I
nte
rna
t
io
na
l J
o
urna
l o
f
P
u
bli
c
H
ea
lt
h Science
(
I
J
P
H
S)
Vo
l.
10
,
No
.
2
,
J
u
n
e
2
0
2
1
,
p
p
.
2
89
~
2
97
I
SS
N:
2
2
5
2
-
8806,
DOI
: 1
0
.
1
1
5
9
1
/i
j
p
h
s
.
v
1
0
i
2
.
2
0
6
6
6
289
Jo
u
r
n
a
l h
o
mep
a
g
e
:
h
ttp
:
//ij
p
h
s
.
ia
esco
r
e.
co
m
Effec
t
o
f
a
cu
te
su
b
m
a
x
i
m
a
l
phys
ic
a
l exercise be
fore
deco
m
p
ress
io
n di
v
e on tu
m
o
r n
ecr
o
sis
f
a
ctor alp
ha
co
ncentration
a
mo
ng
m
a
le
trained
div
ers
Chi
k
i
h
Chi
kih
1
,
G
urit
no
Su
r
y
o
k
us
u
m
o
2
,
Astr
i
d Sul
i
s
t
o
mo
3
1
,
2,
3
P
o
stg
ra
d
u
a
te
P
r
o
g
ra
m
Oc
c
u
p
a
ti
o
n
a
l
M
e
d
icin
e
,
F
a
c
u
lt
y
o
f
M
e
d
icin
e
,
Un
iv
e
rsitas
In
d
o
n
e
sia
,
I
n
d
o
n
e
sia
1
Klin
ik
Hijau
P
u
ti
h
2
9
,
P
rim
a
r
y
He
a
lt
h
Ca
re
P
r
o
v
id
e
r,
I
n
d
o
n
e
sia
Art
icle
I
nfo
AB
ST
RAC
T
A
r
ticle
his
to
r
y:
R
ec
eiv
ed
Sep
2
4
,
2
0
2
0
R
ev
i
s
ed
Feb
1
3
,
2
0
2
1
A
cc
ep
ted
Ma
r
1
2
,
2
0
2
1
T
h
e
in
c
re
a
se
o
f
i
n
f
la
m
m
a
to
r
y
b
io
m
a
r
k
e
rs
d
u
e
to
d
e
c
o
m
p
re
ss
io
n
d
iv
e
is
o
n
e
o
f
th
e
f
a
c
to
rs
th
a
t
c
o
u
ld
c
a
u
se
d
e
c
o
m
p
re
ss
io
n
sic
k
n
e
ss
(
DCS
)
,
o
n
e
o
f
th
e
m
is
t
u
m
o
r
n
e
c
ro
sis
a
lp
h
a
(
T
NFα
)
.
A
c
c
o
rd
in
g
to
th
e
p
re
c
o
n
d
i
ti
o
n
i
n
g
th
e
o
ry
,
e
x
e
rc
is
e
b
e
f
o
re
d
iv
e
c
a
n
re
d
u
c
e
a
m
o
u
n
t
o
f
g
a
s
b
u
b
b
le
to
p
re
v
e
n
t
DCS.
T
h
is
stu
d
y
a
i
m
e
d
to
p
ro
v
e
th
a
t
e
x
e
r
c
ise
b
e
f
o
re
d
iv
in
g
c
a
n
p
re
v
e
n
t
i
n
c
re
a
se
o
f
T
NFα.
T
h
is
stu
d
y
e
m
p
lo
y
e
d
q
u
a
si
-
e
x
p
e
ri
m
e
n
tal
d
e
sig
n
w
it
h
tra
in
e
d
m
a
le
d
iv
e
rs.
T
h
e
su
b
jec
t
d
iv
id
e
d
in
t
o
tw
o
g
ro
u
p
s,
trea
t
m
e
n
t
a
n
d
c
o
n
tr
o
l.
T
h
e
trea
t
m
e
n
t
g
ro
u
p
g
o
t
su
b
m
a
x
i
m
a
l
e
x
e
rc
is
e
w
it
h
7
0
%
h
e
a
rt
ra
te i
n
te
n
sity
,
u
sin
g
c
y
c
le
e
r
g
o
m
e
ter
w
it
h
y
o
u
n
g
m
e
n
'
s
Ch
risti
a
n
a
ss
o
c
iatio
n
(
YMCA
)
p
ro
c
e
d
u
re
m
o
d
ify
b
y
G
u
rit
n
o
,
2
4
h
o
u
rs
b
e
f
o
re
d
e
c
o
m
p
re
ss
io
n
d
iv
e
2
8
0
k
P
a
b
o
t
t
o
m
ti
m
e
8
0
m
in
u
te
w
it
h
US
-
NA
V
Y
tab
le,
w
h
e
re
a
s
th
e
c
o
n
tro
l
g
ro
u
p
o
n
ly
d
o
d
e
c
o
m
p
re
ss
io
n
d
iv
e
.
T
NFα
e
x
p
re
ss
io
n
w
a
s
c
h
e
c
k
e
d
th
re
e
ti
m
e
s,
a
t
b
e
g
in
n
in
g
o
f
stu
d
y
,
b
e
f
o
re
d
iv
e
a
n
d
a
f
ter
d
iv
e
.
In
trea
t
m
e
n
t
g
ro
u
p
t
h
e
re
w
a
s
in
sig
n
i
f
ica
n
t
d
e
c
re
a
se
T
NFα,
f
r
o
m
7
.
0
6
±1
.
8
5
p
g
.
/m
l
to
6
.
7
5
±
1
.
8
1
p
g
.
/m
l,
w
h
e
re
a
s
th
e
c
o
n
tro
l
g
ro
u
p
sh
o
w
e
d
a
sig
n
if
ica
n
t
in
c
re
a
se
d
T
NFα,
f
ro
m
8
.
2
2
(1
.
4
5
to
1
3
.
1
1
)p
g
.
/m
l
to
8
.
3
9
(1
.
7
3
to
1
2
.
1
8
)
p
g
/m
l,
a
n
d
sig
n
if
ica
n
t
d
if
fe
re
n
c
e
w
a
s
f
o
u
n
d
b
e
tw
e
e
n
th
e
m
e
a
n
d
iff
e
r
e
n
c
e
f
o
r
t
w
o
g
ro
u
p
s
p
<
0
.
0
5
.
It
c
a
n
b
e
c
o
n
c
l
u
d
e
d
t
h
a
t
a
c
u
te su
b
m
a
x
i
m
a
l
e
x
e
rc
is
e
p
re
v
e
n
ts
a
n
in
c
re
a
se
o
f
TNF
α
a
f
te
r
sin
g
le d
iv
e
d
e
c
o
m
p
re
ss
io
n
to
p
re
v
e
n
t
p
o
ss
ib
il
it
y
o
c
c
u
rrin
g
DCS
)
.
K
ey
w
o
r
d
s
:
Dec
o
m
p
r
ess
io
n
d
i
v
e
P
h
y
s
ical
e
x
er
cise
P
r
ec
o
n
d
itio
n
in
g
P
r
ev
en
tio
n
o
f
D
C
S
T
NFα
T
h
is
is
a
n
o
p
e
n
a
c
c
e
ss
a
rticle
u
n
d
e
r th
e
CC B
Y
-
SA
li
c
e
n
se
.
C
o
r
r
e
s
p
o
nd
ing
A
uth
o
r
:
C
h
i
k
i
h
Klin
i
k
Hij
au
P
u
ti
h
2
9
Gr
i
y
a
I
n
d
ah
Ser
p
o
n
g
–
Kab
.
B
o
g
o
r
1
6
3
4
0
,
I
n
d
o
n
esia
E
m
ail:
c
h
i
k
ih
.
m
d
.
d
m
a
@
g
m
ai
l
.
co
m
1.
I
NT
RO
D
UCT
I
O
N
Dec
o
m
p
r
ess
io
n
il
ln
e
s
s
is
a
d
is
ea
s
e
th
at
o
cc
u
r
s
d
u
e
t
o
ch
an
g
e
s
in
e
n
v
ir
o
n
m
e
n
tal
p
r
ess
u
r
e.
Dec
o
m
p
r
ess
io
n
i
lln
e
s
s
ca
n
af
f
ec
t
b
y
d
iv
er
s
,
co
m
p
r
es
s
ed
air
w
o
r
k
er
s
,
av
iato
r
s
an
d
astr
o
n
au
t
s
.
C
h
a
n
g
es
i
n
en
v
ir
o
n
m
e
n
tal
p
r
ess
u
r
e
ca
u
s
e
th
e
f
o
r
m
atio
n
o
f
in
er
t
g
a
s
b
u
b
b
les
in
b
lo
o
d
cir
cu
latio
n
an
d
its
ca
u
s
e
s
d
ec
o
m
p
r
ess
io
n
s
ic
k
n
es
s
(
DC
S
)
[
1
]
.
T
h
e
Div
er
A
ler
t
Net
w
o
r
k
r
ele
ased
th
at
th
e
d
ea
t
h
r
ate
d
u
e
to
d
iv
in
g
in
t
h
e
last
1
0
y
ea
r
s
r
ea
ch
ed
1
0
6
7
ca
s
es,
an
d
s
p
ec
if
ical
l
y
in
2
0
1
9
th
e
n
u
m
b
er
o
f
ca
s
e
s
r
ea
ch
e
d
2
2
8
ca
s
es
w
o
r
ld
w
id
e.
B
y
p
r
esen
tat
io
n
3
7
.
5
%
o
f
d
ea
th
s
w
er
e
d
u
e
to
d
ec
o
m
p
r
es
s
io
n
s
ic
k
n
e
s
s
(
DC
S).
Dec
o
m
p
r
ess
io
n
s
ic
k
n
ess
i
n
2
0
1
9
r
ea
ch
ed
2
4
2
3
in
cid
en
t
s
w
o
r
ld
w
id
e.
T
h
is
f
ig
u
r
e
is
th
e
n
u
m
b
er
o
f
in
cid
en
ts
r
ep
o
r
ted
b
y
p
r
o
f
es
s
io
n
al
d
iv
er
s
w
h
o
h
a
v
e
in
s
u
r
a
n
ce
,
s
o
it
is
al
m
o
s
t
ce
r
tai
n
t
h
at
t
h
e
ac
tu
a
l
i
n
cid
en
ce
i
s
h
i
g
h
er
b
ec
au
s
e
m
an
y
d
i
v
er
s
d
o
n
o
t
w
o
r
k
f
o
r
m
a
ll
y
a
n
d
d
o
n
o
t
h
av
e
in
s
u
r
an
ce
[
2
]
.
Me
an
w
h
i
le
i
n
I
n
d
o
n
esia,
t
h
e
in
cid
e
n
ce
o
f
d
ec
o
m
p
r
ess
io
n
s
ic
k
n
es
s
h
a
s
n
o
t
b
ee
n
r
ep
o
r
ted
n
atio
n
al
l
y
,
b
ec
a
u
s
e
th
e
m
aj
o
r
it
y
o
f
d
iv
er
s
ar
e
tr
ad
itio
n
a
l
d
iv
er
s
.
I
t
w
a
s
n
o
ted
th
a
t
f
is
h
er
m
e
n
i
n
2
0
0
6
i
n
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N:
2
2
5
2
-
8
8
0
6
I
n
t.
J
.
P
u
b
lic
Hea
lth
Sci.,
Vo
l.
1
0
,
No
.
2
,
J
u
n
e
20
21
:
2
89
–
2
97
290
B
u
n
g
in
I
s
lan
d
,
NT
B
5
7
.
5
%
r
e
p
o
r
ted
j
o
in
t
p
ain
,
w
h
ich
i
s
a
d
ir
ec
t
s
y
m
p
to
m
o
f
d
ec
o
m
p
r
es
s
i
o
n
s
ick
n
e
s
s
t
y
p
e
1
,
in
th
e
p
r
a
m
u
k
a
is
la
n
d
s
o
f
J
a
k
ar
ta,
th
e
p
r
ev
ale
n
ce
o
f
d
ec
o
m
p
r
es
s
io
n
s
ick
n
es
s
w
as
as
m
u
c
h
as
6
.
9
%
an
d
cu
m
u
lat
iv
el
y
i
n
k
ar
i
m
u
n
j
a
w
a
is
lan
d
s
b
et
w
ee
n
2
0
0
7
-
2
0
1
4
t
h
er
e
w
er
e
1
0
4
ca
s
es
w
it
h
7
p
eo
p
le
d
ied
[3
]
-
[
4]
.
Ma
n
y
d
iv
er
s
a
n
d
co
m
p
r
es
s
ed
air
w
o
r
k
er
s
h
a
v
e
tr
ied
to
p
r
ev
en
t
d
ec
o
m
p
r
ess
io
n
s
ic
k
n
e
s
s
(
DC
S)
b
y
ca
r
r
y
i
n
g
o
u
t
w
o
r
k
ac
co
r
d
in
g
to
d
ec
o
-
s
t
o
p
p
r
o
ce
d
u
r
es,
b
u
t
d
ec
o
m
p
r
es
s
io
n
s
ic
k
n
e
s
s
i
n
cid
en
t
s
ar
e
s
till
d
if
f
ic
u
lt
to
av
o
id
.
T
h
is
is
in
ac
co
r
d
an
ce
w
it
h
Ma
y
d
en
's
th
eo
r
y
,
w
h
ic
h
s
tate
s
:
Dec
o
m
p
r
ess
io
n
s
ic
k
n
ess
d
u
e
to
d
iv
es
n
o
t
o
n
l
y
ca
u
s
ed
b
y
b
u
b
b
le
g
as,
it
ca
n
b
e
ca
u
s
ed
b
y
en
d
o
t
h
elial
d
y
s
f
u
n
ctio
n
[
5
]
.
E
n
d
o
th
elial
d
y
s
f
u
n
ctio
n
d
u
e
to
d
iv
es
is
tr
ig
g
er
ed
b
y
h
y
p
er
o
x
ia
-
in
d
u
ce
d
v
aso
co
n
s
tr
ictio
n
a
t
d
ep
th
t
h
at
ca
u
s
e
s
O
x
id
ati
v
e
S
tr
ess
.
I
n
s
t
u
d
ies
co
n
d
u
cted
w
it
h
r
ats,
an
as
s
o
ciatio
n
w
as
f
o
u
n
d
b
et
w
ee
n
th
e
i
n
cid
en
ce
o
f
en
d
o
th
elial
d
y
s
f
u
n
ctio
n
a
n
d
g
as
b
u
b
b
les
[
5
]
.
T
h
is
ca
n
b
e
s
ee
n
f
r
o
m
c
h
an
g
es
i
n
i
n
f
la
m
m
ato
r
y
b
i
o
m
ar
k
er
s
s
u
c
h
a
s
e
ndot
he
l
i
n
-
1
(
ET
-
1
)
,
6
-
k
et
o
pr
os
t
ag
l
an
di
n
F1α
(
6
-
k
eto
-
P
GF1
α
)
,
i
nt
er
c
el
l
ul
ar
a
dhes
i
on
m
ol
ec
ul
e
-
1
(
I
C
AM
-
1
)
,
v
as
cul
a
r
ce
l
l
adhe
s
i
on
p
r
ot
ei
n
-
1
(
VC
A
M
-
1
)
an
d
m
al
ondi
a
l
dehy
d
(
M
DA
)
,
w
h
ile
s
er
u
m
n
i
t
r
i
c
oxi
de
(
N
O
)
d
ec
r
ea
s
ed
f
o
llo
w
in
g
r
ap
id
d
ec
o
m
p
r
ess
io
n
an
d
also
t
h
e
in
cr
ea
s
ed
o
f
t
u
m
o
r
n
ec
r
o
s
is
f
ac
to
r
a
lp
h
a
(
T
N
Fα
)
ex
p
r
es
s
io
n
[6
]
,
[
7]
.
