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Original Article
Timing of bone marrow cell therapy is more important than repeated
injections after myocardial infarction
Yan Zhanga, Richard E. Sieversa, Megha Prasada, Rachel Mirskya, Henry Shiha,
Maelene L. Wonga, Franca S. Angelia, Jianqin Yea, Junya Takagawaa, Juha W. Koskenvuoa,
Matthew L. Springera,b,c, William Grossmana, Andrew J. Boylea,c, Yerem Yeghiazariansa,c,⁎
aDivision of Cardiology, Department of Medicine, University of California, San Francisco, CA 94143-0103, USA
bCardiovascular Research Institute, University of California, San Francisco, CA 94143-0103, USA
cEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143-0103, USA
Received 7 December 2009; received in revised form 1 June 2010; accepted 21 June 2010
Background: Bone marrow cell treatment has been proposed as a therapy for myocardial infarction, but the optimal timing and number of
injections remain unknown. Methods: Myocardial infarction was induced in mice followed by ultrasound-guided injection of mouse bone
marrow cells at different time points post myocardial infarction (Days 3, 7, and 14) as monotherapy and at Days 3+7 as "double" therapy and
at Days 3+7+14 as "triple" therapy. Controls received saline injections at Day 3 and Days 3+7+14. Left ventricular ejection fraction was
evaluated post myocardial infarction prior to any therapy and at Day 28. Hearts were analyzed at Day 28 for infarct size and survival of donor
cells. Results: Left ventricular ejection fraction decreased from 55.3±0.9% to 37.6±0.6% (Pb.001) 2 days post myocardial infarction in all
groups. Injection of bone marrow cells at Day 3 post myocardial infarction resulted in smaller infarct size (17.8±3.6% vs. 36.6±7.1%; P=.05)
and improved LV function (left ventricular ejection fraction 40.3±2.0% vs. 31.1±8.3%; Pb.05) compared to control. However, delayed
therapy at Day 7 or 14 did not. Multiple injections of bone marrow cells, either double therapy or triple therapy, did not result in reduction in
infarct size, but led to improvements in left ventricular ejection fraction at Day 28 compared to control (39.9±3.6% and 38.8±5.5% vs.
34.8±5.3%; all Pb.05). The number of donor cells surviving at Day 28 did not correlate with improvement in left ventricular ejection
fraction. Conclusions: Injection of bone marrow cells at Day 3 reduced infarct size and improved left ventricular function. Multiple
injections of bone marrow cells had no additive effect. Delaying cell therapy post myocardial infarction resulted in no functional benefit at
all. These results will help inform future clinical trials. Published by Elsevier Inc.
Keywords: Mouse bone marrow cell; Myocardial infarction; Remodeling; Repeated injection; Intramyocardial injection
1. Introduction
Bone marrow-derived cell treatment has been proposed as
a novel therapy for ischemic heart disease [1–4]. However,
the recent literature contains numerous contradictory results,
ranging from no improvement of cardiac function to
significant benefit in the contractile function after myocar-
dial infarction (MI) [3,5–14]. The exact mechanism(s) of the
possible benefits of cell-based therapies remains unclear
[3,5–7,10,15]. Additionally, it has been proposed that the
timing of stem cell therapy post-MI may influence whether
the cardiac function will improve after cell delivery. In the
largest randomized, multicenter, placebo-controlled, clinical
trial using bone marrow cells (BMCs) to date, the REPAIR-
AMI Trial, a significant improvement in left ventricular
ejection fraction (LVEF) was reported post-MI in those
patients with larger infarcts (e.g., LVEF prior to cell therapy
of b49%) or in those who received the cell therapy at least
Cardiovascular Pathology xx (2010) xxx–xxx
This work was supported in part by the UCSF Cardiac Stem Cell
Foundation to Y.Y. and a grant from the Wayne and Gladys Valley
Foundation to W.G. and Y.Y.
⁎Corresponding author. Division of Cardiology, Department of
Medicine, Box 0103, Eli and Edythe Broad Center of Regeneration
Medicine and Stem Cell Research, University of California, San Francisco,
CA 94143-0103, USA. Tel.: +1 415 353 3817; fax: +1 415 353 3090.
E-mail address: email@example.com (Y. Yeghiazarians).
1054-8807/10/$ – see front matter. Published by Elsevier Inc.
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5 days after MI [12]. No benefit was seen if therapy was
given within 5 days of the MI. More recently, Yao et al. [16]
reported in a small single-center study that therapy of
patients post-MI with repeated intracoronary administration
of BMC Days 3–7 post infarct and again at 3 months was
safe and more effective than single therapy at an early time
point. Whether the timing of therapy is indeed critical or
whether multiple injections of cell therapy post-MI result in
even more improvement of cardiac function is unknown and
these questions form the basis for this current research.
Small animal rodent models are frequently used to
assess the functional benefits of stem cell therapies
[5,10,15,17–20]; however, given the high mortality of
repeated open-chest surgery in these animals for cell
delivery, it has not been possible to reliably assess how
delayed cell therapy and multiple injections of stem cells
would affect the cardiac function post-MI. We have recently
developed a closed-chest ultrasound-guided intramyocardial
injection technique for use in the mouse MI model and this
approach has allowed us to perform studies at a clinically
more relevant time points by delivering the cells to the heart
several days post-MI, which mimics the conditions of
ongoing clinical trials [5,12,13,21,22]. Notably, the animal
mortality rate with this technique is almost zero, allowing
delayed or multiple injections to be undertaken successfully.
Using this approach, we have shown that injection of BMCs
3 days post-MI significantly improved cardiac function,
resulted in smaller left ventricular systolic and diastolic
volumes, and limited the extent of the infarct scar [5].
Despite these benefits, under our experimental conditions,
there was no evidence that donor cells (identified as GFP+
cells) differentiated into cardiomyocytes, and relatively few
implanted cells were detected several weeks later [5].
It has been suggested that there is a time window in early
post-MI in which delivery of cells will result in cardiac
functional improvement and that delaying this therapy longer
post-MI will have less or no benefit [23]. In addition, the
effects of multiple injections of BMCs at different time
points post-MI on the cardiac function are unknown. This
study was designed to answer the following questions: (1)
Does the timing of BMC delivery post-MI affect the
outcome? (2) Do multiple cell injections post-MI have
additive benefits in improving cardiac function? These issues
have direct clinical implications.
2. Methods
to the guidelines of the Institutional Animal Care and Use
Committee of the University of California, San Francisco.
2.1. Myocardial infarction
MIs were induced surgically by a permanent ligation of
the left anterior descending coronary artery (LAD) as
previously described [21,24]. Briefly, permanent ligation
of the LAD is made by a 7-0 suture in the anterior
myocardium at 50% of the length of the heart from the
anterior–inferior edge of the left atrium to the apex. Each
group was allotted 10–12 animals for MI induction and eight
to nine survived to study completion without any differences
among the groups.
2.2. Collection of bone marrow cells
BMCs were harvested from 12- to 16-week-old C57BL/6
mice that constitutively express GFP [5,25]. The BMCs were
flushed from tibias and femurs with buffer (HBSS with 0.5%
BSA). The cell suspension was strained through a 70-μm
nylon filter and washed twice with buffer. The concentration
of the cells was adjusted to 105viable cells/μl, and the cell
viability was checked using Trypan blue with an average of
95% viability before injection.
2.3. Echocardiography
Echocardiograms (Vevo 660, VisualSonics, Toronto,
ON, Canada) were obtained at baseline, 2 days post-MI
(before injection), and at Day 28 post-MI, and LVEF and LV
volumes [end-diastolic (EDV) and end-systolic (ESV)
volumes] were measured as previously described [5,26].
The analyses of the echocardiography images were
performed by a blinded investigator.
2.4. Ultrasound-guided cell delivery
Ultrasound-guided injection of cells into the myocar-
dium (Vevo 660) was performed as previously described in
detail [5,21]. Briefly, eight to nine hearts per group were
injected with 10 μl solution of either HBSS or BMCs (total
of 1×106cells divided into two adjacent 5 μl injections) into
the LV myocardium at different times post-MI as either
monotherapy (Day 3, 7, or 14) or at multiple time points as
follows: Days 3+7 as "double" therapy vs. Days 3+7+14 as
"triple" therapy (Fig. 1). Injections were targeted to the peri-
infarct border zone. Cardiac function was evaluated at Day
28 in all groups. Animals in the control group were
administered HBSS injections at Day 3 and also at Days 3+
7+14. We developed an echocardiographic scoring system
to assess successful injections: 1=no echocardiographic
evidence during or after injection; 2=contrast signal in the
LV cavity and no wall thickness changes notable during or
after injection; 3=either injection site wall thickening during
or after injection, or echo contrast enhancement at the
injection site during or after injection; 4=evidence of
injection site myocardial thickening and echo contrast
enhancement in the injected myocardium during or after
injection. Injections warranting a score of 3 or above were
considered to be successful. All animals were judged to be
optimally injected and none of the animals needed to be
removed from the study due to poor injections.
