Most O | |
amyotrophic O | |
lateral O | |
sclerosis O | |
( O | |
ALS O | |
) O | |
cases O | |
are O | |
considered O | |
sporadic O | |
, O | |
without O | |
a O | |
known O | |
genetic O | |
basis O | |
, O | |
and O | |
lifestyle O | |
factors O | |
are O | |
suspected O | |
to O | |
play O | |
an O | |
etiologic O | |
role O | |
. O | |
We O | |
previously O | |
observed O | |
increased O | |
risk O | |
of O | |
ALS O | |
associated O | |
with O | |
high O | |
nail O | |
mercury O | |
levels O | |
as O | |
an O | |
exposure O | |
biomarker O | |
and O | |
thus O | |
hypothesized O | |
that O | |
mercury O | |
exposure O | |
via O | |
fish O | |
consumption O | |
patterns O | |
increases O | |
ALS O | |
risk O | |
. O | |
Lifestyle O | |
surveys O | |
were O | |
obtained O | |
from O | |
ALS O | |
patients O | |
( O | |
n O | |
= O | |
165 O | |
) O | |
and O | |
n O | |
= O | |
330 O | |
age- O | |
and O | |
sex O | |
- O | |
matched O | |
controls O | |
without O | |
ALS O | |
enrolled O | |
in O | |
New B-LOC | |
Hampshire I-LOC | |
, O | |
Vermont B-LOC | |
, O | |
or O | |
Ohio B-LOC | |
, O | |
USA I-LOC | |
. O | |
We O | |
estimated O | |
their O | |
annual O | |
intake O | |
of O | |
mercury O | |
and O | |
omega-3 O | |
polyunsaturated O | |
fatty O | |
acid O | |
( O | |
PUFA O | |
) O | |
via O | |
self O | |
- O | |
reported O | |
seafood O | |
consumption O | |
habits O | |
, O | |
including O | |
species O | |
and O | |
frequency O | |
. O | |
In O | |
our O | |
multivariable O | |
model O | |
, O | |
family O | |
income O | |
showed O | |
a O | |
significant O | |
positive O | |
association O | |
with O | |
ALS O | |
risk O | |
( O | |
p O | |
= O | |
0.0003 O | |
, O | |
adjusted O | |
for O | |
age O | |
, O | |
sex O | |
, O | |
family O | |
history O | |
, O | |
education O | |
, O | |
and O | |
race O | |
) O | |
. O | |
Neither O | |
the O | |
estimated O | |
annual O | |
mercury O | |
nor O | |
omega-3 O | |
PUFA O | |
intakes O | |
via O | |
seafood O | |
were O | |
associated O | |
with O | |
ALS O | |
risk O | |
. O | |
ALS O | |
incidence B-EPI | |
is O | |
associated O | |
with O | |
socioeconomic O | |
status O | |
; O | |
however O | |
, O | |
consistent O | |
with O | |
a O | |
prior O | |
international O | |
study O | |
, O | |
this O | |
relationship O | |
is O | |
not O | |
linked O | |
to O | |
mercury O | |
intake O | |
estimated O | |
via O | |
fish O | |
or O | |
seafood O | |
consumption O | |
patterns O | |
. O | |
Background O | |
Plague O | |
is O | |
a O | |
re O | |
- O | |
emerging O | |
flea O | |
- O | |
borne O | |
infectious O | |
disease O | |
of O | |
global O | |
importance O | |
and O | |
in O | |
recent O | |
years O | |
, O | |
Zambia B-LOC | |
has O | |
periodically O | |
experienced O | |
increased O | |
incidence B-EPI | |
of O | |
outbreaks O | |
of O | |
this O | |
disease O | |
. O | |
However O | |
, O | |
there O | |
are O | |
currently O | |
no O | |
studies O | |
in O | |
the O | |
country O | |
that O | |
provide O | |
a O | |
quantitative O | |
assessment O | |
of O | |
the O | |
ability O | |
of O | |
the O | |
disease O | |
to O | |
spread O | |
during O | |
these O | |
outbreaks O | |
. O | |
This O | |
limits O | |
our O | |
understanding O | |
of O | |
the O | |
epidemiology O | |
of O | |
the O | |
disease O | |
especially O | |
for O | |
planning O | |
and O | |
implementing O | |
quantifiable O | |
and O | |
cost O | |
- O | |
effective O | |
control O | |
measures O | |
. O | |
To O | |
fill O | |
this O | |
gap O | |
, O | |
the O | |
basic O | |
reproduction O | |
number O | |
, O | |
R0 O | |
, O | |
for O | |
bubonic O | |
plague O | |
was O | |
estimated O | |
in O | |
this O | |
study O | |
, O | |
using O | |
data O | |
from O | |
the O | |
2015 B-DATE | |
Nyimba B-LOC | |
district I-LOC | |
outbreak O | |
, O | |
in O | |
the O | |
Eastern I-LOC | |
province I-LOC | |
of O | |
Zambia B-LOC | |
. O | |
R0 O | |
is O | |
the O | |
average O | |
number O | |
of O | |
secondary O | |
infections O | |
arising O | |
from O | |
a O | |
single O | |
infectious O | |
individual O | |
during O | |
their O | |
infectious O | |
period O | |
in O | |
an O | |
entirely O | |
susceptible O | |
population O | |
. O | |
Methodology O | |
/ O | |
principal O | |
findings O | |
Secondary O | |
epidemic O | |
data O | |
for O | |
the O | |
most O | |
recent O | |
2015 B-DATE | |
Nyimba B-LOC | |
district I-LOC | |
bubonic O | |
plague O | |
outbreak O | |
in O | |
Zambia B-LOC | |
was O | |
analyzed O | |
. O | |
R0 O | |
was O | |
estimated O | |
as O | |
a O | |
function O | |
of O | |
the O | |
average O | |
epidemic O | |
doubling O | |
time O | |
based O | |
on O | |
the O | |
initial O | |
exponential O | |
growth O | |
rate O | |
of O | |
the O | |
outbreak O | |
and O | |
the O | |
average O | |
infectious O | |
period O | |
for O | |
bubonic O | |
plague O | |
. O | |
R0 O | |
was O | |
estimated O | |
to O | |
range O | |
between O | |
1.5599 O | |
[ O | |
95 O | |
% O | |
CI O | |
: O | |
1.382 O | |
- O | |
1.7378 O | |
] O | |
and O | |
1.9332 O | |
[ O | |
95 O | |
% O | |
CI O | |
: O | |
1.6366 O | |
- O | |
2.2297 O | |
] O | |
, O | |
with O | |
average O | |
of O | |
1.7465 O | |
[ O | |
95 O | |
% O | |
CI O | |
: O | |
1.5093 O | |
- O | |
1.9838 O | |
] O | |
. O | |
Further O | |
, O | |
an O | |
SIR O | |
deterministic O | |
mathematical O | |
model O | |
was O | |
derived O | |
for O | |
this O | |
infection O | |
and O | |
this O | |
estimated O | |
R0 O | |
to O | |
be O | |
between O | |
1.4 O | |
to O | |
1.5 O | |
, O | |
which O | |
was O | |
within O | |
the O | |
range O | |
estimated O | |
above O | |
. O | |
Conclusions O | |
/ O | |
significance O | |
This O | |
estimated O | |
R0 O | |
for O | |
bubonic O | |
plague O | |
is O | |
an O | |
indication O | |
that O | |
each O | |
bubonic O | |
plague O | |
case O | |
can O | |
typically O | |
give O | |
rise O | |
to O | |
almost O | |
two O | |
new O | |
cases O | |
during O | |
these O | |
outbreaks O | |
. O | |
This O | |
R0 O | |
estimate O | |
can O | |
now O | |
be O | |
used O | |
to O | |
quantitatively O | |
analyze O | |
and O | |
plan O | |
measurable O | |
interventions O | |
against O | |
future O | |
plague O | |
outbreaks O | |
in O | |
Zambia B-LOC | |
. O | |
Background O | |
Mucopolysaccharidoses O | |
( O | |
MPS O | |
) O | |
are O | |
rare O | |
, O | |
inherited O | |
lysosomal O | |
storage O | |
disorders O | |
characterized O | |
by O | |
progressive O | |
multiorgan O | |
involvement O | |
. O | |
Previous O | |
studies O | |
on O | |
incidence B-EPI | |
and O | |
prevalence B-EPI | |
of O | |
MPS O | |
mainly O | |
focused O | |
on O | |
countries O | |
other O | |
than O | |
the B-LOC | |
United I-LOC | |
States I-LOC | |
( O | |
US B-LOC | |
) O | |
, O | |
showing O | |
considerable O | |
variation O | |
by O | |
country O | |
. O | |
This O | |
study O | |
aimed O | |
to O | |
identify O | |
MPS O | |
incidence B-EPI | |
and O | |
prevalence B-EPI | |
in O | |
the O | |
US B-LOC | |
at O | |
a O | |
national O | |
and O | |
state O | |
level O | |
to O | |
guide O | |
clinicians O | |
and O | |
policy O | |
makers O | |
. O | |
Methods O | |
This O | |
retrospective O | |
study O | |
examined O | |
all O | |
diagnosed O | |
cases O | |
of O | |
MPS O | |
from O | |
1995 B-DATE | |
to I-DATE | |
2015 I-DATE | |
in O | |
the O | |
US B-LOC | |
using O | |
the O | |
National O | |
MPS O | |
Society O | |
database O | |
records O | |
. O | |
Data O | |
included O | |
year O | |
of O | |
birth O | |
, O | |
patient O | |
geographic O | |
location O | |
, O | |
and O | |
MPS O | |
variant O | |
type O | |
. O | |
US O | |
population O | |
information O | |
was O | |
obtained O | |
from O | |
the O | |
National O | |
Center O | |
for O | |
Health O | |
Statistics O | |
. O | |
The O | |
incidence B-EPI | |
and O | |
prevalence B-EPI | |
rates I-EPI | |
were O | |
calculated O | |
for O | |
each O | |
disease O | |
. O | |
Incidence B-EPI | |
rates I-EPI | |
were O | |
calculated O | |
for O | |
each O | |
state O | |
. O | |
Results O | |
We O | |
obtained O | |
information O | |
from O | |
789 O | |
MPS O | |
patients O | |
during O | |
a O | |
20 O | |
- O | |
year O | |
period O | |
. O | |
Incidence B-EPI | |
of O | |
MPS O | |
in O | |
the O | |
US B-LOC | |
was O | |
found O | |
to O | |
be O | |
0.98 B-STAT | |
per I-STAT | |
100,000 I-STAT | |
live I-STAT | |
births I-STAT | |
. O | |
Prevalence B-EPI | |
was O | |
found O | |
to O | |
be O | |
2.67 B-STAT | |
per I-STAT | |
1 I-STAT | |
million I-STAT | |
. O | |
MPS O | |
I O | |
, O | |
II O | |
, O | |
and O | |
III O | |
had O | |
the O | |
highest O | |
incidence B-EPI | |
rate I-EPI | |
at O | |
birth B-EPI | |
( O | |
0.26/100,000 B-STAT | |
) O | |
and O | |
prevalence B-EPI | |
rates I-EPI | |
of O | |
0.70 B-STAT | |
- I-STAT | |
0.71 I-STAT | |
per I-STAT | |
million I-STAT | |
. O | |
Birth B-EPI | |
incidences I-EPI | |
of O | |
MPS O | |
IV O | |
, O | |
VI O | |
, O | |
and O | |
VII O | |
were O | |
0.14 B-STAT | |
, I-STAT | |
0.04 I-STAT | |
and I-STAT | |
0.027 I-STAT | |
per I-STAT | |
100,000 I-STAT | |
live I-STAT | |
births I-STAT | |
. O | |
Conclusions O | |
This O | |
is O | |
the O | |
most O | |
comprehensive O | |
review O | |
of O | |
MPS O | |
incidence B-EPI | |
and O | |
prevalence B-EPI | |
rates I-EPI | |
in O | |
the O | |
US B-LOC | |
. O | |
Due O | |
to O | |
the O | |
large O | |
US O | |
population O | |
and O | |
state O | |
fragmentation O | |
, O | |
US O | |
incidence B-EPI | |
and O | |
prevalence B-EPI | |
were O | |
found O | |
to O | |
be O | |
lower O | |
than O | |
other O | |
countries O | |
. O | |
Nonetheless O | |
, O | |
state O | |
- O | |
level O | |
studies O | |
in O | |
the O | |
US B-LOC | |
supported O | |
these O | |
figures O | |
. O | |
Efforts O | |
should O | |
be O | |
focused O | |
in O | |
the O | |
establishment O | |
of O | |
a O | |
national O | |
rare O | |
disease O | |
registry O | |
with O | |
mandated O | |
reporting O | |
from O | |
every O | |
state O | |
as O | |
well O | |
as O | |
newborn O | |
screening O | |
of O | |
MPS O | |
. O | |
Purpose O | |
of O | |
review O | |
Obstructive O | |
sleep O | |
apnea O | |
syndrome O | |
( O | |
OSAS O | |
) O | |
has O | |
a O | |
high O | |
prevalence B-EPI | |
in O | |
western O | |
countries O | |
. O | |
Many O | |
papers O | |
have O | |
been O | |
published O | |
with O | |
the O | |
purpose O | |
of O | |
demonstrating O | |
that O | |
OSAS O | |
acts O | |
as O | |
an O | |
arrhythmia O | |
trigger O | |
and O | |
is O | |
responsible O | |
for O | |
an O | |
increase O | |
in O | |
cardiovascular O | |
morbidity O | |
and O | |
mortality O | |
. O | |
The O | |
aim O | |
of O | |
this O | |
study O | |
was O | |
to O | |
review O | |
our O | |
knowledge O | |
on O | |
this O | |
topic O | |
. O | |
Recent O | |
findings O | |
There O | |
is O | |
a O | |
lot O | |
of O | |
evidence O | |
demonstrating O | |
the O | |
relationship O | |
between O | |
OSAS O | |
and O | |
arrhythmias O | |
, O | |
but O | |
there O | |
remains O | |
a O | |
lack O | |
of O | |
an O | |
interventional O | |
randomized O | |
trial O | |
to O | |
demonstrate O | |
that O | |
by O | |
treating O | |
OSAS O | |
we O | |
can O | |
reduce O | |
arrhythmia O | |
burden O | |
. O | |
OSAS O | |
is O | |
a O | |
highly O | |
prevalent B-EPI | |
illness O | |
in O | |
western O | |
countries O | |
and O | |
is O | |
clearly O | |
related O | |
to O | |
an O | |
increase O | |
in O | |
cardiovascular O | |
mortality O | |
and O | |
morbidity O | |
. O | |
Cardiac O | |
arrhythmias O | |
are O | |
triggered O | |
by O | |
a O | |
repetitive O | |
hypoxemia O | |
, O | |
hypercapnia O | |
, O | |
acidosis O | |
, O | |
intrathoracic O | |
pressure O | |
fluctuations O | |
, O | |
reoxygenation O | |
, O | |
and O | |
arousals O | |
during O | |
apnea O | |
and O | |
hypopnea O | |
episodes O | |
. O | |
Early O | |
diagnosis O | |
and O | |
treatment O | |
of O | |
these O | |
patients O | |
can O | |
reduce O | |
further O | |
cardiovascular O | |
morbidity O | |
and O | |
mortality O | |
. O | |
Objective O | |
We O | |
sought O | |
to O | |
determine O | |
the O | |
risk O | |
factors O | |
, O | |
incidence B-EPI | |
, O | |
and O | |
mortality O | |
of O | |
very O | |
late O | |
onset O | |
bacterial O | |
infection O | |
( O | |
blood O | |
, O | |
urine O | |
, O | |
or O | |
cerebrospinal O | |
fluid O | |
culture O | |
positive O | |
occurring O | |
after O | |
day O | |
of O | |
life O | |
120 O | |
) O | |
in O | |
preterm O | |
infants O | |
. O | |
Study O | |
design O | |
A O | |
retrospective O | |
observational O | |
cohort O | |
study O | |
of O | |
all O | |
very O | |
low O | |
birth O | |
weight O | |
infants O | |
cared O | |
for O | |
between O | |
day O | |
of O | |
life O | |
120 O | |
and O | |
365 O | |
in O | |
292 O | |
neonatal O | |
intensive O | |
care O | |
units O | |
in O | |
the B-LOC | |
United I-LOC | |
States I-LOC | |
from O | |
1997 B-DATE | |
to I-DATE | |
2008 I-DATE | |
. O | |
Results O | |
We O | |
identified O | |
3918 O | |
infants O | |
who O | |
were O | |
hospitalized O | |
beyond O | |
120 O | |
days O | |
of O | |
life O | |
. O | |
Of O | |
these O | |
, O | |
1027 O | |
( O | |
26 O | |
% O | |
) O | |
were O | |
evaluated O | |
with O | |
at O | |
least O | |
1 O | |
culture O | |
( O | |
blood O | |
, O | |
urine O | |
, O | |
or O | |
cerebrospinal O | |
fluid O | |
) O | |
, O | |
and O | |
276 O | |
( O | |
27 O | |
% O | |
) O | |
of O | |
the O | |
evaluated O | |
infants O | |
had O | |
414 O | |
episodes O | |
of O | |
culture O | |
- O | |
positive O | |
infection O | |
. O | |
Gram O | |
- O | |
positive O | |
organisms O | |
caused O | |
most O | |
of O | |
the O | |
infections O | |
( O | |
48 O | |
% O | |
) O | |
. O | |
The O | |
risk O | |
of O | |
death O | |
was O | |
higher O | |
in O | |
infants O | |
with O | |
positive O | |
cultures O | |
( O | |
odds O | |
ratio O | |
; O | |
10.5 O | |
, O | |
95 O | |
% O | |
confidence O | |
interval O | |
[ O | |
7.2 O | |
- O | |
15.5 O | |
] O | |
) O | |
or O | |
negative O | |
cultures O | |
( O | |
4.8 O | |
, O | |
[ O | |
3.5 O | |
- O | |
6.7 O | |
] O | |
) O | |
compared O | |
to O | |
infants O | |
that O | |
were O | |
never O | |
evaluated O | |
with O | |
a O | |
culture O | |
( O | |
p<0.001 O | |
) O | |
. O | |
Mortality O | |
was O | |
highest O | |
with O | |
fungal O | |
infections O | |
( O | |
8/24 O | |
, O | |
33 O | |
% O | |
) O | |
followed O | |
by O | |
Gram O | |
- O | |
positive O | |
cocci O | |
( O | |
40/142 O | |
, O | |
28 O | |
% O | |
) O | |
. O | |
Conclusions O | |
Important O | |
predictive O | |
risk O | |
factors O | |
for O | |
early O | |
and O | |
late O | |
onset O | |
sepsis O | |
( O | |
birth O | |
weight O | |
and O | |
gestational O | |
age O | |
) O | |
did O | |
not O | |
contribute O | |
to O | |
risk O | |
of O | |
developing O | |
very O | |
late O | |
onset O | |
infection O | |
. O | |
Evaluation O | |
for O | |
infection O | |
( O | |
whether O | |
positive O | |
or O | |
negative O | |
) O | |
was O | |
a O | |
significant O | |
risk O | |
factor O | |
for O | |
death O | |
. O | |
GPC O | |
and O | |
fungal O | |
infections O | |
were O | |
associated O | |
with O | |
high O | |
mortality O | |
. O | |
Background O | |
In O | |
this O | |
nationwide O | |
study O | |
, O | |
we O | |
used O | |
the O | |
unique O | |
Danish O | |
registries O | |
to O | |
estimate O | |
the O | |
risk O | |
of O | |
suicide O | |
and O | |
deliberate O | |
self O | |
- O | |
harm O | |
in O | |
patients O | |
with O | |
congenital O | |
heart O | |
disease O | |
( O | |
CHD O | |
) O | |
. O | |
Methods O | |
and O | |
Results O | |
We O | |
identified O | |
all O | |
Danish B-ETHN | |
citizens O | |
receiving O | |
a O | |
diagnosis O | |
of O | |
CHD O | |
between B-DATE | |
1977 I-DATE | |
and I-DATE | |
2007 I-DATE | |
. O | |
As O | |
a O | |