T
u
m
o
r
n
ec
r
o
s
i
s
alp
h
a
(
T
NFα
)
is
a
p
leio
tr
o
p
ic
ac
u
te
cy
to
k
in
e
t
h
at
i
n
itiate
s
c
y
to
k
in
e
c
ascad
e
b
y
in
cr
ea
s
i
n
g
m
e
m
b
r
an
e
p
er
m
e
ab
ilit
y
o
f
th
e
b
lo
o
d
v
ess
el
s
,
th
i
s
co
n
tr
ib
u
tin
g
to
t
h
e
b
o
d
y
's
d
ef
e
n
s
e
s
a
n
d
s
ti
m
u
la
tin
g
ce
ll
g
r
o
w
th
.
E
x
c
ess
i
v
e
T
NFα
ac
ti
v
atio
n
i
n
cr
ea
s
es
t
h
e
r
is
k
o
f
t
u
m
o
r
an
d
c
ell
d
ea
th
.
T
NFα
i
s
in
f
lu
e
n
tia
l
i
n
t
h
e
p
r
o
ce
s
s
o
f
f
at
m
etab
o
lis
m
,
i
n
t
h
e
h
y
p
er
ch
o
lest
er
o
le
m
ia
d
iv
er
T
NFα
lev
els
is
ab
o
v
e
t
h
e
n
o
r
m
al
v
al
u
e.
T
NFα
also
i
n
cr
ea
s
es
w
it
h
r
eg
ar
d
to
th
e
ar
ter
o
s
cler
o
tic
p
r
o
ce
s
s
o
r
th
e
ag
i
n
g
p
r
o
ce
s
s
o
f
b
lo
o
d
v
es
s
els,
i
n
o
b
ese
p
atien
ts
a
n
d
in
cr
ea
s
ed
b
lo
o
d
s
u
g
ar
T
NFα
also
in
cr
ea
s
ed
[
8
]
.
R
esear
ch
i
n
p
r
o
f
ess
io
n
al
d
i
v
e
r
s
in
I
n
d
o
n
esia,
d
ec
o
m
p
r
ess
io
n
d
iv
e
in
d
u
ce
d
i
n
f
la
m
m
ato
r
y
b
io
m
ar
k
es
ch
an
g
es
l
ik
e
th
e
d
ec
r
ea
s
e
o
f
endot
h
el
i
a
l
-
NOS
(
eNO
S
)
s
y
n
t
h
esi
s
,
in
cr
ea
s
ed
i
n
ter
le
u
k
in
-
1
s
y
n
t
h
esi
s
an
d
in
cr
ea
s
ed
th
r
o
m
b
o
c
y
te
ag
g
r
eg
atio
n
p
r
o
ce
s
s
e
[9
]
-
[
11]
.
P
r
ec
au
t
io
n
s
ag
a
in
s
t
th
e
o
cc
u
r
r
en
ce
o
f
o
x
id
ati
v
e
s
tr
e
s
s
d
u
e
t
o
d
ec
o
m
p
r
ess
io
n
d
i
v
e
is
by
p
r
o
v
id
in
g
a
p
r
e
-
d
iv
e
co
n
d
itio
n
,
k
n
o
w
n
a
s
p
r
ec
o
n
d
itio
n
i
n
g
t
h
eo
r
y
.
O
n
e
o
f
t
h
e
m
i
s
p
h
y
s
ical
ex
er
cise
b
ef
o
r
e
d
i
v
in
g
.
P
h
y
s
ical
e
x
er
cise
b
ef
o
r
e
d
iv
e
s
w
i
th
s
p
ec
i
f
ic
in
ten
s
it
y
,
d
u
r
atio
n
an
d
f
r
eq
u
e
n
c
y
h
as
b
ee
n
s
h
o
w
n
to
r
ed
u
ce
b
u
b
b
le
g
as
f
o
r
m
atio
n
[
1
2
]
,
[
1
3
]
.
No
s
tu
d
ies
h
a
v
e
y
et
r
ep
o
r
ted
o
n
p
r
e
-
d
iv
e
ex
er
ci
s
e
o
n
t
h
e
ex
p
r
ess
io
n
o
f
a
n
ti
-
in
f
la
m
m
a
to
r
y
b
io
m
ar
k
er
s
.
A
s
w
e
k
n
o
w
t
h
at
p
h
y
s
ical
e
x
er
cise
w
ith
s
p
ec
i
f
ic
i
n
ten
s
it
y
,
d
u
r
atio
n
an
d
p
lan
n
ed
f
r
eq
u
en
c
y
i
n
cr
ea
s
es
m
etab
o
lis
m
a
n
d
ad
ap
tatio
n
r
esp
o
n
s
e
th
r
o
u
g
h
i
n
cr
ea
s
ed
an
tio
x
id
an
t
en
z
y
m
es
[
1
3
]
.
I
t
in
cr
ea
s
es
o
x
y
g
en
co
n
s
u
m
p
tio
n
r
esu
l
tin
g
i
n
th
e
f
o
r
m
atio
n
o
f
h
y
d
r
o
g
en
p
er
o
x
id
e
th
at
p
r
o
v
id
es
p
h
y
s
io
lo
g
ical
r
esp
o
n
s
es
t
h
r
o
u
g
h
r
ed
o
x
-
s
en
s
itiv
e
f
ac
to
r
tr
an
s
cr
ip
tio
n
t
h
at
s
u
p
p
r
es
s
es
in
f
la
m
m
ato
r
y
c
y
to
k
in
e
s
y
n
th
e
s
is
lik
e
t
u
m
o
r
n
ec
r
o
s
i
s
f
ac
to
r
a
lp
h
a
(
T
NFα
)
a
n
d
i
n
cr
ea
s
es
a
n
tii
n
f
la
m
m
ato
r
y
c
y
to
k
in
e
s
[7
]
,
[
14]
.
An
d
also
th
e
ab
s
en
c
e
h
as
ab
o
u
t
th
e
e
f
f
ec
t
o
f
d
ec
o
m
p
r
ess
io
n
d
iv
e
o
n
t
u
m
o
r
n
ec
r
o
s
is
f
ac
to
r
a
lp
h
a
(
T
NFα
)
ex
p
r
es
s
io
n
i
n
h
u
m
a
n
s
,
a
n
d
it
h
as
n
o
t
b
ee
n
p
r
o
v
en
also
a
b
o
u
t
th
e
ef
f
ec
t
o
f
p
h
y
s
ica
l
ex
er
cise
o
n
m
ar
k
er
s
o
f
T
NFα
a
s
an
i
n
f
la
m
m
ato
r
y
b
io
m
ar
k
er
s
.
So
th
a
t
th
i
s
s
t
u
d
y
ai
m
s
to
p
r
o
v
e
th
at
p
h
y
s
ical
e
x
er
cise
b
ef
o
r
e
d
ec
o
m
p
r
ess
io
n
d
iv
in
g
ca
n
p
r
ev
en
t
th
e
o
cc
u
r
r
en
ce
o
f
o
x
id
ati
v
e
s
tr
ess
d
u
e
to
d
ec
o
m
p
r
es
s
io
n
d
iv
in
g
,
th
i
s
is
s
ee
n
f
r
o
m
t
h
e
p
r
ev
en
tio
n
o
f
a
n
in
cr
ea
s
e
i
n
i
n
f
la
m
m
a
to
r
y
m
ar
k
er
s
t
u
m
o
r
n
ec
r
o
s
is
f
ac
to
r
a
lp
h
a
an
d
h
o
p
e
it
ca
n
b
e
u
s
ed
to
p
r
ev
en
t
o
f
o
cc
u
r
r
in
g
d
ec
o
m
p
r
ess
io
n
s
ick
n
es
s
i
n
d
u
ce
d
f
r
o
m
o
x
id
ati
v
e
s
tr
e
s
s
i
n
d
iv
in
g
.
I
n
t
h
i
s
s
t
u
d
y
,
w
e
al
s
o
w
a
n
ted
to
s
ee
t
h
e
ef
f
ec
t
o
f
ag
e,
s
m
o
k
i
n
g
h
ab
it
s
,
b
o
d
y
m
as
s
i
n
d
ex
(
B
MI
)
o
n
t
u
m
o
r
n
ec
r
o
s
is
f
ac
to
r
a
lp
h
a
(
T
NFα
)
e
x
p
r
ess
io
n
i
n
h
ea
lt
h
y
d
i
v
er
s
.
2.
RE
S
E
ARCH
M
E
T
H
O
D
T
h
is
r
esear
ch
is
a
co
llab
o
r
atio
n
s
t
u
d
y
w
it
h
an
q
u
asi
-
e
x
p
er
i
m
en
tal
d
esi
g
n
,
s
u
b
j
ec
ts
w
er
e
d
i
v
id
ed
in
to
t
w
o
g
r
o
u
p
s
,
tr
ea
t
m
en
t
an
d
co
n
tr
o
l
b
ased
o
n
ag
e
g
r
o
u
p
s
,
w
i
th
p
r
e
an
d
p
o
s
t
d
esig
n
s
,
w
h
ic
h
w
a
s
ca
r
r
ied
o
u
t
in
2
0
1
6
.
T
h
is
q
u
asi
-
ex
p
er
i
m
e
n
t
al
r
esear
ch
i
m
p
le
m
en
ted
b
y
lo
o
k
in
g
at
th
e
ef
f
ec
t
o
f
s
u
b
m
a
x
i
m
al
p
h
y
s
ical
ex
er
cise
w
it
h
s
u
b
m
ax
i
m
al
in
t
en
s
it
y
o
f
e
x
er
cise
7
0
%
m
a
x
i
m
al
h
ea
r
t
r
ate
f
r
eq
u
e
n
c
y
,
g
i
v
en
2
4
h
o
u
r
s
b
e
f
o
r
e
d
iv
es,
p
h
y
s
ical
e
x
er
cise
g
iv
e
n
u
s
in
g
m
u
lti
s
ta
g
e
y
o
u
n
g
m
en
's
C
h
r
is
tian
as
s
o
ciatio
n
(
YM
C
A
)
c
y
cle
-
er
g
o
m
eter
m
o
d
i
f
b
y
Gu
r
it
n
o
’
s
a
s
s
h
o
w
n
in
Fi
g
u
r
e
1
[
1
5
]
,
[
1
6
]
.
E
v
er
y
s
u
b
j
ek
h
as
t
h
eir
o
w
n
e
x
er
cise
i
n
te
n
s
it
y
tar
g
et,
in
te
n
s
it
y
ca
lc
u
latio
n
u
s
in
g
h
e
ar
t
r
ate.
Hea
r
t
r
ate
is
ca
lcu
lat
ed
b
y
t
h
e
f
o
r
m
u
la
2
2
0
-
a
g
e
x
7
0
%
(
s
u
b
m
a
x
s
i
m
al
in
te
n
s
it
y
)
.
Dec
o
m
p
r
es
s
io
n
d
i
v
e
is
d
o
n
e
b
y
u
s
in
g
h
y
p
er
b
ar
ic
ch
a
m
b
er
w
it
h
p
r
es
s
u
r
e
2
8
0
k
P
a
w
i
th
b
o
tto
m
ti
m
e
8
0
m
i
n
u
tes,
r
ec
o
m
p
r
ess
io
n
w
it
h
U
.
S
.
Na
v
y
d
i
v
i
n
g
p
r
o
ce
d
u
r
e.
T
h
e
T
NFα
lev
el
e
x
p
r
ess
io
n
was p
er
f
o
r
m
ed
th
r
ee
ti
m
e
s
at
th
e
b
eg
in
n
i
n
g
o
f
t
h
e
s
tu
d
y
,
b
ef
o
r
e
d
iv
in
g
an
d
af
t
er
d
iv
in
g
.
T
h
e
to
tal
ch
o
lest
er
o
l
lev
el
an
d
l
ow
-
dens
i
t
y
l
i
p
opr
o
t
e
i
n
(
LD
L
)
lev
el
p
er
f
o
m
ed
o
n
l
y
o
n
e
ti
m
e
in
th
e
b
eg
in
n
i
n
g
o
f
s
t
u
d
y
.
T
h
e
en
tire
s
t
u
d
y
s
u
b
j
ec
ts
w
er
e
tr
ai
n
ed
m
ale
d
i
v
er
s
,
w
h
o
h
ad
m
et
t
h
e
cr
iter
i
a
an
d
w
il
l
b
e
d
iv
id
e
in
to
tr
ea
t
m
e
n
t
a
n
d
co
n
tr
o
l
g
r
o
u
p
.
T
h
e
tr
ea
t
m
e
n
t
g
r
o
u
p
was
th
e
g
r
o
u
p
t
h
at
r
ec
ei
v
ed
th
e
ac
u
te
s
u
b
m
ax
i
m
al
p
h
y
s
ical
e
x
er
cise
o
f
p
r
e
-
d
iv
e
an
d
th
e
co
n
tr
o
l
g
r
o
u
p
d
id
n
o
t
r
ec
eiv
e
ac
u
te
s
u
b
m
a
x
i
m
al
p
h
y
s
ical
e
x
er
cise.
T
h
i
s
cr
iter
io
n
is
m
ad
e
to
co
n
tr
o
l
th
e
co
n
f
o
u
n
d
in
g
f
ac
to
r
s
f
o
r
T
NFα
ex
p
r
ess
io
n
,
th
e
cr
iter
i
a
d
iv
id
e
in
to
i
n
cl
u
s
io
n
a
n
d
ex
clu
s
io
n
cr
iter
ia.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t.
J
.
P
u
b
lic
Hea
lth
Sci.
I
SS
N:
2
2
5
2
-
8806
E
ffect
o
f a
cu
te
s
u
b
ma
xima
l
p
h
ysica
l e
xe
r
cise b
ef
o
r
e
d
ec
o
mp
r
ess
io
n
d
ive
o
n
tu
mo
r
…
(
C
h
ik
ih
)
291
I
n
clu
s
io
n
cr
it
er
ia
u
s
ed
(
1
)
T
r
ain
ed
d
iv
er
s
a
g
ed
2
1
-
4
0
y
ea
r
s
,
(
2
)
Fit
d
o
d
iv
e,
(
3
)
Did
n
o
t
d
iv
e
in
t
h
e
la
s
t
4
8
h
o
u
r
s
b
e
f
o
r
e
th
e
r
esear
c
h
,
(
4
)
Did
n
o
t
d
o
p
h
y
s
ical
e
x
er
cise
in
t
h
e
la
s
t
4
8
h
o
u
r
s
b
e
f
o
r
e
th
e
r
esear
ch
,
(
5
)
Did
n
o
t
co
n
s
u
m
e
p
ain
k
iller
,
a
n
ti
-
in
f
la
m
m
a
to
r
y
o
r
h
er
b
a
l
m
ed
i
cin
e,
(
6
)
No
t
c
u
r
r
en
tl
y
s
u
f
f
e
r
in
g
f
r
o
m
c
h
r
o
n
ic
d
is
ea
s
e.
T
h
e
ex
clu
s
io
n
cr
iter
ia
in
th
is
s
t
u
d
y
w
er
e;
(
1
)
T
NFα
lev
els
ar
e
lo
w
er
th
a
n
0
.
5
4
p
g
/µ,
(
2
)
T
NFα
lev
el
s
ar
e
h
ig
h
er
t
h
an
1
5
p
g
/µ,
(
3
)
T
o
tal
ch
o
lest
er
o
l
lev
e
ls
ar
e
m
o
r
e
th
an
2
4
0
m
g
/d
l,
(
4
)
Low
-
d
ens
i
t
y
l
i
pop
r
o
t
ei
n
(
L
D
L
)
lev
e
ls
ar
e
m
o
r
e
t
h
an
1
6
0
m
g
/d
l.
T
h
e
r
esear
ch
m
e
t
t
h
e
r
esear
ch
et
h
ic
o
n
t
h
e
et
h
ics
co
m
m
i
s
s
io
n
o
f
t
h
e
m
ed
ical
f
ac
u
lt
y
U
n
i
v
er
s
itas
I
n
d
o
n
esia.