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2.5. Histology
At Day 28, the hearts were injected with a saturated
solution of KCl (0.1 ml) to arrest in diastole. The hearts
were removed, and the left and right atria and large vessels
were resected. After a saline wash, the hearts were
immersed in 0.5% paraformaldehyde (PFA) solution for
1–2 h, then in 20% sucrose overnight. Hearts were then
embedded in OCT compound (Sakura Finetechnical USA,
Torrance, CA, USA), frozen in a bath of 2-methylbutane
with dry ice and stored at −80°C. The histologic analyses
were performed by investigators who were blinded to the
identity of the sections.
2.6. GFP Retention
Sections were first fixed in 1.5% PFA solution. The
fixed frozen sections were incubated in a Peroxidazed
solution (Biocare Medical, Concord, CA, USA) to quench
endogenous peroxidases followed by a 30-min incubation
in Rodent Block M (Biocare Medical) and rabbit
polyclonal antibody against GFP (Invitrogen/Molecular
Probes, 1:1000 dilution) for 1 h, washed with PBS, and
then incubated in an HRP-conjugated goat anti-rabbit IgG
(Biocare Medical) for 30 min. A negative staining control
lacking primary antibody was performed. Stain was
developed using DAB. GFP+ cells were then counted
manually in each of three zones: infarct zone (IZ), border
zone (BZ), and remote zone (RZ).
2.7. Infarct size
All histological sections were stained with Masson's
trichrome and quantified with a Nikon Eclipse E800
microscope using a 1× objective lens with the use of Openlab
software (Improvision, Lexington, MA, USA). ImagePro
Plus 6.0 software was used to measure lengths [24] and
infarcted LV areas. Scar size was analyzed at the mid-
papillary level by an investigator who was blinded to the
identity of the sections. The percent scar within the IZ was
determined by manually tracing the areas of interest and
measured automatically by the computer. IZ was defined as
an area continuously enclosed by scar spanning N50% of the
wall thickness. The area of the tissue staining positive with
analine blue was then traced manually and the percentage of
assess the circumferential extent of the infarct, the epicardial
and endocardial infarct lengths and epicardial and endocar-
dial circumferences were traced manually using ImagePro
Plus. Epicardial infarct ratio was obtained by dividing the
epicardial infarct length by the epicardial circumference.
Endocardial infarct ratio was calculated similarly. The
circumferential extent of the infarct was calculated as
[(epicardial infarct ratio+endocardial infarct ratio)/2]×100.
2.8. Measurement of vascularity
In order to assess vascularity, sections were stained for
the vascular markers CD31 and alpha smooth muscle actin
Fig. 1. Study scheme of the experiments. Myocardial infarction (MI) was induced in male mice by permanent mid-LAD ligation at Day 0. Ultrasound-
guided injection of mouse bone marrow cells (BMCs) (1×106/10 μl) to the peri-IZ was performed (n=8–9/group) at different time points post-MI (Days 3,
7, and 14) as monotherapy, and at Days 3+7 as double therapy and at Days 3+7+14 as triple therapy. Control group was injected with HBSS at Day 3 and
at Days 3+7+14.
3Y. Zhang et al. / Cardiovascular Pathology xx (2010) xxx–xxx
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(SMA). Sections were first fixed in 1.5% PFA solution.
After rinsing in distilled water, the sections were treated
with a peroxidase solution (Biocare). The sections were
rinsed with Tris buffered solution (TBS) and then treated
with a universal block (Rodent Block M, Biocare) for
30 min. A primary rat antibody against CD31 (Biocare,
1:50 dilution in Da Vinci Green Diluent) was applied to the
sections for 2 h at room temperature. A Rat Detection Kit
(Biocare) was used to detect the rat anti-CD31 antibody.
The stain was developed using DAB (Biocare). Sections
were again blocked using Rodent Block M and then stained
using a mouse primary antibody against alpha SMA
(Sigma-Aldrich, St. Louis, MO, USA; 1:200 dilution in
TBS) for 1 h, and a Mouse on Mouse Polymer (Biocare)
conjugated to alkaline phosphatase was applied to the
sections for 20 min at room temperature. The sections were
washed in TBS again, and the stain was developed using a
Ferangi Blue Chromogen Kit (Biocare). The negative
controls were treated using the same methodology, omitting
the primary antibody and replacing it with the Da Vinci
Green Diluent. Low power (4×) photomicrographs were
taken of three regions: IZ, BZ, and RZ. ImagePro Plus 6.0
software was used to select brown CD31+ staining after
manually selecting the region of interest, and the percentage
vessel area was obtained for each of the three regions.
Additionally, the number of vessels staining positive for
alpha SMA per high-power field (HPF) was counted within
each region. The number of vessels in the IZ and BZ
regions was adjusted by the number of vessels in the RZ
region for both small and large vessels.
Fig.2. Therapeuticeffect of BMCs at differenttime points,andmultiple vs.monotherapyon left ventricular function measuredby echocardiography.Injection of
BMCs at Day 3, Days 3+7, and Days 3+7+14 led to similar and significant improvements in LVEF at Day 28 compared to the control group (Pb.05). There were
no significant differences between these three groups at Day 28. Delaying the injection time to Day 7 or Day 14 post-MI did not improve LV function compared
to the controls. (A and D) LVEF: each line represents the mean of one experimental group. (B and E) ESV and (C and F) EDV at Day 28. Data are shown as
mean±S.E.M.; n=8–9/group.
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2.9. Statistical analyses
Data were presented as mean±S.E.M. For the comparison
of echocardiographic parameters and histological data
between groups, ANOVA with LSD post hoc tests was
used. For the comparison of LVEFchanges at Day 2 and Day
28 within each group, paired t test was used. A P value of
b.05 was considered statistically significant.
3. Results
3.1. Timing of therapy
The results of the monotherapy groups are described
first. In all groups, LVEF was uniformly reduced from an
average of 55.1±2.8% before MI to 37.9±1.3% (Pb.001) at
2 days post-MI (Fig. 2). At 28 days post-MI, LVEF
improved significantly in the Day 3 group compared to the
control group (40.3±2.0% vs. 31.1±8.3%, Pb.05). In
contrast, groups injected with BMC at Day 7 or Day 14
showed no improvement in LVEF compared to control
(35.5±6.1% and 34.5±3.9% vs. 31.1±8.3% respectively;
P=ns). LVESV and LVEDV were significantly smaller in
the Day 3 BMC injection group compared to the control
group (Pb.05; Fig. 2A–C), demonstrating less LV dilation
in this group. BMC injection at Day 7 reduced LVESV, but
not LVEDV, suggesting a modest beneficial effect when
cell therapy was delayed to Day 7, but no effect when
delayed to Day 14 post-MI. Of note, none of the animals in
any group suffered from sudden death using the echo-
guided delayed injections.
The infarct size was reduced when BMC therapy was
administered at Day 3 compared with control (17.8±3.6%
vs. 36.6±7.1%, P=.05) (Fig. 3A). BMC therapy at Day 7
or at Day 14 was not significantly different from control.
There appears to be a trend towards decreased benefit
with BMC therapy with delaying the injections when
comparing treatments at Days 3, 7, and 14 (Fig. 3A–B).
Early BMC therapy at Day 3 resulted in significantly
more viable tissue within the IZ (44.7±4.8%) compared to
monotherapies at Day 7 (29.2±4.2%; P=.03) and Day 14
(20.3±5.7%; P=.002) and control (27.1±9.1%; P=.01)
(Fig. 3B).
differences were observed between any of the treatment
groups for CD31+ vessel density in the IZ (Days 3, 7, and 14,
respectively; 0.66±0.26, 0.66±0.14; 0.58±0.22; P=NS) and
the BZ (0.72±0.10, 1.03±0.19; 1.1±0.2; P=NS) or the
number of SMA+ vessels per HPF in the IZ (Days 3, 7, and
14, respectively; 2.33±1.44, 1.88±0.6; 1.69±0.72; P=NS)
and the BZ (1.77±0.34, 4.10±1.66; 3.61±1.32; P=NS).