reference O | |
cohort O | |
, O | |
we O | |
randomly O | |
selected O | |
10 O | |
citizens O | |
for O | |
each O | |
patient O | |
, O | |
matched O | |
by O | |
sex O | |
and O | |
birth O | |
year O | |
. O | |
Using O | |
the O | |
Fine O | |
and O | |
Gray O | |
competing O | |
risk O | |
regression O | |
, O | |
we O | |
estimated O | |
the O | |
cumulative B-EPI | |
incidences I-EPI | |
of O | |
suicide O | |
and O | |
self O | |
- O | |
harm O | |
, O | |
and O | |
Cox O | |
proportional O | |
regression O | |
analysis O | |
was O | |
used O | |
to O | |
compare O | |
the O | |
risk O | |
of O | |
suicide O | |
and O | |
deliberate O | |
self O | |
- O | |
harm O | |
in O | |
patients O | |
with O | |
CHD O | |
with O | |
the O | |
reference O | |
cohort O | |
. O | |
We O | |
identified O | |
14 O | |
433 O | |
patients O | |
with O | |
CHD O | |
. O | |
Mean O | |
follow O | |
- O | |
up O | |
was O | |
21.3 O | |
years O | |
, O | |
with O | |
a O | |
maximum O | |
follow O | |
- O | |
up O | |
of O | |
42 O | |
years O | |
. O | |
Since O | |
the O | |
time O | |
of O | |
diagnosis O | |
, O | |
2659 O | |
patients O | |
had O | |
died O | |
, O | |
with O | |
a O | |
median O | |
age O | |
of O | |
death O | |
of O | |
23 O | |
years O | |
. O | |
A O | |
total O | |
of O | |
15 O | |
patients O | |
had O | |
died O | |
by O | |
suicide O | |
, O | |
compared O | |
with O | |
232 O | |
suicides O | |
in O | |
the O | |
reference O | |
cohort O | |
. O | |
Patients O | |
with O | |
CHD O | |
had O | |
a O | |
low O | |
and O | |
similar O | |
risk O | |
of O | |
dying O | |
by O | |
suicide O | |
when O | |
compared O | |
with O | |
the O | |
reference O | |
cohort O | |
( O | |
cause O | |
- O | |
specific O | |
hazard O | |
ratio O | |
, O | |
0.81 O | |
; O | |
95 O | |
% O | |
CI O | |
, O | |
0.48 O | |
- O | |
1.37 O | |
; O | |
and O | |
subhazard O | |
ratio O | |
, O | |
0.68 O | |
; O | |
95 O | |
% O | |
CI O | |
, O | |
0.41 O | |
- O | |
1.16 O | |
) O | |
. O | |
We O | |
identified O | |
336 O | |
events O | |
of O | |
self O | |
- O | |
harm O | |
among O | |
patients O | |
with O | |
CHD O | |
, O | |
and O | |
3484 O | |
events O | |
in O | |
the O | |
reference O | |
group O | |
. O | |
The O | |
overall O | |
risk O | |
of O | |
deliberate O | |
self O | |
- O | |
harm O | |
was O | |
not O | |
increased O | |
in O | |
patients O | |
with O | |
CHD O | |
when O | |
compared O | |
with O | |
the O | |
reference O | |
group O | |
( O | |
subhazard O | |
ratio O | |
, O | |
0.95 O | |
; O | |
95 O | |
% O | |
CI O | |
, O | |
0.85 O | |
- O | |
1.06 O | |
) O | |
. O | |
Conclusions O | |
This O | |
is O | |
the O | |
first O | |
study O | |
to O | |
estimate O | |
the O | |
risk O | |
of O | |
suicide O | |
and O | |
deliberate O | |
self O | |
- O | |
harm O | |
in O | |
patients O | |
with O | |
CHD O | |
. O | |
We O | |
found O | |
that O | |
patients O | |
with O | |
CHD O | |
do O | |
not O | |
have O | |
an O | |
increased O | |
risk O | |
of O | |
suicide O | |
or O | |
deliberate O | |
self O | |
- O | |
harm O | |
when O | |
compared O | |
with O | |
a O | |
large O | |
reference O | |
cohort O | |
. O | |
Introduction O | |
A O | |
congenital O | |
lung O | |
abnormality O | |
( O | |
CLA O | |
) O | |
is O | |
often O | |
found O | |
in O | |
conjunction O | |
with O | |
other O | |
abnormalities O | |
but O | |
screening O | |
guidelines O | |
for O | |
newborns O | |
with O | |
CLA O | |
have O | |
not O | |
yet O | |
been O | |
reported O | |
. O | |
We O | |
aimed O | |
to O | |
assess O | |
the O | |
incidence B-EPI | |
of O | |
associated O | |
anomalies O | |
in O | |
CLA O | |
patients O | |
born O | |
or O | |
followed O | |
up O | |
at O | |
our O | |
centre O | |
and O | |
the O | |
need O | |
for O | |
additional O | |
screening O | |
of O | |
newborns O | |
with O | |
a O | |
CLA O | |
. O | |
Methods O | |
From O | |
a O | |
retrospective O | |
chart O | |
review O | |
of O | |
all O | |
patients O | |
born O | |
with O | |
a O | |
CLA O | |
between B-DATE | |
January I-DATE | |
1999 I-DATE | |
and I-DATE | |
January I-DATE | |
2019 I-DATE | |
, O | |
we O | |
identified O | |
patients O | |
diagnosed O | |
with O | |
a O | |
congenital O | |
pulmonary O | |
airway O | |
malformation O | |
, O | |
bronchopulmonary O | |
sequestration O | |
, O | |
congenital O | |
lobar O | |
overinflation O | |
, O | |
bronchogenic O | |
cyst O | |
, O | |
or O | |
lung O | |
agenesis O | |
. O | |
Associated O | |
anomalies O | |
were O | |
noted O | |
and O | |
categorized O | |
according O | |
to O | |
the O | |
affected O | |
organ O | |
system O | |
. O | |
Results O | |
Twenty O | |
- O | |
eight O | |
( O | |
14 O | |
% O | |
) O | |
of O | |
196 O | |
CLA O | |
patients O | |
had O | |
a O | |
major O | |
associated O | |
anomaly O | |
. O | |
This O | |
was O | |
most O | |
frequent O | |
in O | |
conjunction O | |
with O | |
a O | |
lung O | |
agenesis O | |
( O | |
100 O | |
% O | |
) O | |
or O | |
bronchogenic O | |
cyst O | |
( O | |
29 O | |
% O | |
) O | |
. O | |
Congenital O | |
heart O | |
defects O | |
( O | |
32 O | |
% O | |
) O | |
and O | |
gastrointestinal O | |
defects O | |
( O | |
18 O | |
% O | |
) O | |
were O | |
the O | |
most O | |
frequently O | |
associated O | |
anomalies O | |
. O | |
Examination O | |
of O | |
newborns O | |
with O | |
a O | |
CLA O | |
should O | |
focus O | |
on O | |
the O | |
cardiovascular O | |
and O | |
gastrointestinal O | |
tract O | |
, O | |
and O | |
a O | |
chest O | |
and O | |
abdominal O | |
radiograph O | |
may O | |
be O | |
useful O | |
to O | |
assess O | |
signs O | |
of O | |
major O | |
associated O | |
anomalies O | |
, O | |
regardless O | |
of O | |
the O | |
clinical O | |
course O | |
. O | |
A O | |
molecular O | |
epidemiological O | |
study O | |
was O | |
conducted O | |
in O | |
a O | |
population O | |
of O | |
9422 O | |
blood O | |
donors O | |
in O | |
the O | |
province O | |
of O | |
Corrientes B-LOC | |
, O | |
Northeastern B-LOC | |
Argentina I-LOC | |
, O | |
to O | |
determine O | |
the O | |
prevalence B-EPI | |
of O | |
Human O | |
T O | |
- O | |
cell O | |
lymphotropic O | |
virus O | |
types O | |
1 O | |
and O | |
2 O | |
( O | |
HTLV-1/2 O | |
) O | |
, O | |
the O | |
phylogenetic O | |
identification O | |
of O | |
HTLV-1 O | |
and O | |
2 O | |
subtypes O | |
/ O | |
subgroups O | |
and O | |
perform O | |
a O | |
mutation O | |
analysis O | |
. O | |
Based O | |
on O | |
the O | |
results O | |
obtained O | |
, O | |
it O | |
was O | |
shown O | |
that O | |
both O | |
HTLV-1 O | |
and O | |
HTLV-2 O | |
are O | |
circulating O | |
in O | |
a O | |
low O | |
- O | |
risk O | |
population O | |
of O | |
Corrientes B-LOC | |
, O | |
although O | |
with O | |
a O | |
similar O | |
prevalence B-EPI | |
to O | |
that O | |
of O | |
non O | |
- O | |
endemic O | |
areas O | |
. O | |
Phylogenetic O | |
studies O | |
identified O | |
the O | |
HTLV-1 O | |
Cosmopolitan O | |
subtype O | |
Transcontinental O | |
subgroup O | |
( O | |
Aa O | |
) O | |
, O | |
and O | |
the O | |
HTLV-2 O | |
subtype O | |
b. O | |
Infected O | |
donors O | |
reported O | |
neither O | |
a O | |
history O | |
of O | |
risk O | |
factors O | |
such O | |
as O | |
transfusions O | |
, O | |
intravenous O | |
drug O | |
use O | |
, O | |
nor O | |
risky O | |
or O | |
HTLV-1/2 O | |
seropositive O | |
sexual O | |
partners O | |
. O | |
These O | |
results O | |
suggest O | |
that O | |
these O | |
viruses O | |
were O | |
transmitted O | |
from O | |
mother B-SEX | |
to O | |
child O | |
, O | |
possibly O | |
from O | |
generation O | |
to O | |
generation O | |
, O | |
and O | |
that O | |
these O | |
strains O | |
were O | |
introduced O | |
into O | |
the O | |
Caucasian B-ETHN | |
population O | |
of O | |
this O | |
region O | |
from O | |
ancestors O | |
originating O | |
from O | |
endemic O | |
areas O | |
of O | |
the O | |
country O | |
either O | |
from O | |
or O | |
through O | |
contact O | |
with O | |
individuals O | |
from O | |
other O | |
countries O | |
years O | |
ago O | |
. O | |
Our O | |
results O | |
demonstrate O | |
for O | |
the O | |
first O | |
time O | |
the O | |
presence O | |
of O | |
HTLV-1 O | |
and O | |
HTLV-2 O | |
in O | |
the O | |
province O | |
of O | |
Corrientes B-LOC | |
. O | |
Moreover O | |
, O | |
although O | |
the O | |
province O | |
can O | |
be O | |
considered O | |
a O | |
non O | |
- O | |
endemic O | |
area O | |
, O | |
the O | |
need O | |
to O | |
include O | |
these O | |
retroviruses O | |
in O | |
a O | |
national O | |
Public O | |
Health O | |
program O | |
is O | |
highlighted O | |
, O | |
in O | |
order O | |
to O | |
have O | |
qualified O | |
professionals O | |
duly O | |
trained O | |
to O | |
make O | |
their O | |
diagnosis O | |
and O | |
provide O | |
the O | |
necessary O | |
information O | |
in O | |
relation O | |
to O | |
primary O | |
care O | |
and O | |
patient O | |
follow O | |
- O | |
up O | |
. O | |
Background O | |
Entamoeba O | |
species O | |
harbored O | |
by O | |
humans O | |
have O | |
different O | |
degrees O | |
of O | |
pathogenicity O | |
. O | |
The O | |
present O | |
study O | |
explores O | |
the O | |
intra- O | |
and O | |
interspecific O | |
diversity O | |
, O | |
phylogenetic O | |
relationships O | |
, O | |
prevalence B-EPI | |
and O | |
distribution O | |
of O | |
tetra- O | |
and O | |
octonucleated O | |
cyst O | |
- O | |
producing O | |
Entamoeba O | |
in O | |
different O | |
Brazilian B-ETHN | |
regions O | |
. O | |
Methods O | |
Cross O | |
- O | |
sectional O | |
studies O | |
were O | |
performed O | |
to O | |
collect O | |
fecal O | |
samples O | |
( O | |
n O | |
= O | |
1728 O | |
) O | |
and O | |
sociodemographic O | |
data O | |
in O | |
communities O | |
located O | |
in O | |
four O | |
Brazilian B-ETHN | |
biomes O | |
: O | |
Atlantic B-LOC | |
Forest I-LOC | |
, O | |
Caatinga B-LOC | |
, O | |
Cerrado B-LOC | |
, O | |
and O | |
Amazon B-LOC | |
. O | |
Fecal O | |
samples O | |
were O | |
subjected O | |
to O | |
molecular O | |
analysis O | |
by O | |
partial O | |
small O | |
subunit O | |
ribosomal O | |
DNA O | |
sequencing O | |
( O | |
SSU O | |
rDNA O | |
) O | |
and O | |
phylogenetic O | |
analysis O | |
. O | |
Results O | |
Light O | |
microscopy O | |
analysis O | |
revealed O | |
that O | |
tetranucleated O | |
cysts O | |
were O | |
found O | |
in O | |
all O | |
the O | |
studied O | |
biomes O | |
. O | |
The O | |
highest O | |
positivity O | |
rates O | |
were O | |
observed O | |
in O | |
the O | |
age O | |
group O | |
6 O | |
- O | |
10 O | |
years O | |
( O | |
23.21 O | |
% O | |
) O | |
. O | |
For O | |
octonucleated O | |
cysts O | |
, O | |
positivity O | |
rates O | |
ranged O | |
from O | |
1 O | |
to O | |
55.1 O | |
% O | |
. O | |
Sixty O | |
SSU O | |
rDNA O | |
Entamoeba O | |
sequences O | |
were O | |
obtained O | |
, O | |
and O | |
four O | |
different O | |
species O | |
were O | |
identified O | |
: O | |
the O | |
octonucleated O | |
E. O | |
coli O | |
, O | |
and O | |
the O | |
tetranucleated O | |
E. O | |
histolytica O | |
, O | |
E. O | |
dispar O | |
, O | |
and O | |
E. O | |
hartmanni O | |
. O | |
Novel O | |
haplotypes O | |
( O | |
n O | |
= O | |
32 O | |
) O | |
were O | |
characterized O | |
; O | |
however O | |
, O | |
new O | |
ribosomal O | |
lineages O | |
were O | |
not O | |
identified O | |
. O | |
The O | |
Entamoeba O | |
coli O | |
ST1 O | |
subtype O | |
predominated O | |
in O | |
Atlantic B-LOC | |
Forest O | |
and O | |
Caatinga B-LOC | |
, O | |
and O | |
the O | |
ST2 O | |
subtype O | |
was O | |
predominant O | |
in O | |
the O | |
Amazon B-LOC | |
biome O | |
. O | |
E. O | |
histolytica O | |
was O | |
detected O | |
only O | |
in O | |
the O | |
Amazon B-LOC | |
biome O | |
. O | |
In O | |
phylogenetic O | |
trees O | |
, O | |
sequences O | |
were O | |
grouped O | |
in O | |
two O | |
groups O | |
, O | |
the O | |
first O | |
containing O | |
uni- O | |
and O | |
tetranucleated O | |
and O | |
the O | |
second O | |
containing O | |
uni- O | |
and O | |
octonucleated O | |
cyst O | |
- O | |
producing O | |
Entamoeba O | |
species O | |
. O | |
Molecular O | |
diversity O | |
indexes O | |
revealed O | |
a O | |
high O | |
interspecific O | |
diversity O | |
for O | |
tetra- O | |
and O | |
octonucleated O | |
Entamoeba O | |
spp O | |
. O | |
( O | |
H O | |
± O | |
SD O | |
= O | |
0.9625 O | |
± O | |
0.0126 O | |
) O | |
. O | |
The O | |
intraspecific O | |
diversity O | |
varied O | |
according O | |
to O | |
species O | |
or O | |
subtype O | |
: O | |
E. O | |
dispar O | |
and O | |
E. O | |
histolytica O | |
showed O | |
lower O | |
diversity O | |
than O | |
E. O | |
coli O | |
subtypes O | |
ST1 O | |
and O | |
ST2 O | |
and O | |
E. O | |
hartmanni O | |
. O | |
Conclusions O | |
Tetra- O | |
and O | |
octonucleated O | |
cyst O | |
- O | |
producing O | |
Entamoeba O | |
are O | |
endemic O | |
in O | |
the O | |
studied O | |
communities O | |
; O | |
E. O | |
histolytica O | |
was O | |
found O | |
in O | |
a O | |
low O | |
proportion O | |
and O | |
only O | |
in O | |
the O | |
Amazon B-LOC | |
biome O | |
. O | |
With O | |
regard O | |
to O | |
E. O | |
coli O | |
, O | |
subtype O | |
ST2 O | |
was O | |
predominant O | |
in O | |
the O | |
Amazon B-LOC | |
biome O | |
. O | |
The O | |
molecular O | |
epidemiology O | |
of O | |
Entamoeba O | |
spp O | |
. O | |
is O | |
a O | |
field O | |
to O | |
be O | |
further O | |
explored O | |
and O | |
provides O | |
information O | |
with O | |
important O | |
implications O | |
for O | |
public O | |
health O | |
. O | |
Genetic O | |
predisposition O | |
has O | |
been O | |
always O | |
noted O | |
in O | |
the O | |
context O | |
of O | |
familial O | |
hematological O | |
malignancies O | |
. O | |
Epidemiological O | |
studies O | |
have O | |
provided O | |
evidence O | |
consisting O | |
of O | |
an O | |
increased O | |
risk O | |
to O | |
develop O | |
blood O | |
cancer O | |
in O | |
relatives O | |
diagnosed O | |
with O | |
the O | |
same O | |
pathology O | |
and O | |
characterized O | |
by O | |
early O | |
age O | |
at O | |
diagnosis O | |
and O | |
higher O | |
severity O | |
compared O | |
to O | |
sporadic O | |
forms O | |
. O | |
With O | |
the O | |
emergence O | |
of O | |
new O | |
genomic O | |
testing O | |
approaches O | |
, O | |
the O | |
prevalence B-EPI | |
of O | |
familial O | |
aggregations O | |
of O | |
hematological O | |
malignancies O | |
seems O | |
to O | |
be O | |
under O | |
estimated O | |
. O | |
The O | |
heterogeneity O | |
of O | |
clinical O | |
features O | |
explains O | |
the O | |
wide O | |
number O | |
of O | |
genes O | |
' O | |
mutations O | |
reported O | |
to O | |
date O | |
and O | |
the O | |
variable O | |
penetrance O | |
of O | |
variants O | |
. O | |
Nevertheless O | |
, O | |
the O | |
genetic O | |
basis O | |
of O | |
familial O | |
hematological O | |
malignancies O | |
is O | |
still O | |
not O | |
well O | |
understood O | |
. O | |
Identifying O | |
the O | |
genetic O | |
background O | |
in O | |
familial O | |
aggregations O | |
provides O | |
a O | |
valuable O | |
tool O | |
for O | |
prognostic O | |
evaluation O | |
, O | |
personalized O | |
treatment O | |
and O | |
better O | |
genetic O | |
counseling O | |
in O | |
high O | |
- O | |
risk O | |
families O | |
. O | |
Herein O | |
, O | |
we O | |
provide O | |
an O | |
overview O | |
of O | |
genes O | |
reported O | |
in O | |
the O | |
last O | |
few O | |
years O | |
in O | |
association O | |
to O | |
hematological O | |
malignancies O | |
including O | |
familial O | |
form O | |
of O | |
Hodgkin O | |
Lymphoma O | |
, O | |
Non O | |
- O | |
Hodgkin O | |
Lymphoma O | |
, O | |
Chronic O | |
Lymphocytic O | |
Leukemia O | |
, O | |
acute O | |
Myeloid O | |
Leukemia O | |
and O | |
acute O | |
Lymphoblastic O | |
Leukemia O | |
. O | |
Objective O | |
To O | |
determine O | |
whether O | |