T
h
e
T
NFα
lev
el
at
th
e
b
eg
i
n
n
in
g
o
f
t
h
e
s
t
u
d
y
,
c
h
o
lest
er
o
l
to
tal
an
d
l
ow
-
dens
i
t
y
l
i
p
opr
o
t
e
i
n (
L
DL
)
wa
s
u
s
ed
to
s
ee
if
a
n
y
s
u
b
j
ec
ts
w
o
u
ld
b
e
ex
cl
u
d
ed
.
Fig
u
r
e
1
.
YC
M
A
p
r
o
ce
d
u
r
e
m
o
d
if
y
b
y
G
u
r
it
n
o
T
h
e
ca
lcu
latio
n
o
f
t
h
e
n
u
m
b
e
r
o
f
r
esear
ch
s
u
b
j
ec
ts
is
b
ase
d
o
n
th
e
r
esear
ch
o
f
Ye
C
h
en
,
et
a
l
.
[
7
]
.
T
h
is
is
b
ec
a
u
s
e
t
h
er
e
ar
e
n
o
s
tu
d
ies
i
n
h
u
m
an
s
t
h
at
h
a
v
e
s
e
en
t
h
e
p
r
o
v
is
io
n
o
f
ac
cli
m
atio
n
b
ef
o
r
e
d
i
v
in
g
b
y
d
o
in
g
p
h
y
s
ical
e
x
er
cise
i
n
p
r
ev
en
t
in
g
o
x
id
ati
v
e
s
tr
e
s
s
b
y
lo
o
k
in
g
at
T
NFα
ex
p
r
es
s
io
n
.
T
h
e
s
a
m
p
l
e
s
ize
w
a
s
ca
lcu
lated
as
a
p
o
w
er
o
f
9
0
%
an
d
a
to
ler
ab
le
er
r
o
r
o
f
t
y
p
e
o
n
e
w
as
5
%.
A
f
ter
ca
lcu
l
atin
g
,
t
h
e
n
u
m
b
er
o
f
r
esear
ch
s
u
b
j
ec
ts
r
eq
u
ir
ed
is
3
4
p
eo
p
le.
Ho
w
e
v
er
,
i
n
t
h
i
s
s
tu
d
y
,
4
4
r
esear
ch
s
u
b
j
ec
ts
w
er
e
o
b
tain
ed
.
T
h
en
al
l
s
elec
ted
s
u
b
j
ec
ts
w
er
e
s
o
r
ted
a
lp
h
ab
etica
ll
y
i
n
o
r
d
er
to
o
b
ta
in
a
s
a
m
p
li
n
g
f
r
a
m
e,
th
e
s
u
b
j
ec
ts
d
iv
id
ed
in
to
t
w
o
ag
e
g
r
o
u
p
s
,
n
a
m
el
y
2
1
-
3
0
y
ea
r
s
an
d
3
1
-
4
0
y
ea
r
s
,
th
en
t
h
e
s
u
b
j
ec
ts
w
er
e
s
elec
ted
b
y
r
an
d
o
m
s
a
m
p
l
in
g
in
ea
c
h
ag
e
g
r
o
u
p
.
T
o
tal
4
4
r
esear
ch
s
u
b
j
ec
ts
w
er
e
o
b
tain
ed
an
d
d
i
v
id
ed
in
to
2
2
p
eo
p
le
in
t
h
e
2
1
-
3
0
y
ea
r
a
g
e
g
r
o
u
p
an
d
2
2
p
eo
p
le
in
th
e
3
1
-
4
0
y
e
ar
ag
e
g
r
o
u
p
,
w
h
ic
h
w
er
e
d
iv
i
d
ed
p
r
o
p
o
r
tio
n
all
y
i
n
to
2
2
p
eo
p
le
in
th
e
tr
ea
t
m
en
t
g
r
o
u
p
an
d
2
2
p
eo
p
le
in
th
e
co
n
tr
o
l g
r
o
u
p
.
Statis
t
ical
an
al
y
s
i
s
w
as
p
er
f
o
r
m
ed
u
s
i
n
g
SP
SS
v
er
s
io
n
2
2
,
d
ata
an
a
l
y
s
is
w
as
ad
j
u
s
ted
to
th
e
r
esu
lt
s
o
f
th
e
d
i
s
tr
ib
u
tio
n
o
f
d
ata
f
r
o
m
r
esear
ch
s
u
b
j
ec
ts
,
d
ata
d
is
tr
ib
u
tio
n
te
s
ts
w
er
e
p
er
f
o
r
m
ed
u
s
i
n
g
t
h
e
S
h
ap
h
ir
o
W
ilk
test
.
P
air
ed
t
-
test
is
p
er
f
o
r
m
ed
if
d
ata
d
is
tr
ib
u
tio
n
is
n
o
r
m
al,
an
d
n
o
n
-
p
ar
a
m
etr
ic
o
r
W
ilco
x
o
n
test
is
p
er
f
o
r
m
ed
w
h
e
n
d
ata
d
is
tr
ib
u
tio
n
i
s
ab
n
o
r
m
al.
T
h
e
ca
lc
u
latio
n
o
f
t
h
e
m
ea
n
d
i
f
f
er
en
c
e
b
et
w
ee
n
th
e
t
w
o
g
r
o
u
p
s
w
as c
ar
r
ied
o
u
t u
s
i
n
g
t
h
e
Ma
n
n
-
W
h
it
n
e
y
test
.
R
e
st
W
a
r
mi
n
g
u
p
5
mi
n
u
t
e
0
W
1
st
S
t
e
p
1
5
0
.
k
g
.
m
.
m
-
1
H
R
<
80
HR
81
-
89
HR
90
-
1
0
0
H
R
>
1
0
0
2
nd
S
t
a
g
e
7
5
0
.
k
g
.
m.
m
-
1
1
2
5
W
3
rd
S
t
a
g
e
9
0
0
.
k
g
.
m.
m
-
1
1
5
0
W
4
th
S
t
a
g
e
1
0
5
0
.
k
g
.
m.m
-
1
1
7
5
W
2
nd
S
t
a
g
e
6
0
0
.
k
g
.
m.
m
-
1
1
0
0
W
2
nd
S
t
a
g
e
4
5
0
.
k
g
.
m.
m
-
1
7
5
W
2
nd
S
t
a
g
e
3
0
0
.
k
g
.
m.
m
-
1
5
0
W
3
rd
S
t
a
g
e
7
5
0
.
k
g
.
m.
m
-
1
1
2
5
W
3
rd
S
t
a
g
e
6
0
0
.
k
g
.
m.
m
-
1
1
0
0
W
3
rd
S
t
a
g
e
4
5
0
.
k
g
.
m.
m
-
1
7
5
W
4
th
S
t
a
g
e
9
0
0
.
k
g
.
m.
m
-
1
1
5
0
W
4
th
S
t
a
g
e
7
5
0
.
k
g
.
m.
m
-
1
1
2
5
W
4
th
S
t
a
g
e
6
0
0
.
k
g
.
m.
m
-
1
1
0
0
W
R
e
st
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N:
2
2
5
2
-
8
8
0
6
I
n
t.
J
.
P
u
b
lic
Hea
lth
Sci.,
Vo
l.
1
0
,
No
.
2
,
J
u
n
e
20
21
:
2
89
–
2
97
292
3.
RE
SU
L
T
S
A
ND
D
I
SCU
SS
I
O
N
T
o
tal
s
u
b
j
ec
ts
w
er
e
4
4
r
ese
ar
ch
s
u
b
j
ec
t.
B
u
t
o
n
l
y
4
0
r
esear
ch
s
u
b
j
ec
ts
w
h
o
ca
n
co
m
p
lete
t
h
e
r
esear
ch
an
d
s
t
ill
m
ee
t
t
h
e
d
ata
p
r
o
ce
s
s
in
g
cr
iter
ia.
T
h
is
is
b
ec
au
s
e
in
th
e
tr
ea
t
m
e
n
t
g
r
o
u
p
th
er
e
w
er
e
t
w
o
s
u
b
j
ec
ts
w
h
o
w
er
e
ex
cl
u
d
ed
b
ec
au
s
e
t
h
eir
to
ta
l
c
h
o
lest
er
o
l,
l
ow
-
dens
i
t
y
l
i
po
pr
o
t
e
i
n
(
L
D
L
)
a
n
d
T
NFα
lev
els
e
x
ce
ed
ed
th
e
s
p
ec
i
f
ied
li
m
it
s
a
n
d
i
n
co
n
tr
o
l
g
r
o
u
p
t
h
er
e
th
er
e
ar
e
t
w
o
s
u
b
j
ec
ts
w
h
o
w
i
th
d
r
e
w
f
r
o
m
t
h
e
r
esear
ch
d
u
e
to
r
ea
s
o
n
s
o
f
g
e
ttin
g
a
s
u
d
d
en
ass
ig
n
m
en
t
lett
er
f
r
o
m
t
h
e
lead
er
s
h
ip
.
T
o
tal
4
0
s
u
b
j
ec
t
w
it
h
a
n
ag
e
r
an
g
e
o
f
3
0
±
4
.
0
3
y
ea
r
s
.
T
h
e
m
ea
n
b
o
d
y
m
a
s
s
i
n
d
ex
(
B
MI
)
o
f
th
e
s
tu
d
y
s
u
b
j
ec
ts
w
as
2
4
.
3
±
2
.
5
3
k
g
/
m
2
,
w
it
h
4
5
% o
f
t
h
e
s
u
b
j
ec
ts
as s
m
o
k
er
s
a
s
s
h
o
w
n
i
n
T
ab
le
1
.
T
h
e
eq
u
iv
alen
ce
te
s
t
b
ased
o
n
th
e
r
es
u
lt
s
o
f
t
h
e
b
aselin
e
t
um
or
n
ec
r
osi
s
f
ac
t
or
a
l
ph
a
(
T
NFα
)
ex
a
m
in
at
io
n
b
et
w
ee
n
t
h
e
tr
ea
t
m
en
t
g
r
o
u
p
an
d
t
h
e
co
n
tr
o
l
g
r
o
u
p
u
s
i
n
g
t
h
e
p
ar
a
m
etr
ic
te
s
t
s
h
o
w
ed
t
h
at
t
h
er
e
w
a
s
n
o
s
i
g
n
i
f
ica
n
t
d
i
f
f
er
e
n
ce
b
et
w
ee
n
t
h
e
tr
ea
t
m
e
n
t
g
r
o
u
p
a
n
d
t
h
e
co
n
tr
o
l
g
r
o
u
p
(
p
=0
.
2
2
0
)
,
m
ea
n
in
g
th
at
t
h
e
T
NFα
lev
el
at
t
h
e
b
eg
i
n
n
i
n
g
o
f
th
e
s
tu
d
y
w
as e
q
u
iv
ale
n
t a
s
s
h
o
w
n
i
n
T
ab
le
2
.
T
ab
le
1
.
Dis
tr
ib
u
tio
n
o
f
s
u
b
j
ec
ts
ac
co
r
d
in
g
to
d
e
m
o
g
r
ap
h
ic
an
d
g
r
o
u
p
ch
ar
ac
ter
is
t
ics
V
a
r
i
a
b
l
e
T
r
e
a
t
me
n
t
n=
20
C
o
n
t
r
o
l
n=
20
T
o
t
a
l
F
r
e
q
u
e
n
c
y
%
F
r
e
q
u
e
n
c
y
%
A
g
e
:
21
-
3
0
y
e
a
r
s
31
-
4
0
y
e
a
r
s
10
10
50
50
10
10
50
50
20
20
B
M
I
(
k
g
/
m
2
)
:
N
o
r
m w
e
i
g
h
t
O
v
e
r
w
e
i
g
h
t
13
7
65
35
15
5
75
25
28
12
S
mo
k
i
n
g
h
a
b
i
t
N
o
n
-
smo
k
e
r
S
mo
k
e
r
13
7
65
38
9
11
45
62
22
18
T
ab
le
2
.
T
NFα
b
eg
in
n
in
g
o
f
t
h
e
s
t
u
d
y
eq
u
i
v
ale
n
ce
i
n
b
o
th
g
r
o
u
p
s
V
a
r
i
a
b
l
e
T
r
e
a
t
me
n
t
C
o
n
t
r
o
l
p
T
N
F
α (p
g
/
ml
)
7
.
0
6
±
1
.
8
5
7
.
6
9
±
3
.
0
8
0
.
2
2
0
3
.
1
.
T
he
ef
f
ec
t
iv
eness
o
f
t
he
pre
-
div
e
t
re
a
t
m
ent
T
o
ass
ess
t
h
e
ef
f
ec
ti
v
e
n
es
s
tr
ea
t
m
e
n
t
g
r
o
u
p
,
a
n
a
n
al
y
s
i
s
was
ca
r
r
ied
o
u
t
o
n
th
e
m
ea
n
T
NFα
at
t
h
e
b
eg
in
n
i
n
g
o
f
t
h
e
s
tu
d
y
a
n
d
T
NFα
a
f
ter
t
h
e
d
i
v
e.
T
NFα
d
i
s
tr
ib
u
tio
n
at
t
h
e
b
eg
in
n
i
n
g
o
f
th
e
s
t
u
d
y
a
n
d
af
ter
d
iv
in
g
in
t
h
e
tr
ea
t
m
e
n
t
g
r
o
u
p
h
ad
a
n
o
r
m
al
d
is
tr
ib
u
tio
n
.
W
h
ile
th
e
T
NFα
d
is
tr
ib
u
tio
n
at
th
e
b
eg
in
n
in
g
o
f
th
e
s
tu
d
y
a
n
d
af
ter
d
iv
i
n
g
i
n
t
h
e
c
o
n
tr
o
l
g
r
o
u
p
h
ad
a
n
ab
n
o
r
m
al
d
is
tr
ib
u
tio
n
.
B
iv
ar
iate
a
n
al
y
s
i
s
o
f
T
NFα
le
v
els
a
t
th
e
b
eg
i
n
n
in
g
o
f
t
h
e
s
t
u
d
y
with
a
f
ter
d
iv
i
n
g
i
n
t
h
e
tr
ea
t
m
en
t
g
r
o
u
p
w
it
h
t
h
e
p
ar
a
m
etr
i
c
test
,
th
er
e
w
as
a
d
ec
r
ea
s
e
in
th
e
m
ea
n
T
NFα
lev
el
a
f
ter
d
iv
i
n
g
co
m
p
ar
ed
to
th
e
b
eg
i
n
n
in
g
o
f
th
e
s
t
u
d
y
,
b
u
t
it
w
a
s
n
o
t
s
tatis
t
icall
y
s
ig
n
i
f
ica
n
t,
o
r
in
o
th
er
w
o
r
d
s
th
e
tr
ea
t
m
e
n
t
p
r
ev
en
ted
an
i
n
cr
ea
s
e
in
T
NFα
l
ev
els
a
f
ter
th
e
d
iv
e.
B
iv
ar
iate
an
al
y
s
i
s
o
f
T
NFα
lev
els
at
t
h
e
b
eg
i
n
n
i
n
g
o
f
th
e
s
tu
d
y
w
it
h
a
f
ter
d
iv
in
g
i
n
th
e
co
n
tr
o
l
g
r
o
u
p
w
it
h
n
o
n
-
p
ar
a
m
etr
ic
test
,
t
h
er
e
w
a
s
a
s
ig
n
i
f
ica
n
t
in
cr
ea
s
e
in
th
e
m
e
an
o
f
T
NFα
le
v
el
af
ter
d
iv
i
n
g
co
m
p
ar
ed
to
th
e
b
eg
in
n
i
n
g
o
f
th
e
s
t
u
d
y
,
o
r
in
o
th
er
w
o
r
d
s
,
d
ec
o
m
p
r
ess
io
n
d
iv
in
g
ca
u
s
ed
an
i
n
cr
ea
s
e
in
T
NFα
le
v
els
as
s
h
o
w
n
in
T
ab
le
3
.