Fig. 3. Early therapy at Day 3 was associated with reduction in scar size. The infarct size was reduced when BMC therapy was administered at Day 3 compared
with Day 14 and control (A). Early therapy (Day 3) was associated with more viable myocardium in the IZ compared to Day 7 and Day 14 therapy, and control
(B). On the other hand, monotherapy at Day 3 was associated with reduction of infarct size (C) and an increase in viable tissue within the IZ at Day 28 (D)
compared with BMC triple therapy. Data are shown as mean±S.E.M.; n=8–9/group.
5Y. Zhang et al. / Cardiovascular Pathology xx (2010) xxx–xxx
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The numbers of GFP+ donor cells were quantified at
Day 28. No GFP+ cells were detected in the HBSS group.
The total number of GFP+ cells per section increased with
delayed injections comparing Days 3, 7, and 14, respectively
(2.33±1.28 vs. 5.57±3.61 vs. 29.17±11.88 cells per section)
(Fig. 4), and it was significantly higher in the Day 14 group
vs. the Day 3 group (Pb.05). The persistent presence of
donor BMCs does not correlate with the functional benefit of
cell therapy. The majority of GFP+ cells appear to localize
at the IZ and the least are present in the remote myocardium.
3.2. Multiple injections
In all groups, LVEF was uniformly reduced from an
average of 56.1±0.9% before MI to 37.5±1.1% (Pb.001) at
2 days post-MI (Fig. 2). At Day 28, LVEF improved
significantly with Day 3 monotherapy, Days 3+7 double
therapy, and Days 3+7+14 triple therapy groups compared to
HBSS control triple therapy group (40.3±2.0%, 39.9±3.6%
and 38.8±5.5%, vs. 34.8±5.3%, Pb.05) (Fig. 2D). However,
there was no significant difference between the triple and
double therapy groups vs. the Day 3 monotherapy group.
EDV and ESV were significantly preserved in the Day 3
monotherapy and double therapy groups vs. the HBSS triple
therapy group (all Pb.05) (Fig. 2E–F). However, the trend of
preservation of the left ventricular volumes in the triple
therapy group was not significant (P=.07). Of note, none of
the animals in any group suffered from sudden death using
the echo-guided repeated injections.
The infarct size was significantly reduced with BMC
monotherapy at Day 3 compared with triple therapy and
HBSS triple therapy control [17.8±3.6% vs. 37.8±8.1%
(P=.03) and 43.9±6.1% (P=.01)] (Fig. 3C). As shown in
Fig. 3D, in terms of the percent of viable tissue within the IZ,
monotherapy at Day 3 showed significantly more viable
myocardium (44.7±4.8%) compared to double therapy
(30.8±4.6%; P=.04), triple therapy (22.3±4.0%; P=.002),
and HBSS triple therapy (29.0±6.3%; P=.03).
In regard to blood vessel numbers at Day 28, capillary
density within the BZ was increased with triple therapy
(1.3±0.4 %) compared to monotherapy (Day 3) (0.72±0.1%,
P=.03). However, there were no significant differences in the
number of arterioles between groups (triple, double,
monotherapy Day 3, and control, respectively: 3.1±1.7,
2.1±0.9, 1.8±0.3, 1.8±1.2 per HPF).
No GFP+ cells were detected in the HBSS group. The
number of GFP+ cells was greater in triple therapy vs.
double therapy, and Day 3 monotherapy (34.0±21.5 vs.
5.33±2.47 and 2.33±1.28, respectively, both Pb.05). Most
donor BMCs were located in the IZ and least in the RZ. The
results show that the persistent presence of BMCs does not
correlate with the functional benefit of cell therapy.
4. Discussion
In this study, we report the following: (1) delivery of cells
into the mouse myocardium many days post-MI can be
Fig. 4. Retention of GFP+ cells at the IZ at Day 28. The total number of GFP+ cells per section was greater in triple therapy vs. double therapy, Day 3 and Day 7
monotherapies (Pb.05). However, there was no significant difference between triple therapy and Day 14 monotherapy. Arrows demonstrate the presence of
GFP+ cells by brown DAB staining to avoid the artifacts of autofluorescence.
6Y. Zhang et al. / Cardiovascular Pathology xx (2010) xxx–xxx
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safely and successfully accomplished using the ultrasound-
guided technique without a need of resternotomy; (2)
multiple intramyocardial injections can be successfully
made with minimal mortality; (3) there appears to be a
critical time window in post-MI (around 3 days) during
which cell therapy is most successful in improving cardiac
function; and (4) multiple injections do not appear to have an
additive beneficial effect on cardiac function post-MI. In this
infarct model, double therapy at Days 3+7 or triple therapy at
Days 3+7+14 did not improve the cardiac function any more
than monotherapy at Day 3. The results also show that
despite persistence of BMCs, there is no additional
functional benefit with multiple injections.
The closed-chest ultrasound-guided approach has allowed
us to successfully perform repeated injections with almost
zero mortality and enabled us to address a number of
important and clinically relevant issues. Based on the
echocardiographic scoring system outlined in the Methods
section, all animals were judged to be optimally injected and
none of the animals needed to be removed from the study due
to poor injections. We found that injection at Day 3 defined
the best time window for therapy in the mouse infarct model
and that delaying the injection did not have any effect on
improving the heart function. This is of interest because Day
3 post-MI in the mouse model may correspond to
approximately Days 6–7 post-MI in humans when consid-
ering inflammatory changes [22,27], although direct extrap-
olation of the timing in the mouse model to the human
situation is not known.
As pointed out earlier, the REPAIR-AMI Trial [12]
reported on the benefit of cell therapy if the cells were
delivered 5 days or more after MI. In that study, most
patients with benefit of cell therapy were treated at Days 6–7
post-MI and it is unclear whether patients who received the
therapy much later post-MI had any benefit. Our results
would suggest that delaying the cell therapy too long post-
MI might no longer result in any clinical benefit. It is likely
that once the scar tissue begins to form several days after an
MI, the tissue is less receptive to therapies and thus has no
benefit. In fact, we have recently shown that early therapy
post-MI with BM-derived cells results in decreased cardio-
myocyte apoptosis and more blood vessel formation which
results in a smaller scar early after MI [5]. It is notable that
too early a therapy post-MI may also be of no benefit as
shown in the REPAIR-AMI trial and recently reported in a
meta-analysis by Zhang et al. [23]. The reason(s) for this is
not known, but it is possible that the inflammatory milieu
that is present immediately post-MI creates an environment
that may not benefit from the delivery of even more cells into
the myocardium. In our study, we did not test cell delivery at
the time of the infarct as this is not clinically very relevant
since bone marrow-derived cells are not available clinically
for use in patients at the time of their acute MI.
In addition to the timing of therapy, our current study is
the first to comprehensively assess the safety and efficacy of
repeated intramyocardial cell injections post-MI. We found
that multiple injections did not have an additive effect on
improving the heart function. This is consistent with the
Danish Stem Cell study, which was a prospective non-
randomized study assessing repeated intracoronary BMC
infusion in patients with ischemic heart disease [28]. Even
though this study reported an association with symptomatic
relief and transiently improved exercise capacity, the authors
were unable to detect any improvement in LVEF or in the
wall motion score index. In fact, in our study, multiple
injections were associated with worsening trends in the left
ventricular volumes. One possibility for this is that repetitive
needle puncture may have resulted in significant local
damage at the peri-infarct myocardium in these small hearts,
and repeated injections could have disturbed the healing of
the infarcts.
Our research also differs from the findings of Yao et al.
[16] that therapy of patients post-MI with repeated
intracoronary administration of BMC Days 3–7 post-MI
and again at 3 months was more effective than single therapy
at the early time point. The disparities may have resulted
from numerous differences in the study designs. Our study
involved a direct intramyocardial injection in the rodent
model in contrast to the intracoronary infusion in patients
used by Yao et al. [16]. The studies also used different cell
fractions (whole BMCs vs. component mononuclear cells).
Notably, our study compared single to multiple deliveries
within the first several weeks, while their patients came back
3 months later after a first-week infusion.
We were able to detect the presence of the injected GFP+
cells in the treated groups. Interestingly, increased presence
of cells, either via delayed injection or via repeated
injections, did not show a direct correlation in terms of the
therapeutic functional benefit. It seems conceptually enticing
that more cells would result in greater benefit, but we could
not demonstrate this in our model [5]. Notably, cell retention
in the heart even after direct intramyocardial delivery is poor.
We have previously shown a significant disappearance of
GFP transcripts over time despite the use of closed-chest
ultrasound-guided approach [5]. Consistently, others have
also shown poor retention of stem cells in the heart after
direct cell delivery [29,30]. Yasuda et al. [30] have reported
that only 50% of cells remained in the myocardium after only
1 h and that cell survival progressively decreased further
over the 4-week study. In our study, while Day 3 therapy
leads to fewer surviving cells at Day 28, the cells (or their
extract as we have reported) exert their beneficial effects at a
critical time point post-MI. Thus, we propose that additional
injections are not as important as figuring out the best timing
of therapy post-MI.