the O | |
two O | |
most O | |
common O | |
genetic O | |
mutations O | |
seen O | |
in O | |
Stickler O | |
Syndrome O | |
( O | |
SS O | |
) O | |
( O | |
COL2A1 O | |
and O | |
COL11A1 O | |
) O | |
affect O | |
the O | |
incidence B-EPI | |
of O | |
mandibular O | |
distraction O | |
osteogenesis O | |
( O | |
MDO O | |
) O | |
and O | |
what O | |
impact O | |
Robin O | |
sequence O | |
( O | |
RS O | |
) O | |
has O | |
on O | |
diagnosis O | |
. O | |
SS O | |
is O | |
an O | |
autosomal O | |
dominant O | |
connective O | |
tissue O | |
disorder O | |
characterized O | |
by O | |
almost O | |
complete O | |
penetrance O | |
. O | |
COL2A1 O | |
and O | |
COL11A1 O | |
are O | |
the O | |
two O | |
most O | |
common O | |
mutations O | |
seen O | |
in O | |
SS O | |
patients O | |
. O | |
SS O | |
often O | |
presents O | |
at O | |
birth O | |
with O | |
RS O | |
, O | |
which O | |
is O | |
characterized O | |
by O | |
the O | |
triad O | |
of O | |
micrognathia O | |
, O | |
glossoptosis O | |
, O | |
and O | |
tongue O | |
- O | |
based O | |
airway O | |
obstruction O | |
. O | |
MDO O | |
is O | |
one O | |
surgical O | |
intervention O | |
that O | |
has O | |
been O | |
shown O | |
to O | |
be O | |
successful O | |
in O | |
relieving O | |
tongue O | |
base O | |
obstruction O | |
and O | |
is O | |
the O | |
surgical O | |
intervention O | |
of O | |
choice O | |
for O | |
this O | |
condition O | |
. O | |
Methods O | |
A O | |
retrospective O | |
chart O | |
review O | |
was O | |
performed O | |
on O | |
all O | |
patients O | |
with O | |
a O | |
diagnosis O | |
of O | |
SS O | |
at O | |
a O | |
tertiary O | |
pediatric O | |
hospital O | |
between B-DATE | |
January I-DATE | |
1 I-DATE | |
, I-DATE | |
2003 I-DATE | |
and I-DATE | |
December I-DATE | |
31 I-DATE | |
, I-DATE | |
2018 I-DATE | |
. O | |
The O | |
included O | |
patient O | |
charts O | |
were O | |
reviewed O | |
for O | |
demographic O | |
information O | |
, O | |
SS O | |
mutation O | |
, O | |
and O | |
history O | |
of O | |
MDO O | |
. O | |
Forty O | |
- O | |
six O | |
patients O | |
had O | |
a O | |
clinical O | |
diagnosis O | |
of O | |
SS O | |
. O | |
Of O | |
those O | |
, O | |
31 O | |
met O | |
inclusion O | |
criteria O | |
which O | |
involved O | |
having O | |
a O | |
molecular O | |
diagnosis O | |
of O | |
SS O | |
and O | |
sufficient O | |
follow O | |
up O | |
information O | |
to O | |
determine O | |
if O | |
MDO O | |
was O | |
indicated O | |
or O | |
performed O | |
. O | |
Twenty O | |
- O | |
two O | |
of O | |
the O | |
31 O | |
included O | |
patients O | |
had O | |
a O | |
diagnosis O | |
of O | |
RS O | |
( O | |
70.96 O | |
% O | |
) O | |
. O | |
Thirteen O | |
of O | |
the O | |
31 O | |
patients O | |
( O | |
41.94 O | |
% O | |
) O | |
included O | |
in O | |
this O | |
study O | |
required O | |
MDO O | |
as O | |
a O | |
neonate O | |
. O | |
Results O | |
Fifty O | |
- O | |
percent O | |
of O | |
patients O | |
with O | |
type O | |
I O | |
( O | |
COL2A1 O | |
) O | |
required O | |
MDO O | |
as O | |
a O | |
neonate O | |
compared O | |
to O | |
only O | |
31 O | |
% O | |
of O | |
patients O | |
with O | |
type O | |
II O | |
( O | |
COL11A1 O | |
) O | |
, O | |
though O | |
the O | |
difference O | |
between O | |
the O | |
two O | |
groups O | |
was O | |
not O | |
statistically O | |
significant O | |
. O | |
Conclusion O | |
The O | |
findings O | |
of O | |
this O | |
study O | |
suggest O | |
that O | |
patients O | |
with O | |
type O | |
I O | |
mutation O | |
may O | |
have O | |
a O | |
higher O | |
incidence B-EPI | |
of O | |
MDO O | |
than O | |
patients O | |
with O | |
a O | |
type O | |
II O | |
mutation O | |
, O | |
though O | |
further O | |
research O | |
with O | |
larger O | |
sample O | |
sizes O | |
is O | |
needed O | |
. O | |
This O | |
information O | |
is O | |
helpful O | |
in O | |
counseling O | |
those O | |
with O | |
SS O | |
or O | |
family O | |
history O | |
of O | |
SS O | |
about O | |
what O | |
they O | |
can O | |
expect O | |
related O | |
to O | |
RS O | |
and O | |
need O | |
for O | |
MDO O | |
based O | |
on O | |
genetic O | |
findings O | |
. O | |
Level O | |
of O | |
evidence O | |
3 O | |
. O | |
Glucose-6 O | |
- O | |
phosphate O | |
dehydrogenase O | |
( O | |
G6PD O | |
) O | |
deficiency O | |
is O | |
the O | |
most O | |
common O | |
enzymatic O | |
disorder O | |
of O | |
red O | |
blood O | |
cells O | |
worldwide B-LOC | |
. O | |
The O | |
severity O | |
of O | |
hemolytic O | |
anemia O | |
varies O | |
among O | |
individuals O | |
with O | |
G6PD O | |
deficiency O | |
, O | |
depending O | |
on O | |
the O | |
genetic O | |
variant O | |
in O | |
the O | |
G6PD O | |
gene O | |
; O | |
this O | |
makes O | |
the O | |
diagnosis O | |
of O | |
the O | |
condition O | |
more O | |
challenging O | |
in O | |
some O | |
cases O | |
. O | |
In O | |
this O | |
report O | |
, O | |
we O | |
present O | |
a O | |
case O | |
of O | |
severe O | |
hemolytic O | |
anemia O | |
and O | |
methemoglobinemia O | |
in O | |
a O | |
patient O | |
with O | |
G6PD O | |
deficiency O | |
who O | |
had O | |
been O | |
exposed O | |
to O | |
hydroxychloroquine O | |
prescribed O | |
for O | |
severe O | |
acute O | |
respiratory O | |
syndrome O | |
coronavirus O | |
2 O | |
( O | |
SARS O | |
- O | |
CoV-2 O | |
) O | |
infection O | |
. O | |
To O | |
the O | |
best O | |
of O | |
our O | |
knowledge O | |
and O | |
based O | |
on O | |
a O | |
literature O | |
search O | |
, O | |
this O | |
is O | |
one O | |
of O | |
the O | |
first O | |
case O | |
reports O | |
in O | |
the O | |
literature O | |
about O | |
hemolytic O | |
crisis O | |
and O | |
methemoglobinemia O | |
in O | |
a O | |
patient O | |
with O | |
critical O | |
illness O | |
due O | |
to O | |
severe O | |
coronavirus O | |
disease O | |
2019 O | |
( O | |
COVID-19 O | |
) O | |
who O | |
was O | |
exposed O | |
to O | |
hydroxychloroquine O | |
. O | |
It O | |
is O | |
critical O | |
for O | |
physicians O | |
and O | |
caregivers O | |
to O | |
recognize O | |
the O | |
effects O | |
of O | |
oxidative O | |
stressors O | |
such O | |
as O | |
hydroxychloroquine O | |
, O | |
particularly O | |
in O | |
this O | |
era O | |
of O | |
the O | |
COVID-19 O | |
pandemic O | |
and O | |
in O | |
regions O | |
with O | |
a O | |
high O | |
prevalence B-EPI | |
of O | |
G6PD O | |
deficiency O | |
, O | |
for O | |
the O | |
appropriate O | |
management O | |
of O | |
this O | |
unique O | |
subset O | |
of O | |
patients O | |
. O | |
Background O | |
Many O | |
studies O | |
have O | |
been O | |
conducted O | |
to O | |
assess O | |
the O | |
incidence B-EPI | |
of O | |
congenital O | |
heart O | |
disease O | |
( O | |
CHD O | |
) O | |
. O | |
However O | |
, O | |
results O | |
were O | |
greatly O | |
inconsistent O | |
among O | |
these O | |
studies O | |
with O | |
a O | |
broad O | |
range O | |
of O | |
findings O | |
. O | |
Methods O | |
A O | |
prospective O | |
census O | |
- O | |
based O | |
cohort O | |
study O | |
was O | |
conducted O | |
in O | |
Qingdao B-LOC | |
, I-LOC | |
China I-LOC | |
, O | |
from O | |
August B-DATE | |
1 I-DATE | |
, I-DATE | |
2018 I-DATE | |
to I-DATE | |
April I-DATE | |
30 I-DATE | |
, I-DATE | |
2019 I-DATE | |
. O | |
All O | |
of O | |
the O | |
local O | |
registered O | |
pregnant O | |
women B-SEX | |
were O | |
continuously O | |
investigated O | |
and O | |
followed O | |
from O | |
15 O | |
to O | |
20 O | |
weeks O | |
of O | |
gestation O | |
to O | |
delivery O | |
, O | |
tracking O | |
the O | |
CHD O | |
cases O | |
in O | |
both O | |
the O | |
fetal O | |
and O | |
neonatal O | |
stages O | |
. O | |
A O | |
logistic O | |
regression O | |
model O | |
was O | |
applied O | |
to O | |
assess O | |
the O | |
association O | |
between O | |
CHD O | |
and O | |
possible O | |
risk O | |
factors O | |
. O | |
Results O | |
The O | |
positive O | |
rate O | |
of O | |
prenatal O | |
CHD O | |
screening O | |
was O | |
14.36 B-STAT | |
per I-STAT | |
1000 I-STAT | |
fetuses I-STAT | |
and O | |
the O | |
incidence B-EPI | |
of O | |
CHD O | |
was O | |
9.38 B-STAT | |
per I-STAT | |
1000 I-STAT | |
live I-STAT | |
births I-STAT | |
. O | |
Results O | |
from O | |
logistic O | |
regression O | |
indicated O | |
that O | |
, O | |
living O | |
in O | |
the O | |
countryside O | |
( O | |
odds O | |
ratio O | |
, O | |
( O | |
OR O | |
): O | |
0.771 O | |
; O | |
95 O | |
% O | |
confidence O | |
interval O | |
, O | |
( O | |
CI O | |
): O | |
0.628 O | |
- O | |
0.946 O | |
) O | |
and O | |
having O | |
a O | |
childbearing O | |
history O | |
( O | |
OR O | |
: O | |
0.802 O | |
; O | |
95%CI O | |
: O | |
0.676 O | |
- O | |
0.951 O | |
) O | |
were O | |
negatively O | |
associated O | |
with O | |
CHD O | |
. O | |
However O | |
, O | |
twin O | |
pregnancy O | |
( O | |
OR O | |
: O | |
1.957 O | |
, O | |
95 O | |
% O | |
CI O | |
: O | |
1.245 O | |
- O | |
3.076 O | |
) O | |
, O | |
illness O | |
in O | |
the O | |
first O | |
trimester O | |
( O | |
OR O | |
: O | |
1.306 O | |
; O | |
95 O | |
% O | |
CI O | |
: O | |
1.048 O | |
- O | |
1.628 O | |
) O | |
, O | |
a O | |
family O | |
history O | |
of O | |
CHD O | |
( O | |
OR O | |
: O | |
7.156 O | |
; O | |
95 O | |
% O | |
CI O | |
: O | |
3.293 O | |
- O | |
15.552 O | |
) O | |
, O | |
and O | |
having O | |
a O | |
child O | |
with O | |
a O | |
birth O | |
defect O | |
( O | |
OR O | |
: O | |
2.086 O | |
; O | |
95 O | |
% O | |
CI O | |
: O | |
1.167 O | |
- O | |
3.731 O | |
) O | |
were O | |
positively O | |
associated O | |
with O | |
CHD O | |
. O | |
Conclusion O | |
CHD O | |
is O | |
a O | |
serious O | |
health O | |
problem O | |
in O | |
Qingdao B-LOC | |
. O | |
The O | |
CHD O | |
incidence B-EPI | |
found O | |
in O | |
this O | |
study O | |
was O | |
similar O | |
to O | |
existing O | |
research O | |
. O | |
The O | |
positive O | |
rate O | |
of O | |
prenatal O | |
CHD O | |
screening O | |
was O | |
higher O | |
than O | |
the O | |
incidence B-EPI | |
of O | |
neonatal O | |
CHD O | |
. O | |
Moreover O | |
, O | |
CHD O | |
risk O | |
factors O | |
were O | |
identified O | |
in O | |
our O | |
study O | |
, O | |
and O | |
our O | |
findings O | |
may O | |
have O | |
great O | |
implications O | |
for O | |
formation O | |
CHD O | |
intervention O | |
strategies O | |
. O | |
The O | |
Global O | |
Atmospheric O | |
Passive O | |
Sampling O | |
( O | |
GAPS O | |
) O | |
network O | |
, O | |
initiated O | |
in O | |
2005 B-DATE | |
across O | |
55 O | |
global O | |
sites O | |
, O | |
supports O | |
the O | |
global O | |
monitoring O | |
plan O | |
( O | |
GMP O | |
) O | |
of O | |
the O | |
Stockholm O | |
Convention O | |
on O | |
Persistent O | |
Organic O | |
Pollutants O | |
( O | |
POPs O | |
) O | |
by O | |
providing O | |
information O | |
on O | |
POP O | |
concentrations O | |
in O | |
air O | |
on O | |
a O | |
global O | |
scale O | |
. O | |
These O | |
data O | |
inform O | |
assessments O | |
of O | |
the O | |
long O | |
- O | |
range O | |
transport O | |
potential O | |
of O | |
POPs O | |
and O | |
the O | |
effectiveness O | |
evaluation O | |
of O | |
chemical O | |
regulation O | |
efforts O | |
, O | |
by O | |
observing O | |
changes O | |
in O | |
concentrations O | |
over O | |
time O | |
. O | |
Currently O | |
, O | |
measurements O | |
spanning O | |
5 O | |
- O | |
10 O | |
sampling O | |
years O | |
are O | |
available O | |
for O | |
40 O | |
sites O | |
from O | |
the O | |
GAPS O | |
Network O | |
. O | |
This O | |
study O | |
was O | |
the O | |
first O | |
time O | |
that O | |
POP O | |
concentrations O | |
in O | |
air O | |
were O | |
reported O | |
on O | |
a O | |
global O | |
scale O | |
for O | |
an O | |
extended O | |
time O | |
period O | |
and O | |
the O | |
first O | |
to O | |
evaluate O | |
worldwide B-LOC | |
trends O | |
with O | |
an O | |
internally O | |
consistent O | |
sample O | |
set O | |
. O | |
For O | |
consistency O | |
between O | |
sampling O | |
years O | |
, O | |
site- O | |
and O | |
sample O | |
specific O | |
sampling O | |
rates O | |
were O | |
calculated O | |
with O | |
a O | |
new O | |
, O | |
public O | |
online O | |
model O | |
, O | |
which O | |
accounts O | |
for O | |
the O | |
effects O | |
of O | |
wind O | |
speed O | |
variability O | |
. O | |
Concentrations O | |
for O | |
legacy O | |
POPs O | |
in O | |
air O | |
between B-DATE | |
2005 I-DATE | |
and I-DATE | |
2014 I-DATE | |
show O | |
different O | |
trends O | |
for O | |
different O | |
organochlorine O | |
pesticides O | |
( O | |
OCPs O | |
) O | |
and O | |
polychlorinated O | |
biphenyls O | |
( O | |
PCBs O | |
) O | |
. O | |
The O | |
POPs O | |
discussed O | |
in O | |
this O | |
study O | |
were O | |
chosen O | |
due O | |
to O | |
being O | |
the O | |
most O | |
frequently O | |
detected O | |
, O | |
with O | |
detection O | |
at O | |
the O | |
majority O | |
of O | |
sites O | |
. O | |
PCB O | |
, O | |
endosulfan O | |
, O | |
and O | |
hexachlorocyclohexane O | |
( O | |
HCH O | |
) O | |
concentrations O | |
in O | |
air O | |
are O | |
decreasing O | |
at O | |
most O | |
sites O | |
. O | |
The O | |
global O | |
trends O | |
reflect O | |
global O | |
sources O | |
and O | |
recycling O | |
of O | |
HCH O | |
, O | |
ongoing O | |
emissions O | |
from O | |
old O | |
stockpiles O | |
for O | |
PCBs O | |
, O | |
and O | |
recent O | |
use O | |
restrictions O | |
for O | |
endosulfan O | |
. O | |
These O | |
chlorinated O | |
OCPs O | |
continue O | |
to O | |
present O | |
exposure O | |
threat O | |
to O | |
humans O | |
and O | |
ecosystems O | |
worldwide B-LOC | |
. O | |
Concentrations O | |
of O | |
other O | |
OCPs O | |
, O | |
such O | |
as O | |
chlordanes O | |
, O | |
heptachlor O | |
and O | |
dieldrin O | |
, O | |
are O | |
steady O | |
and/or O | |
declining O | |
slowly O | |
at O | |
the O | |
majority O | |
of O | |
sites O | |
, O | |
reflecting O | |
a O | |
transition O | |
from O | |
primary O | |
to O | |
secondary O | |
sources O | |
( O | |
i.e. O | |
, O | |
re O | |
- O | |
emission O | |
from O | |
reservoirs O | |
where O | |
these O | |
POPs O | |
have O | |
accumulated O | |
historically O | |
) O | |
which O | |
now O | |
control O | |
ambient O | |
air O | |
burdens O | |
. O | |
Background O | |
The O | |
increase O | |
of O | |
chronic O | |
diseases O | |
prevalence B-EPI | |
has O | |
created O | |
the O | |
need O | |
to O | |
adapt O | |
care O | |
models O | |
and O | |
to O | |
provide O | |
greater O | |
home O | |
supervision O | |
. O | |
Objective O | |
The O | |
objective O | |
of O | |
our O | |
study O | |
was O | |
to O | |
evaluate O | |
the O | |
impact O | |
of O | |
telemonitoring O | |
on O | |
patients O | |
with O | |
long O | |
- O | |
term O | |
conditions O | |
at O | |
high O | |
risk O | |
for O | |
rehospitalization O | |
or O | |
an O | |
emergency O | |
department O | |
visit O | |
, O | |
in O | |
terms O | |
of O | |
target O | |
disease O | |
control O | |
( O | |
diabetes O | |
, O | |
hypertension O | |
, O | |
heart O | |
failure O | |
, O | |
and O | |
chronic O | |
obstructive O | |
pulmonary O | |
disease O | |
) O | |
. O | |
Methods O | |
We O | |
conducted O | |
a O | |
quasi O | |
- O | |
experimental O | |
study O | |
with O | |
a O | |
before O | |
- O | |
and O | |
- O | |
after O | |
analysis O | |
to O | |
assess O | |
the O | |
effectiveness O | |
of O | |
the O | |
ValCrònic O | |
program O | |
after O | |
1 O | |
year O | |
of O | |
primary O | |
care O | |
monitoring O | |
. O | |
The O | |
study O | |
included O | |
high O | |
- O | |
risk O | |
patients O | |
with O | |
1 O | |
or O | |
more O | |
of O | |
the O | |
following O | |
conditions O | |
: O | |
diabetes O | |
, O | |
high O | |
blood O | |
pressure O | |
, O | |
heart O | |
failure O | |
, O | |
and O | |
chronic O | |
obstructive O | |
pulmonary O | |
disease O | |
. O | |
We O | |
assessed O | |