T
ab
le
3
.
Dif
f
er
en
ce
s
in
m
ea
n
T
NFα
b
eg
in
n
i
n
g
o
f
th
e
s
tu
d
y
an
d
af
ter
d
iv
i
n
g
V
a
r
i
a
b
l
e
B
e
g
i
n
n
i
n
g
o
f
st
u
d
y
A
f
t
e
r
d
i
v
i
n
g
9
0
%C
I
o
f
d
i
f
f
e
r
e
n
c
e
p
T
N
F
α t
r
e
a
t
me
n
t
(
p
g
/
ml
)
7
.
0
6
±
1
.
8
5
6
,
7
5
±
1
,
8
1
(
-
0
.
6
8
-
0
.
5
9
)
0
.
0
8
1
5
T
N
F
α c
o
n
t
r
o
l
(
p
g
/
ml
)
7
.
6
9
±
3
.
0
8
7
.
9
4
±
0
.
5
1
(
0
.
1
3
-
0
.
4
6
)
0
.
0
0
5
*
*
N
o
n
p
a
r
a
me
t
r
i
c
t
e
st
T
h
e
d
if
f
er
en
ce
d
elta
m
ea
n
i
n
T
NFα
lev
el
s
af
ter
d
iv
i
n
g
an
d
th
e
b
eg
i
n
n
in
g
o
f
t
h
e
s
t
u
d
y
h
ad
an
ab
n
o
r
m
al
d
is
tr
ib
u
tio
n
.
T
h
e
d
if
f
er
en
ce
m
ea
n
ch
a
n
g
es
i
n
T
NFα
le
v
els
b
et
w
ee
n
t
h
e
tr
ea
t
m
e
n
t
an
d
co
n
tr
o
l
g
r
o
u
p
s
u
s
i
n
g
t
h
e
n
o
n
-
p
ar
a
m
et
r
ic
test
,
f
o
u
n
d
a
s
tat
is
tical
l
y
s
i
g
n
i
f
ica
n
t
d
i
f
f
er
en
ce
i
n
T
NFα
lev
els
b
et
w
ee
n
th
e
tr
ea
t
m
e
n
t g
r
o
u
p
s
a
s
s
h
o
w
n
i
n
T
ab
le
4
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t.
J
.
P
u
b
lic
Hea
lth
Sci.
I
SS
N:
2
2
5
2
-
8806
E
ffect
o
f a
cu
te
s
u
b
ma
xima
l
p
h
ysica
l e
xe
r
cise b
ef
o
r
e
d
ec
o
mp
r
ess
io
n
d
ive
o
n
tu
mo
r
…
(
C
h
ik
ih
)
293
T
ab
le
4
.
T
h
e
d
if
f
er
en
ce
i
n
T
NFα
le
v
els at
b
eg
in
n
i
n
g
a
n
d
af
t
er
d
iv
in
g
in
b
o
th
g
r
o
u
p
s
T
N
F
α
M
e
d
i
a
n
(
M
i
n
-
M
a
x
)
p
ΔT
N
F
α t
r
e
a
t
me
n
t
g
r
o
u
p
(
p
g
/
ml
)
-
0
.
2
4
(
-
2.
7
4
–
1
.
6
7
)
0
.
0
0
1
5
*
ΔT
N
F
α c
o
n
t
r
o
l
g
r
o
u
p
(
p
g
/
ml
)
0
.
4
5
(
-
0
.
9
4
–
0.
95)
*
N
o
n
p
a
r
a
me
t
r
i
c
t
e
st
I
n
a
p
r
eli
m
i
n
ar
y
s
t
u
d
y
co
n
d
u
cted
o
n
m
ice,
it
w
a
s
f
o
u
n
d
th
at
g
i
v
in
g
ac
cli
m
at
io
n
to
m
ice
b
ef
o
r
e
d
ec
o
m
p
r
ess
io
n
d
i
v
in
g
ca
n
r
ed
u
ce
T
NFα
le
v
el
s
[
6
]
.
P
h
y
s
ical
ex
er
cise
w
ith
i
n
ten
s
it
y
o
f
7
0
%
m
a
x
i
m
u
m
h
ea
r
t
r
ate
2
4
h
o
u
r
s
b
ef
o
r
e
d
iv
in
g
in
th
e
tr
ea
t
m
en
t
g
r
o
u
p
,
d
ec
r
ea
s
ed
T
NFα
lev
els
af
ter
a
s
i
n
g
le
d
i
v
e
2
8
0
k
P
a
d
ec
o
m
p
r
ess
io
n
8
0
m
i
n
u
tes
b
o
tto
m
ti
m
e
co
m
p
ar
ed
to
th
e
i
n
itial
ex
p
r
es
s
io
n
o
f
th
e
s
t
u
d
y
,
o
r
in
o
t
h
er
w
o
r
d
s
p
h
y
s
ical
ex
er
ci
s
e
b
ef
o
r
e
d
iv
in
g
ca
n
p
r
ev
e
n
t
t
h
e
in
cr
ea
s
e
i
n
T
NFα
af
ter
d
iv
e.
T
h
is
s
it
u
atio
n
is
r
ei
n
f
o
r
ce
d
b
y
th
e
th
eo
r
y
th
at
P
h
y
s
ica
l
ex
er
c
is
e
w
it
h
in
te
n
s
it
y
,
d
u
r
at
io
n
s
a
n
d
p
lan
n
ed
f
r
eq
u
en
cie
s
,
ca
u
s
e
a
g
o
o
d
ad
ap
tatio
n
r
esp
o
n
s
e
.
I
n
th
eo
r
y
,
a
n
i
n
cr
ea
s
e
i
n
t
h
e
i
m
m
u
n
e
s
y
s
te
m
ca
n
o
cc
u
r
th
r
o
u
g
h
th
e
m
ec
h
an
is
m
o
f
in
cr
ea
s
in
g
t
h
e
n
u
m
b
er
o
f
leu
k
o
c
y
tes
i
n
th
e
cir
cu
lato
r
y
s
y
s
te
m
,
an
in
cr
ea
s
e
in
b
o
d
y
te
m
p
er
atu
r
e
w
h
ich
ca
u
s
e
s
a
h
o
r
m
o
n
al
r
esp
o
n
s
e
tr
o
u
g
h
ep
in
ep
h
r
i
n
e
a
n
d
n
o
r
ep
in
ep
h
r
i
n
e
ac
t
iv
at
io
n
[1
7
]
.
I
n
an
o
th
er
m
ec
h
a
n
i
s
m
,
ae
r
o
b
ic
ex
er
cise
w
ill
in
cr
ea
s
e
o
x
y
g
en
co
n
s
u
m
p
tio
n
1
5
tim
e
s
g
r
ea
ter
t
h
an
n
o
r
m
a
l
in
ce
ll
u
lar
m
e
tab
o
lis
m
.
T
h
is
in
cr
ea
s
e
e
m
er
g
e
s
f
r
o
m
t
h
e
i
n
cr
ea
s
ed
d
e
m
an
d
f
o
r
ade
nos
i
ne
t
r
i
p
hosph
at
e
(
A
T
P
)
d
u
r
in
g
e
x
er
cise,
w
h
i
l
e
th
e
i
n
tr
ac
ell
u
lar
s
u
p
p
l
y
o
f
ade
nosi
ne
t
r
i
ph
o
spha
t
e
(
A
T
P
)
is
v
er
y
li
m
ite
d
.
A
s
a
r
esu
lt
f
r
o
m
a
co
n
ti
n
u
o
u
s
d
e
m
a
n
d
f
o
r
ade
nos
i
ne
t
r
i
pho
spha
t
e
(
A
T
P
)
p
r
o
d
u
ctio
n
th
r
o
u
g
h
o
x
id
ati
v
e
p
r
o
ce
s
s
es,
Kr
eb
s
-
c
y
cle
a
n
d
elec
tr
o
n
tr
an
s
f
er
th
e
co
n
s
u
m
p
tio
n
o
f
o
x
y
g
e
n
i
n
th
e
r
esp
ir
ato
r
y
ch
a
in
i
n
cr
ea
s
e
d
,
an
d
its
p
r
o
d
u
ce
th
e
f
o
r
m
ati
o
n
o
f
f
r
ee
r
ad
icals.
Fre
e
r
ad
ical
lik
e
r
ea
ctiv
e
o
x
y
g
e
n
s
p
ec
ies
(
R
OS
)
is
i
n
cr
ea
s
e;
it
ca
u
s
ed
b
y
a
n
i
m
p
er
f
e
ct
elec
tr
o
n
tr
an
s
f
er
p
r
o
ce
s
s
ca
u
s
es
t
h
e
r
ed
u
ctio
n
o
f
o
x
y
g
e
n
m
o
lec
u
le
s
to
p
r
o
d
u
ce
s
u
p
er
o
x
id
e
io
n
s
.
R
ea
cti
v
e
o
x
y
g
e
n
s
p
ec
ies
(
R
OS
)
is
a
ls
o
i
n
f
lu
e
n
ce
d
b
y
t
h
e
au
to
-
o
x
id
atio
n
o
f
m
y
o
g
lo
b
in
a
n
d
h
e
m
o
g
lo
b
i
n
d
u
r
i
n
g
e
x
er
cise.
Su
p
er
o
x
id
e
io
n
is
f
o
r
m
ed
f
r
o
m
o
x
y
h
e
m
o
g
lo
b
in
an
d
o
x
y
m
y
o
g
lo
b
i
n
b
ase
d
o
n
m
etal
ca
tal
y
s
is
r
ea
ctio
n
s
.
T
h
e
s
u
p
er
o
x
id
e
io
n
p
r
o
d
u
ce
d
in
lar
g
e
q
u
an
t
ities
,
ce
ll
m
a
k
e
an
ad
ap
ti
v
e
r
esp
o
n
s
e
b
y
i
n
cr
ea
s
i
n
g
th
e
a
m
o
u
n
t
o
f
t
h
e
en
z
y
m
e
s
u
p
er
o
x
id
e
d
is
m
u
tase
(
SOD
)
s
o
th
at
t
h
e
s
u
p
er
o
x
id
e
io
n
is
c
o
n
v
er
ted
i
n
to
h
y
d
r
o
g
e
n
p
er
o
x
id
e
[1
8
]
.
Hy
d
r
o
g
en
p
er
o
x
id
e
ac
ts
as
a
2
n
d
m
e
s
s
e
n
g
er
w
h
o
ca
n
p
r
o
v
id
e
a
p
o
s
itiv
e
r
esp
o
n
s
e
as
w
ell
as
a
n
eg
a
tiv
e
r
esp
o
n
s
e
f
r
o
m
th
e
b
o
d
y
.
I
n
n
o
r
m
al
le
v
els
le
s
s
th
a
n
0
.
4
µm
o
l
h
y
d
r
o
g
e
n
p
er
o
x
id
e
ac
ts
as
a
2
nd
m
e
s
s
e
n
g
e
r
to
NF
-
κβ
an
d
its
r
eg
u
late
s
t
h
e
f
o
r
m
a
tio
n
a
n
d
ac
tiv
atio
n
o
f
a
n
ti
-
o
x
id
an
t
en
z
y
m
es
s
u
c
h
as
s
u
p
er
o
x
id
e
d
is
m
u
tase
(
SO
D
)
,
zin
c
s
u
p
er
o
x
id
e
d
is
m
u
tase
(
Zn
-
SO
D
)
,
f
er
r
iti
n
h
ea
v
y
c
h
ai
n
(
FH
C
)
,
C
atala
s
e,
th
io
r
ed
o
x
i
n
-
1
(
T
r
x
-
1
)
,
t
h
io
r
ed
o
x
in
-
2
(
Trx
-
2
)
,
g
l
u
tat
h
io
n
e
p
er
o
x
id
as
e
(
GP
X
)
w
h
ich
p
r
o
v
id
e
a
p
r
o
t
ec
tiv
e
e
f
f
ec
t
a
g
ain
s
t
o
x
id
ativ
e
s
tr
ess
th
r
o
u
g
h
t
h
e
m
ec
h
a
n
i
s
m
o
f
in
cr
ea
s
i
n
g
en
z
y
m
atic
r
ea
ctio
n
s
in
th
e
m
etab
o
lis
m
o
f
r
ea
cti
v
e
o
x
y
g
e
n
s
p
ec
ie
s
(
R
OS
)
.
H
y
d
r
o
g
en
p
er
o
x
id
e
ac
ts
as
a
r
eg
u
lato
r
o
f
th
e
a
u
to
p
h
a
g
y
m
ec
h
a
n
is
m
,
i
m
p
r
o
v
es
t
h
e
i
m
m
u
n
e
s
y
s
te
m
,
s
u
p
p
r
ess
es
t
h
e
in
cr
ea
s
e
i
n
i
n
f
la
m
m
ato
r
y
f
ac
t
o
r
s
,
o
n
e
o
f
w
h
ic
h
i
s
T
NF
-
α
b
y
in
cr
ea
s
in
g
t
h
e
ac
ti
v
it
y
o
f
t
u
m
o
r
n
ec
r
o
s
is
f
ac
to
r
r
ec
ep
to
r
an
tig
en
(
T
NFR
A
)
[
1
4
]
,
[
1
9
]
,
[
20
]
.
T
h
e
ac
tiv
atio
n
tu
m
o
r
n
ec
r
o
s
is
f
ac
to
r
r
ec
ep
to
r
an
tig
e
n
(
T
NFR
A
)
p
r
o
v
id
e
b
y
t
u
m
o
r
n
ec
r
o
s
i
s
f
ac
to
r
r
ec
ep
to
r
-
2
(
T
NFR
2
)
p
ath
w
a
y
t
h
r
o
u
g
h
t
h
e
m
ito
g
e
n
-
ac
ti
v
ated
p
r
o
tein
k
i
n
as
e
(
MA
P
K
)
p
ath
w
a
y
to
s
ti
m
u
la
te
g
e
n
e
f
o
r
m
at
io
n
,
i
n
cr
ea
s
ed
ce
ll
p
r
o
lif
er
atio
n
,
i
n
cr
ea
s
ed
ce
ll
d
i
f
f
er
e
n
tiatio
n
th
er
eb
y
i
n
cr
ea
s
i
n
g
t
h
e
r
esp
o
n
s
e
o
f
ce
ll r
esis
ta
n
ce
to
d
ec
o
m
p
r
ess
io
n
d
i
v
e
[
1
2
]
,
[
2
1
]
.
I
n
th
e
s
tu
d
y
r
es
u
lt,
t
h
e
r
ed
u
cti
o
n
in
T
NFα
lev
el
s
a
f
ter
d
iv
e
b
ased
o
n
th
e
li
ter
a
tu
r
e
i
s
d
u
e
to
in
cr
ea
s
ed
tu
m
o
r
n
ec
r
o
s
is
f
ac
to
r
r
ec
ep
to
r
a
n
tig
e
n
(
T
NFR
A
)
ac
tiv
it
y
[
1
4
]
.
P
h
y
s
ical
e
x
er
cise
also
r
esu
lt
s
in
i
n
cr
ea
s
ed
p
las
m
a
of
sol
ubl
e
t
um
or
nec
r
osi
s f
a
ct
o
r
-
α re
ce
pt
o
r
(
s
T
N
F
-
αR
)
le
v
el
s
w
h
ic
h
o
cc
u
r
s
s
i
n
ce
th
r
ee
h
o
u
r
s
a
f
ter
p
h
y
s
ical
ex
er
ci
s
e,
r
ea
ch
es
a
p
ea
k
w
it
h
i
n
2
4
h
o
u
r
s
a
n
d
ca
n
g
r
ad
u
all
y
d
is
ap
p
ea
r
u
p
to
f
o
u
r
d
ay
s
a
f
ter
ex
er
cise,
th
is
h
u
m
an
sol
ubl
e
t
um
or
nec
r
o
si
s
f
ac
t
o
r
-
α
r
ec
ept
o
r
(
s
T
NF
-
aR
)
w
h
ic
h
m
a
in
ta
in
s
an
d
s
u
p
p
r
ess
es
t
h
e
a
m
o
u
n
t
o
f
T
NFα
i
n
p
las
m
a
to
r
em
a
i
n
i
n
a
n
o
r
m
al
r
an
g
e
s
tate
an
d
also
g
i
v
es
t
h
e
ef
f
ec
t
o
f
g
r
o
w
t
h
an
d
in
cr
ea
s
ed
ce
ll
s
tr
en
g
th
[
1
4
]
,
[
2
1
]
,
[
2
2
]
.