It should be noted that in order to restrict analyses to a
constant time during the remodeling process post-MI
(28 days), the Day of functional analysis must necessarily
be at different times after BMC implantation; that is, 28 days
post-MI analysis of a Day 3 injection is 25 days post-
injection, whereas 28 days post-MI analysis of a Day 14
injection is 14 days postinjection. However, we feel that this
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is the most valid approach because it is the only way to
compare different treatments at comparable stages of cardiac
remodeling. Moreover, we have previously reported that the
number of remaining BMCs declines rapidly [5] and it is
unlikely that additional therapeutic effect will be exerted
during the last 14 days.
The mechanisms underlying the beneficial effects of
BMC implantation into post-MI hearts are complex and
controversial. We and others have reported that BMCs can
aid in tissue preservation post-MI via a paracrine mecha-
nism. In our previous report [5], we demonstrated an early
increase in vascularity at Day 6 but not at Day 28, and that
injection of BMCs increased vessel area density and had a
higher number of arterioles in the infarct BZ. At Day 28, this
increase in vascularity equilibrated back to the expected level
in normal tissue, while the overall cardiac functional benefits
appear to have lasted for a longer time period. We
hypothesize that increased vascularity early after MI rescues
ischemic cardiomyocytes from apoptosis, thereby salvaging
myocardium. After the first few weeks post-MI, the viable
myocardial tissue and scar remodel to have their appropriate
vascular supply. What we see as the infarct BZ, then, in the
treated animals would have become scar tissue in the
untreated animals. Enhancing neovascularization post-MI
"moves" the BZ. These results are consistent with prior
studies by Schuleri et al. [31] who demonstrated that an early
increase in myocardial perfusion resulted in longer term
functional improvement. Indeed, these authors also show no
increase in capillary number after 8 weeks.
Our study has several limitations. First, the duration of the
study is only 28 days. Longer duration and survival studies
should be performed in the future, especially in the delayed
and multiple therapeutic arms. Secondly, earlier time points
before Day 3 or other time points post-MI were not tested to
allow successful completion of an already challenging
experimental design. Our experimental protocol was
designed before the results of the REPAIR-AMI Trial were
available and Day 3 post-MI was selected to mimic a
reasonable time period that a human subject may be treated
with bone marrow-derived cell therapies clinically post-MI.
Third, histology at early time points after cell delivery are not
available as the size of the study would have been too large
to include more animals for early sacrifice time points.
Fourth, it is unknown which stem cells hold the best
therapeutic promise in treating patients post-MI. Whether
other stem cells would have additive benefits with multiple
injections post-MI is unknown and this is outside the scope
of our current research. Lastly, this is a descriptive report and
our previous publication has addressed the detailed mecha-
nistic questions in regard to the cells which were used in this
manuscript and because of space limitations these data have
not been presented here [5].
In summary, we have shown that in the mouse MI
model, multiple injections of BMC did not have an additive
effect on improving LVEF post-MI compared to a single
therapy at Day 3. Moreover, further delaying the time of
cell therapy post-MI resulted in no functional benefit and, in
fact, led to a worse outcome. These results have direct
clinical implications and further clinical research is
warranted to delineate the optimal timing of cell therapy
in patients post-MI.
The authors acknowledge Mr. Petros Minasi for his
administrative support in conducting the experiments.
[1] Lee N, Thorne T, Losordo DW, Yoon YS. Repair of ischemic heart
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[2] Reffelmann T, Konemann S, Kloner RA. Promise of blood- and bone
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Endresen K, Ilebekk A, Mangschau A, Fjeld JG, et al. Intracoronary
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Hecker H, Schaefer A, Arseniev L, Hertenstein B, et al. Intracoronary
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Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, et al.
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[11] Orlic D, Kajstura J, Chimenti S, JakoniukI, AndersonSM, Li B, Pickel
J, McKay R, Nadal-Ginard B, Bodine DM, et al. Bone marrow cells
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Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, et al.
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Page 9
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dial infarction. N Engl J Med 2006;355(12):1210–21.
[13] Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R,
Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, et al.
Improved clinical outcome after intracoronary administration of bone-
marrow-derived progenitor cells in acute myocardial infarction: final
1-year results of the REPAIR-AMI trial. Eur Heart J 2006;27(23):
[14] Roncalli J, Leobon B, Massabuau P, Galinier M, Parini A, Pathak A,
Bourin P, Hagege AA, Menasche P, Fournial G, et al. Cardiac cellular
therapy: from cells to the first clinical uses. Arch Mal Coeur Vaiss
[15] Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F,
Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Mobilized bone
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[16] Yao K, Huang R, Sun A, Qian J, Liu X, Ge L, Zhang Y, Zhang S, Niu
Y, Wang Q, et al. Repeated autologous bone marrow mononuclear cell
therapy in patients with large myocardial infarction. Eur J Heart Fail
[17] Dawn B, Stein AB, Urbanek K, Rota M, Whang B, Rastaldo R, Torella
D, Tang XL, Rezazadeh A, Kajstura J, et al. Cardiac stem cells
delivered intravascularly traverse the vessel barrier, regenerate
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[18] Kudo M, Wang Y, Wani MA, Xu M, Ayub A, Ashraf M. Implantation
of bone marrow stem cells reduces the infarction and fibrosis in
ischemic mouse heart. J Mol Cell Cardiol 2003;35(9):1113–9.
[19] Uemura R, Xu M, Ahmad N, Ashraf M. Bone marrow stem cells
prevent left ventricular remodeling of ischemic heart through paracrine
signaling. Circ Res 2006;98(11):1414–21.
[20] Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De
Angelis A, Hosoda T, Chimenti S, Baker M, Limana F, et al. Cardiac
stem cells possess growth factor-receptor systems that after activation
regenerate the infarcted myocardium, improving ventricular function
and long-term survival. Circ Res 2005;97(7):663–73.
[21] Springer ML, Sievers RE, Viswanathan MN, Yee MS, Foster E,
Grossman W, Yeghiazarians Y. Closed-chest cell injections into
mouse myocardium guided by high-resolution echocardiography. Am
J Physiol Heart Circ Physiol 2005;289(3):H1307–1314.
[22] Yang F, Liu YH, Yang XP, Xu J, Kapke A, Carretero OA. Myocardial
infarction and cardiac remodelling in mice. Exp Physiol 2002;87(5):
[23] Zhang S, Sun A, Xu D, Yao K, Huang Z, Jin H, Wang K, Zou Y, Ge J.
Impact of timing on efficacy and safety of intracoronary autologous
bone marrow stem cells transplantation in acute myocardial infarction:
a pooled subgroup analysis of randomized controlled trials. Clin
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[24] Takagawa J, Zhang Y, Wong ML, Sievers RE, Kapasi NK, Wang Y,
Yeghiazarians Y, Lee RJ, Grossman W, Springer ML. Myocardial
infarct size measurement in the mouse chronic infarction model:
comparison of area- and length-based approaches. J Appl Physiol
[25] Okabe M, Ikawa M, Kominami K, Nakanishi T, Nishimune Y. 'Green
mice' as a source of ubiquitous green cells. FEBS Lett 1997;407(3):
[26] Zhang Y, Takagawa J, Sievers RE, Khan MF, Viswanathan MN,
Springer ML, Foster E, Yeghiazarians Y. Validation of the wall motion
score and myocardial performance indexes as novel techniques to
assess cardiac function in mice after myocardial infarction. Am J
Physiol Heart Circ Physiol 2007;292(2):H1187–1192.
[27] Fishbein MC, Maclean D, Maroko PR. The histopathologic evolution
of myocardial infarction. Chest 1978;73(6):843–9.
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Saekmose SG, Barington T, Kristiansen M, Kassem M. Effect of
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stem cells. Am J Physiol Heart Circ Physiol 2008;294(5):
9Y. Zhang et al. / Cardiovascular Pathology xx (2010) xxx–xxx


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Street Style: Stony Brook University
Not everyone dresses up to attend long-winding lectures on astrology or sociology. However, at Stony Brook University, some students put their best foot forward and create sartorial sensations. Here are a few. -- Matthew T. Murray
Long Island and New York City's top photos Long Island polar bear plunges Places we loved on Long Island LuHi girls in Fed final LI softball players to watch in 2015 Fire destroys Cherry Grove landmarks Your Instagram, Twitter snow photos St. Agnes Cathedral renovations Promotions, hires on Long Island LuHi boys in Fed semifinals Half Hollow Hills West vs. Smithtown East Nassau, CHSAA girls lacrosse players to watch in 2015

subset: commoncrawl


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Calendar Email eLearning MyUNIverse A-Z Index Directory Rod Library Jobs@UNI
Katy Slaven graduated from our department in 2010, and has recently been admitted to the acting training program at Florida Atlantic University. Here's what she reports about her activity since leaving UNI:
Congratulations to graduating Senior Stephanie Wessels, who is about to start an internship with Theatre Communications Group (TCG) as the Communications and Conferences Intern for the 2012 winter/spring term. See the full story on UNI's home page! http://www.uni.edu/this-is-uni/its-graduation-timeso-whats-next
UNI Theatre Alumni Reunion, April 13-14, 2012.