risk O | |
according O | |
to O | |
the O | |
Community O | |
Assessment O | |
Risk O | |
Screen O | |
. O | |
Participants O | |
used O | |
an O | |
electronic O | |
device O | |
( O | |
tablet O | |
) O | |
to O | |
self O | |
- O | |
report O | |
relevant O | |
health O | |
information O | |
, O | |
which O | |
was O | |
then O | |
automatically O | |
entered O | |
into O | |
their O | |
eHealth O | |
record O | |
for O | |
consultation O | |
. O | |
Results O | |
The O | |
total O | |
sample O | |
size O | |
was O | |
521 O | |
patients O | |
. O | |
Compared O | |
with O | |
the O | |
preintervention O | |
year O | |
, O | |
there O | |
were O | |
significant O | |
reductions O | |
in O | |
weight O | |
( O | |
82.3 O | |
kg O | |
before O | |
vs O | |
80.1 O | |
kg O | |
after O | |
; O | |
P=.001 O | |
) O | |
and O | |
in O | |
the O | |
proportion O | |
of O | |
people O | |
with O | |
high O | |
systolic O | |
( O | |
≥140 O | |
mmHg O | |
; O | |
190 O | |
, O | |
36.5 O | |
% O | |
vs O | |
170 O | |
, O | |
32.6 O | |
% O | |
; O | |
P=.001 O | |
) O | |
and O | |
diastolic O | |
( O | |
≥90 O | |
mmHg O | |
; O | |
72 O | |
, O | |
13.8 O | |
% O | |
vs O | |
40 O | |
, O | |
7.7 O | |
% O | |
; O | |
P=.01 O | |
) O | |
blood O | |
pressures O | |
, O | |
and O | |
hemoglobin O | |
A O | |
1c O | |
≥8 O | |
% O | |
( O | |
186 O | |
, O | |
35.7 O | |
% O | |
vs O | |
104 O | |
, O | |
20.0 O | |
% O | |
; O | |
P=.001 O | |
) O | |
. O | |
There O | |
was O | |
also O | |
a O | |
decrease O | |
in O | |
the O | |
proportion O | |
of O | |
participants O | |
who O | |
used O | |
emergency O | |
services O | |
in O | |
primary O | |
care O | |
( O | |
68 O | |
, O | |
13.1 O | |
% O | |
vs O | |
33 O | |
, O | |
6.3 O | |
% O | |
; O | |
P<.001 O | |
) O | |
and O | |
in O | |
hospital O | |
( O | |
98 O | |
, O | |
18.8 O | |
% O | |
vs O | |
67 O | |
, O | |
12.8 O | |
% O | |
; O | |
P<.001 O | |
) O | |
. O | |
Likewise O | |
, O | |
fewer O | |
participants O | |
required O | |
hospital O | |
admission O | |
due O | |
to O | |
an O | |
emergency O | |
( O | |
105 O | |
, O | |
20.2 O | |
% O | |
vs O | |
71 O | |
, O | |
13.6 O | |
% O | |
; O | |
P<.001 O | |
) O | |
or O | |
disease O | |
exacerbation O | |
( O | |
55 O | |
, O | |
10.5 O | |
% O | |
vs O | |
42 O | |
, O | |
8.1 O | |
% O | |
; O | |
P<.001 O | |
) O | |
. O | |
Conclusions O | |
The O | |
ValCrònic O | |
telemonitoring O | |
program O | |
in O | |
patients O | |
at O | |
high O | |
risk O | |
for O | |
rehospitalization O | |
or O | |
an O | |
emergency O | |
department O | |
visit O | |
appears O | |
to O | |
be O | |
useful O | |
to O | |
improve O | |
target O | |
disease O | |
control O | |
and O | |
to O | |
reduce O | |
the O | |
use O | |
of O | |
resources O | |
. O | |
Alport O | |
syndrome O | |
is O | |
an O | |
inherited O | |
disorder O | |
characterized O | |
by O | |
the O | |
association O | |
of O | |
a O | |
progressive O | |
haematuric O | |
nephropathy O | |
with O | |
ultrastructural O | |
abnormalities O | |
of O | |
the O | |
glomerular O | |
basement O | |
membranes O | |
, O | |
a O | |
progressive O | |
sensorineural O | |
hearing O | |
loss O | |
and O | |
sometimes O | |
ocular O | |
involvement O | |
. O | |
Its O | |
incidence B-EPI | |
is O | |
less B-STAT | |
than I-STAT | |
1 I-STAT | |
per I-STAT | |
5000 I-STAT | |
individuals I-STAT | |
and O | |
the O | |
disease O | |
is O | |
the O | |
cause O | |
of O | |
about O | |
2 O | |
% O | |
of O | |
end O | |
stage O | |
renal O | |
disease O | |
in O | |
Europe B-LOC | |
and O | |
the B-LOC | |
United I-LOC | |
States I-LOC | |
. O | |
Alport O | |
syndrome O | |
is O | |
clinically O | |
and O | |
genetically O | |
heterogeneous O | |
. O | |
It O | |
is O | |
related O | |
to O | |
mutations O | |
in O | |
the O | |
genes O | |
encoding O | |
one O | |
of O | |
three O | |
chains O | |
, O | |
[alpha]3 O | |
, O | |
[alpha]4 O | |
[alpha]5 O | |
of O | |
type O | |
IV O | |
collagen O | |
, O | |
the O | |
main O | |
component O | |
of O | |
basement O | |
membranes O | |
, O | |
expressed O | |
in O | |
the O | |
glomerular O | |
basement O | |
membrane O | |
. O | |
COL4A5 O | |
mutations O | |
are O | |
associated O | |
with O | |
X O | |
- O | |
linked O | |
Alport O | |
syndrome O | |
, O | |
which O | |
represents O | |
80 O | |
to O | |
85 O | |
% O | |
of O | |
cases O | |
and O | |
is O | |
more O | |
severe O | |
in O | |
boys B-SEX | |
than O | |
in O | |
girls B-SEX | |
. O | |
Mutations O | |
in O | |
COL4A3 O | |
or O | |
COL4A4 O | |
are O | |
associated O | |
with O | |
autosomal O | |
Alport O | |
syndrome O | |
. O | |
The O | |
expression O | |
of O | |
collagen O | |
chains O | |
in O | |
skin O | |
and O | |
kidney O | |
basement O | |
membranes O | |
allows O | |
for O | |
the O | |
diagnosis O | |
and O | |
characterization O | |
of O | |
the O | |
mode O | |
of O | |
transmission O | |
in O | |
most O | |
patients O | |
. O | |
It O | |
is O | |
necessary O | |
to O | |
diagnose O | |
this O | |
syndrome O | |
because O | |
its O | |
family O | |
involvement O | |
, O | |
its O | |
severity O | |
, O | |
and O | |
the O | |
importance O | |
of O | |
genetic O | |
counseling O | |
. O | |
Angiotensin O | |
blockers O | |
are O | |
increasingly O | |
prescribed O | |
in O | |
proteinuric O | |
patients O | |
. O | |
Prospective O | |
studies O | |
are O | |
needed O | |
to O | |
assess O | |
the O | |
effectiveness O | |
of O | |
these O | |
treatments O | |
on O | |
proteinuria O | |
and O | |
progression O | |
of O | |
kidney O | |
failure O | |
, O | |
and O | |
to O | |
specify O | |
indications O | |
. O | |
Animal O | |
studies O | |
have O | |
shown O | |
the O | |
potential O | |
value O | |
of O | |
different O | |
molecules O | |
( O | |
protease O | |
inhibitors O | |
, O | |
chemokine O | |
receptor O | |
blockers O | |
, O | |
transforming O | |
growth O | |
factor O | |
- O | |
[beta]01 O | |
inhibitors O | |
, O | |
hydroxy O | |
- O | |
methyl O | |
- O | |
coenzyme O | |
A O | |
reductase O | |
inhibitors O | |
, O | |
bone O | |
morphogenetic O | |
protein-7 O | |
inhibitors O | |
) O | |
, O | |
hematopoietic O | |
stem O | |
cells O | |
, O | |
and O | |
of O | |
a O | |
anti O | |
- O | |
micro O | |
- O | |
RNA O | |
. O | |
Introduction O | |
Globally B-LOC | |
, O | |
eye O | |
diseases O | |
are O | |
considered O | |
as O | |
one O | |
of O | |
the O | |
major O | |
contributors O | |
of O | |
nonfatal O | |
disabling O | |
conditions O | |
. O | |
In O | |
Bangladesh B-LOC | |
, O | |
1.5 O | |
% O | |
of O | |
adults O | |
are O | |
blind O | |
and O | |
21.6 O | |
% O | |
have O | |
low O | |
vision O | |
. O | |
Therefore O | |
, O | |
this O | |
paper O | |
aimed O | |
to O | |
identify O | |
the O | |
community O | |
- O | |
based O | |
prevalence B-EPI | |
and O | |
associated O | |
risk O | |
factors O | |
of O | |
eye O | |
diseases O | |
among O | |
slum O | |
dwellers O | |
of O | |
Dhaka B-LOC | |
city I-LOC | |
. O | |
Methods O | |
The O | |
study O | |
was O | |
carried O | |
out O | |
in O | |
two O | |
phases O | |
. O | |
In O | |
the O | |
first O | |
phase O | |
, O | |
a O | |
survey O | |
was O | |
conducted O | |
using O | |
multistage O | |
cluster O | |
sampling O | |
among O | |
1320 O | |
households O | |
of O | |
three O | |
purposively O | |
selected O | |
slums O | |
in O | |
Dhaka B-LOC | |
city I-LOC | |
. O | |
From O | |
each O | |
household O | |
, O | |
one O | |
family O | |
member O | |
( O | |
≥ O | |
18 O | |
years O | |
old O | |
) O | |
was O | |
randomly O | |
interviewed O | |
by O | |
trained O | |
data O | |
collectors O | |
using O | |
a O | |
structured O | |
questionnaire O | |
. O | |
After O | |
that O | |
, O | |
each O | |
of O | |
the O | |
participants O | |
was O | |
requested O | |
to O | |
take O | |
part O | |
in O | |
the O | |
second O | |
phase O | |
of O | |
the O | |
study O | |
. O | |
Following O | |
the O | |
request O | |
, O | |
432 O | |
participants O | |
out O | |
of O | |
1320 O | |
participants O | |
came O | |
into O | |
the O | |
tertiary O | |
care O | |
hospitals O | |
where O | |
they O | |
were O | |
clinically O | |
assessed O | |
by O | |
ophthalmologist O | |
for O | |
presence O | |
of O | |
eye O | |
diseases O | |
. O | |
A O | |
number O | |
of O | |
descriptive O | |
and O | |
inferential O | |
statistics O | |
were O | |
performed O | |
using O | |
Stata O | |
13 O | |
. O | |
Result O | |
The O | |
majority O | |
of O | |
total O | |
432 O | |
study O | |
participants O | |
were O | |
female B-SEX | |
( O | |
68.6 O | |
% O | |
) O | |
, O | |
married O | |
( O | |
82.6 O | |
% O | |
) O | |
and O | |
Muslim B-ETHN | |
( O | |
98.8 O | |
% O | |
) O | |
. O | |
Among O | |
them O | |
almost O | |
all O | |
( O | |
92.8 O | |
% O | |
) O | |
were O | |
clinically O | |
diagnosed O | |
with O | |
eye O | |
disease O | |
. O | |
The O | |
most O | |
prevalent O | |
eye O | |
diseases O | |
were O | |
refractive O | |
error O | |
( O | |
63.2 O | |
% O | |
) O | |
, O | |
conjunctivitis O | |
( O | |
17.1 O | |
% O | |
) O | |
, O | |
visual O | |
impairment O | |
( O | |
16.4 O | |
% O | |
) O | |
and O | |
cataract O | |
( O | |
7.2 O | |
% O | |
) O | |
. O | |
Refractive O | |
error O | |
was O | |
found O | |
significantly O | |
associated O | |
with O | |
older O | |
age O | |
, O | |
female B-SEX | |
gender O | |
and O | |
income O | |
generating O | |
work O | |
. O | |
Cataract O | |
was O | |
found O | |
negatively O | |
associated O | |
with O | |
the O | |
level O | |
of O | |
education O | |
, O | |
however O | |
, O | |
opposite O | |
relationship O | |
was O | |
found O | |
between O | |
cataract O | |
and O | |
visual O | |
impairment O | |
. O | |
Conclusion O | |
Our O | |
study O | |
provides O | |
epidemiologic O | |
data O | |
on O | |
the O | |
prevalence B-EPI | |
of O | |
eye O | |
diseases O | |
among O | |
adult O | |
population O | |
in O | |
low O | |
- O | |
income O | |
urban O | |
community O | |
of O | |
Dhaka B-LOC | |
city I-LOC | |
. O | |
The O | |
high O | |
prevalence B-EPI | |
of O | |
refractive O | |
error O | |
, O | |
allergic O | |
conjunctivitis O | |
, O | |
visual O | |
impairment O | |
, O | |
and O | |
cataract O | |
among O | |
this O | |
group O | |
of O | |
people O | |
suggests O | |
the O | |
importance O | |
of O | |
increasing O | |
access O | |
to O | |
eye O | |
care O | |
services O | |
. O | |
Epidemiological O | |
data O | |
on O | |
the O | |
14 O | |
cases O | |
of O | |
adrenal O | |
cortical O | |
tumour O | |
registered O | |
with O | |
the O | |
Manchester B-LOC | |
Children O | |
's O | |
Tumour O | |
Registry O | |
from O | |
1954 B-DATE | |
and I-DATE | |
1985 I-DATE | |
are O | |
presented O | |
. O | |
The O | |
incidence B-EPI | |
of O | |
adrenal O | |
cortical O | |
carcinomas O | |
was O | |
0.3 O | |
% O | |
, O | |
mainly O | |
in O | |
girls B-SEX | |
, O | |
most O | |
of O | |
whom O | |
presented O | |
with O | |
virilisation O | |
. O | |
The O | |
incidence B-EPI | |
of O | |
neoplastic O | |
disease O | |
among O | |
close O | |
relatives O | |
was O | |
ascertained O | |
, O | |
but O | |
, O | |
except O | |
in O | |
siblings O | |
, O | |
this O | |
was O | |
not O | |
significantly O | |
higher O | |
than O | |
would O | |
be O | |
expected O | |
. O | |
Evidence O | |
from O | |
extended O | |
pedigrees O | |
, O | |
however O | |
, O | |
indicates O | |
that O | |
at O | |
least O | |
four O | |
of O | |
the O | |
children O | |
could O | |
be O | |
members O | |
of O | |
families O | |
with O | |
the O | |
SBLA O | |
( O | |
sarcoma O | |
, O | |
breast O | |
and O | |
brain O | |
tumour O | |
, O | |
leukaemia O | |
, O | |
laryngeal O | |
and O | |
lung O | |
cancer O | |
, O | |
and O | |
adrenal O | |
cortical O | |
carcinoma O | |
) O | |
cancer O | |
family O | |
syndrome O | |
, O | |
and O | |
that O | |
other O | |
relatives O | |
may O | |
be O | |
at O | |
risk O | |
of O | |
developing O | |
such O | |
neoplasms O | |
. O | |
Background O | |
The O | |
prevalence B-EPI | |
of O | |
developmental O | |
alterations O | |
associated O | |
with O | |
in O | |
- O | |
utero O | |
Zika O | |
virus O | |
( O | |
ZIKV O | |
) O | |
exposure O | |
in O | |
children O | |
is O | |
not O | |
well O | |
understood O | |
. O | |
Furthermore O | |
, O | |
estimation O | |
of O | |
the O | |
Population O | |
Attributable O | |
Fraction O | |
( O | |
PAF O | |
) O | |
of O | |
developmental O | |
alterations O | |
attributed O | |
to O | |
ZIKV O | |
has O | |
not O | |
been O | |
performed O | |
due O | |
to O | |
lack O | |
of O | |
population O | |
- O | |
based O | |
cohorts O | |
with O | |
data O | |
on O | |
symptomatic O | |
and O | |
asymptomatic O | |
ZIKV O | |
exposures O | |
and O | |
an O | |
appropriate O | |
control O | |
group O | |
. O | |
The O | |
aim O | |
of O | |
this O | |
study O | |
was O | |
to O | |
characterize O | |
neurodevelopmental O | |
outcomes O | |
of O | |
children O | |
at O | |
11 O | |
to O | |
32 O | |
months O | |
of O | |
age O | |
with O | |
intrauterine O | |
ZIKV O | |
exposure O | |
and O | |
estimate O | |
the O | |
PAF O | |
of O | |
alterations O | |
secondary O | |
to O | |
ZIKV O | |
exposure O | |
. O | |
Methodology O | |
/ O | |
principal O | |
findings O | |
We O | |
performed O | |
a O | |
cohort O | |
of O | |
biannual O | |
community O | |
- O | |
based O | |
prospective O | |
serosurveys O | |
in O | |
a O | |
slum O | |
community O | |
in O | |
Salvador B-LOC | |
, I-LOC | |
Brazil I-LOC | |
. O | |
We O | |
recruited O | |
women B-SEX | |
participating O | |
in O | |
our O | |
cohort O | |
, O | |
with O | |
a O | |
documented O | |
pregnancy O | |
from O | |
January B-DATE | |
2015 I-DATE | |
to I-DATE | |
December I-DATE | |
2016 I-DATE | |
and O | |
children O | |
born O | |
to O | |
those O | |
mothers O | |
. O | |
Children O | |
were O | |
classified O | |
as O | |
ZIKV O | |
exposed O | |
in O | |
utero O | |
( O | |
born O | |
from O | |
women B-SEX | |
with O | |
ZIKV O | |
seroconversion O | |
during O | |
pregnancy O | |
) O | |
or O | |
unexposed O | |
( O | |
born O | |
from O | |
women B-SEX | |
without O | |
ZIKV O | |
seroconversion O | |
or O | |
that O | |
seroconverted O | |
before O | |
/ O | |
after O | |
pregnancy O | |
) O | |
by O | |
using O | |
an O | |
IgG O | |
monoclonal O | |
antibody O | |
blockade O | |
- O | |
of O | |
- O | |
binding O | |
( O | |
BoB O | |
) O | |
. O | |
We O | |
interviewed O | |
mothers O | |
and O | |
performed O | |
anthropometric O | |
, O | |
audiometric O | |
, O | |
ophthalmological O | |
, O | |
neurologic O | |
, O | |
and O | |
neurodevelopmental O | |
evaluations O | |
of O | |
their O | |
children O | |
at O | |
11 O | |
to O | |
32 O | |
months O | |
of O | |
age O | |
. O | |
Among O | |
the O | |
655 O | |
women B-SEX | |
participating O | |
in O | |
the O | |
cohort O | |
, O | |
66 O | |
( O | |
10 O | |
% O | |
) O | |
were O | |
pregnant O | |
during O | |
the O | |
study O | |
period O | |
. O | |
46 O | |
( O | |
70 O | |
% O | |
) O | |
of O | |
them O | |
completed O | |
follow O | |
- O | |
up O | |
, O | |
of O | |
whom O | |
ZIKV O | |
seroconversion O | |
occurred O | |
before O | |
, O | |
during O | |
, O | |
and O | |
after O | |
pregnancy O | |
in O | |
25 O | |
( O | |
54 O | |
% O | |
) O | |
, O | |
13 O | |
( O | |
28 O | |
% O | |
) O | |
, O | |
and O | |
1 O | |
( O | |
2 O | |
% O | |
) O | |
, O | |
respectively O | |
. O | |
The O | |
rest O | |
of O | |
women B-SEX | |
, O | |
7 O | |
( O | |
21.2 O | |
% O | |
) O | |
, O | |
did O | |
not O | |
present O | |
ZIKV O | |
seroconversion O | |
. O | |
At O | |
11 O | |
to O | |
32 O | |
months O | |
of O | |
life O | |
, O | |
the O | |
13 O | |
ZIKV O | |
- O | |
exposed O | |
children O | |
had O | |
increased O | |
risk O | |
of O | |
mild O | |
cognitive O | |
delay O | |
( O | |
RR O | |
5.1 O | |
; O | |
95%CI O | |
1.1 O | |
- O | |
24.4 O | |