A
n
o
th
er
m
ec
h
a
n
is
m
,
th
e
r
e
s
p
o
n
s
e
a
f
ter
ex
er
ci
s
e
,
th
e
p
r
ess
u
r
e
in
t
h
e
ao
r
ta
in
cr
ea
s
es
d
u
e
to
an
i
n
cr
ea
s
e
in
h
ea
r
t
r
ate
an
d
s
y
s
to
lic
p
r
ess
u
r
e.
I
n
cr
ea
s
ed
p
r
ess
u
r
e
in
th
e
ao
r
ta
r
esu
lt
s
i
n
an
e
x
tr
ao
r
d
in
ar
y
s
tr
ain
o
n
e
n
d
o
th
elial
ce
lls
,
b
io
m
ar
k
er
s
o
f
en
d
o
t
h
elial
ce
l
l
v
a
s
c
u
lar
,
in
cl
u
d
in
g
i
n
cr
ea
s
ed
en
d
o
th
elial
n
i
tr
ic
o
x
id
e
s
y
n
t
h
ase
(
eNO
S),
e
n
d
o
th
elial
-
d
er
iv
ed
h
y
p
er
p
o
lar
izatio
n
f
ac
to
r
s
y
n
th
a
s
e
(
E
DH
F)
an
d
c
y
t
ochr
om
es
P45
0
(
C
YP
4
5
0
)
,
as
w
ell
as
i
n
cr
ea
s
ed
r
elea
s
e
o
f
r
ea
ctiv
e
o
x
y
g
en
s
p
ec
ie
s
(
R
OS)
f
o
r
m
s
s
u
ch
h
y
d
r
o
g
e
n
p
er
o
x
id
e.
H
y
d
r
o
g
e
n
p
er
o
x
id
e
(
H
2
O
2
)
is
a
s
ig
n
al
to
ac
tiv
ate
e
x
p
r
ess
io
n
o
f
ad
h
esi
o
n
m
o
lecu
le
s
,
s
u
c
h
as
i
n
ter
ce
llu
lar
ad
h
esio
n
m
o
l
ec
u
les
(
I
C
A
M)
,
s
elec
t
in
,
a
n
d
ch
e
m
o
tactic
p
r
o
tein
m
o
n
o
c
y
tes
-
1
(
M
C
P
-
1
)
,
th
i
s
in
d
ir
ec
tl
y
p
r
ev
e
n
t
s
v
aso
co
n
s
tr
i
ctio
n
at
d
ep
th
d
u
e
to
d
ec
o
m
p
r
ess
io
n
d
i
v
e
[2
3
]
.
I
n
th
e
co
n
tr
o
l
g
r
o
u
p
,
th
er
e
was
an
in
cr
ea
s
e
i
n
t
h
e
m
ea
n
le
v
els
o
f
T
NFα
a
f
ter
d
ec
o
m
p
r
e
s
s
io
n
d
iv
e
co
m
p
ar
ed
to
t
h
e
b
e
g
in
n
i
n
g
o
f
t
h
e
d
i
v
e
w
h
ic
h
ca
u
s
ed
a
s
i
g
n
i
f
ica
n
t
d
if
f
er
en
ce
.
T
h
i
s
h
a
p
p
en
ed
b
ec
au
s
e
i
n
d
iv
in
g
ac
tiv
it
y
,
t
h
e
d
iv
er
b
r
ea
t
h
es
b
y
u
s
in
g
th
e
p
r
ess
u
r
ized
air
an
d
w
ith
a
n
in
cr
ea
s
e
d
en
v
ir
o
n
m
e
n
tal
p
r
ess
u
r
e,
th
is
ca
u
s
i
n
g
an
i
n
cr
ea
s
e
in
p
ar
tial
p
r
ess
u
r
e
o
f
g
a
s
f
r
o
m
t
h
e
b
r
ea
th
m
ed
ia
in
t
h
e
b
o
d
y
.
I
t
is
c
alled
as
h
y
p
er
o
x
ia
-
in
d
u
ce
d
v
a
s
o
co
n
s
tr
ic
tio
n
i
n
d
ep
th
.
I
n
t
h
is
s
tate
t
h
e
in
cr
ea
s
e
of
r
ea
ctiv
e
o
x
y
g
en
(
R
OS
)
s
u
c
h
as
s
u
p
er
o
x
id
e
io
n
s
an
d
h
y
d
r
o
g
en
p
er
o
x
id
es
tr
ig
g
er
th
e
o
cc
u
r
r
en
ce
o
f
o
x
id
ativ
e
s
tr
es
s
[
5
]
.
S
u
p
er
o
x
id
e
io
n
an
d
h
y
d
r
o
g
e
n
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N:
2
2
5
2
-
8
8
0
6
I
n
t.
J
.
P
u
b
lic
Hea
lth
Sci.,
Vo
l.
1
0
,
No
.
2
,
J
u
n
e
20
21
:
2
89
–
2
97
294
p
er
o
x
id
e
io
n
s
ac
t
as
s
ec
o
n
d
m
e
s
s
e
n
g
er
s
v
ia
r
ed
o
x
-
s
en
s
i
tiv
e
p
ath
w
a
y
s
.
T
h
ese
r
ed
o
x
-
s
en
s
iti
v
e
p
ath
w
a
y
s
in
cl
u
d
e
r
ec
ep
to
r
an
d
n
o
n
-
r
e
ce
p
to
r
ty
r
o
s
i
n
e
k
i
n
ase,
t
y
r
o
s
in
e
p
h
o
s
p
h
atase,
s
er
i
n
e
t
h
r
eo
n
in
e
k
i
n
ase,
a
n
d
tr
an
s
cr
ip
tio
n
f
ac
to
r
s
s
u
c
h
as
ac
tiv
ato
r
p
r
o
tein
(
AP
-
1
)
,
n
u
cl
ea
r
f
ac
to
r
k
ap
p
a
-
β
(
NF
-
κB
)
,
tu
m
o
r
p
r
o
tein
P
5
3
(
p53
)
,
n
u
clea
r
f
ac
to
r
o
f
ac
ti
v
ated
T
-
ce
lls
(
NF
A
T
)
,
h
y
p
o
x
i
a
-
i
n
d
u
cib
le
f
ac
to
r
s
(
HI
F
-
1
)
[
2
3
]
.
T
u
m
o
r
n
ec
r
o
s
is
f
ac
to
r
alp
h
a
(
T
NFα
)
also
p
la
y
s
a
r
o
le
in
ca
u
s
i
n
g
en
d
o
th
e
lial
d
y
s
f
u
n
ctio
n
,
th
r
o
u
g
h
t
h
e
m
ec
h
an
is
m
o
f
in
h
ib
itio
n
o
f
n
itric
o
x
id
e
(
NO
)
s
y
n
th
e
s
is
th
r
o
u
g
h
t
h
e
ac
ti
v
atio
n
b
ar
r
ier
o
f
th
e
ar
g
i
n
i
n
o
s
u
cc
in
a
te
s
y
n
t
etase
en
z
y
m
e
th
a
t
in
h
ib
its
ci
tr
u
li
n
e
a
n
d
L
-
ar
g
i
n
e
m
etab
o
lis
m
t
h
er
eb
y
r
ed
u
ci
n
g
th
e
p
r
o
d
u
ctio
n
o
f
en
d
o
th
elial
ni
t
r
i
c
oxi
de
sy
nt
has
e
(
eNOS
)
[8
]
,
[
2
5
]
.
T
h
is
s
tu
d
y
r
es
u
lt
al
s
o
co
n
s
i
s
t
en
t
w
it
h
p
r
eli
m
i
n
ar
y
s
tu
d
ie
s
w
it
h
t
h
e
o
b
j
ec
t
o
f
r
esear
ch
i
n
r
ats,
w
h
i
ch
f
o
u
n
d
an
in
cr
ea
s
e
i
n
T
NFα
lev
el
s
d
u
e
to
d
ec
o
m
p
r
es
s
io
n
d
iv
i
n
g
a
n
d
also
a
n
o
th
er
in
f
la
m
m
a
to
r
y
c
y
to
k
i
n
e
[7
]
,
[
2
6
]
.
I
n
th
i
s
co
n
tr
o
l
g
r
o
u
p
,
also
in
ac
co
r
d
an
ce
w
ith
Sp
is
n
i
e
t
a
l
.
w
h
o
s
tated
th
at
th
e
d
ec
o
-
s
to
p
s
tr
ate
g
y
p
r
o
v
id
es
an
ad
v
a
n
ta
g
e
i
n
ter
m
s
o
f
i
n
h
ib
itin
g
g
as
e
x
p
an
s
io
n
,
b
u
t
o
t
h
er
th
i
n
g
s
s
h
o
w
th
at
th
e
d
ec
o
-
s
to
p
p
r
o
ce
d
u
r
e
ca
n
n
o
t
g
u
ar
a
n
tee
th
a
t
th
e
d
i
v
er
is
f
r
ee
f
r
o
m
d
ec
o
m
p
r
es
s
io
n
s
ic
k
n
es
s
(
DC
S)
,
t
h
is
i
s
b
ec
au
s
e
t
h
er
e
i
s
s
t
ill
a
n
i
n
cr
e
ase
i
n
i
n
f
la
m
m
at
io
n
b
io
m
ar
k
er
s
ec
r
etio
n
,
t
h
at
ca
u
s
e
s
v
asc
u
lar
d
a
m
a
g
e,
a
n
d
it
s
ee
n
f
r
o
m
b
io
m
ar
k
er
s
o
f
C
-
C
m
ot
i
f
che
m
ok
i
ne
l
i
g
and
-
2
(
C
C
L
2
)
an
d
C
-
C
m
o
ti
f
c
h
e
m
o
k
i
n
e
li
g
a
n
d
-
5
(
C
C
L
5
)
[2
7
]
.
3
.
2
.
E
f
f
ec
t
o
f
s
ub
m
a
x
i
m
a
l i
nte
ns
i
t
y
ex
er
cise o
n T
NF
α
e
x
pre
s
s
i
o
n
I
n
t
h
is
s
ec
tio
n
,
th
e
d
is
c
u
s
s
io
n
co
n
ce
r
n
s
T
NF
α
ex
p
r
es
s
io
n
2
4
h
o
u
r
s
p
o
s
t
-
e
x
er
cise
i
n
b
o
th
s
t
u
d
y
g
r
o
u
p
s
.
B
iv
ar
iate
a
n
al
y
s
i
s
o
f
T
NFα
ex
p
r
ess
io
n
at
th
e
b
e
g
i
n
n
in
g
o
f
th
e
s
t
u
d
y
w
it
h
T
NFα
b
ef
o
r
e
d
iv
in
g
i
n
th
e
tr
ea
t
m
e
n
t
g
r
o
u
p
an
a
l
y
s
e
u
s
i
n
g
p
ar
a
m
etr
ic
te
s
t.
Me
a
n
w
h
ile,
i
n
t
h
e
co
n
tr
o
l g
r
o
u
p
,
t
h
e
d
i
s
tr
ib
u
tio
n
o
f
T
NF
α
d
ata
w
a
s
n
o
t n
o
r
m
al,
s
o
a
n
o
n
-
p
ar
am
etr
ic
b
iv
ar
iate
a
n
al
y
s
i
s
w
as c
ar
r
ied
o
u
t
as sh
o
w
n
i
n
T
ab
le
5.
T
ab
le
5
.
E
f
f
ec
t o
f
s
u
b
m
a
x
i
m
al
ex
er
ci
s
e
o
n
T
NFα
le
v
els b
ef
o
r
e
d
iv
in
g
V
a
r
i
a
b
l
e
B
e
g
i
n
n
i
n
g
o
f
st
u
d
y
B
e
f
o
r
e
d
i
v
i
n
g
9
0
%C
I
o
f
d
i
f
f
e
r
e
n
c
e
p
T
N
F
α t
r
e
a
t
me
n
t
(
p
g
/
ml
)
7
.
0
6
±
1
.
8
5
7
.
4
6
±
2
.
0
7
(
-
0
.
6
8
-
0
.
5
9
)
0
.
0
6
6
T
N
F
α c
o
n
t
r
o
l
(
p
g
/
ml
)
7
.
6
9
±
3
.
0
8
7
.
6
3
±
3
.
0
1
(
-
1
.
1
2
-
0
.
2
4
)
0
.
2
6
1
*
*
N
o
n
p
a
r
a
me
t
r
i
c
t
e
st
T
h
e
d
if
f
er
en
ce
d
elta
m
ea
n
in
T
NFα
lev
els
b
e
f
o
r
e
d
iv
i
n
g
an
d
th
e
b
eg
in
n
i
n
g
o
f
t
h
e
s
t
u
d
y
h
ad
a
n
ab
n
o
r
m
al
d
is
tr
ib
u
tio
n
.
T
h
e
d
if
f
er
en
ce
m
ea
n
ch
a
n
g
es
i
n
T
NFα
le
v
els
b
et
w
ee
n
t
h
e
tr
ea
t
m
e
n
t
an
d
co
n
tr
o
l
g
r
o
u
p
s
u
s
i
n
g
t
h
e
n
o
n
-
p
ar
a
m
et
r
ic
test
,
f
o
u
n
d
a
s
tat
is
tical
l
y
s
i
g
n
i
f
ica
n
t
d
i
f
f
er
en
ce
i
n
T
NFα
lev
els
b
et
w
ee
n
th
e
tr
ea
t
m
e
n
t a
n
d
co
n
tr
o
l g
r
o
u
p
s
a
s
s
h
o
w
n
i
n
T
ab
le
6
.
T
ab
le
6
.
T
h
e
d
if
f
er
en
ce
i
n
m
e
an
ch
a
n
g
e
s
i
n
T
NFα
lev
el
s
b
ef
o
r
e
d
iv
in
g
tr
ea
t
m
e
n
t a
n
d
co
n
tr
o
l g
r
o
u
p
T
N
F
α
M
e
d
i
a
n
(
M
i
n
-
M
a
x
)
p
ΔT
N
F
α t
r
e
a
t
me
n
t
g
r
o
u
p
(
p
g
/
ml
)
-
0
.
2
4
(
-
2
.
7
4
–
1
.
67)
0
.
0
0
1
5
*
ΔT
N
F
α c
o
n
t
r
o
l
g
r
o
u
p
(
p
g
/
ml
)
0
.
4
5
(
-
0
.
9
4
–
0.
9
5
)
*
N
o
n
p
a
r
a
me
t
r
i
c
t
e
st
A
c
u
te
s
u
b
m
ax
i
m
al
p
h
y
s
ical
e
x
er
cise
a
f
f
ec
ts
T
NFα
le
v
els
2
4
h
o
u
r
s
af
ter
ex
er
cise,
t
h
is
is
illu
s
tr
ated
b
y
an
i
n
cr
ea
s
e
in
m
ea
n
T
NFα
lev
els
2
4
h
o
u
r
s
a
f
ter
p
h
y
s
ical
ex
er
cise
b
u
t
it
i
s
n
o
t
s
tat
is
tical
l
y
s
ig
n
i
f
ica
n
t.
