Rocca, Kirsten M. J.Thompson,
Cynthia C.harper. Pregnancy:not a disease but still a healthrisk.Contraception. 2013;88, 481-484.
[10] Gerald C. Psychological Aspects of Maternity Care, Am J
Public Health. 1957; 47, 25-31.

Author address

kamiya.miki@a.mbox.nagoya-u.ac.jp- 95 -

List of Participants – Yonsei University
Department

First nameLast Name

Hae-Jong

LEE

Kang-Hyun

LEE

Yong-Hyun

CHUNG

Sang-Hyun

CHO

Professor

Woo-Chol

CHOI

Associate Professor

Hye-Seon

JEON

Professor

Si-Hyun

KIM

Research Professor

Hyun-A

KIM

Doctoral Course

Jong-Seok

HWANG

Doctoral Course

Hyeo-Bin

YOON

Master Course

Hae-Yean

PARK

Assistant Professor

A-ReumHAN

Assistant Professor

Sang-Mi

PARK

integrated PhD programHyun-Jung

KIM

Master Course

Ga-In

SHIN

Master Course

Kyu-WonLEE

Master Course

Won-Seuk

CHOI

Master Course

Chul-Hee

MIN

Associate Professor

Kyu-Seok

KIM

Doctoral Course

Radiological Sci.

Chan-Woo

PARK

integrated PhD program& TechIn-SooKANG

integrated PhD program

Ji-WonJANG

integrated PhD program

Chang-Soo

YUN

Master Course

Ki-Jong

RHEE

Associate Professor

Bo-Young

JEON

Associate Professor

Seong-Jae

KANG

integrated PhD program

Biomedical Sci. &Hye-Jin

KWON

integrated PhD program

Lab.

Sezim

MONOLDOROVA

integrated PhD program

Soon-Jae

HWANG

integrated PhD program

Byung-Chul

JUNG

Master Course

Su-Ji

LEE

integrated PhD program

Ji-HeaCHOIAssistant Professor

Bo-Kyoung

KIM

Research Fellow

In-SunCHEON

Master Course

Ah-Reum

JEONG

Master Course

HealthAdministration
Emergency
Medicine
Biomedical Sci. &Lab.

Physical Therapy

Occupational
Therapy

Nursing- 96 -

Title
Dean(College of Health Science)
Dean(College of Medicine)
Vice Dean(College of Health Science)List of Participants – Nagoya University
Department

First nameLast Name

Tetsuhito

KOJIMA

Yasushi

UCHIYAMA

Professor

Yoshiki

TSUCHIDA

Master Course

Yo

ISHIMARU

Master Course

Junichi

UEMURA

Associate Professor

Occupational

Aiko

HOSHINO

Associate Professor

Therapy

TakutoSAKUMA

Master Course

RyosukeSUZUKI

Master Course

Kuniharu

IMAI

Professor

Radiological

Masataka

KOMORI

Associate Professor

Technology

TakuyaYABE

Master Course

Takashi

MIZUNO

Master Course

Jun

UEYAMA

Associate Professor

TakutoSAKUMA

Master Course

RyosukeSUZUKI

Master Course

Yuki

TAKAHASHI

Associate Professor

Natsuki

NAKAYAMA

Associate Professor

Akiko

YAMADA

Master Course

HarukaFURUSHO

Master Course

MegumiYOKOYAMA

Master Course

Miki

KAMIYA

Master Course

Aoi

KONO

Master Course

PathophysiologicalLab. Tech.
Physical Therapy

PathophysiologicalLab. & Tech.

Nursing- 97 -

Title
Director(Graduate School of Medicine)