) O | |
compared O | |
with O | |
the O | |
33 O | |
children O | |
unexposed O | |
, O | |
with O | |
a O | |
PAF O | |
of O | |
53.5 O | |
% O | |
. O | |
Exposed O | |
children O | |
also O | |
had O | |
increased O | |
risk O | |
of O | |
altered O | |
auditory O | |
behavior O | |
( O | |
RR O | |
6.0 O | |
; O | |
95%CI O | |
1.3 O | |
- O | |
26.9 O | |
) O | |
, O | |
with O | |
a O | |
PAF O | |
of O | |
59.5 O | |
% O | |
. O | |
Conclusions O | |
A O | |
significant O | |
proportion O | |
of O | |
children O | |
exposed O | |
in O | |
utero O | |
to O | |
ZIKV O | |
developed O | |
mild O | |
cognitive O | |
delay O | |
and O | |
auditory O | |
behavioral O | |
abnormalities O | |
even O | |
in O | |
the O | |
absence O | |
of O | |
gross O | |
birth O | |
defects O | |
such O | |
as O | |
microcephaly O | |
and O | |
other O | |
neurodevelopmental O | |
domains O | |
. O | |
Furthermore O | |
, O | |
our O | |
findings O | |
suggest O | |
that O | |
over O | |
half O | |
of O | |
these O | |
abnormalities O | |
could O | |
be O | |
attributed O | |
to O | |
intrauterine O | |
ZIKV O | |
exposure O | |
. O | |
Cone O | |
- O | |
rod O | |
dystrophy O | |
( O | |
CORD O | |
) O | |
is O | |
one O | |
of O | |
the O | |
inherited O | |
retinal O | |
diseases O | |
that O | |
result O | |
in O | |
central O | |
visual O | |
field O | |
deterioration O | |
and O | |
decreased O | |
visual O | |
acuity O | |
( O | |
VA O | |
) O | |
. O | |
In O | |
CORD O | |
patients O | |
, O | |
impaired O | |
photoreceptor O | |
cells O | |
are O | |
observed O | |
as O | |
the O | |
disruption O | |
of O | |
ellipsoid O | |
zone O | |
( O | |
EZ O | |
) O | |
on O | |
optical O | |
coherence O | |
tomography O | |
( O | |
OCT O | |
) O | |
images O | |
. O | |
In O | |
the O | |
present O | |
study O | |
, O | |
we O | |
calculated O | |
the O | |
index O | |
of O | |
residual O | |
EZ O | |
( O | |
rEZ O | |
) O | |
to O | |
quantify O | |
the O | |
function O | |
of O | |
photoreceptor O | |
cells O | |
and O | |
investigated O | |
the O | |
correlation O | |
between O | |
rEZ O | |
index O | |
and O | |
visual O | |
functions O | |
. O | |
Twenty O | |
- O | |
six O | |
eyes O | |
of O | |
13 O | |
patients O | |
with O | |
clinical O | |
suspicion O | |
of O | |
CORD O | |
were O | |
examined O | |
. O | |
Visual O | |
field O | |
was O | |
tested O | |
with O | |
the O | |
Humphrey O | |
Visual O | |
Field O | |
Analyzer O | |
( O | |
HFA O | |
10 O | |
- O | |
2 O | |
program O | |
) O | |
. O | |
We O | |
simultaneously O | |
obtained O | |
OCT O | |
images O | |
and O | |
calculated O | |
the O | |
area O | |
of O | |
decreased O | |
EZ O | |
intensity O | |
( O | |
EZa O | |
) O | |
. O | |
Using O | |
the O | |
binarized O | |
OCT O | |
images O | |
, O | |
the O | |
percentage O | |
of O | |
the O | |
rEZ O | |
in O | |
a O | |
3 O | |
× O | |
3 O | |
mm O | |
area O | |
surrounding O | |
the O | |
macula O | |
was O | |
analyzed O | |
. O | |
To O | |
clarify O | |
interrator O | |
reproducibility O | |
, O | |
intraclass O | |
correlation O | |
coefficient O | |
( O | |
ICC O | |
) O | |
was O | |
calculated O | |
. O | |
Moreover O | |
, O | |
we O | |
investigated O | |
the O | |
association O | |
between O | |
OCT O | |
parameters O | |
and O | |
VA O | |
as O | |
well O | |
as O | |
the O | |
mean O | |
deviation O | |
( O | |
MD O | |
) O | |
value O | |
measured O | |
with O | |
HFA O | |
. O | |
The O | |
mean O | |
age O | |
of O | |
the O | |
patients O | |
was O | |
48.5 O | |
± O | |
16.9 O | |
years O | |
. O | |
The O | |
mean O | |
central O | |
retinal O | |
thickness O | |
was O | |
122.7 O | |
± O | |
73.2 O | |
[mu]m O | |
. O | |
The O | |
mean O | |
EZa O | |
and O | |
rEZ O | |
were O | |
22.2 O | |
± O | |
23.6 O | |
[mu]m O | |
2 O | |
and O | |
0.35 O | |
± O | |
0.31 O | |
, O | |
respectively O | |
. O | |
The O | |
ICC O | |
of O | |
each O | |
rEZ O | |
index O | |
was O | |
0.91 O | |
( O | |
95 O | |
% O | |
CI O | |
: O | |
0.89 O | |
< O | |
ICC O | |
< O | |
0.93 O | |
) O | |
. O | |
Multivariate O | |
analysis O | |
indicated O | |
rEZ O | |
was O | |
significantly O | |
related O | |
to O | |
logMAR O | |
VA O | |
( O | |
p O | |
= O | |
0.05 O | |
) O | |
and O | |
rEZ O | |
and O | |
EZa O | |
were O | |
associated O | |
with O | |
the O | |
MD O | |
value O | |
( O | |
p O | |
= O | |
0.014 O | |
and O | |
p O | |
= O | |
0.009 O | |
, O | |
linear O | |
mixed O | |
model O | |
) O | |
. O | |
Furthermore O | |
, O | |
rEZ O | |
was O | |
also O | |
associated O | |
with O | |
photopic O | |
a- O | |
and O | |
b O | |
- O | |
wave O | |
amplitudes O | |
( O | |
p O | |
= O | |
0.027 O | |
and O | |
p O | |
= O | |
0.0024 O | |
, O | |
respectively O | |
, O | |
linear O | |
mixed O | |
model O | |
) O | |
. O | |
Taken O | |
together O | |
, O | |
the O | |
current O | |
results O | |
suggested O | |
the O | |
usefulness O | |
of O | |
rEZ O | |
quantification O | |
for O | |
predicting O | |
visual O | |
functions O | |
in O | |
CORD O | |
patients O | |
. O | |
The O | |
relationship O | |
between O | |
smoking O | |
and O | |
illness O | |
perceptions O | |
among O | |
congenital O | |
heart O | |
disease O | |
( O | |
CHD O | |
) O | |
survivors O | |
is O | |
unknown O | |
. O | |
The O | |
primary O | |
aims O | |
of O | |
the O | |
present O | |
study O | |
were O | |
to O | |
compare O | |
the O | |
smoking O | |
prevalence B-EPI | |
among O | |
CHD O | |
survivors O | |
to O | |
a O | |
nationally O | |
representative O | |
U.S. B-LOC | |
sample O | |
and O | |
examine O | |
the O | |
relationship O | |
between O | |
smoking O | |
and O | |
illness O | |
perceptions O | |
. O | |
CHD O | |
survivors O | |
( O | |
N O | |
= O | |
744 O | |
) O | |
from O | |
six O | |
U.S. O | |
sites O | |
participated O | |
in O | |
the O | |
study O | |
. O | |
The O | |
smoking O | |
prevalence B-EPI | |
among O | |
CHD O | |
survivors O | |
( O | |
9.3 O | |
% O | |
) O | |
was O | |
lower O | |
than O | |
the O | |
general O | |
population O | |
( O | |
15.3 O | |
% O | |
) O | |
. O | |
However O | |
, O | |
23.3 O | |
% O | |
of O | |
CHD O | |
survivors O | |
with O | |
severe O | |
functional O | |
limitations O | |
smoked O | |
. O | |
Smoking O | |
prevalence B-EPI | |
differed O | |
by O | |
U.S. O | |
region O | |
, O | |
with O | |
a O | |
greater O | |
proportion O | |
of O | |
those O | |
attending O | |
CHD O | |
care O | |
in O | |
the O | |
Midwest O | |
reporting O | |
smoking O | |
( O | |
11.8 O | |
% O | |
) O | |
. O | |
The O | |
illness O | |
perception O | |
dimensions O | |
of O | |
Concern O | |
and O | |
Emotional O | |
Response O | |
were O | |
independently O | |
associated O | |
with O | |
smoking O | |
. O | |
Differences O | |
in O | |
illness O | |
perceptions O | |
enhance O | |
our O | |
understanding O | |
of O | |
smoking O | |
among O | |
CHD O | |
survivors O | |
and O | |
may O | |
guide O | |
interventions O | |
promoting O | |
positive O | |
health O | |
behaviors O | |
. O | |
The O | |
protocol O | |
for O | |
the O | |
study O | |
from O | |
which O | |
the O | |
present O | |
analyses O | |
were O | |
conducted O | |
was O | |
recorded O | |
at O | |
ClinicalTrials.gov O | |
: O | |
NCT02150603 O | |
. O | |
Since O | |
2013 B-DATE | |
, O | |
a O | |
high O | |
incidence B-EPI | |
of O | |
bilateral O | |
symmetrical O | |
alopecia O | |
has O | |
been O | |
observed O | |
in O | |
free O | |
- O | |
ranging O | |
Formosan O | |
macaques O | |
( O | |
Macaca O | |
cyclopis O | |
) O | |
in O | |
Mt. O | |
Longevity O | |
, O | |
Taiwan B-LOC | |
. O | |
We O | |
hypothesized O | |
that O | |
stress O | |
induces O | |
alopecia O | |
in O | |
this O | |
population O | |
. O | |
To O | |
verify O | |
our O | |
hypothesis O | |
, O | |
we O | |
evaluated O | |
the O | |
histopathological O | |
characteristics O | |
of O | |
skin O | |
biopsy O | |
and O | |
used O | |
a O | |
validated O | |
enzyme O | |
immunoassay O | |
( O | |
EIA O | |
) O | |
for O | |
fecal O | |
glucocorticoid O | |
metabolite O | |
( O | |
FGM O | |
) O | |
analysis O | |
, O | |
which O | |
act O | |
as O | |
an O | |
indicator O | |
of O | |
stress O | |
experienced O | |
by O | |
the O | |
individual O | |
. O | |
Follicular O | |
densities O | |
were O | |
lower O | |
( O | |
2.1 O | |
- O | |
3.0 O | |
mm O | |
2 O | |
) O | |
in O | |
individuals O | |
with O | |
symmetrical O | |
alopecia O | |
than O | |
in O | |
those O | |
with O | |
normal O | |
hair O | |
conditions O | |
( O | |
4.7 O | |
mm O | |
2 O | |
) O | |
. O | |
Furthermore O | |
, O | |
anagen O | |
to O | |
catagen O | |
/ O | |
telogen O | |
ratios O | |
were O | |
lower O | |
in O | |
individuals O | |
with O | |
alopecia O | |
( O | |
0 O | |
- O | |
1.4 O | |
) O | |
than O | |
in O | |
those O | |
with O | |
normal O | |
hair O | |
( O | |
4.0 O | |
) O | |
. O | |
The O | |
histopathological O | |
characteristics O | |
of O | |
alopecia O | |
were O | |
similar O | |
to O | |
those O | |
of O | |
telogen O | |
effluvium O | |
, O | |
which O | |
indicates O | |
that O | |
stress O | |
is O | |
one O | |
of O | |
the O | |
possible O | |
etiologies O | |
. O | |
On O | |
the O | |
basis O | |
of O | |
the O | |
analytical O | |
and O | |
biological O | |
validation O | |
of O | |
EIAs O | |
for O | |
FGM O | |
analysis O | |
, O | |
11[beta]0 O | |
- O | |
hydroxyetiocholanolone O | |
was O | |
considered O | |
suitable O | |
for O | |
monitoring O | |
adrenocortical O | |
activity O | |
in O | |
both O | |
sexes O | |
of O | |
Formosan B-ETHN | |
macaques O | |
. O | |
The O | |
mean O | |
concentrations O | |
( O | |
standard O | |
error O | |
; O | |
sample O | |
size O | |
) O | |
of O | |
11[beta]0 O | |
- O | |
hydroxyetiocholanolone O | |
were O | |
2.02 O | |
( O | |
0.17 O | |
; O | |
n O | |
= O | |
10 O | |
) O | |
and O | |
1.41 O | |
( O | |
0.10 O | |
; O | |
n O | |
= O | |
31 O | |
) O | |
[mu]g O | |
/ O | |
g O | |
for O | |
individuals O | |
with O | |
and O | |
without O | |
alopecia O | |
, O | |
respectively O | |
. O | |
Furthermore O | |
, O | |
the O | |
results O | |
of O | |
logistic O | |
regression O | |
analysis O | |
show O | |
that O | |
11[beta]0 O | |
- O | |
hydroxyetiocholanolone O | |
( O | |
p O | |
= O | |
0.012 O | |
) O | |
concentration O | |
was O | |
positively O | |
associated O | |
with O | |
alopecia O | |
. O | |
Thus O | |
, O | |
stress O | |
was O | |
the O | |
most O | |
likely O | |
to O | |
trigger O | |
symmetrical O | |
alopecia O | |
in O | |
Formosan B-ETHN | |
macaques O | |
in O | |
Mt. O | |
Longevity O | |
. O | |
Although O | |
stress O | |
can O | |
decrease O | |
the O | |
fitness O | |
of O | |
an O | |
individual O | |
, O | |
considering O | |
the O | |
population O | |
status O | |
of O | |
Formosan O | |
macaques O | |
in O | |
Taiwan B-LOC | |
is O | |
stable O | |
and O | |
alopecia O | |
was O | |
only O | |
observed O | |
in O | |
our O | |
study O | |
area O | |
, O | |
which O | |
is O | |
isolated O | |
from O | |
other O | |
populations O | |
, O | |
the O | |
impact O | |
on O | |
the O | |
total O | |
population O | |
of O | |
Formosan O | |
macaque O | |
in O | |
Taiwan B-LOC | |
is O | |
limited O | |
. O | |
Nonetheless O | |
, O | |
stress O | |
- O | |
induced O | |
immunosuppression O | |
and O | |
alopecia O | |
might O | |
affect O | |
the O | |
local O | |
abundance O | |
and O | |
increase O | |
zoonosis O | |
risk O | |
due O | |
to O | |
frequent O | |
human O | |
- O | |
macaque O | |
contact O | |
in O | |
Mt. O | |
Longevity O | |
. O | |
Future O | |
studies O | |
are O | |
suggested O | |
to O | |
focus O | |
on O | |
the O | |
causative O | |
factor O | |
of O | |
stress O | |
and O | |
the O | |
effects O | |
of O | |
stress O | |
and O | |
alopecia O | |
on O | |
the O | |
health O | |
and O | |
welfare O | |
in O | |
the O | |
Formosan B-ETHN | |
macaques O | |
. O | |
Incidence B-EPI | |
of O | |
nontuberculous O | |
mycobacterial O | |
infections O | |
has O | |
increased O | |
during O | |
the O | |
past O | |
decades O | |
. O | |
Disseminated O | |
infections O | |
are O | |
relatively O | |
rare O | |
and O | |
associated O | |
with O | |
immunocompromised O | |
status O | |
. O | |
We O | |
report O | |
a O | |
case O | |
of O | |
disseminated O | |
Mycobacterium O | |
szulgai O | |
infection O | |
of O | |
cervical O | |
lymphadenitis O | |
and O | |
pulmonary O | |
involvement O | |
with O | |
positive O | |
anti O | |
- O | |
interferon O | |
- O | |
gamma O | |
autoantibodies O | |
. O | |
The O | |
patient O | |
was O | |
successfully O | |
treated O | |
with O | |
rifampin O | |
, O | |
ethambutol O | |
, O | |
and O | |
clarithromycin O | |
. O | |
The O | |
case O | |
reports O | |
and O | |
series O | |
through O | |
search O | |
engines O | |
of O | |
Pubmed O | |
and O | |
Google O | |
with O | |
the O | |
keyword O | |
of O | |
disseminated O | |
infection O | |
of O | |
M. O | |
szulgai O | |
were O | |
reviewed O | |
. O | |
Fifteen O | |
patients O | |
of O | |
disseminated O | |
M. O | |
szulgai O | |
infection O | |
were O | |
reviewed O | |
and O | |
included O | |
. O | |
Disseminated O | |
M. O | |
szulgai O | |
infection O | |
involves O | |
bone O | |
, O | |
skin O | |
and O | |
lymph O | |
node O | |
more O | |
common O | |
instead O | |
of O | |
pulmonary O | |
involvement O | |
, O | |
and O | |
most O | |
are O | |
associated O | |
with O | |
immunocompromised O | |
status O | |
with O | |
neoplastic O | |
hematologic O | |
disorders O | |
. O | |
In O | |
patients O | |
with O | |
disseminated O | |
M. O | |
szulgai O | |
infection O | |
, O | |
long O | |
term O | |
anti O | |
- O | |
mycobacterial O | |
agents O | |
are O | |
necessary O | |
. O | |
Most O | |
patients O | |
will O | |
respond O | |
to O | |
rifampin O | |
and O | |
ethambutol O | |
combination O | |
regimens O | |
. O | |
Kuwait B-LOC | |
has O | |
a O | |
cosmopolitan B-ETHN | |
population O | |
of O | |
1.7 O | |
million O | |
, O | |
mostly O | |
Arabs B-ETHN | |
. O | |
This O | |
population O | |
is O | |
a O | |
mosaic O | |
of O | |
large O | |
and O | |
small O | |
minorities O | |
representing O | |
most O | |
Arab B-ETHN | |
communities O | |
. O | |
In O | |
general O | |
, O | |
Kuwait B-LOC | |
's O | |
population O | |
is O | |
characterized O | |
by O | |
a O | |
rapid O | |
rate O | |
of O | |
growth O | |
, O | |
large O | |
family O | |
size O | |
, O | |
high O | |
rates O | |
of O | |
consanguineous O | |
marriages O | |
within O | |
the O | |
Arab B-ETHN | |
communities O | |
with O | |
low O | |
frequency O | |
of O | |
intermarriage O | |
between O | |
them O | |
, O | |
and O | |
the O | |
presence O | |
of O | |
genetic O | |
isolates O | |
and O | |
semi O | |
- O | |
isolates O | |
in O | |
some O | |
extended O | |
families O | |
and O | |
Bedouin B-ETHN | |
tribes O | |
. O | |
Genetic O | |
services O | |
have O | |
been O | |
available O | |
in O | |
Kuwait B-LOC | |
for O | |
over O | |
a O | |
decade O | |
. O | |
During O | |
this O | |
time O | |
it O | |
has O | |
become O | |
clear O | |
that O | |
Arabs O | |
have O | |
a O | |
high O | |
frequency O | |
of O | |
genetic O | |
disorders O | |
, O | |
and O | |
in O | |
particular O | |
autosomal O | |
recessive O | |
traits O | |
. O | |
Their O | |
pattern O | |
is O | |
unique O | |
and O | |
some O | |
disorders O | |
are O | |
relatively O | |
common O | |
. O | |
Examples O | |
are O | |
Bardet O | |
- O | |
Biedl O | |
and O | |
Meckel O | |
syndromes O | |
, O | |
phenylketonuria O | |
, O | |
and O | |
familial O | |
Mediterranean O | |
fever O | |
. O | |
A O | |
relatively O | |
large O | |
number O | |
of O | |
new O | |
syndromes O | |
and O | |
variants O | |
have O | |
been O | |
delineated O | |
in O | |
Kuwait B-LOC | |
's O | |
population O | |
, O | |
many O | |
being O | |
the O | |
result O | |
of O | |
homozygosity O | |
for O | |
autosomal O | |
recessive O | |
genes O | |
that O | |
occurred O | |