T
h
i
s
s
itu
a
tio
n
is
i
n
ac
co
r
d
an
ce
w
it
h
th
e
liter
a
t
u
r
e
w
h
ic
h
s
a
y
s
,
p
h
y
s
ical
ex
er
ci
s
e
w
ill
i
n
cr
ea
s
e
T
NFα
p
las
m
a
alo
n
g
w
it
h
a
n
i
n
cr
ea
s
e
i
n
s
T
NF
-
α
r
ec
ep
to
r
ac
tiv
it
y
s
tar
tin
g
t
h
r
e
e
h
o
u
r
s
a
f
ter
e
x
er
cise,
i
n
d
u
c
ed
b
y
a
p
r
o
ce
s
s
o
f
in
cr
ea
s
i
n
g
ti
s
s
u
e
l
y
m
p
h
o
c
y
te
m
o
b
il
izatio
n
i
n
r
esp
o
n
s
e
to
in
cr
ea
s
ed
k
er
ati
n
k
i
n
ase
d
u
e
t
o
p
h
y
s
ical
ex
er
ci
s
e
[2
8
]
,
[
2
9
]
.
A
cc
o
r
d
in
g
to
th
e
t
h
eo
r
y
; p
h
y
s
ical
ex
er
ci
s
e
w
it
h
g
o
o
d
d
o
s
e,
w
h
ic
h
m
ea
n
i
n
t
h
is
ca
s
e
th
e
ap
p
r
o
p
r
iate
in
te
n
s
it
y
,
d
u
r
atio
n
a
n
d
f
r
eq
u
e
n
c
y
g
i
v
e
a
p
o
s
iti
v
e
ad
ap
tatio
n
r
esp
o
n
s
e
to
th
e
b
o
d
y
.
T
h
e
h
ig
h
e
s
t
s
u
p
er
o
x
id
e
d
is
m
u
tase
(
SOD
)
en
z
y
m
e
ac
t
iv
atio
n
i
s
6
0
m
i
n
u
tes
p
o
s
t
-
ex
er
cise
w
h
ic
h
r
ea
ch
es
1
0
0
0
0
±
2
8
2
8
an
d
r
etu
r
n
s
to
n
o
r
m
al
le
v
el
s
7
2
h
o
u
r
s
a
f
ter
t
r
ain
in
g
[
1
4
]
.
A
l
s
o
in
t
h
eo
r
y
,
t
h
is
h
ap
p
en
d
u
e
to
an
i
n
cr
ea
s
e
in
sol
ubl
e
t
um
or
nec
r
o
si
s
f
ac
t
or
-
α
r
ec
ep
t
or
(
s
T
NF
-
αR
)
i
n
p
las
m
a,
w
h
ic
h
i
n
t
h
eo
r
y
i
n
cr
ea
s
e
s
s
in
ce
th
r
ee
h
o
u
r
s
p
o
s
t
-
e
x
er
cise
an
d
r
ea
ch
es
a
p
ea
k
o
f
2
4
h
o
u
r
s
p
o
s
t
-
ex
er
ci
s
e,
an
d
p
er
s
is
ts
f
o
r
u
p
to
f
o
u
r
d
ay
s
p
o
s
t
-
e
x
er
cise
[
1
4
]
,
[
21
]
.
T
h
is
is
also
in
ac
co
r
d
an
ce
w
it
h
t
h
e
r
e
s
ea
r
ch
o
f
Ha
m
ad
a
et
a
l
.
w
h
o
e
x
p
lain
ed
t
h
at
th
e
ac
u
te
ex
er
ci
s
e
ca
n
s
ti
m
u
late
t
h
e
m
o
b
il
izatio
n
o
f
h
e
m
ato
p
o
ietic
s
te
m
ce
l
ls
f
r
o
m
b
o
n
e
m
ar
r
o
w
an
d
o
ld
i
m
m
u
n
e
ce
lls
f
r
o
m
p
er
ip
h
er
al
tis
s
u
e
s
to
th
e
cir
c
u
latio
n
.
I
n
ad
d
itio
n
,
e
x
er
cise
i
n
cr
ea
s
es
th
e
ac
tio
n
o
f
n
o
r
ad
r
en
alin
e
w
h
ich
is
r
esp
o
n
s
ib
le
f
o
r
th
e
ef
f
ec
t
o
f
ac
u
te
e
x
er
cise
o
n
l
y
m
p
h
o
c
y
te
c
h
a
n
g
e
s
,
i
n
clu
d
i
n
g
n
at
u
r
al
k
il
ler
(
NK)
-
ce
l
l
a
n
d
T
-
ce
ll
ac
tiv
it
y
a
n
d
i
n
cr
ea
s
ed
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t.
J
.
P
u
b
lic
Hea
lth
Sci.
I
SS
N:
2
2
5
2
-
8806
E
ffect
o
f a
cu
te
s
u
b
ma
xima
l
p
h
ysica
l e
xe
r
cise b
ef
o
r
e
d
ec
o
mp
r
ess
io
n
d
ive
o
n
tu
mo
r
…
(
C
h
ik
ih
)
295
ca
tech
o
la
m
in
e
g
r
o
w
t
h
-
m
ed
iat
ed
h
o
r
m
o
n
e
s
to
ca
r
r
y
o
u
t
n
e
u
tr
o
p
h
il
c
h
a
n
g
e
s
a
n
d
i
n
cr
ea
s
e
in
T
NF
-
α
m
R
N
A
[
30
]
.
I
n
th
is
s
t
u
d
y
,
w
e
d
id
n
o
t
ex
a
m
i
n
e
s
o
lu
b
le
tu
m
o
r
n
ec
r
o
s
is
f
ac
to
r
-
α
r
ec
ep
to
r
(
s
T
NF
-
αR
)
an
d
t
u
m
o
r
n
ec
r
o
s
is
f
ac
to
r
alp
h
a
-
m
es
s
en
g
er
R
N
A
(
T
NF
-
α
m
R
N
A
)
b
io
m
ar
k
er
s
,
s
o
w
e
ca
n
n
o
t
c
o
n
clu
d
e
th
e
ca
u
s
e
.
Me
an
w
h
ile
i
n
th
e
co
n
tr
o
l g
r
o
u
p
th
er
e
w
a
s
n
o
ch
a
n
g
e
in
T
NFα
ex
p
r
ess
io
n
.
3
.
3
.
E
f
f
ec
t
o
f
s
ub
j
ec
t
cha
ra
ct
er
is
t
ics o
n T
NF
α
e
x
pres
s
io
n a
t
t
he
beg
inn
i
ng
o
f
s
t
ud
y
T
h
is
s
t
u
d
y
a
ls
o
w
a
n
ted
to
s
ee
,
th
e
e
f
f
ec
t
o
f
T
NFα
e
x
p
r
ess
i
o
n
at
t
h
e
b
e
g
in
n
i
n
g
o
f
th
e
s
t
u
d
y
o
n
t
h
e
ch
ar
ac
ter
is
tic
s
o
f
t
h
e
r
esear
c
h
s
u
b
j
ec
ts
co
n
s
is
t
in
g
o
f
a
g
e,
b
o
d
y
m
a
s
s
in
d
e
x
(
B
M
I)
an
d
s
m
o
k
in
g
h
ab
it
s
.
C
h
ar
ac
ter
is
tics
o
f
r
e
s
ea
r
ch
s
u
b
j
ec
ts
w
er
e
m
ad
e
b
ased
o
n
d
ich
o
to
m
o
u
s
ca
te
g
o
r
ies.
B
o
d
y
m
as
s
in
d
e
x
(
B
MI
)
g
r
o
u
p
ed
in
to
n
o
r
m
w
ei
g
h
t
an
d
o
v
er
w
ei
g
h
t,
s
m
o
k
i
n
g
h
ab
its
a
r
e
m
ad
e
i
n
to
s
m
o
k
er
s
an
d
n
o
n
-
s
m
o
k
er
s
as
s
h
o
w
n
in
T
ab
le
7
.
T
ab
le
7
.
E
f
f
ec
t o
f
s
u
b
j
ec
t c
h
ar
ac
ter
is
tics
o
n
T
NFα
e
x
p
r
ess
io
n
at
th
e
b
eg
in
n
i
n
g
o
f
s
t
u
d
y
V
a
r
i
a
b
l
e
T
N
F
α (n
=
4
0
)
9
0
%
C
I
o
f
d
i
f
f
e
r
e
n
c
e
p
A
g
e
:
1.
21
-
3
0
y
e
a
r
s
2.
31
-
4
0
y
e
a
r
s
7
.
0
8
±
2
.
8
3
p
g
/
ml
7
.
6
8
±
2
.
2
2
p
g
/
ml
(
-
1
.
9
5
-
0
.
7
6
)
0
.
2
3
S
m
o
k
i
n
g
h
a
b
i
t
s
:
1.
N
o
n
-
smo
k
e
r
s
2.
S
mo
k
e
r
s
7
.
1
4
±
3
.
0
3
p
g
/
ml
7
.
6
7
±
1
.
7
8
p
g
/
ml
(
-
1
.
9
0
-
0
.
8
3
)
0
.
2
5
7
B
M
I
:
1.
N
o
r
m w
e
i
g
h
t
2.
O
v
e
r
w
e
i
g
h
t
6
.
9
4
±
2
.
6
4
p
g
/
ml
8
.
5
4
±
1
.
8
4
p
g
/
ml
(
-
3
.
0
6
-
0
.
1
3
)
0
.
0
3
7
T
NFα
at
th
e
b
eg
in
n
i
n
g
o
f
t
h
e
s
tu
d
y
w
it
h
s
m
o
k
in
g
s
ta
tu
s
,
th
e
r
e
w
as
n
o
s
i
g
n
i
f
ican
t d
if
f
er
en
c
e
b
et
w
ee
n
n
o
n
-
s
m
o
k
er
s
a
n
d
s
m
o
k
er
s
,
w
h
ic
h
m
ea
n
t
T
NFα
lev
e
ls
wer
e
n
o
t
a
f
f
ec
ted
b
y
s
m
o
k
i
n
g
h
ab
its
.
A
s
f
o
r
t
h
e
class
i
f
icatio
n
o
f
B
o
d
y
Ma
s
s
I
n
d
ex
,
th
e
i
n
itial T
NFα
e
x
p
r
ess
i
o
n
o
f
th
e
s
tu
d
y
w
it
h
n
o
r
m
w
ei
g
h
t a
n
d
o
v
er
w
ei
g
h
t
b
o
d
y
m
a
s
s
i
n
d
ex
(
B
MI
)
th
er
e
w
a
s
a
s
ig
n
i
f
ica
n
t
d
if
f
er
en
ce
,
o
r
in
o
th
er
w
o
r
d
s
T
NFα
lev
el
s
m
a
y
i
n
f
l
u
en
ce
d
b
y
b
o
d
y
m
a
s
s
in
d
e
x
(
B
MI
)
.
I
t
ap
p
ea
r
s
th
at
s
u
b
j
ec
ts
w
h
o
ar
e
o
v
er
w
eig
h
t
h
av
e
h
ig
h
er
lev
el
s
o
f
T
NFα
th
an
n
o
r
m
w
ei
g
h
t.
B
u
t
o
v
er
w
e
ig
h
t
h
er
e
is
n
o
t
r
e
lated
to
th
e
a
m
o
u
n
t
o
f
ch
o
lest
er
o
l
in
th
e
b
lo
o
d
,
b
u
t
r
elate
d
to
th
e
an
th
r
o
p
o
m
etr
y
o
f
th
e
s
u
b
j
e
ct'
s
b
o
d
y
w
i
th
m
u
s
c
u
lar
o
r
f
at
m
a
s
s
.
T
h
is
i
s
i
n
l
in
e
w
it
h
r
esear
c
h
w
h
ic
h
s
ta
tes
t
h
at
T
NFα
w
il
l
in
c
r
ea
s
e
w
i
th
t
h
e
o
cc
u
r
r
en
ce
o
f
b
o
d
y
m
ass
i
n
d
ex
(
B
MI
)
,
th
is
is
d
u
e
to
ch
an
g
es
i
n
ce
ll
u
lar
m
etab
o
lic
p
r
o
ce
s
s
es
d
u
e
to
b
ein
g
o
v
er
w
ei
g
h
t,
an
d
it
ca
n
b
e
ca
u
s
ed
b
y
m
u
s
cu
lar
m
ass
o
r
b
o
d
y
co
m
p
o
s
itio
n
an
d
lep
tin
[3
1
]
.
Oth
er
s
tu
d
ies
s
u
g
g
est
t
h
at,
T
NFα
b
io
m
a
r
k
er
co
n
ce
n
tr
atio
n
i
s
n
o
t
o
n
l
y
r
elate
d
to
b
o
d
y
co
m
p
o
s
i
tio
n
b
u
t
m
a
y
d
ep
en
d
o
n
in
d
iv
id
u
al
v
ar
iatio
n
in
ad
i
p
o
cy
to
k
in
e
s
an
d
m
y
o
s
i
n
s
ec
r
etio
n
as
a
r
esu
lt
o
f
v
ar
io
u
s
g
e
n
etic
f
ac
to
r
s
[3
2
]
.
Ho
w
e
v
er
,
i
n
t
h
is
s
t
u
d
y
,
b
o
d
y
co
m
p
o
s
i
tio
n
,
lep
ti
n
,
ad
ip
o
c
y
to
k
in
e
s
a
n
d
m
y
o
k
i
n
es
w
er
e
n
o
t e
x
a
m
in
ed
,
s
o
w
e
ca
n
n
o
t c
o
n
clu
d
e
t
h
e
ca
u
s
e.
3
.
4
.
L
i
m
it
a
t
io
ns
T
h
is
s
t
u
d
y
o
n
l
y
u
s
ed
o
n
e
r
ese
ar
ch
b
io
m
ar
k
er
t
u
m
o
r
n
ec
r
o
s
i
s
f
ac
to
r
alp
h
a
.
Fo
r
th
e
f
u
t
u
r
e
r
esear
ch
,
i
t
is
n
ec
ess
ar
y
to
e
x
a
m
in
e
o
t
h
er
s
u
p
p
o
r
tin
g
b
io
m
ar
k
er
s
s
u
c
h
as
endot
he
l
i
a
l
ni
t
r
i
c
oxi
de
sy
nt
ha
se
,
I
n
ter
leu
k
i
n
-
6
,
I
n
ter
le
u
k
i
n
-
1
,
sol
ub
l
e
t
um
or
nec
r
os
i
s
f
ac
t
o
r
-
α
r
ec
ept
o
r
a
nd
t
um
or
nec
r
osi
s
f
a
ct
o
r
a
l
ph
a
-
m
es
se
ng
er
R
N
A
as
m
ar
k
er
s
o
f
en
d
o
th
elial
d
y
s
f
u
n
ctio
n
.
A
n
d
also
in
th
is
s
t
u
d
y
u
s
i
n
g
tr
ain
ed
d
iv
er
as
a
s
u
b
j
ec
t
,
w
h
ich
d
o
n
o
t r
ef
lec
t t
h
e
s
a
m
e
lev
e
l o
f
f
itn
e
s
s
as t
h
e
co
m
m
u
n
it
y
.
4
.
CO
NCLU
SI
O
N
P
re
-
d
iv
e
p
h
y
s
ical
e
x
er
cise
with
a
tar
g
et
e
x
er
cise
i
n
te
n
s
it
y
o
f
7
0
%
o
f
h
ea
r
t
r
ate
(
s
u
b
m
ax
i
m
a
l)
p
er
f
o
r
m
ed
o
n
ce
(
ac
u
te)
2
4
h
o
u
r
s
b
e
f
o
r
e
s
i
n
g
le
d
iv
e
2
8
0
k
P
a
b
o
tto
m
ti
m
e
8
0
m
i
n
u
tes
ca
n
p
r
ev
en
t
th
e
i
n
cr
ea
s
e
in
T
NFα
lev
els
a
f
ter
d
iv
in
g
.