Mark your calendars today and plan to return to campus for an alumni reunion and the Strayer-Wood Theatre production of Bat Boy: The Musical.
A block of rooms has been established at Comfort Suite, Cedar Falls. Call 319-273-9999 and ask for the UNI Theatre Alumni Reunion Rate of $89.99
The UNI Department of Theatre hosted the 2011 Iowa Thespian Festival November 11-12, 2011. Students got the chance to try UNI's famous Interlude Dance. You can watch the YouTube video here.
Thespians, welcome to UNI! We are excited to host, once again, an exciting weekend of outstanding high school performances and workshops, November 11 & 12, 2011.
Click here for more info about ThesFest.
Click here to sign-up for our ThesFest Twitter Updates.
Mad Forest appears in the on-line version of the Waterloo Courier.
The audition requirements for Dying City have been posted! Auditions are open to all UNI students, and will be held November 7 and 8, 2011.
Consumer Information | Safety | Diversity Matters | Sustainability | Accessibility | Visit UNI | Contact UNI | Equal Opportunity/Non-Discrimination Statement
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Copyright © 2014 All rights reserved University of Northern Iowa, Cedar Falls, Iowa (319) 273-2311
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Not all silk vendors are created equal. Manito is headquartered in North America where we maintain inventory. We offer Free Shipping anywhere in North America for orders of $50 or more. Manito designs its products here, for western colors, tastes and style. Our parent company manufactures everything we sell. Buy with absolute confidence.
The Best Silk Pillowcases for Hair and Skin
A silk pillowcase for hair and skin is a must if you truly want to take full advantage of your beauty sleep. Whether you want to enhance your youthful appearance, or protect your hair from breakage, you will love the benefits of sleeping on silk pillowcases.
Silken Hair
Silk is a luxurious, hypoallergenic fabric that allows your ...
Celebs who love Manito, Holiday Edition: June Squibb.
As the holidays fast approach, so many of us turn our thoughts to family. Hey, it may not be all good, but come time for the holidays we all want to remember the best parts and have the best times and give (and receive) the best gifts:)
Here at Manito, we've been cozying up this holiday ...
Mulberry Silk. Explained.
A Mulberry Farm
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Saudi Arabia
Rand Paul: Foreign donations to Clinton Foundation 'thinly veiled bribes'
He'll call on the foundation to return money received from countries that abuse the rights of women.
Saudi Arabia condemns 'terrorist' act in North Carolina
The country calls for an end to incitement against Muslims.
Cruz offers rare praise of an Obama
He thanks first lady Michelle Obama for not covering her head while visiting Saudi Arabia.
How Democrats killed Obama's college savings plan
Nancy Pelosi and Chris Van Hollen were key opponents of a tax on 529 plans.
Michelle Obama's uncovered head draws Saudi Twitter critique
They chastise the first lady for being disrespectful to Saudi traditions.
Letter from Riyadh: Not much mourning
New Saudi king lavishes Obama with personal attention as aides and reporters gawk.
Obama defends Saudi ties
The president avoids answering a question on whether he would speak to Saudi officials about human rights.
Obama courts a 'so-called' ally
Obama's trip to Riyadh is a chance to show how the two countries need one another.
Dear King Salman: Why I'm Terrified About Our Saudi Future
From a loyal subject pleading for change.
Dempsey seeks essay contest to honor late Saudi king
The National Defense University would run the competition.
King Salman's war
Why the new Saudi ruler will likely ratchet up the region-wide conflict with Iran.
Je suis Abdullah
How and why Obama upended his plans to go to Riyadh but not Paris.
Obama cuts shorts India trip, adds Saudi Arabia stop
The president scraps his Taj Mahal visit to pay his respects to the late Saudi king.
Senator: New Saudi king alert, 'engaging'
John Barrasso, who visited with five other senators, says Salman showed no signs of dementia.
Obama hails the late Saudi King Abdullah
In his statement, he stresses the durability of U.S.-Saudi ties.
Saudi Arabia's King Abdullah dies
His expected successor is his 79-year-old half-brother, Prince Salman.
Of course it is Islam
All this dancing around the obvious makes it impossible to take Islamic terrorists seriously on their own terms.
Glenn Beck loses bid to dismiss Saudi's libel suit
Judge: Student investigated and cleared in Boston Marathon bombing can press case against conservative commentator
How the Middle East's First Nuclear War Started
A fictional story.
Syria debate roils administration
Chuck Hagel sends Susan Rice a memo that faults the administration's outlook on the conflict.


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GPS Tracking of State Worker Raises Privacy Issues 173
from the you-can-trust-us dept.
We've improved Slashdot's video section; now you can view our video interviews, product close-ups and site visits with all the usual Slashdot options to comment, share, etc. No more walled garden! It's a work in progress -- we hope you'll check it out (Learn more about the recent updates).
As alluded to in the article, they were looking into his timesheets and his assertion that he worked odd hours.
It looks like the state thought he was lying about his hours, and so used the GPS tracker to catch him in a lie concerning hours worked. It seems a touch excessive, but government jobs likely require a high standard of proof in order to fire an employee.
Maybe a better solution would have been to provide him a state vehicle with a hidden GPS tracker.
Or an Obvious one, functional or not. That might have got him back into line if there was wrong doing, or show he wasn't worth keeping, either way it would have been far cheaper than a lawsuit even if they win it.
the problem was they were tracking him 24/7, and that's illigal.
That, and attaching a device to his personal car should be considered some kind of tresspassing/vandalism.
What's truly fucked up here is that they felt that they couldn't fire him simply because of his "pattern of misconduct". They appear to have felt that they needed more proof or something.
I interpret that to mean "there wasn't actually a pattern of misconduct, we went on a fishing expedition hoping to find one".
These days most employers have some boilerplate they hand out when you take a job that says they will do this if they feel it necessary. Really you should assume they monitoring you while you are on the job, if for no reason than protect themselves from things like that $2 billion loss UBS is stuck with.
The point is that these were government workers. Your constitutional rights trump most of what they would ask you to waive. And courts have said that, say, your fourth amendment right require informed consent to waive, which a blanket waiver cannot satisfy.
"We don't care. We don't have to. We're the Phone Company."


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Give Her Mind Blowing Orgasms Every Single Time - 3 Proven Sex Techniques
When it comes to giving women mind blowing orgasms every single time there are a variety of different sex techniques that will help you accomplish just that.
In this article we will go over 3 proven sex techniques that will give her mind blowing orgasms every single time.
The first and most important thing you can do when it comes to giving a woman a mind blowing orgasm each and every time is spending a lot of time in the sexual foreplay aspects before moving on to more intimate activities.
Basically, the longer you can go without actually touching or stimulating her breasts or vaginal area the more she is going to want you to which will lead to a better sexual experience for her.
Sexual foreplay is your opportunity to help the woman relax and get comfortable which are very important when it comes to giving women the kind of mind blowing orgasms that you want to give her.
The next proven sex technique is actually a combination of two of the most effective ways to help a woman climax.
First, after the woman that you are with becomes highly aroused apply G Female Stimulating Gel or any of the other high quality female arousal creams and gels underneath the hood of her clitoris which will greatly enhance her pleasure.
Next, you are going to want to move into a variety of different sexual positions in which the woman is on top which will allow you to continue to stimulate her clitoris while she finds the right rhythm and position on top of you so that she can hit her G-Spot.
Last but not least, you are going to want to last longer in bed as most women cant have an orgasm during intercourse if the session ends too quickly. In the end, as long as you make sure to spend some quality time in the sexual foreplay aspects of the experience and use G Female Stimulating Gel once she is highly aroused you will find that giving her the kind of mind blowing orgasms that you desire to give her to be a relatively easy process.
Discuss this Article
What's the most effective way to make her climax in a way that has her having mind blowing orgasms. In this article, get ready to enjoy a special sex technique that will make her orgasm so powerfully that the two of you will more than likely come up with your own special name for this really special sex technique.