because O | |
of O | |
inbreeding O | |
. O | |
Some O | |
of O | |
these O | |
syndromes O | |
have O | |
subsequently O | |
been O | |
found O | |
in O | |
other O | |
parts O | |
of O | |
the O | |
world O | |
, O | |
negating O | |
the O | |
concept O | |
of O | |
the O | |
private O | |
syndrome O | |
. O | |
This O | |
paper O | |
provides O | |
an O | |
overview O | |
of O | |
autosomal O | |
recessive O | |
disorders O | |
among O | |
the O | |
Arabs O | |
in O | |
Kuwait B-LOC | |
from O | |
a O | |
personal O | |
perspective O | |
and O | |
published O | |
studies O | |
, O | |
and O | |
highlights O | |
the O | |
need O | |
for O | |
genetic O | |
services O | |
in O | |
Arab B-ETHN | |
countries O | |
with O | |
the O | |
goal O | |
of O | |
prevention O | |
and O | |
treatment O | |
of O | |
genetic O | |
disorders O | |
. O | |
Introduction O | |
Niemann O | |
- O | |
Pick O | |
type O | |
C O | |
( O | |
NPC O | |
) O | |
is O | |
a O | |
lysosomal O | |
storage O | |
disease O | |
that O | |
is O | |
progressive O | |
and O | |
life O | |
- O | |
limiting O | |
, O | |
with O | |
an O | |
estimated B-EPI | |
incidence I-EPI | |
of O | |
1:120,000 B-STAT | |
live I-STAT | |
births I-STAT | |
. O | |
In O | |
addition O | |
to O | |
systemic O | |
manifestation O | |
with O | |
( O | |
hepato-)splenomegaly O | |
, O | |
there O | |
are O | |
a O | |
number O | |
of O | |
neurological O | |
manifestations O | |
( O | |
ataxia O | |
, O | |
dysarthria O | |
, O | |
dementia O | |
, O | |
cataplexy O | |
, O | |
epileptic O | |
seizures O | |
, O | |
and O | |
psychiatric O | |
disorders O | |
) O | |
. O | |
Characteristic O | |
is O | |
vertical O | |
supranuclear O | |
gaze O | |
palsy O | |
, O | |
which O | |
is O | |
often O | |
overlooked O | |
. O | |
Early O | |
diagnosis O | |
and O | |
start O | |
of O | |
therapy O | |
improve O | |
quality O | |
of O | |
life O | |
. O | |
This O | |
study O | |
aimed O | |
to O | |
characterize O | |
oculomotor O | |
dysfunction O | |
of O | |
NPC O | |
patients O | |
, O | |
and O | |
to O | |
provide O | |
ophthalmologic O | |
data O | |
including O | |
retinal O | |
imaging O | |
. O | |
Methods O | |
Eighteen O | |
patients O | |
with O | |
biochemically O | |
or O | |
genetically O | |
diagnosed O | |
NPC O | |
completed O | |
oculomotor O | |
and O | |
ophthalmologic O | |
examination O | |
. O | |
Ten O | |
of O | |
them O | |
performed O | |
saccadometry O | |
by O | |
infrared O | |
based O | |
video O | |
- O | |
oculography O | |
. O | |
Saccadic O | |
parameters O | |
were O | |
compared O | |
to O | |
100 O | |
healthy O | |
controls O | |
, O | |
and O | |
were O | |
correlated O | |
with O | |
clinical O | |
variables O | |
. O | |
Another O | |
subgroup O | |
of O | |
eight O | |
patients O | |
received O | |
optical O | |
coherence O | |
tomography O | |
( O | |
OCT O | |
) O | |
of O | |
the O | |
optic O | |
disc O | |
and O | |
the O | |
macula O | |
, O | |
of O | |
which O | |
the O | |
segmented O | |
layers O | |
were O | |
analysed O | |
using O | |
a O | |
crude O | |
linear O | |
mixed O | |
model O | |
, O | |
and O | |
one O | |
adjusted O | |
for O | |
age O | |
, O | |
sex O | |
, O | |
and O | |
spherical O | |
equivalent O | |
. O | |
Results O | |
Saccadometry O | |
revealed O | |
slowed O | |
peak O | |
velocity O | |
compared O | |
to O | |
controls O | |
most O | |
evident O | |
vertically O | |
. O | |
Peak O | |
velocity O | |
correlated O | |
negatively O | |
with O | |
SARA O | |
- O | |
Score O | |
, O | |
but O | |
correlation O | |
with O | |
clinical O | |
assessment O | |
of O | |
saccades O | |
was O | |
not O | |
significant O | |
. O | |
Clinical O | |
features O | |
in O | |
the O | |
assessment O | |
of O | |
vertical O | |
saccades O | |
were O | |
intensive O | |
blinking O | |
and O | |
head O | |
movements O | |
to O | |
initiate O | |
gaze O | |
changes O | |
, O | |
and O | |
lateral O | |
trajectory O | |
of O | |
the O | |
eyes O | |
. O | |
Macular O | |
OCT O | |
revealed O | |
significant O | |
total O | |
retinal O | |
thinning O | |
in O | |
the O | |
fovea O | |
, O | |
specifically O | |
of O | |
the O | |
outer O | |
nuclear O | |
layer O | |
and O | |
outer O | |
retinal O | |
layer O | |
. O | |
Para- O | |
and O | |
perifoveal O | |
retinal O | |
thicknesses O | |
, O | |
as O | |
well O | |
as O | |
peripapillary O | |
retinal O | |
nerve O | |
fibre O | |
layer O | |
were O | |
normal O | |
. O | |
Conclusions O | |
Foveal O | |
thinning O | |
was O | |
revealed O | |
in O | |
NPC O | |
. O | |
It O | |
remains O | |
to O | |
be O | |
shown O | |
, O | |
whether O | |
OCT O | |
will O | |
prove O | |
to O | |
be O | |
useful O | |
to O | |
monitor O | |
progression O | |
. O | |
Saccadic O | |
impairment O | |
reflects O | |
CNS O | |
involvement O | |
and O | |
therefore O | |
is O | |
a O | |
parameter O | |
to O | |
demonstrate O | |
the O | |
progression O | |
of O | |
NPC O | |
, O | |
and O | |
potentially O | |
also O | |
the O | |
efficacy O | |
of O | |
new O | |
therapies O | |
. O | |
Saccadometry O | |
, O | |
in O | |
contrast O | |
to O | |
clinical O | |
investigation O | |
, O | |
allows O | |
the O | |
precise O | |
evaluation O | |
of O | |
saccades O | |
. O | |
Summary O | |
Emerging O | |
and O | |
re O | |
- O | |
emerging O | |
infectious O | |
disease O | |
in O | |
otorhinolaryngology O | |
( O | |
ENT O | |
) O | |
are O | |
an O | |
area O | |
of O | |
growing O | |
epidemiological O | |
and O | |
clinical O | |
interest O | |
. O | |
The O | |
aim O | |
of O | |
this O | |
section O | |
is O | |
to O | |
comprehensively O | |
report O | |
on O | |
the O | |
epidemiology O | |
of O | |
key O | |
infectious O | |
disease O | |
in O | |
otorhinolaryngology O | |
, O | |
reporting O | |
on O | |
their O | |
burden O | |
at O | |
the O | |
national O | |
and O | |
international O | |
level O | |
, O | |
expanding O | |
of O | |
the O | |
need O | |
of O | |
promoting O | |
and O | |
implementing O | |
preventive O | |
interventions O | |
, O | |
and O | |
the O | |
rationale O | |
of O | |
applying O | |
evidence O | |
- O | |
based O | |
, O | |
effective O | |
and O | |
cost- O | |
effective O | |
diagnostic O | |
, O | |
curative O | |
and O | |
preventive O | |
approaches O | |
. O | |
In O | |
particular O | |
, O | |
we O | |
focus O | |
on O | |
i O | |
) O | |
ENT O | |
viral O | |
infections O | |
( O | |
HIV O | |
, O | |
Epstein O | |
- O | |
Barr O | |
virus O | |
, O | |
Human O | |
Papilloma O | |
virus O | |
) O | |
, O | |
retrieving O | |
the O | |
available O | |
evidence O | |
on O | |
their O | |
oncogenic O | |
potential O | |
; O | |
ii O | |
) O | |
typical O | |
and O | |
atypical O | |
mycobacteria O | |
infections O | |
; O | |
iii O | |
) O | |
non O | |
- O | |
specific O | |
granulomatous O | |
lymphadenopathy O | |
; O | |
iv O | |
) O | |
emerging O | |
paediatric O | |
ENT O | |
infectious O | |
diseases O | |
and O | |
the O | |
prevention O | |
of O | |
their O | |
complications O | |
; O | |
v O | |
) O | |
the O | |
growing O | |
burden O | |
of O | |
antimicrobial O | |
resistance O | |
in O | |
ENT O | |
and O | |
the O | |
strategies O | |
for O | |
its O | |
control O | |
in O | |
different O | |
clinical O | |
settings O | |
. O | |
We O | |
conclude O | |
by O | |
outlining O | |
knowledge O | |
gaps O | |
and O | |
action O | |
needed O | |
in O | |
ENT O | |
infectious O | |
diseases O | |
research O | |
and O | |
clinical O | |
practice O | |
and O | |
we O | |
make O | |
references O | |
to O | |
economic O | |
analysis O | |
in O | |
the O | |
field O | |
of O | |
ENT O | |
infectious O | |
diseases O | |
prevention O | |
and O | |
care O | |
. O | |
Background O | |
The O | |
prevalence B-EPI | |
of O | |
metabolic O | |
disease O | |
in O | |
Nepal B-LOC | |
is O | |
largely O | |
unknown B-STAT | |
. O | |
Some O | |
consideration O | |
has O | |
been O | |
given O | |
by O | |
the O | |
nepalese B-ETHN | |
government O | |
for O | |
high O | |
prevalence B-EPI | |
of O | |
congenital O | |
disorders O | |
in O | |
some O | |
populations O | |
, O | |
but O | |
disorders O | |
due O | |
to O | |
enzymatic O | |
deficiencies O | |
have O | |
not O | |
been O | |
considered O | |
as O | |
a O | |
class O | |
of O | |
diseases O | |
where O | |
timely O | |
diagnosis O | |
and O | |
intervention O | |
might O | |
be O | |
possible O | |
. O | |
No O | |
case O | |
for O | |
these O | |
disorders O | |
has O | |
been O | |
made O | |
so O | |
far O | |
, O | |
however O | |
, O | |
findings O | |
of O | |
many O | |
rare O | |
metabolic O | |
diseases O | |
have O | |
been O | |
reported O | |
in O | |
literature O | |
by O | |
the O | |
nepalese B-ETHN | |
medical O | |
fraternity O | |
. O | |
Methods O | |
A O | |
search O | |
for O | |
case O | |
reports O | |
on O | |
metabolic O | |
disorders O | |
listed O | |
according O | |
to O | |
International O | |
Classification O | |
of O | |
Diseases O | |
-11 O | |
was O | |
performed O | |
using O | |
the O | |
google O | |
search O | |
engine O | |
. O | |
Results O | |
A O | |
total O | |
of O | |
443 O | |
cases O | |
have O | |
been O | |
discovered O | |
presented O | |
in O | |
the O | |
literature O | |
. O | |
This O | |
does O | |
not O | |
include O | |
disorders O | |
that O | |
might O | |
be O | |
due O | |
to O | |
lifestyle O | |
and O | |
behaviour O | |
. O | |
Most O | |
of O | |
the O | |
reported O | |
cases O | |
have O | |
been O | |
identified O | |
based O | |
on O | |
clinical O | |
acumen O | |
, O | |
radiological O | |
and O | |
histopathological O | |
findings O | |
. O | |
Conclusions O | |
Glucose O | |
6 O | |
phosphate O | |
dehydrogenase O | |
deficiency O | |
, O | |
Wilson O | |
's O | |
disease O | |
and O | |
lysosomal O | |
disorders O | |
should O | |
be O | |
considered O | |
for O | |
early O | |
diagnosis O | |
through O | |
newborn O | |
screening O | |
along O | |
with O | |
the O | |
acknowledged O | |
disorders O | |
hypothyroidism O | |
and O | |
hemoglobinopathies O | |
in O | |
Nepal O | |
. O | |
Early O | |
intervention O | |
in O | |
these O | |
disorders O | |
can O | |
significantly O | |
reduce O | |
morbidity O | |
and O | |
mortality O | |
in O | |
infancy O | |
. O | |
Rare O | |
diseases O | |
are O | |
usually O | |
genetic O | |
, O | |
chronic O | |
and O | |
incurable O | |
disorders O | |
with O | |
a O | |
relatively O | |
low O | |
incidence B-EPI | |
. O | |
Developments O | |
in O | |
the O | |
diagnosis O | |
and O | |
management O | |
of O | |
rare O | |
diseases O | |
have O | |
been O | |
relatively O | |
slow O | |
due O | |
to O | |
a O | |
lack O | |
of O | |
sufficient O | |
profit O | |
motivation O | |
and O | |
market O | |
to O | |
attract O | |
research O | |
by O | |
companies O | |
. O | |
However O | |
, O | |
due O | |
to O | |
the O | |
attention O | |
of O | |
government O | |
and O | |
society O | |
as O | |
well O | |
as O | |
economic O | |
development O | |
, O | |
rare O | |
diseases O | |
have O | |
been O | |
gradually O | |
become O | |
an O | |
increasing O | |
concern O | |
. O | |
As O | |
several O | |
dental O | |
- O | |
craniofacial O | |
manifestations O | |
are O | |
associated O | |
with O | |
rare O | |
diseases O | |
, O | |
we O | |
summarize O | |
them O | |
in O | |
this O | |
study O | |
to O | |
help O | |
dentists O | |
and O | |
oral O | |
maxillofacial O | |
surgeons O | |
provide O | |
an O | |
early O | |
diagnosis O | |
and O | |
subsequent O | |
management O | |
for O | |
patients O | |
with O | |
these O | |
rare O | |
diseases O | |
. O | |
Osteoporosis O | |
, O | |
characterized O | |
by O | |
reduced O | |
bone O | |
mass O | |
and O | |
increased O | |
bone O | |
fragility O | |
, O | |
is O | |
a O | |
disease O | |
prevalent B-EPI | |
in O | |
women B-SEX | |
. O | |
Likewise O | |
, O | |
breast O | |
cancer O | |
is O | |
a O | |
multifactorial O | |
disease O | |
and O | |
considered O | |
the O | |
major O | |
cause O | |
of O | |
mortality O | |
in O | |
premenopausal O | |
and O | |
postmenopausal O | |
women B-SEX | |
worldwide B-LOC | |
. O | |
Our O | |
data O | |
demonstrated O | |
the O | |
association O | |
of O | |
the O | |
MYLK O | |
gene O | |
and O | |
PTGS1 O | |
gene O | |
variants O | |
with O | |
osteoporosis O | |
and O | |
benign O | |
breast O | |
tumor O | |
risk O | |
and O | |
the O | |
impact O | |
of O | |
ovariectomy O | |
on O | |
osteoporosis O | |
in O | |
Korean B-ETHN | |
women B-SEX | |
. O | |
We O | |
performed O | |
a O | |
genome O | |
- O | |
wide O | |
association O | |
study O | |
( O | |
GWAS O | |
) O | |
of O | |
women B-SEX | |
with O | |
osteoporosis O | |
and O | |
benign O | |
breast O | |
tumors O | |
. O | |
There O | |
were O | |
60 O | |
single O | |
nucleotide O | |
polymorphisms O | |
( O | |
SNPs O | |
) O | |
and O | |
12 O | |
SNPs O | |
in O | |
the O | |
MYLK O | |
and O | |
PTGS1 O | |
genes O | |
, O | |
associated O | |
with O | |
benign O | |
breast O | |
tumors O | |
and O | |
osteoporosis O | |
. O | |
Our O | |
study O | |
showed O | |
that O | |
women B-SEX | |
with O | |
homozygous O | |
MYLK O | |
rs12163585 O | |
major O | |
alleles O | |
had O | |
an O | |
increased O | |
risk O | |
of O | |
osteoporosis O | |
following O | |
ovariectomy O | |
compared O | |
to O | |
those O | |
with O | |
minor O | |
alleles O | |
. O | |
Women B-SEX | |
carrying O | |
the O | |
minor O | |
PTGS1 O | |
rs1213265 O | |
allele O | |
and O | |
not O | |
treated O | |
via O | |
ovariectomy O | |
carried O | |
a O | |
higher O | |
risk O | |
of O | |
osteoporosis O | |
than O | |
those O | |
who O | |
underwent O | |
ovariectomy O | |
with O | |
a O | |
homozygous O | |
genotype O | |
at O | |
the O | |
major O | |
alleles O | |
. O | |
Our O | |
results O | |
suggest O | |
that O | |
both O | |
the O | |
MYLK O | |
and O | |
PTGS1 O | |
genes O | |
are O | |
genetic O | |
factors O | |
associated O | |
with O | |
the O | |
phenotypes O | |
, O | |
and O | |
these O | |
associations O | |
appear O | |
to O | |
be O | |
modulated O | |
by O | |
ovariectomy O | |
. O | |
Transient O | |
congenital O | |
hypothyroidism O | |
( O | |
CH O | |
) O | |
refers O | |
to O | |
a O | |
temporary O | |
deficiency O | |
of O | |
thyroid O | |
hormone O | |
identified O | |
after O | |
birth O | |
, O | |
with O | |
low O | |
thyroxine O | |
( O | |
T4 O | |
) O | |
and O | |
elevated O | |
thyrotropin O | |
( O | |
TSH O | |
) O | |
, O | |
which O | |
later O | |
recovers O | |
to O | |
improved O | |
thyroxine O | |
production O | |
, O | |
typically O | |
in O | |
first O | |
few O | |
months O | |
of O | |
infancy O | |
. O | |
Approximately O | |
17 O | |
% O | |
to O | |
40 O | |
% O | |
of O | |
children O | |
diagnosed O | |
with O | |
CH O | |
by O | |
newborn O | |
screening O | |
( O | |
NBS O | |
) O | |
programs O | |
were O | |
later O | |
determined O | |
to O | |
have O | |
transient O | |
hypothyroidism O | |
. O | |
Causes O | |
of O | |
transient O | |
CH O | |
are O | |
prematurity O | |
, O | |
iodine O | |
deficiency O | |
, O | |
maternal O | |
thyrotropin O | |
receptor O | |
blocking O | |
antibodies O | |
, O | |
maternal O | |
intake O | |
of O | |
anti O | |
- O | |
thyroid O | |
drugs O | |
, O | |
maternal O | |
or O | |
neonatal O | |
iodine O | |
exposure O | |
, O | |
loss O | |
of O | |
function O | |
mutations O | |
and O | |
hepatic O | |
hemangiomas O | |
. O | |
The O | |
classic O | |
clinical O | |
symptoms O | |
and O | |
signs O | |
of O | |
CH O | |
are O | |
usually O | |
absent O | |
immediately O | |
after O | |
birth O | |
in O | |
vast O | |
majority O | |
of O | |
infants O | |
due O | |
to O | |
temporary O | |
protection O | |
from O | |
maternal O | |
thyroxine O | |
. O | |
NBS O | |
has O | |
been O | |
largely O | |
successful O | |
in O | |
preventing O | |
intellectual O | |
disability O | |
by O | |
early O | |
detection O | |
of O | |
CH O | |
by O | |
performing O | |