T
h
er
e
w
as
a
s
i
g
n
if
ican
t
d
if
f
er
en
ce
b
et
w
ee
n
th
e
le
v
els
o
f
T
NFα
af
ter
d
iv
in
g
an
d
th
e
b
eg
i
n
n
in
g
o
f
t
h
e
s
tu
d
y
b
et
w
ee
n
t
h
e
tr
ea
t
m
e
n
t
g
r
o
u
p
w
h
o
r
ec
eiv
ed
ac
u
te
s
u
b
m
a
x
i
m
al
p
h
y
s
ical
e
x
er
cise
2
4
h
o
u
r
s
b
e
f
o
r
e
d
iv
in
g
a
n
d
th
e
c
o
n
tr
o
l
g
r
o
u
p
w
h
o
d
id
n
o
t
r
ec
eiv
e
p
h
y
s
ica
l
ex
er
ci
s
e.
I
n
t
h
is
s
tu
d
y
,
th
er
e
w
a
s
a
s
ig
n
i
f
ica
n
t
in
cr
ea
s
e
i
n
T
NFα
lev
els
d
u
e
to
s
in
g
le
d
iv
e
2
8
0
k
P
a
d
ec
o
m
p
r
ess
io
n
8
0
m
i
n
u
tes
b
o
tto
m
ti
m
e
i
n
th
e
g
r
o
u
p
th
at
d
id
n
o
t
g
et
p
h
y
s
ical
ex
er
cise
b
ef
o
r
e
d
iv
in
g
.
A
c
u
t
e
s
u
b
m
a
x
i
m
al
p
h
y
s
ical
ex
er
ci
s
e
in
cr
ea
s
ed
T
NFα
lev
els
af
ter
2
4
h
o
u
r
s
af
ter
ex
er
cise
b
u
t
it
w
a
s
n
o
t
s
i
g
n
i
f
ican
t.
So
,
ex
er
cise
b
ef
o
r
e
d
iv
i
n
g
ca
n
b
e
u
s
ed
as
o
n
e
o
f
th
e
p
r
ev
e
n
tio
n
o
f
o
x
id
ati
v
e
s
t
r
ess
t
h
at
ca
n
in
d
u
ce
D
C
S
o
n
d
iv
er
s
.
F
u
r
t
h
er
s
t
u
d
ies
ar
e
n
e
ed
ed
r
eg
ar
d
in
g
th
e
p
r
ev
en
tio
n
o
f
d
ec
o
m
p
r
ess
io
n
s
ick
n
es
s
d
u
e
to
d
iv
in
g
-
in
d
u
ce
d
m
e
tab
o
lic
ch
a
n
g
e
s
,
th
r
o
u
g
h
ad
m
in
i
s
tr
atio
n
o
f
an
tio
x
id
a
n
ts
o
r
h
y
p
er
b
ar
ic
o
x
y
g
e
n
t
h
er
ap
y
(H
B
OT
)
b
ef
o
r
e
i
m
m
er
s
io
n
a
s
s
ee
n
f
r
o
m
T
NFα
b
io
m
ar
k
er
s
as
a
co
m
p
ar
is
o
n
o
f
e
f
f
ec
tiv
e
n
es
s
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N:
2
2
5
2
-
8
8
0
6
I
n
t.
J
.
P
u
b
lic
Hea
lth
Sci.,
Vo
l.
1
0
,
No
.
2
,
J
u
n
e
20
21
:
2
89
–
2
97
296
ACK
NO
WL
E
D
G
E
M
E
NT
S
T
h
an
k
y
o
u
to
tu
to
r
s
,
as
w
el
l
as
f
r
ien
d
s
w
h
o
ca
r
r
y
o
u
t
j
o
in
t
r
esear
ch
.
T
h
an
k
y
o
u
to
P
R
ODI
A
lab
o
r
ato
r
y
,
w
h
ich
f
ac
i
litates
t
h
e
e
x
a
m
in
at
io
n
o
f
b
io
m
ar
k
er
s
.
A
n
d
al
s
o
t
h
e
r
esear
c
h
er
h
er
eb
y
d
ec
lar
es
th
a
t
th
er
e
ar
e
n
o
co
n
f
l
icts
o
f
i
n
ter
e
s
t a
n
d
n
o
s
p
o
n
s
o
r
s
h
ip
f
u
n
d
s
.
RE
F
E
R
E
NC
E
S
[1
]
R.
D.
V
a
n
n
,
F
.
K.
Bu
tl
e
r,
S
.
J.
M
it
c
h
e
ll
,
a
n
d
R.
E.
M
o
o
n
,
“
De
c
o
m
p
re
ss
io
n
il
ln
e
ss
,
”
L
a
n
c
e
t
,
v
o
l.
3
7
7
,
n
o
.
9
7
6
0
,
p
p
.
153
-
1
6
4
,
2
0
1
1
,
d
o
i:
1
0
.
1
0
1
6
/S
0
1
4
0
-
6
7
3
6
(
1
0
)
6
1
0
8
5
-
9.
[2
]
lu
c
ia
m
a
ri
a
a
v
e
rsa
V
il
lela
,
DAN
An
n
u
a
l
Div
in
g
Rep
o
rt
2
0
1
9
,
2
0
1
9
t
h
e
d
.
,
v
o
l.
5
3
,
n
o
.
9
.
Div
e
rs
A
lert
Ne
t
w
o
rk
,
2
0
1
9
.
[3
]
Ra
h
m
a
d
a
y
a
n
ti
,
Bu
d
iy
o
n
o
,
a
n
d
Yu
sn
iar,
“
Risk
F
a
c
to
rs
f
o
r
Dist
u
rb
a
n
c
e
Du
e
to
Div
e
rs
in
T
ra
d
it
io
n
a
l
Div
e
rs
in
Ka
ri
m
u
n
Ja
w
a
J
e
p
a
ra
,
”
Ke
s
e
h
a
t
a
n
M
a
sy
a
r
a
k
a
t
,
v
o
l.
5
,
n
o
.
1
,
p
p
.
1
-
9
,
2
0
1
7
,
[
On
l
in
e
]
.
A
v
a
il
a
b
le:
h
tt
p
s:/
/ejo
u
r
n
a
l3
.
u
n
d
i
p
.
a
c
.
id
/
in
d
e
x
.
p
h
p
/
jk
m
/article
/
v
ie
w
/1
5
7
9
9
.
[4
]
D.
R.
W
ij
a
y
a
,
A
.
Z.
A
b
d
u
ll
a
h
,
S
.
P
a
l
u
tt
u
r
i,
F
.
K.
M
a
s
y
a
ra
k
a
t,
a
n
d
F
.
K.
M
a
s
y
a
r
a
k
a
t,
“
Risk
f
a
c
to
rs
w
o
rk
in
g
li
f
e
a
n
d
b
re
a
k
ti
m
e
to
d
e
c
o
m
p
re
ss
io
n
si
c
k
n
e
ss
in
f
is
h
e
r
m
a
n
,
”
v
o
l.
1
,
n
o
.
3
,
p
p
.
3
1
8
-
3
2
7
,
2
0
1
8
,
[
O
n
li
n
e
]
.
A
v
a
il
a
b
le:
h
tt
p
:
//
jo
u
rn
a
l
.
u
n
h
a
s.ac
.
id
/i
n
d
e
x
.
p
h
p
/j
k
m
m
u
n
h
a
s/a
rti
c
le/d
o
w
n
lo
a
d
/
8
8
2
3
/
4
5
7
1
.
[5
]
L
.
A
.
M
a
d
d
e
n
a
n
d
G
.
L
a
d
e
n
,
“
G
a
s b
u
b
b
les
m
a
y
n
o
t
b
e
t
h
e
u
n
d
e
rly
i
n
g
c
a
u
se
o
f
d
e
c
o
m
p
re
ss
io
n
il
ln
e
ss
-
T
h
e
a
t
-
d
e
p
th
e
n
d
o
t
h
e
li
a
l
d
y
s
f
u
n
c
ti
o
n
h
y
p
o
th
e
sis,”
M
e
d
ica
l
Hy
p
o
th
e
se
s
,
v
o
l.
7
2
,
n
o
.
4
,
p
p
.
3
8
9
-
3
9
2
,
2
0
0
9
,
d
o
i:
1
0
.
1
0
1
6
/
j.
m
e
h
y
.
2
0
0
8
.
1
1
.
0
2
2
.
[6
]
K.
Zh
a
n
g
,
D.
W
a
n
g
,
Z.
Jia
n
g
,
X
.
Ni
n
g
,
P
.
B
u
z
z
a
c
o
tt
,
a
n
d
W
.
Xu
,
“
E
n
d
o
th
e
li
a
l
d
y
sf
u
n
c
ti
o
n
c
o
rre
late
s
w
it
h
d
e
c
o
m
p
re
ss
io
n
b
u
b
b
les
i
n
ra
ts,
”
S
c
ien
ti
fi
c
Rep
o
rts
v
o
l.
Vo
l.
6
,
n
o
.
3
3
3
9
0
,
p
p
.
1
-
1
1
,
2
0
1
6
,
d
o
i:
1
0
.
1
0
3
8
/sre
p
3
3
3
9
0
.
[7
]
Y.
Ch
e
n
,
E.
M
o
n
tca
lm
-
S
m
it
h
,
C.
S
c
h
lae
rth
,
C.
A
u
k
e
r,
a
n
d
R.
M
.
M
c
Ca
rro
n
,
“
A
c
c
li
m
a
ti
o
n
to
d
e
c
o
m
p
re
ss
io
n
:
S
tres
s
a
n
d
c
y
to
k
in
e
g
e
n
e
e
x
p
re
ss
io
n
in
ra
t
lu
n
g
s,”
J
o
u
rn
a
l
o
f
Ap
p
li
e
d
P
h
y
sio
lo
g
y
,
v
o
l.
1
1
1
,
n
o
.
4
,
p
p
.
1
0
0
7
-
1
0
1
3
,
2
0
1
1
,
d
o
i:
1
0
.
1
1
5
2
/j
a
p
p
lp
h
y
sio
l.
0
1
4
0
2
.
2
0
1
0
.
[8
]
H.
Zh
a
n
g
e
t
a
l.
,
“
Ro
le
o
f
T
NF
-
α
in
v
a
sc
u
lar
d
y
s
f
u
n
c
ti
o
n
,
”
Cli
n
ica
l
S
c
ien
c
e
,
v
o
l.
1
1
6
,
n
o
.
3
,
p
p
.
2
1
9
-
2
3
0
,
2
0
0
9
,
d
o
i:
1
0
.
1
0
4
2
/C
S
2
0
0
8
0
1
9
6
.
[9
]
A
.
H
a
n
d
o
k
o
,
A
.
R
o
e
s
tam
,
a
n
d
G
.
S
u
r
y
o
k
u
s
u
m
o
,
“
S
i
n
g
l
e
d
e
c
o
m
p
r
e
ss
i
o
n
d
i
v
e
s
r
e
d
u
c
e
s
e
N
O
S
e
x
p
r
e
ss
io
n
a
s
a
m
a
rk
e
r
s
e
n
d
o
t
h
e
l
i
a
l
d
y
sf
u
n
c
t
i
o
n
i
n
d
i
s
l
a
m
b
a
i
r
I
n
d
o
n
e
s
i
a
n
n
a
v
y
d
i
v
e
r
,
”
T
h
e
s
is
,
U
n
i
v
e
r
s
i
ty
o
f
I
n
d
o
n
e
s
i
a
,
Ja
k
a
r
t
a
,
p
.
9
4
,
2
0
1
5
.
[1
0
]
I.
D.
A
stu
ty
,
A
.
S
u
li
sto
m
o
,
a
n
d
G
.
S
u
ry
o
k
u
su
m
o
,
“
Ef
fe
c
ts
o
f
sin
g
le
d
iv
e
d
e
c
o
m
p
re
ss
io
n
o
n
in
c
re
a
se
d
e
x
p
re
ss
io
n
o
f
in
terle
u
k
in
1
a
s
m
a
rk
e
rs
o
f
e
n
d
o
t
h
e
li
a
l
d
y
sf
u
n
c
ti
o
n
i
n
n
a
v
y
d
iv
e
r,
”
T
h
e
sis
,
Un
iv
e
rsit
y
o
f
In
d
o
n
e
sia
,
Ja
k
a
rta,
p
.
9
6
,
2
0
1
6
,
[
O
n
li
n
e
].
A
v
a
il
a
b
le:
h
tt
p
:/
/l
o
n
tar.
u
i.
a
c
.
id
/d
e
tail?id
=
2
0
4
2
3
4
9
0
&
lo
k
a
si=
lo
k
a
l.
[1
1
]
W
il
l
y
,
A
.
S
u
li
sto
m
o
,
a
n
d
G
.
S
u
r
y
o
k
u
su
m
o
,
“
T
h
e
e
ff
e
c
t
o
f
sin
g
le
d
e
c
o
m
p
re
s
sio
n
d
iv
e
s
o
n
in
c
re
a
se
d
th
e
p
e
rc
e
n
tag
e
o
f
m
a
x
i
m
a
l
p
late
let
a
g
g
r
e
g
a
ti
o
n
in
d
islam
b
a
ir
d
iv
e
r
s,
”
T
h
e
sis,
Un
iv
e
rsit
y
o
f
In
d
o
n
e
sia
,
Ja
k
a
rta
,
p
.
8
5
,
2
0
1
5
,
[
On
li
n
e
]
.
A
v
a
il
a
b
le:
h
tt
p
s://
li
b
ra
ry
.
u
i.
a
c
.
id
/d
e
tail?id
=
2
0
4
1
5
2
9
3
&
lo
k
a
si=
lo
k
a
l.
[1
2
]
Ž.
Du
ji
ć
e
t
a
l
.
,
“
A
e
ro
b
ic
e
x
e
rc
i
se
b
e
f
o
re
d
iv
in
g
re
d
u
c
e
s
v
e
n
o
u
s
g
a
s
b
u
b
b
le
f
o
rm
a
ti
o
n
in
h
u
m
a
n
s,”
J
o
u
r
n
a
l
o
f
Ph
y
sio
l
o
g
y
,
v
o
l
.
5
5
5
,
n
o
.
3
,
p
p
.
6
3
7
-
6
4
2
,
2
0
0
4
,
d
o
i:
1
0
.
1
1
1
3
/
jp
h
y
si
o
l.
2
0
0
3
.
0
5
9
3
6
0
.
[1
3
]
U.
W
islø
ff
,
R.
S
.
Rich
a
rd
s
o
n
,
a
n
d
A
.
O.
Bru
b
a
k
k
,
“
Ex
e
rc
ise
a
n
d
n
it
ric
o
x
id
e
p
re
v
e
n
t
b
u
b
b
le
f
o
rm
a
ti
o
n
:
A
n
o
v
e
l
a
p
p
ro
a
c
h
t
o
th
e
p
re
v
e
n
ti
o
n
o
f
d
e
c
o
m
p
re
ss
io
n
sic
k
n
e
ss
?
,
”
J
o
u
rn
a
l
o
f
Ph
y
sio
l
o
g
y
,
v
o
l
.
5
5
5
,
n
o
.
3
,
p
p
.
8
2
5
-
8
2
9
,
2
0
0
4
,
d
o
i:
1
0
.
1
1
1
3
/j
p
h
y
sio
l.
2
0
0
3
.
0
5
5
4
6
7
.
[1
4
]
R.
P
.
S
l
o
a
n
e
t
a
l.
,
“
A
e
ro
b
ic
e
x
e
rc
ise
a
tt
e
n
u
a
tes
in
d
u
c
i
b
le
T
NF
p
ro
d
u
c
ti
o
n
in
h
u
m
a
n
s,”
J
o
u
rn
a
l
o
f
A
p
p
li
e
d
Ph
y
sio
l
o
g
y
,
v
o
l
.
1
0
3
,
n
o
.
3
,
p
p
.