How do you turn a woman into the kind of woman that wants to be with you every night? For starters you can begin to learn the different kinds of sex tips, positions and techniques that will make her climax again and again. In fact, in this article, you will discover some of the best kept secrets in regards to how to make a woman climax as we reveal to you 3 magical sex positions that will have her having the kind of mind blowing orgasms that will have her running home to be with you...
Let's face it, when it comes to making a woman climax, if you truly care about her you are going to want to know a variety of different sex techniques that have been proven to give her mind blowing orgasms. It isn't enough to simply learn one or two different ways to make the woman that you are with climax; instead you need a variety of different sex techniques that you can pull out of your sexual toolbox that will lead her to orgasmic bliss...
Did you know that 8 out of 10 men have absolutely no idea how to make a woman climax? You've probably noticed that the woman that you are with may or may not think that you are one of those 8 men. Now, is the time to do something extraordinary by continuing to read this article in order to learn more about 3 great sex techniques that will make a woman climax and give her the most mind blowing orgasms ever!
Sure Shot Ways to Make Any Girl Climax Fast! Giving Her Mind Blowing Orgasms Will Be Easy After This
When it comes to making a girl climax in a way that will give her mind blowing orgasms it can be quite easy if you know the right way to turn her on. Once you begin to realize that making a girl climax is all about sexual foreplay and a using a few sex techniques and tools from your sexual toolbox you will quickly have the woman that you are with experiencing the kind of mind blowing orgasms that you both desire.
Do you want to impress your lover with by giving her hot steamy orgasms? Then take the time to learn how to love her. These 4 basic techniques will give you a lot of mileage in the bedroom.
Learn how to give her a mind blowing orgasm and make your lovemaking unforgettable. Women deserves to get what they want and men should know how to satisfy their woman.
Wife orgasm, in this write today, we shall be discussing about a few ultra simple yet very effective tips that you can implement to constantly give your wife multiple mind blowing orgasms. Orgasm as you may or may not know is that point during a sexual encounter when all the muscles that tensed up in a female's body due to sensual stimulation suddenly relaxes thus sending her through waves and waves of earth shattering pleasure.
For the most part when it comes to giving women the kind of mind blowing orgasms that every woman fantasizes about most men settle on either stimulating her clitoris in order to give her what she wants or attempt to find her G-Spot in the hopes of giving her one that way. However, if you truly want to give the woman that you are with the kind of mind blowing orgasms that will have her wanting to be with you again and again the best thing you can do is become skillful at giving her blended orgasm
Sex tips can help men improve their sexual encounters. When considering such tips, remember that the condition of the bedroom has an impact on sex.
Uncontrolled penis odor can result in a major date disaster. Men want to make sure they take appropriate steps to eliminate unwanted penis odor before an outing with a potential partner.
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While some causes of penis bumps require treatment, others are natural and harmless. Men can learn about three types of bumps that may affect the penis but are not causes for concern here.
It's hard to fully enjoy sex when one has a numb penis. Restoring lost sensitivity (or preventing it from occurring) enables a man to enjoy sexual pleasure to the fullest.
An itchy penis is a common problem for many men, but it may present a special problem for those with a latex allergy, as it may make using condoms an issue.
Exercise is beneficial to several areas of one's life, including sex. Learn the best exercises for better sex.
2 Secrets Alpha Men and Bad Boys Use To Make Women Have Mind Blowing Orgasms and Become Addicted to Sex
It's no secret that bad boys and alpha men generally have the opportunity to sleep with a variety of different women if they want. However, did you know that part of the reason they are able to do so is because they either know or are utilizing 2 powerful secrets that not only attracts women it also has the potential to lead a woman into a state of orgasmic bliss.
Do you want to learn a really simple and powerful sexual technique that will lead to the woman that you are with having the most mind boggling orgasms that she has ever had? If you really are interested in learning a simple and powerful sexual technique that will have your woman entering states of orgasmic bliss that you can't even begin to imagine then continue reading this article and let the sexual journey begin again.
Today, more than ever we live in the kind of society that for whatever reason has been conditioned to believe that the "size" of a man's penis really does make a difference when it comes to sexually satisfying a woman.
A lot of people seem to feel that in order for a man and a woman to have a great sex life requires the man to have a bigger penis size rather than a smaller penis. In fact, a question that you will find people asking fairly often is "Does Penis Size Matter?" That's why as you continue to read this article you will find yourself discovering 3 monumental sex tips that will make you absolutely certain that penis size really doesn't matter when it comes to having a great sex life.
In this article, you will discover some of the best kept secrets that you absolutely most know in regards to love making techniques as we reveal 3 enchanting sex positions that have been proven to give her the kind of mind blowing orgasms that she will never forget.
Are you looking for ways to bring the woman that you are with the most incredible and intense sexual pleasure that you can imagine? Have you and your partner fallen into the same old love making routine night after night and are looking to change it up a little? If questions like these intrigue you then you are definitely going to want to learn about the 3 charming ways you can bring her sexual pleasure in this article.
It's no secret that the more love making techniques you can learn that make her orgasm the better lover you will be. In this article, get ready to enjoy a delightful lovemaking technique that will make her orgasm and have her thinking about those orgasms all day and all night.
When it comes to the different female stimulating arousal creams and gels on the market, the one that a lot of people have heard a lot about is KY Intense Arousal Gel which makes sense when you consider how much money they spend on advertising each year. In this article, you will discover the truth about K-Y Intense and whether or not it is the real secret to female orgasms and sexual satisfaction.


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Photo Gallery
Missile successfully shot down in test off Kauai
1 of 1
A Standard Missile 3 (SM-#) Block 1B interceptor was launched from the USS Lake Eerie during a test off Kauai today. (Courtesy Missile Defense Agency)
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Harness the power of centrifugal force and set this awesome light up toy in motion! Place the Gyro Wheel on the hand held rail and move your hand and wrist to make it spin. The faster it spins, the more the lights flash. After a bit of practice you can throw the top onto your desk or other flat surface and watch the strobe-like light show of the spinning top! See all Fidget Toys here!
Hand held rail is approximately 3" tall x 2.75" wide x 8" long, hard plastic handle with metal rail. Top is 1" tall x 2.5" wide x 2.5" long, hard plastic with metal fitments and light up mechanism inside. Requires 3 LR44 batteries (included). Assorted Colors **Randomly Selected & Sold Individually** This item comes in assorted colors, including red, pink, blue, and green. How to select color/style WARNING: Choking Hazard - Small parts. Not for children under 3 years.
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Hannah Davis definitely earned that Swimsuit Issue cover.
Hannah Davis definitely earned that Swimsuit Issue cover.
A photo posted by LOVE MAGAZINE (@thelovemagazine) on Feb 11, 2015 at 7:24pm PST Is your girlfriend going to give you an actual gift for Valentine's Day.
DirecTv's latest advertising campaign will make you forget all about all those different Rob Lowes.
Derek Jeter may have retired from baseball, but he did not resign from his playboy lifestyle.
Future Hall of Famer and current blogger Derek Jeter has jumped into retirement with both feet, catching up on projects he was forced to put on the back burner during his playing career.
Hmmm, now that Derek Jeter's retired I wonder if Hannah Davis will still be interested in hanging out with him.
The last time we saw model Hannah Davis she was doing her dead best not to slip a nip.
Just when we were about through with these Ice Bucket Challenge videos comes Katy Perry in a bikini and we're sucked right back in.
Hannah Davis is still Derek Jeter's girlfriend, right.
What's the best way to talk about six of the coolest white tees available today.


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"Ordered this for my daughter's Sweet 16. We were thrilled with the quality when it arrived. The card has a texture and is thick. Ordered the white rectangular envelopes that are fitted so that you don't incur extra postage and they look fine with it. It really is a beautiful invitation and makes a classy statement."
"The colors are bold and well, colorful, without being neon or cartoonish. The invitation was an excellent choice for a 50th birthday. Like always, Tinyprints printed and shipped quickly. I am never disappointed."
"Got the invitations for my daughter's birthday party. They are very elegant and sophisticated. Love the quality of the print and paper too!"
"I am flabbergasted by how beautiful my daughters invitation turned out!! I chose with the pearl shimmer and it just makes the photos so exquisite. We have received many many compliments by friends and family on the quality of the invitation, this is for sure an invitation people will keep and not throw out. I am EXTREMELY satisfied to say the least."
"The teacups are delicate and detailed... beautiful enough to carry the otherwise simple invitation. The colors came out subtler than they appear onscreen, which I actually liked more. Most noticeably, the contrast between the green border and the ecru background was significantly less pronounced. The only paper option of Signature Ecru Textured was perfect for the watercolor effect. I found the default font for the emphasized/pink lines too thin even at the largest size option. I opted for Thirsty Rough instead. It wasn't exactly what I was looking for as far as style but the uneven coloring of the Thirsty Rough font echoed the uneven coloring of the watercolored teacups very nicely."