thyroid O | |
function O | |
tests O | |
in O | |
infants O | |
with O | |
abnormal O | |
screening O | |
results O | |
. O | |
In O | |
this O | |
review O | |
we O | |
present O | |
the O | |
evidence O | |
for O | |
decision O | |
making O | |
regarding O | |
treatment O | |
vs. O | |
withholding O | |
treatment O | |
in O | |
infants O | |
with O | |
transient O | |
CH O | |
and O | |
present O | |
a O | |
rational O | |
approach O | |
to O | |
identifying O | |
transient O | |
CH O | |
based O | |
on O | |
American B-ETHN | |
Academy O | |
of O | |
Pediatrics O | |
( O | |
AAP O | |
) O | |
recommendation O | |
. O | |
Orthostatic O | |
tremor O | |
is O | |
a O | |
rare O | |
condition O | |
, O | |
though O | |
its O | |
exact B-EPI | |
prevalence B-EPI | |
is O | |
unknown B-STAT | |
, O | |
which O | |
is O | |
clinically O | |
characterized O | |
by O | |
a O | |
feeling O | |
of O | |
unsteadiness O | |
or O | |
being O | |
about O | |
to O | |
fall O | |
on O | |
standing O | |
and O | |
which O | |
disappears O | |
on O | |
walking O | |
, O | |
sitting O | |
, O | |
or O | |
lying O | |
down O | |
. O | |
It O | |
is O | |
generally O | |
accepted O | |
that O | |
classic O | |
orthostatic O | |
tremor O | |
manifests O | |
with O | |
a O | |
high O | |
- O | |
frequency O | |
tremor O | |
( O | |
> O | |
13 O | |
Hz O | |
) O | |
of O | |
the O | |
legs O | |
when O | |
standing O | |
. O | |
However O | |
, O | |
a O | |
number O | |
of O | |
patients O | |
initially O | |
reported O | |
as O | |
orthostatic O | |
tremor O | |
did O | |
not O | |
actually O | |
have O | |
such O | |
electrophysiological O | |
features O | |
. O | |
It O | |
is O | |
our O | |
experience O | |
that O | |
there O | |
is O | |
a O | |
clinical O | |
spectrum O | |
of O | |
different O | |
conditions O | |
presenting O | |
as O | |
shaking O | |
on O | |
standing O | |
, O | |
and O | |
this O | |
highlights O | |
the O | |
importance O | |
of O | |
the O | |
electrophysiology O | |
to O | |
aid O | |
the O | |
differential O | |
diagnosis O | |
of O | |
these O | |
disorders O | |
. O | |
Here O | |
, O | |
we O | |
provide O | |
a O | |
critical O | |
review O | |
of O | |
the O | |
clinical O | |
spectrum O | |
of O | |
shaking O | |
on O | |
standing O | |
, O | |
along O | |
with O | |
demonstrative O | |
electrophysiological O | |
recordings O | |
of O | |
some O | |
of O | |
these O | |
conditions O | |
. O | |
The O | |
number O | |
of O | |
patients O | |
with O | |
spinocerebellar O | |
degeneration O | |
( O | |
SCD O | |
) O | |
has O | |
recently O | |
exceeds O | |
20,000 O | |
in O | |
Japan B-LOC | |
. O | |
Among O | |
them O | |
, O | |
sporadic O | |
form O | |
is O | |
the O | |
most O | |
common O | |
form O | |
( O | |
67.2 O | |
% O | |
) O | |
. O | |
Among O | |
the O | |
hereditary O | |
forms O | |
of O | |
SCD O | |
, O | |
autosomal O | |
dominant O | |
( O | |
AD O | |
) O | |
form O | |
comprises O | |
27.0 O | |
% O | |
, O | |
while O | |
autosomal O | |
recessive O | |
( O | |
AR O | |
) O | |
form O | |
is O | |
rare O | |
( O | |
1.8 O | |
% O | |
) O | |
. O | |
Because O | |
of O | |
the O | |
rare O | |
occurrence B-EPI | |
of O | |
AR O | |
- O | |
SCD O | |
, O | |
the O | |
molecular O | |
genetic O | |
studies O | |
have O | |
been O | |
difficult O | |
to O | |
conduct O | |
. O | |
Recent O | |
progresses O | |
in O | |
molecular O | |
genetics O | |
, O | |
however O | |
, O | |
have O | |
enabled O | |
identification O | |
of O | |
causative O | |
genes O | |
for O | |
the O | |
majority O | |
of O | |
AR O | |
- O | |
SCD O | |
. O | |
Although O | |
Friedreich O | |
's O | |
ataxia O | |
is O | |
the O | |
most O | |
representative O | |
form O | |
of O | |
AR O | |
- O | |
SCD O | |
, O | |
patients O | |
with O | |
molecular O | |
diagnosis O | |
of O | |
Friedreich O | |
's O | |
ataxia O | |
have O | |
not O | |
been O | |
described O | |
in O | |
the O | |
Japanese B-ETHN | |
population O | |
. O | |
Among O | |
the O | |
various O | |
forms O | |
of O | |
AR O | |
- O | |
SCD O | |
, O | |
early O | |
- O | |
onset O | |
ataxia O | |
with O | |
ocular O | |
motor O | |
apraxia O | |
and O | |
hypoalbuminemia O | |
( O | |
EAOH O | |
) O | |
seems O | |
to O | |
be O | |
the O | |
most O | |
common O | |
form O | |
in O | |
the O | |
Japanese B-ETHN | |
population O | |
. O | |
Aprataxin O | |
, O | |
the O | |
causative O | |
gene O | |
for O | |
EAOH O | |
, O | |
has O | |
been O | |
suggested O | |
to O | |
play O | |
a O | |
role O | |
in O | |
the O | |
single O | |
strand O | |
DNA O | |
break O | |
repair O | |
. O | |
Interestingly O | |
, O | |
abnormalities O | |
in O | |
DNA O | |
break O | |
repair O | |
processes O | |
have O | |
been O | |
implicated O | |
in O | |
several O | |
forms O | |
of O | |
AR O | |
- O | |
SCD O | |
including O | |
AOA2 O | |
, O | |
SCAN1 O | |
and O | |
ataxia O | |
telangiectasia O | |
. O | |
In O | |
this O | |
group O | |
of O | |
AR O | |
- O | |
SCD O | |
, O | |
cerebellar O | |
atrophy O | |
is O | |
more O | |
marked O | |
compared O | |
to O | |
that O | |
observed O | |
in O | |
Friedreich O | |
's O | |
ataxia O | |
. O | |
Taken O | |
together O | |
, O | |
abnormalities O | |
in O | |
DNA O | |
break O | |
repair O | |
processes O | |
may O | |
play O | |
an O | |
essential O | |
role O | |
in O | |
cerebellar O | |
degeneration O | |
in O | |
this O | |
group O | |
of O | |
AR O | |
- O | |
SCD O | |
. O | |
Background O | |
Acute O | |
colonic O | |
pseudo O | |
- O | |
obstruction O | |
( O | |
ACPO O | |
) O | |
or O | |
Ogilvie O | |
's O | |
syndrome O | |
occurs B-EPI | |
in O | |
0.22%-7 O | |
% O | |
of O | |
patients O | |
undergoing O | |
surgery O | |
, O | |
with O | |
a O | |
mortality O | |
of O | |
up O | |
to O | |
46 O | |
% O | |
. O | |
ACPO O | |
increased O | |
median O | |
hospital O | |
days O | |
versus O | |
control O | |
in O | |
spinal O | |
surgery O | |
( O | |
14 O | |
vs. O | |
6 O | |
days O | |
; O | |
P O | |
< O | |
0.001 O | |
) O | |
. O | |
If O | |
defined O | |
as O | |
postoperative O | |
ileus O | |
, O | |
the O | |
incidence B-EPI | |
was O | |
7%-13.4 B-STAT | |
% I-STAT | |
. O | |
Postoperative O | |
ileus O | |
is O | |
associated O | |
with O | |
2.9 O | |
additional O | |
hospital O | |
days O | |
and O | |
an O | |
$ O | |
80,000 O | |
increase O | |
in O | |
cost O | |
per O | |
patient O | |
. O | |
We O | |
present O | |
a O | |
case O | |
of O | |
ACPO O | |
in O | |
an O | |
adult O | |
patient O | |
undergoing O | |
spinal O | |
fusion O | |
for O | |
correction O | |
of O | |
scoliosis O | |
and O | |
review O | |
the O | |
available O | |
literature O | |
to O | |
outline O | |
clinical O | |
characteristics O | |
and O | |
surgical O | |
outcomes O | |
. O | |
Case O | |
description O | |
The O | |
patient O | |
was O | |
a O | |
31 O | |
- O | |
year O | |
- O | |
old O | |
woman B-SEX | |
with O | |
untreated O | |
advanced O | |
scoliosis O | |
with O | |
no O | |
history O | |
of O | |
neurologic O | |
issues O | |
. O | |
T2 O | |
- O | |
L3 O | |
spinal O | |
instrumentation O | |
and O | |
fusion O | |
was O | |
completed O | |
. O | |
Plain O | |
abdominal O | |
radiography O | |
showed O | |
of O | |
dilated O | |
cecum O | |
11 O | |
cm O | |
and O | |
the O | |
department O | |
of O | |
general O | |
surgery O | |
was O | |
consulted O | |
. O | |
Neostigmine O | |
administration O | |
was O | |
planned O | |
after O | |
conservative O | |
treatment O | |
failure O | |
after O | |
transfer O | |
to O | |
the O | |
intensive O | |
care O | |
unit O | |
. O | |
The O | |
patient O | |
was O | |
discharged O | |
home O | |
with O | |
no O | |
recurrence O | |
> O | |
60 O | |
days O | |
. O | |
Thirty O | |
cases O | |
were O | |
found O | |
in O | |
our O | |
literature O | |
review O | |
using O | |
PubMed O | |
and O | |
Embase O | |
databases O | |
and O | |
summarized O | |
. O | |
Conclusions O | |
Of O | |
30 O | |
cases O | |
reviewed O | |
, O | |
only O | |
3 O | |
cases O | |
of O | |
ACPO O | |
were O | |
specific O | |
to O | |
patients O | |
undergoing O | |
spinal O | |
fusion O | |
for O | |
scoliosis O | |
. O | |
According O | |
to O | |
the O | |
literature O | |
, O | |
20 O | |
% O | |
of O | |
patients O | |
had O | |
resolution O | |
with O | |
conservative O | |
treatment O | |
, O | |
40 O | |
% O | |
with O | |
neostigmine O | |
, O | |
and O | |
30 O | |
% O | |
with O | |
surgical O | |
intervention O | |
. O | |
Other O | |
noninvasive O | |
treatments O | |
may O | |
have O | |
similar O | |
efficacy O | |
in O | |
preventing O | |
complications O | |
leading O | |
to O | |
surgical O | |
invention O | |
. O | |
Sixty O | |
clinical O | |
trials O | |
and O | |
9 O | |
systematic O | |
reviews O | |
were O | |
summarized O | |
with O | |
an O | |
updated O | |
management O | |
algorithm O | |
. O | |
Background O | |
/ O | |
aims O | |
Pseudohypoparathyroidism O | |
type O | |
1a O | |
( O | |
PHP1a O | |
) O | |
is O | |
a O | |
rare O | |
genetic O | |
disorder O | |
. O | |
This O | |
study O | |
aimed O | |
to O | |
determine O | |
the O | |
prevalence B-EPI | |
of O | |
sleep O | |
apnea O | |
in O | |
children O | |
with O | |
PHP1a O | |
. O | |
Methods O | |
Nineteen O | |
patients O | |
with O | |
PHP1a O | |
between O | |
the O | |
age O | |
of O | |
2 O | |
and O | |
21 O | |
years O | |
were O | |
enrolled O | |
prospectively O | |
using O | |
online O | |
advertisements O | |
. O | |
Parents O | |
completed O | |
a O | |
medical O | |
history O | |
and O | |
surveys O | |
to O | |
assess O | |
sleep O | |
behavior O | |
. O | |
Polysomnography O | |
records O | |
were O | |
obtained O | |
when O | |
available O | |
. O | |
In O | |
addition O | |
, O | |
18 O | |
subjects O | |
were O | |
identified O | |
in O | |
a O | |
retrospective O | |
chart O | |
review O | |
of O | |
de O | |
- O | |
identified O | |
medical O | |
records O | |
with O | |
2.3 O | |
million O | |
patient O | |
charts O | |
. O | |
Results O | |
Parents O | |
reported O | |
sleep O | |
disturbance O | |
( O | |
94 O | |
% O | |
) O | |
and O | |
daytime O | |
somnolence O | |
( O | |
81 O | |
% O | |
) O | |
in O | |
their O | |
children O | |
with O | |
PHP1a O | |
. O | |
In O | |
the O | |
retrospective O | |
chart O | |
review O | |
, O | |
39 O | |
% O | |
had O | |
a O | |
history O | |
of O | |
sleep O | |
apnea O | |
versus O | |
8.8 O | |
% O | |
of O | |
a O | |
similarly O | |
obese O | |
control O | |
group O | |
. O | |
In O | |
the O | |
combined O | |
analysis O | |
( O | |
n O | |
= O | |
31 O | |
) O | |
, O | |
52 O | |
% O | |
had O | |
a O | |
history O | |
of O | |
snoring O | |
and O | |
45 O | |
% O | |
had O | |
a O | |
diagnosis O | |
of O | |
sleep O | |
apnea O | |
. O | |
Patients O | |
were O | |
obese O | |
with O | |
a O | |
mean O | |
BMI O | |
z O | |
- O | |
score O | |
of O | |
2.20 O | |
± O | |
0.59 O | |
. O | |
Patients O | |
with O | |
sleep O | |
apnea O | |
were O | |
significantly O | |
younger O | |
than O | |
those O | |
without O | |
a O | |
diagnosis O | |
( O | |
8.1 O | |
± O | |
5.4 O | |
vs. O | |
12.8 O | |
± O | |
5.0 O | |
years O | |
, O | |
p O | |
= O | |
0.02 O | |
) O | |
. O | |
Conclusions O | |
Children O | |
with O | |
PHP1a O | |
have O | |
a O | |
4.4 O | |
- O | |
fold O | |
greater O | |
relative O | |
risk O | |
of O | |
sleep O | |
apnea O | |
than O | |
similarly O | |
obese O | |
children O | |
. O | |
Screening O | |
for O | |
sleep O | |
apnea O | |
in O | |
this O | |
population O | |
may O | |
be O | |
warranted O | |
to O | |
prevent O | |
adverse O | |
health O | |
outcomes O | |
. O | |
Background O | |
Methylmalonic O | |
acidemia O | |
( O | |
MMA O | |
) O | |
and O | |
propionic O | |
acidemia O | |
( O | |
PA O | |
) O | |
are O | |
two O | |
kinds O | |
of O | |
diseases O | |
caused O | |
by O | |
inborn O | |
errors O | |
of O | |
metabolism O | |
. O | |
So O | |
far O | |
, O | |
the O | |
epidemiological O | |
data O | |
on O | |
them O | |
are O | |
limited O | |
in O | |
China B-LOC | |
. O | |
The O | |
aim O | |
of O | |
our O | |
study O | |
is O | |
to O | |
investigate O | |
the O | |
proportion O | |
and O | |
characteristics O | |
of O | |
hospitalized O | |
pediatric O | |
patients O | |
with O | |
MMA O | |
and O | |
PA O | |
in O | |
China B-LOC | |
. O | |
Methods O | |
The O | |
data O | |
in O | |
this O | |
study O | |
were O | |
obtained O | |
from O | |
the O | |
Hospital O | |
Quality O | |
Monitoring O | |
System O | |
, O | |
a O | |
national O | |
inpatient O | |
database O | |
in O | |
China B-LOC | |
, O | |
with O | |
information O | |
on O | |
the O | |
patients O | |
hospitalized O | |
during O | |
the O | |
period O | |
from O | |
2013 B-DATE | |
to I-DATE | |
2017 I-DATE | |
. O | |
We O | |
identified O | |
the O | |
data O | |
related O | |
to O | |
the O | |
patients O | |
who O | |
were O | |
under O | |
18 O | |
years O | |
old O | |
and O | |
were O | |
diagnosed O | |
with O | |
MMA O | |
/ O | |
PA O | |
, O | |
and O | |
extracted O | |
the O | |
information O | |
on O | |
demographic O | |
characteristics O | |
, O | |
hospital O | |
location O | |
, O | |
total O | |
cost O | |
and O | |
other O | |
related O | |
clinical O | |
presentations O | |
from O | |
the O | |
data O | |
. O | |
Results O | |
Among O | |
all O | |
hospitalized O | |
pediatric O | |
patients O | |
with O | |
liver O | |
diseases O | |
, O | |
there O | |
were O | |
increasing O | |
trends O | |
in O | |
the O | |
proportion O | |
of O | |
individuals O | |
diagnosed O | |
with O | |
MMA O | |
or O | |
PA O | |
during O | |
the O | |
period O | |
from O | |
2013 B-DATE | |
( O | |
0.76 O | |
% O | |
for O | |
MMA O | |
; O | |
0.13 O | |
% O | |
for O | |
PA O | |
) O | |
to I-DATE | |
2017 I-DATE | |
( O | |
1.61 O | |
% O | |
for O | |
MMA O | |
; O | |
0.32 O | |
% O | |
for O | |
PA O | |
) O | |
. O | |
For O | |
both O | |
MMA O | |
and O | |
PA O | |
, O | |
children O | |
under O | |
2 O | |
- O | |
year O | |
- O | |
old O | |
accounted O | |
for O | |
the O | |
highest O | |
proportion O | |
. O | |
The O | |
median O | |
of O | |
total O | |
cost O | |
per O | |
hospitalization O | |
was O | |
relatively O | |
high O | |
( O | |
RMB O | |
7388.53 O | |
for O | |
MMA O | |
; O | |
RMB O | |
4999.66 O | |
for O | |
PA O | |
) O | |
. O | |
Moreover O | |
, O | |
most O | |
patients O | |
hospitalized O | |
in O | |
tertiary O | |
class O | |
A O | |
hospitals O | |
( O | |
MMA O | |
: O | |
80.96 O | |
% O | |
, O | |
PA O | |
: O | |
76.21 O | |
% O | |
) O | |
; O | |
and O | |
a O | |
majority O | |
of O | |
pediatric O | |
patients O | |
admitted O | |
in O | |
the O | |
hospitals O | |
in O | |
Shanghai B-LOC | |
and O | |
Beijing B-LOC | |
are O | |
from O | |
outside O | |
districts O | |
. O | |
Manifestations O | |
of O | |
nervous O | |
system O | |
- O | |
related O | |
symptoms O | |
, O | |
and O | |
metabolic O | |
acidosis O | |
or O | |
anemia O | |
in O | |
laboratory O | |
findings O | |
were O | |
more O | |
common O | |
during O | |
hospitalization O | |
. O | |
Conclusions O | |
The O | |
study O | |
is O | |
the O | |
first O | |
nationwide O | |
one O | |
in O | |
providing O | |
epidemiological O | |
and O | |
clinical O | |
information O | |
on O | |
hospitalized O | |
pediatric O | |
patients O | |
with O | |
MMA O | |
/ O | |
PA O | |
. O | |
An O | |
increasing O | |
hospitalization O | |
with O | |
various O | |
presentations O | |
and O | |
a O | |
heavy O | |
financial O | |
burden O | |
were O | |
observed O | |
. O | |
In O | |
addition O | |
, O | |
geographically O | |
, O | |
the O | |
medical O | |
resources O | |
in O | |
China B-LOC | |
have O | |
been O | |
unevenly O | |
distributed O | |
. O | |
Objective O | |
This O | |
study O | |
was O | |
undertaken O | |
to O | |
measure O | |
the O | |
incidence B-EPI | |
and O | |
prevalence B-EPI | |
of O | |
active O | |
psychogenic O | |
nonepileptic O | |
seizures O | |