1
0
0
7
-
1
0
1
1
,
2
0
0
7
,
d
o
i:
1
0
.
1
1
5
2
/
jap
p
lp
h
y
sio
l.
0
0
1
4
7
.
2
0
0
7
.
[1
5
]
T
.
W
.
S
.
Ch
rist
o
p
h
e
r
B.
C
o
o
p
e
r,
“
T
e
stin
g
m
e
th
o
d
s,”
in
Exe
rc
ise
tes
ti
n
g
a
n
d
i
n
ter
p
re
ta
t
io
n
,
1
st
e
d
.
,
v
o
l.
4
,
n
o
.
1
,
Ca
m
b
rig
e
Un
iv
e
rsit
y
P
re
ss
,
2
0
1
6
,
p
p
.
5
1
-
9
1
.
[1
6
]
S
u
h
a
d
i,
M
.
S
.
G
u
rit
n
o
,
a
n
d
M
.
Av
o
n
g
sa
,
“
H
y
p
e
rb
a
ric
h
y
p
e
r
o
x
ia
e
ff
e
c
ts
o
n
stro
k
e
v
o
lu
m
e
h
e
a
rt
ra
te
a
n
d
c
a
rd
iac
o
u
t
p
u
t
o
f
d
iv
e
rs
f
ro
g
m
e
n
d
u
rin
g
su
b
m
a
x
i
m
a
l
e
x
e
rc
i
se
a
t
a
d
e
p
th
o
f
5
m
e
ters
,
”
T
h
e
sis
,
Un
iv
e
rsit
y
o
f
In
d
o
n
e
sia
,
Ja
k
a
rta,
2
0
1
5
.
[1
7
S
.
A
.
P
lo
wm
a
n
a
n
d
D.
L
.
S
m
it
h
,
“
T
h
e
i
m
m
u
n
e
r
e
sp
o
n
to
e
x
e
r
c
ise
,
”
in
Exe
rc
ise
Ph
y
sio
lo
g
y
F
o
r
He
a
lt
h
Fi
tn
e
s
Per
fo
rm
a
n
c
e
,
Em
il
y
L
u
p
a
sh
,
Ed
.
P
h
il
a
d
e
l
p
ia:
L
ip
p
i
n
c
o
tt
W
il
li
a
m
s
&
W
il
k
in
s,
a
W
o
lt
e
rs
Klu
we
r
b
u
sin
e
ss
,
2
0
1
1
,
p
p
.
6
5
6
-
6
8
6
.
[1
8
]
S
.
A
.
P
lo
w
m
a
n
a
n
d
D.
L
.
S
m
it
h
,
“
Ae
ro
b
ic
M
e
tab
o
li
sm
Du
rin
g
Ex
e
rc
ise
,
”
in
Exe
rc
ise
Ph
y
sio
lo
g
y
F
o
r
He
a
lt
h
Fi
tn
e
s
Per
fo
rm
a
n
c
e
,
2
0
1
1
t
h
e
d
.
,
Em
il
y
L
u
p
a
sh
,
E
d
.
P
h
i
lad
e
lp
ia:
L
ip
p
i
n
c
o
tt
W
il
li
a
m
s
&
W
il
k
in
s,
a
W
o
lt
e
r
s
Klu
w
e
r
b
u
sin
e
ss
,
2
0
1
1
,
p
p
.
9
2
-
1
1
1
.
[1
9
]
G
.
O
l
m
o
s
a
n
d
J.
L
lad
ó
,
“
T
u
m
o
r
n
e
c
ro
sis
fa
c
to
r
a
lp
h
a
:
A
li
n
k
b
e
twe
e
n
n
e
u
ro
in
f
lam
m
a
ti
o
n
a
n
d
e
x
c
it
o
to
x
icity
,
”
M
e
d
ia
to
rs
In
fl
a
mm
a
ti
o
n
,
v
o
l
.
V
o
l
.
2
0
1
4
,
n
o
.
8
6
1
2
3
1
,
p
.
1
2
p
a
g
e
s,
2
0
1
4
,
d
o
i:
1
0
.
1
1
5
5
/2
0
1
4
/
8
6
1
2
3
1
.
[
20
]
S
.
G
u
o
e
t
a
l.
,
“
Ro
le
o
f
A
2
0
in
c
IA
P
-
2
p
ro
tec
ti
o
n
a
g
a
in
st
tu
m
o
r
n
e
c
ro
sis
f
a
c
to
r
α
(
T
NF
-
α)
-
m
e
d
iate
d
a
p
o
p
t
o
sis
in
e
n
d
o
t
h
e
li
a
l
c
e
ll
s,”
In
ter
n
a
ti
o
n
a
l
J
o
u
rn
a
l
o
f
M
o
lec
u
l
a
r
S
c
ien
c
e
s
.
,
v
o
l.
1
5
,
n
o
.
3
,
p
p
.
3
8
1
6
-
3
8
3
3
,
2
0
1
4
,
d
o
i:
1
0
.
3
3
9
0
/
ij
m
s1
5
0
3
3
8
1
6
.
[2
1
]
B.
K.
P
e
n
d
e
rse
n
a
n
d
A
.
D.
T
o
f
t,
“
Eff
e
c
ts
o
f
e
x
e
rc
ise
o
n
ly
m
p
h
o
c
y
tes
a
n
d
c
y
to
k
in
e
s,”
Brit
ish
J
o
u
rn
a
l
o
f
S
p
o
rts
M
e
d
icin
e
,
v
o
l.
3
4
,
n
o
.
4
,
p
p
.
2
4
6
–
2
5
1
,
2
0
0
0
,
d
o
i:
1
0
.
1
1
3
6
/
b
jsm
.
3
4
.
4
.
2
4
6
.
[2
2
]
C.
No
c
e
ll
a
e
t
a
l.
,
“
I
m
p
a
ir
m
e
n
t
b
e
twe
e
n
Ox
id
a
n
t
a
n
d
A
n
ti
o
x
id
a
n
t
S
y
st
e
m
s:
S
h
o
rt
-
a
n
d
L
o
n
g
-
ter
m
I
m
p
li
c
a
ti
o
n
s
f
o
r
A
th
lete
s’ He
a
lt
h
,
”
Nu
trien
t
,
v
o
l.
1
1
,
n
o
.
1
,
p
.
2
8
p
a
g
e
s,
2
0
1
9
,
d
o
i:
1
1
0
6
1
3
5
3
.
[2
3
]
D.
J.
G
re
e
n
,
M
.
T
.
E.
Ho
p
m
a
n
,
J.
P
a
d
il
la,
M
.
H.
L
a
u
g
h
li
n
,
a
n
d
D.
H.
J.
T
h
ij
ss
e
n
,
“
V
a
sc
u
lar ad
a
p
tati
o
n
t
o
e
x
e
rc
ise
in
h
u
m
a
n
s:
Ro
le
o
f
h
e
m
o
d
y
n
a
m
i
c
stim
u
li
,
”
Ph
y
sio
lo
g
ica
l
Rev
iews
,
v
o
l.
9
7
,
n
o
.
2
,
p
p
.
4
9
5
-
5
2
8
,
2
0
1
7
,
d
o
i
:
1
0
.
1
1
5
2
/
p
h
y
sre
v
.
0
0
0
1
4
.
2
0
1
6
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t.
J
.
P
u
b
lic
Hea
lth
Sci.
I
SS
N:
2
2
5
2
-
8806
E
ffect
o
f a
cu
te
s
u
b
ma
xima
l
p
h
ysica
l e
xe
r
cise b
ef
o
r
e
d
ec
o
mp
r
ess
io
n
d
ive
o
n
tu
mo
r
…
(
C
h
ik
ih
)
297
[2
4
]
S
.
T
.
d
e
Dio
s,
Ch
rist
o
p
h
e
r
G
.
S
o
b
e
y
,
a
n
d
G
ra
n
t
R.
Dru
m
m
o
n
d
,
“
Ox
id
a
ti
v
e
stre
ss
a
n
d
e
n
d
o
t
h
e
li
a
l
d
y
s
f
u
n
c
ti
o
n
,
”
i
n
En
d
o
th
e
li
a
l
Dy
sfu
n
c
ti
o
n
a
n
d
I
n
fl
a
mm
a
ti
o
n
,
S
.
M
.
Da
u
p
h
in
e
e
a
n
d
A
l
y
Ka
rs
a
n
,
Ed
s.
Ba
se
l:
S
p
rin
g
e
r
Ba
se
l
AG
,
p
p
.
37
-
6
4
,
2
0
1
0
.
[2
5
]
J.
S
.
P
o
b
e
r
a
n
d
W
.
M
in
,
“
En
d
o
th
e
li
a
l
Ce
ll
Dy
s
f
u
n
c
ti
o
n
,
In
ju
ry
a
n
d
De
a
th
,
”
i
n
Nit
ric
Ox
i
d
e
a
n
d
th
e
Va
sc
u
l
a
r
En
d
o
th
e
li
u
m
,
1
7
6
/II
.
,
S
.
M
o
n
c
a
d
a
a
n
d
A
.
Hig
g
s,
Ed
s.
Ne
w
Yo
rk
:
S
p
rin
g
e
r
Be
rli
n
He
id
e
l
b
e
rg
Ne
w
Yo
rk
,
p
p
.
1
3
5
-
1
5
6
,
2
0
1
6
.
[2
6
]
S
.
Be
re
n
ji
A
rd
e
sta
n
i,
V.
V
.
M
a
t
c
h
k
o
v
,
I.
Ef
ted
a
l,
a
n
d
M
.
P
e
d
e
rse
n
,
“
A
S
in
g
le
S
im
u
late
d
He
li
o
x
Div
e
M
o
d
if
ies
En
d
o
th
e
li
a
l
F
u
n
c
ti
o
n
i
n
th
e
V
a
s
c
u
lar
W
a
ll
o
f
A
p
o
E
Kn
o
c
k
o
u
t
M
a
le
Ra
ts
M
o
re
T
h
a
n
F
e
m
a
les
,
”
Fro
n
ti
e
rs
in
Ph
y
sio
l
o
g
y
,
v
o
l
.
1
0
,
n
o
.
1
3
4
2
,
p
.
1
2
p
a
g
e
s,
2
0
1
9
,
d
o
i:
1
0
.
3
3
8
9
/f
p
h
y
s.2
0
1
9
.
0
1
3
4
2
.
[2
7
]
E.
S
p
is
n
i
e
t
a
l.
,
“
A
c
o
m
p
a
ra
ti
v
e
e
v
a
lu
a
ti
o
n
o
f
tw
o
d
e
c
o
m
p
re
ss
io
n
p
ro
c
e
d
u
re
s
f
o
r
tec
h
n
ica
l
d
iv
in
g
u
sin
g
in
f
la
m
m
a
to
r
y
re
sp
o
n
se
s:
Co
m
p
a
r
tm
e
n
tal
v
e
r
su
s
ra
ti
o
d
e
c
o
,
”
Div
i
n
g
Hy
p
e
rb
a
ric
M
e
d
ici
n
e
,
v
o
l.
4
7
,
n
o
.
1
,
p
p
.
9
-
1
6
,
2
0
1
7
,
d
o
i:
1
0
.
2
8
9
2
0
/d
h
m
4
7
.
1
.
9
-
1
6
.
[2
8
]
G
.
Ko
jd
a
a
n
d
R.
Ha
m
b
re
c
h
t,
“
M
o
lec
u
lar
m
e
c
h
a
n
is
m
s
o
f
v
a
s
c
u
lar
a
d
a
p
tati
o
n
s
to
e
x
e
rc
ise
.
P
h
y
sic
a
l
a
c
ti
v
it
y
a
s
a
n
e
ffe
c
ti
v
e
a
n
ti
o
x
id
a
n
t
t
h
e
ra
p
y
?
,
”
Ca
rd
i
o
v
a
sc
u
la
r
Res
e
a
rc
h
,
v
o
l.
6
7
,
n
o
.
2
,
p
p
.
1
8
7
-
1
9
7
,
2
0
0
5
,
d
o
i
:
1
0
.
1
0
1
6
/
j.
c
a
rd
io
re
s.
2
0
0
5
.
0
4
.
0
3
2
.
[2
9
]
A
.
De
o
ra
e
t
a
l.
,
“
T
ra
n
s
m
e
m
b
ra
n
e
T
NF
-
d
e
p
e
n
d
e
n
t
u
p
tak
e
o
f
a
n
ti
-
TNF
a
n
ti
b
o
d
ies
,
”
M
Ab
s
,
v
o
l.
9
,
n
o
.
4
,
p
p
.
6
8
0
-
6
9
5
,
2
0
1
7
,
d
o
i:
1
0
.
1
0
8
0
/
1
9
4
2
0
8
6
2
.
2
0
1
7
.
1
3
0
4
8
6
9
.
[
30
]
M
.
S
e
ll
a
m
i
e
t
a
l.
,
“
Ef
fe
c
ts
o
f
a
c
u
te
a
n
d
c
h
r
o
n
ic
e
x
e
rc
ise
o
n
imm
u
n
o
lo
g
ica
l
p
a
ra
m
e
ter
s
in
th
e
e
ld
e
rl
y
a
g
e
d
:
Ca
n
p
h
y
sic
a
l
a
c
ti
v
it
y
c
o
u
n
tera
c
t
th
e
e
ff
e
c
ts
o
f
a
g
in
g
?
,
”
Fro
n
ti
e
rs
in
I
mm
u
n
o
l
o
g
y
,
v
o
l
.
9
,
n
o
.
2
1
8
7
,
p
.
1
7
p
a
g
e
s,
2
0
1
8
,
d
o
i:
1
0
.
3
3
8
9
/f
imm
u
.
2
0
1
8
.
0
2
1
8
7
.
[3
1
]
T
.
Ay
e
s
e
r,
M
.
Ba
sa
k
,
K.
A
rsla
n
,
a
n
d
I.
S
a
y
a
n
,
“
In
v
e
stig
a
ti
n
g
th
e
c
o
rre
latio
n
o
f
th
e
n
u
m
b
e
r
o
f
d
iag
n
o
stic
c
rit
e
ria
t
o
se
ru
m
a
d
ip
o
n
e
c
ti
n
,
lep
ti
n
,
re
sisti
n
,
T
NF
-
a
lp
h
a
,
EG
F
R
lev
e
ls
a
n
d
a
b
d
o
m
in
a
l
a
d
ip
o
se
ti
ss
u
e
,
”
Di
a
b
e
tes
M
e
ta
b
o
li
c
S
y
n
d
r
om
Cli
n
ica
l
Res
e
a
rc
h
Rev
iews
,
v
o
l.
1
0
,
n
o
.
2
,
p
p
.
S
1
6
5
-
S
1
6
9
,
2
0
1
6
,
d
o
i:
1
0
.
1
0
1
6
/j
.
d
sx
.
2
0
1
6
.
0
3
.
0
1
0
.
[3
2
]
M
.
A
n
a
sz
e
w
ic
z
e
t
a
l.
,
“
L
e
p
ti
n
,
a
d
ip
o
n
e
c
ti
n
,
tu
m
o
r
n
e
c
ro
sis
f
a
c
to
r
α
,
a
n
d
iri
si
n
c
o
n
c
e
n
tratio
n
s
a
s
fa
c
to
rs
li
n
k
in
g
o
b
e
sity
w
it
h
th
e
risk
o
f
a
tri
a
l
f
ib
ril
latio
n
a
m
o
n
g
in
p
a
ti
e
n
ts
w
it
h
c
a
rd
io
v
a
sc
u
lar
d
ise
a
se
s,”
Ka
rd
io
lo
g
ia
Po
lsk
a
,
v
o
l.
7
7
,
n
o
.
1
1
,
p
p
.
1
0
5
5
-
1
0
6
1
,
2
0
1
9
,
d
o
i:
1
0
.
3
3
9
6
3
/K
P
.
1
4
9
8
9
.
Evaluation Warning : The document was created with Spire.PDF for Python.