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The Canadian Press - ONLINE EDITION
Not just another pretty face: GG relishes foreign policy role in his own way
OTTAWA - When David Johnston takes on a cabinet-level trade assignment this weekend in Latin America, it will be a showcase for what could be the unoffical slogan for his vice-regal reign: bland is beautiful.
The Governor General is quick to point out he means bland as in an effective — if stealthy — exercise of his powers as the Sovereign's representative in Canada.
"This office probably works best when it is rather invisible. Not terribly much involved in controversy. Out of the mainstream of politics. And, I suppose, somewhat bland," Johnston said in a Rideau Hall interview prior to leaving for Mexico City.
Make no mistake: Johnston knows he lacks the panache and media punch of his two most recent predecessors, Michaelle Jean and Adrienne Clarkson. And it doesn't bother him a bit.
He's exchanged the effervescent public profile of those who came before him for something else: access to the prime minister on policy issues.
The trade-off has been a dearth of media attention. Johnston's office has been quietly lobbying the Parliamentary Press Gallery in Ottawa to pay more attention to his scheduled events.
Still, it would be a mistake to confuse "bland" for "vacuous," warns foreign policy analyst Colin Robertson.
"He lacks the charisma of his predecessors, but intellectually, he's a rock star," Robertson said. "The big shift is that Harper has confidence in Johnston. They talk."
The white-haired former law professor and university president was tapped by Prime Minister Stephen Harper in 2010, when minority governments were the norm and constitutional questions an ever-present element of Canadian politics.
Amid today's calmer political waters, though, Johnston is quietly expanding his other roles — promoting volunteerism, travelling the world and speaking about how Canada should become a "smart and caring nation."
Johnston, who is writing a manual on Canadian securities regulation in his spare time, is unapologetically geeky about his passion for international trade and innovation.
He's also a details person: Johnston meticulously rehearsed his ceremonial Grey Cup kick-off at least 100 times, perfecting his strike to the point that he could barely walk down the stairs the next day.
So when Harper asked him to go to Mexico, Peru and Guatemala, he methodically set about learning not just the intricacies of the region's economics and politics, but also carefully assessing how his own presence can complement the efforts of other Canadian business and political leaders.
"One tries to get to know the countries one is visiting as well as one can," he said, describing how he works in tandem with the Department of Foreign Affairs and the Prime Minister's Office to determine goals and priorities.
"It's not a one-off. It's many different parts working in harmony."
Johnston fully appreciates the pomp and circumstance. His overriding goal in visiting Mexico is to "pay respect" to the democratic election of Enrique Pena Nieto — the head of the traditional ruling party PRI, which lost power in 2000 after 71 years at the helm.
For the PRI to make a legitimate comeback, said Johnston, "that's a great victory."
But once the ceremony is over, Johnston's hard work begins.
He said he intends to start by buttonholing several of the other 75 foreign leaders at the ceremony to discuss bilateral relations. Then, he'll turn his attention to increasing two-way trade trade and investment. He also hopes to find more ways to share Canadian expertise in mining, justice, policing and governance.
He is travelling with a sizable entourage of senior officials, members of Parliament, business and education representatives, a judge and several ambassadors.
When he gets back, he'll be reporting, in detail, straight to the prime minister. The two men speak and share ideas regularly, but after a foreign trip, Johnston has a formal responsibility to check in.
"When I come back, (I need to) be pretty candid and say, 'Yep, this is going well,' or, 'No, this is not going well and here's where we have to adjust our approaches,'" Johnston said.
The governor-general's trip to Latin America should be the beginning of a larger Canadian attempt to revive its relationship with the region, Robertson said.
"The flag isn't as present as it could be."
In Guatemala, Johnston will be looking at how Canada can help the country's police and judicial system to deal with the drug trafficking that is destabilizing the entire region.
Ottawa's decision to send the governor-general there is exactly the right level of engagement at this point, Robertson said.
Johnston's staff have a thorough understanding of what's at stake there, and can make some solid recommendations for a path forward, he added.
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OK- it is a pizza buffet. What more can I say. Not outstanding but not garbage either. Kids were running around which made this NOT enjoyable. But the food was decent. I just wish others would corral their kids rather than letting them run amok.
Please tell me what is it about a Buffet that make Restaurants feel that keeping the place Clean is NOT important!!!
I will go there for lunch with a friend or two, OR my Spouse. I see so many Moms in there joking and talking to other Moms while their Kids run all over the place right after they have...
They're pizza is the best and also they're service. It's family accessible and has kids running around.
Pizzas were coming out hot and fast on the buffet, there was two types of salad greens ,, they really needed more "fixings" for the salads, there were 5 types of dressings ( they need to add a vingerette for lo cal ) it was a great place to sit down and just take our time and watch a ball...
I love coming to this CiCi's, the service is great. We can order a specialty pizza if we want to and they always have the buffet stocked. We will certainly return! The only downside is lots of people with lots of kids who run all over the place like wild animals!
For anyone that's never tried a CiCi's, plain and simple, its a great family place, wonderful for kids, and very good value (all u can eat).
Even I go sometimes for those reasons.
But if your in the mood for real pizza, such as NY style, or other styles, CiCi's is certainlt isnt the place to go.
I suspect a...
Fell in love with Ci Ci's many moons ago.
Location originally frequented 40? years ago was an older looking building in the middle of the
shopping center off Northwest Hwy. East of LBJ demolished when shopping center was
re-vamped .
Son's Little League Teams often had their year end festivities there even though the buffet was 1/2 of what it...
Plentiful, hot & good. Love the spinach & cheese. They support the local schools which is great!
Register now for free — and start getting automatic notification of new reviews, responding to traveler feedback, adding new photos to your listing and much more.


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RAW LAND: . Great holding property for the future, priced to sell. Private, 1 acre would make a nice wooded escMore info
SINGLE FAMILY HOME: 5 bed, 3 full bath. 4,700 square foot custom home offers a level of fun and enjoyment rarely seen in the Pacific NorthwMore info
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SINGLE FAMILY HOME: 3 bed, 1.75 full bath. Spectacular 180 degree vintage view 1924 Front Row Columbia craftsman. Completely restored 3 BR andMore info
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SINGLE FAMILY HOME: 2 bed, 1.00 full bath. Check out this well priced Cordata Cottage. Purchased new in 2007 never lived in. This home is as nMore info
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Arsenal picture and frame
This is a great condition picture with frame this is a collectors item. Looking for £20-£15
This is a great condition picture with frame this is a collectors item. Looking for £20-£15
3 treasured bears with movable as and legs immaculate condition. Limited production
Step ladders Good working order Lots of wallpaper stripping on the steps but this can be easily picked off £5
Vintage table £10 Good condition! Collection lower halstow One drawer and shelf to table Ideal for boys room
Medium size dog cage £15 Collection lower Halstow 2 door opening Folds down for easy transportation
Brand new 18th teddy. £5 collection only Kemsley please. Perfect for upcoming 18th birthday 😊
Open to sensible offers. Has little damage at the top and at the bottom. Also lights up at the top. Collection only. Selling due to downsizing Reduced!
Can sell separately if need to. All in good condition as moving and need gone. Collection only Please text me Reduced!
Dark wood coffe table, originally a japanese hibachi, circa 1920. Matching bookcase in dark wood. Pictures to be posted asap. Buyers collects. Sold as set with large brass table lamp.
Solid wood display unit. Comes with glass selves also has light inside. Very heavy and solid piece of furniture.
86cmD x 54cmW x 70cm H. Custom made wrought iron dog bed, lovely and unique. I will clean up prior to purchase. It is somewhat heavy and awkward to post. Only selling on because of upcoming international move.
Black double bed with storage and mattress. Very good condition. Collection only from da122er.
Glass dinning table for sale with 3 chairs brown and cream (see pictures) Table has some scratches but nothing majorly noticeable
Roll top desk lovely piece of furniture cupboard underneath one drawer in good condition
Trouser press makes like work of ironing hardly used at all clean condition
Oak dresser cupboards and two draws lovely piece of furniture clean no scratches
Pine corner unit for kitchen or dining room cupboard underneath very nice
Moving sale; all furniture available. Pick-up only. Prices: 100 for sofa and love seat 100 for TV 10 for TV stand 10 for DVD player or 110 for this set (TV, TV stand, DVD player) 50 for dining set (table and 4 chairs); table is coll
Lovely soft bed cover never used 1500 by 200 cm RRP £20.00 sellinhg for £10.00 any questions please ask
Used Black Can be used to store tools ect. Multi use feature 19 inches width 14 inches deep 62.5 long Cash on collection Any questions can contact me on: 07956912882
HD PVR, Bought for £150 In PC World Under a Year Ago. Was used for Recording YouTube Videos from XBOX 360 and PS3, Great way to start a YouTube channel of! Will record Television Footage from your favourite TV Shows! £50 Located in Maidstone
Only used twice..
Superb bed, perfect for a young boy or girl, they will enjoy spending time there and they have a good night sleep
Dining room table and six black chairs, in used condition. One chair has a rip on the seat section as shown in picture. Looking for £250 ono.
In great condition and perfect working order as will be shown in collection. If requested ....Windows 7, fast speeds, any questions please txt me on 07960294415 anytime.. No emails. Thank u for looking £250
2 Breakfast/ Bar Stools Oak effect wood and aluminium. Height to seat 75cm Overall height 100cm Very good condition. Buyer collects. Will sell individually.
Antique White Chest of Drawers W 100cm x H 110cm x D 46cm 2 small drawers 3 full width drawers. Big deep drawers. Very good quality and very good condition. Fully assembled. Buyer collects.
Antique White Wardrobe and Cupboard unit Double wardrobe W 95cm x H 173cm x D 57cm Hanging rail. 2 full width adjustable shelves. Dismantled for moving. Cupboard/ Drawer unit W 118cm x H 92cm x D 57cm Double door cupboard with adjustable sh
DVD/CD Storage Tower H 189cm x xW 20cm x D 19cm 3 Fixed shelves and 4 adjustable shelves. Very good condition.
Very good condition. Can move the long part to either be left or right. Viewing is allowed need a quick sale.
Excellent condition, slight chip on the Turin. Bought quite a few years back when princess house parties was around, paid £150 want £60
Here are 2 small wall display cabinets.from great little trading company.ideal for girls room or bathroom.few tiny marks ,nothing to noticeable.the doors on units are plastic,and not glass..25.00 for the 2 .they measure 18x18x4 inches
On spoon States : Stainless Chromium Plate Sheffield England Length 5 inches Widest part 1¼ inches Good condition Pet & smoke free home
Johnson Bros China Indies 3 cups 3 saucers states: Dishwasher, Microwave & Freezer Safe Made in England Cup size approx 3½ inches widest part- not including handle Height approx 3 inches Saucer approx 6 inches Slight sign of wear but no chip
I'm selling my 4ft long by 1ft deep by 18inch high fish tank, in good clean condition, only selling as have a bigger one now and used this as a spare, Comes with stand, light unit, fluval+4 filter & heater Any questions please contact me, welcome
8 large mirrors for sale ideal for a salon, shop or hall ways, can be hung either way, in good condition, sale due to salon refit. Size 64"high x 32"wide inclusive of frame. Timber frame covered in suede effect brown material. Can sell individual if


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Young Critics Respond to a "Stereotypical View"Read More »
On Wednesday, The Verge's Joshua Topolsky sat down with film critics A.O. Scott of The New York Times and David Denby of The New Yorker to discuss the big question looming over 2013: Is film dead?Read More »
Recorded at SXSW 2013 last month, this panel features critics Scott Weinberg and Melissa Hanson, "You're Next" screenwriter Simon Barrett, and film marketer Marian Koltai-Levine.Read More »
The review aggregator will shut down at the end of April.Read More »
He says they didn't see the pro-CIA bias in "Zero Dark Thirty."Read More »
"Some reviewers have abdicated their responsibility by chasing celebrity," says Jabbar.Read More »
The weekly paper will no longer print capsule reviews.Read More »
One writer believes "Siskel & Ebert" is to blame for the "death" of film criticism. This writer disagrees. Strongly.Read More »
The long-running trade magazine and website has been publishing criticism for decades.Read More »
"The workload for a film critic today is just so Herculean," he tells Mediabistro.Read More »


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- I've been fortunate enough to work with some amazing photographers on some of my photo manipulations. Photographer Chris Razoyk is no exception. His amazing attention to detail and well trained eye make my job that much more fun.
- The trick to getting this photo just right was the tone of the overhead light. Chris and I spent some time figuring out how it should look and feel in conjunction with the subject matter. After all we are trying to tell a pretty compelling story so it had to be just right. Chris and I also wanted the blue tone in the background to stay prevalent in order to give the photo a good sense of depth. Overall I feel the piece is a great success. I used Photoshop CS6 My trusty Wacom and Red Giant plugins for the lights.
Check out Chris's blog for more details on the shoot and an amazing video about it.
Chris also had a great article written up about his process in ISO1200 Photography Magazine's Blog


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Did You Know?
The Chinese name for the Red Panda is "hunho" or firefox.
Every year, Potter Park Zoo receives many kind offers from people who would like to donate their exotic pets. We understand the concern about placing their valued pets, but the Zoo is not able to accept these pets. Please contact your local Humane Society.


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Workers' Rights
Across America, working families are dedicated to the economic advancement to promote fairness in the workplace and establish policies that help men and women meet the dual demands of work and family. Yet all too often, workers who attempt to join unions, assert other rights in the workplace, or file complaints with protection or civil rights agencies face employer threats, retaliation and discrimination.
Other issues affecting the well-being of working Americans include tax cuts, bankruptcy reform, and the minimum wage.
A Call to Update Critical Workforce Regulations
March 31, 2014 - Posted by Lexer Quamie
The Department of Labor (DOL) announced in 2009 that it would review and revise two sets of regulations and goals for women and minorities in apprenticeships and on federal construction projections.
Senate Passes LGBT Worker Protections
November 7, 2013 - Posted by Patrick McNeil
The Senate passed the Employment Non-Discrimination Act (ENDA) today, voting 64-32 to prohibit employers from discriminating against LGBT employees nationwide.
Senate Committee Hears From Experts on the Benefits of Increasing the Minimum Wage
July 11, 2013 - Posted by Nyle Brand
Raising the minimum wage to keep up with inflation and the cost of living would put money into the hands of low-wage workers, stimulate the economy, and lead to a better quality of life for all Americans, according to a panel of labor and civil rights experts who testified at a hearing before the U.S. Senate Committee on Health, Education, Labor and Pensions (HELP).
Supreme Court's Decisions in Employment Cases Make it Harder to Fight Workplace Discrimination
June 28, 2013 - Posted by Tyler Lewis
This week, The U.S. Supreme Court ruled in two cases, Vance v. Ball State University and University of Texas Southwest Medical Center v. Nassar, dealing heavy blows to federal protections from employment discrimination.
At Confirmation Hearing, Labor Secretary Nominee Tom Perez Says Top Priority Will Be Jobs, Training
April 18, 2013 - Posted by Ron Bigler
During a confirmation hearing before the Senate Health, Education, Labor and Pensions (HELP) Committee today, Tom Perez made clear that his top priority as U.S. Secretary of Labor would be working with all sides in helping American workers obtain the training and support they need to win good jobs in the U.S. economy.
Labor Board Asks Supreme Court to Review Ruling Against Obama Recess Appointments
March 15, 2013 - Posted by Lexer Quamie
The National Labor Relations Board (NLRB) announced this week that it would ask the U.S. Supreme Court to review a lower court ruling finding that President Obama's recess appointments to the NLRB were unconstitutional.
Advocates Emphasize the Need for the Employment Non-Discrimination Act
June 14, 2012 - Posted by Rachel Barr
Employment discrimination against lesbian, gay, bisexual, and transgender Americans occurs throughout the United States, according to testimony given at a recent Senate Health, Education, Labor, and Pensions (HELP) Committee hearing on "Equality at Work: The Employment Non-Discrimination Act."
FedEx, DOL Reach $3 Million Settlement on Hiring Discrimination Case
March 26, 2012 - Posted by Sandy Thomas
Equal opportunity advocates welcomed the recent news that FedEx reached a $3 million settlement with the U.S. Department of Labor (DOL) to address a pattern of hiring discrimination in its ground delivery business.
Senators Introduce Clean Ports Act of 2011 to Improve Labor, Environmental Conditions at the Nation's Ports
December 20, 2011 - Posted by Lexer Quamie
The Leadership Conference on Civil and Human Rights welcomed the Senate introduction last week of the Clean Ports Act to address growing labor and environmental concerns at many of the nation's ports and nearby communities.
Millions Counting on Congress to Extend Unemployment Benefits
December 1, 2011 - Posted by Ron Bigler
More than six million Americans are facing the potential loss of a financial lifeline if Congress fails to pass an extension of emergency unemployment benefits which expires on December 31.
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