( O | |
PNES O | |
) O | |
in O | |
a O | |
Norwegian B-ETHN | |
county I-LOC | |
. O | |
Methods O | |
Using O | |
the O | |
Norwegian B-ETHN | |
patient O | |
registry O | |
, O | |
we O | |
identified O | |
patients O | |
in O | |
Møre B-LOC | |
and I-LOC | |
Romsdal I-LOC | |
County I-LOC | |
in O | |
Norway B-LOC | |
diagnosed O | |
with O | |
F44.5 O | |
( O | |
conversion O | |
disorder O | |
with O | |
seizures O | |
or O | |
convulsions O | |
) O | |
or O | |
R56.8 O | |
( O | |
convulsions O | |
, O | |
not O | |
elsewhere O | |
classified O | |
) O | |
in O | |
the O | |
period O | |
January B-DATE | |
2010 I-DATE | |
to I-DATE | |
January I-DATE | |
2020 I-DATE | |
. O | |
A O | |
review O | |
of O | |
the O | |
patients O | |
' O | |
medical O | |
records O | |
and O | |
an O | |
assessment O | |
of O | |
diagnostic O | |
validity O | |
were O | |
performed O | |
. O | |
PNES O | |
were O | |
diagnosed O | |
according O | |
to O | |
the O | |
recommendations O | |
by O | |
the O | |
International O | |
League O | |
Against O | |
Epilepsy O | |
Nonepileptic O | |
Seizures O | |
Task O | |
Force O | |
. O | |
Point B-EPI | |
prevalence I-EPI | |
of O | |
PNES O | |
on O | |
January B-DATE | |
1 I-DATE | |
, I-DATE | |
2020 I-DATE | |
and O | |
incidence B-EPI | |
rates I-EPI | |
for O | |
the O | |
period O | |
2010 B-DATE | |
- I-DATE | |
2019 I-DATE | |
were O | |
determined O | |
. O | |
Results O | |
Based O | |
on O | |
PNES O | |
within O | |
the O | |
past O | |
5 O | |
years O | |
, O | |
we O | |
found O | |
a O | |
PNES O | |
prevalence B-EPI | |
of O | |
23.8/100000 B-STAT | |
( O | |
95 O | |
% O | |
confidence O | |
interval O | |
[ O | |
CI O | |
] O | |
= O | |
17.9 O | |
- O | |
29.6 O | |
) O | |
, O | |
including O | |
all O | |
levels O | |
of O | |
diagnostic O | |
certainty O | |
. O | |
For O | |
the O | |
highest O | |
level O | |
of O | |
diagnostic O | |
certainty O | |
( O | |
video O | |
- O | |
electroencephalographically O | |
confirmed O | |
) O | |
, O | |
the O | |
prevalence B-EPI | |
was O | |
10.6/100000 B-STAT | |
( O | |
95 O | |
% O | |
CI O | |
= O | |
6.7 O | |
- O | |
14.5 O | |
) O | |
. O | |
The O | |
highest O | |
prevalence B-EPI | |
was O | |
found O | |
in O | |
the O | |
age O | |
group O | |
15 O | |
- O | |
19 O | |
years O | |
, O | |
at O | |
59.5/100000 B-STAT | |
( O | |
95 O | |
% O | |
CI O | |
= O | |
22.6 O | |
- O | |
96.3 O | |
) O | |
. O | |
The O | |
mean O | |
annual B-EPI | |
incidence I-EPI | |
rate I-EPI | |
between B-DATE | |
2010 I-DATE | |
and I-DATE | |
2019 I-DATE | |
was O | |
3.1/100000 B-STAT | |
/ I-STAT | |
year I-STAT | |
( O | |
95 O | |
% O | |
CI O | |
= O | |
2.4 O | |
- O | |
3.7 O | |
) O | |
. O | |
Significance O | |
We O | |
report O | |
for O | |
the O | |
first O | |
time O | |
a O | |
population O | |
- O | |
based O | |
estimate O | |
of O | |
the O | |
prevalence B-EPI | |
of O | |
PNES O | |
. O | |
Our O | |
findings O | |
suggest O | |
that O | |
the O | |
prevalence B-EPI | |
of O | |
PNES O | |
is O | |
within O | |
the O | |
range O | |
of O | |
estimates O | |
from O | |
non O | |
- O | |
population O | |
- O | |
based O | |
data O | |
. O | |
We O | |
found O | |
a O | |
strikingly O | |
high O | |
prevalence B-EPI | |
of O | |
PNES O | |
in O | |
the O | |
15 O | |
- O | |
19 O | |
- O | |
year O | |
age O | |
group O | |
. O | |
With O | |
increasing O | |
maternal O | |
age O | |
in O | |
this O | |
decade O | |
, O | |
there O | |
is O | |
a O | |
parallel O | |
rise O | |
in O | |
the O | |
number O | |
of O | |
pregnant O | |
and O | |
lactating O | |
women B-SEX | |
affected O | |
by O | |
glaucoma O | |
worldwide B-LOC | |
. O | |
Understanding O | |
the O | |
diagnosis O | |
and O | |
management O | |
of O | |
glaucoma O | |
during O | |
pregnancy O | |
and O | |
lactation O | |
is O | |
essential O | |
to O | |
preventing O | |
blindness O | |
from O | |
glaucoma O | |
in O | |
this O | |
vulnerable O | |
population O | |
. O | |
This O | |
report O | |
provides O | |
a O | |
review O | |
of O | |
the O | |
current O | |
literature O | |
and O | |
offers O | |
effective O | |
strategies O | |
that O | |
will O | |
overcome O | |
the O | |
challenges O | |
in O | |
managing O | |
glaucoma O | |
during O | |
pregnancy O | |
and O | |
lactation O | |
. O | |
Practically O | |
, O | |
glaucoma O | |
management O | |
during O | |
pregnancy O | |
and O | |
lactation O | |
presents O | |
a O | |
unique O | |
challenge O | |
for O | |
the O | |
physician O | |
, O | |
as O | |
the O | |
benefit O | |
of O | |
any O | |
treatment O | |
must O | |
be O | |
weighed O | |
against O | |
the O | |
potential O | |
risks O | |
to O | |
the O | |
fetus O | |
. O | |
Prior O | |
to O | |
initiating O | |
or O | |
continuing O | |
treatment O | |
, O | |
the O | |
physician O | |
should O | |
be O | |
familiar O | |
with O | |
the O | |
various O | |
treatment O | |
options O | |
to O | |
manage O | |
intraocular O | |
pressure O | |
during O | |
pregnancy O | |
and O | |
lactation O | |
, O | |
including O | |
the O | |
safety O | |
of O | |
various O | |
anti O | |
- O | |
glaucoma O | |
medications O | |
as O | |
supported O | |
by O | |
the O | |
existing O | |
literature O | |
and O | |
based O | |
on O | |
the O | |
food O | |
and O | |
drug O | |
administration O | |
guidelines O | |
. O | |
A O | |
collaborative O | |
team O | |
effort O | |
between O | |
the O | |
ophthalmologist O | |
, O | |
obstetrician O | |
, O | |
and O | |
neonatologist O | |
in O | |
high O | |
- O | |
risk O | |
pregnancies O | |
is O | |
recommended O | |
to O | |
optimize O | |
care O | |
for O | |
the O | |
mother O | |
and O | |
fetus O | |
. O | |
Background O | |
The O | |
incidence B-EPI | |
of O | |
contralateral O | |
occult O | |
hernia O | |
( O | |
COH O | |
) O | |
varies O | |
from O | |
4.2 O | |
% O | |
to I-STAT | |
57.5 O | |
% O | |
. O | |
Total O | |
extraperitoneal O | |
( O | |
TEP O | |
) O | |
gives O | |
us O | |
opportunity O | |
to O | |
visualize O | |
contralateral O | |
groin O | |
for O | |
occult O | |
hernia O | |
and O | |
its O | |
simultaneous O | |
repair O | |
. O | |
Ultrasonography O | |
( O | |
USG O | |
) O | |
helps O | |
to O | |
diagnose O | |
occult O | |
hernia O | |
preoperatively O | |
with O | |
detection O | |
rate O | |
of O | |
96.6 O | |
% O | |
with O | |
specificity O | |
84.4 O | |
% O | |
. O | |
Objective O | |
The O | |
aims O | |
of O | |
this O | |
study O | |
were O | |
to O | |
identify O | |
the O | |
incidence B-EPI | |
of O | |
contralateral O | |
occult O | |
inguinal O | |
hernia O | |
in O | |
clinically O | |
diagnosed O | |
unilateral O | |
inguinal O | |
hernia O | |
patients O | |
using O | |
USG O | |
as O | |
diagnostic O | |
modality O | |
and O | |
to O | |
compare O | |
the O | |
clinical O | |
outcomes O | |
of O | |
unilateral O | |
TEP O | |
vs. O | |
bilateral O | |
TEP O | |
with O | |
respect O | |
to O | |
pain O | |
, O | |
duration O | |
of O | |
hospital O | |
stay O | |
, O | |
time O | |
for O | |
return O | |
to O | |
normal O | |
work O | |
, O | |
and O | |
postoperative O | |
complications O | |
. O | |
Setting O | |
and O | |
design O | |
This O | |
was O | |
a O | |
prospective O | |
observational O | |
, O | |
single O | |
- O | |
center O | |
study O | |
. O | |
Materials O | |
and O | |
methods O | |
A O | |
total O | |
of O | |
30 O | |
male B-SEX | |
patients O | |
were O | |
included O | |
in O | |
the O | |
study O | |
who O | |
was O | |
having O | |
clinically O | |
diagnosed O | |
unilateral O | |
hernia O | |
. O | |
All O | |
patients O | |
were O | |
assessed O | |
by O | |
USG O | |
for O | |
contralateral O | |
occult O | |
inguinal O | |
hernia O | |
. O | |
Results O | |
Incidence B-EPI | |
of O | |
COH O | |
was O | |
10 O | |
% O | |
, O | |
two O | |
( O | |
6.7 O | |
% O | |
) O | |
had O | |
indirect O | |
defect O | |
, O | |
and O | |
1 O | |
( O | |
3.3 O | |
% O | |
) O | |
had O | |
direct O | |
defect O | |
. O | |
Two O | |
( O | |
6.7 O | |
% O | |
) O | |
patients O | |
underwent O | |
bilateral O | |
TEP O | |
and O | |
28 O | |
( O | |
93.3 O | |
% O | |
) O | |
underwent O | |
unilateral O | |
TEP O | |
. O | |
No O | |
significant O | |
difference O | |
was O | |
observed O | |
in O | |
terms O | |
of O | |
mean O | |
duration O | |
of O | |
hospital O | |
stay O | |
, O | |
duration O | |
of O | |
surgery O | |
, O | |
and O | |
visual O | |
analog O | |
scale O | |
score O | |
for O | |
pain O | |
in O | |
both O | |
unilateral O | |
and O | |
bilateral O | |
TEP O | |
. O | |
The O | |
mean O | |
for O | |
resuming O | |
daily O | |
work O | |
in O | |
unilateral O | |
TEP O | |
was O | |
4.86 O | |
± O | |
0.833 O | |
days O | |
and O | |
in O | |
bilateral O | |
TEP O | |
the O | |
mean O | |
was O | |
7.50 O | |
± O | |
0.70 O | |
days O | |
and O | |
this O | |
showed O | |
statistically O | |
significant O | |
difference O | |
( O | |
P O | |
< O | |
0.001 O | |
) O | |
. O | |
Conclusion O | |
Patients O | |
with O | |
COH O | |
should O | |
be O | |
counselled O | |
for O | |
synchronous O | |
repair O | |
as O | |
there O | |
is O | |
no O | |
significant O | |
difference O | |
in O | |
clinical O | |
outcomes O | |
of O | |
unilateral O | |
and O | |
bilateral O | |
TEP O | |
. O | |
On O | |
the O | |
basis O | |
of O | |
this O | |
pilot O | |
study O | |
, O | |
it O | |
can O | |
be O | |
concluded O | |
that O | |
preoperative O | |
USG O | |
is O | |
mandatory O | |
for O | |
diagnosis O | |
and O | |
simultaneous O | |
management O | |
of O | |
preexisting O | |
contralateral O | |
hernia O | |
. O | |
Autosomal O | |
dominant O | |
cerebellar O | |
ataxia O | |
type O | |
I O | |
is O | |
a O | |
heterogeneous O | |
group O | |
of O | |
spinocerebellar O | |
ataxias O | |
with O | |
variable O | |
neurologic O | |
presentations O | |
, O | |
with O | |
age O | |
of O | |
onset O | |
varying O | |
from O | |
infancy O | |
to O | |
adulthood O | |
. O | |
Autosomal O | |
dominant O | |
cerebellar O | |
ataxia O | |
type O | |
I O | |
is O | |
composed O | |
mainly O | |
of O | |
3 O | |
prevalent B-EPI | |
spinocerebellar O | |
ataxia O | |
types O | |
with O | |
different O | |
pathogenic O | |
loci O | |
, O | |
specifically O | |
spinocerebellar O | |
ataxia O | |
1 O | |
( O | |
6p24 O | |
- O | |
p23 O | |
) O | |
, O | |
spinocerebellar O | |
ataxia O | |
2 O | |
( O | |
12q24.1 O | |
) O | |
, O | |
and O | |
spinocerebellar O | |
ataxia O | |
3 O | |
( O | |
14q32.1 O | |
) O | |
. O | |
The O | |
shared O | |
pathogenic O | |
mutational O | |
event O | |
is O | |
the O | |
expansion O | |
of O | |
the O | |
CAG O | |
repeat O | |
that O | |
results O | |
in O | |
polyglutamine O | |
extended O | |
stretches O | |
in O | |
the O | |
encoded O | |
proteins O | |
. O | |
CAG O | |
repeat O | |
disorders O | |
generally O | |
show O | |
the O | |
phenomenon O | |
of O | |
anticipation O | |
, O | |
which O | |
is O | |
more O | |
often O | |
associated O | |
with O | |
paternal O | |
transmission O | |
. O | |
In O | |
this O | |
report O | |
, O | |
we O | |
describe O | |
a O | |
patient O | |
with O | |
infantile O | |
- O | |
onset O | |
spinocerebellar O | |
ataxia O | |
type O | |
2 O | |
( O | |
~320 O | |
CAG O | |
repeat O | |
) O | |
who O | |
inherited O | |
the O | |
disease O | |
from O | |
his O | |
father O | |
( O | |
47 O | |
CAG O | |
repeats O | |
) O | |
. O | |
We O | |
have O | |
summarized O | |
the O | |
clinical O | |
, O | |
neuroimaging O | |
, O | |
electroencephalographic O | |
( O | |
EEG O | |
) O | |
, O | |
and O | |
molecular O | |
data O | |
of O | |
previous O | |
cases O | |
and O | |
attempt O | |
to O | |
highlight O | |
the O | |
most O | |
consistent O | |
findings O | |
. O | |
Our O | |
intent O | |
is O | |
to O | |
help O | |
treating O | |
clinicians O | |
to O | |
suspect O | |
this O | |
disorder O | |
and O | |
to O | |
offer O | |
timely O | |
genetic O | |
counseling O | |
for O | |
a O | |
currently O | |
potentially O | |
untreatable O | |
disorder O | |
. O | |
Intellectual O | |
disability O | |
( O | |
ID O | |
) O | |
has O | |
an O | |
estimated B-EPI | |
prevalence I-EPI | |
of O | |
1.5%-2 B-STAT | |
% I-STAT | |
. O | |
Whole O | |
exome O | |
sequencing O | |
( O | |
WES O | |
) O | |
studies O | |
have O | |
identified O | |
a O | |
multitude O | |
of O | |
novel O | |
causative O | |
gene O | |
defects O | |
and O | |
have O | |
shown O | |
that O | |
sporadic O | |
ID O | |
cases O | |
result O | |
from O | |
de O | |
novo O | |
mutations O | |
in O | |
genes O | |
associated O | |
with O | |
ID O | |
. O | |
Here O | |
, O | |
we O | |
report O | |
on O | |
a O | |
10 O | |
- O | |
year O | |
- O | |
old O | |
girl B-SEX | |
, O | |
who O | |
has O | |
been O | |
regularly O | |
presented O | |
in O | |
our O | |
neuropediatric O | |
and O | |
genetic O | |
outpatient O | |
clinic O | |
. O | |
A O | |
median O | |
cleft O | |
palate O | |
and O | |
a O | |
heart O | |
defect O | |
were O | |
surgically O | |
corrected O | |
in O | |
infancy O | |
. O | |
Apart O | |
from O | |
ID O | |
, O | |
she O | |
has O | |
behavioral O | |
anomalies O | |
, O | |
muscular O | |
hypotonia O | |
, O | |
scoliosis O | |
, O | |
and O | |
hypermobile O | |
joints O | |
. O | |
The O | |
facial O | |
phenotype O | |
is O | |
characterized O | |
by O | |
arched O | |
eyebrows O | |
, O | |
mildly O | |
upslanting O | |
long O | |
palpebral O | |
fissures O | |
, O | |
prominent O | |
nasal O | |
tip O | |
, O | |
and O | |
large O | |
, O | |
protruding O | |
ears O | |
. O | |
Trio O | |
WES O | |
revealed O | |
a O | |
de O | |
novo O | |
missense O | |
variant O | |
in O | |
MEIS2 O | |
( O | |
c.998G O | |
> O | |
A O | |
; O | |
p. O | |
Arg333Lys O | |
) O | |
. O | |
Haploinsufficiency O | |
of O | |
MEIS2 O | |
had O | |
been O | |
discussed O | |
as O | |
the O | |
most O | |
likely O | |
mechanism O | |
of O | |
the O | |
microdeletion O | |
5q14 O | |
- O | |
associated O | |
complex O | |
phenotype O | |
with O | |
ID O | |
, O | |
cleft O | |
palate O | |
, O | |
and O | |
heart O | |
defect O | |
. O | |
Recently O | |
, O | |
four O | |
studies O | |
including O | |
in O | |
total O | |
17 O | |
individuals O | |
with O | |
intragenic O | |
MEIS2 O | |
variants O | |
were O | |
reported O | |
. O | |
Here O | |
we O | |
present O | |
the O | |
evolution O | |
of O | |
the O | |
clinical O | |
phenotype O | |
and O | |
compare O | |
with O | |
the O | |
data O | |
of O | |
known O | |
individuals O | |
. O | |
Background O | |
Given O | |
recent O | |
reports O | |
of O | |
percutaneous O | |
closure O | |
of O | |
sinus O | |
venosus O | |
atrial O | |
septal O | |
defects O | |
, O | |
we O | |
reviewed O | |
our O | |
experience O | |
with O | |
surgical O | |
repair O | |
. O | |
Owing O | |
to O | |
the O | |
high O | |
incidence B-EPI | |
of O | |
arrhythmias O | |
with O | |
the O | |
two O | |
- O | |
patch O | |
technique O | |
, O | |
since O | |
2001 B-DATE | |
we O | |
have O | |
used O | |
either O | |
one O | |
- O | |
patch O | |
repairs O | |
or O | |
the O | |
Warden O | |
procedure O | |
. O | |
Methods O | |
A O | |
retrospective O | |
review O | |
was O | |
performed O | |
of O | |
pediatric O | |
patients O | |
undergoing O | |
sinus O | |
venosus O | |
atrial O | |
septal O | |
defect O | |
repair O | |
at O | |
our O | |
institution O | |
from O | |
January B-DATE | |
1 I-DATE | |
, I-DATE | |
1990 I-DATE | |
, I-DATE | |
to I-DATE | |
July I-DATE | |
1 I-DATE | |
, I-DATE | |
2018 I-DATE | |
. O | |
Standard O | |
demographic O | |
data O | |
such O | |
as O | |
echocardiographic O | |
and O | |
cross O | |
- O | |
sectional O | |
imaging O | |
along O | |
with O | |
operative O | |
details O | |
and O | |
clinical O | |
echocardiographic O | |
outcomes O | |
were O | |
collected O | |
. O | |
Results O | |
The O | |
cohort O | |
included O | |
144 O | |
patients O | |
with O | |
a O | |
median O | |
age O | |
of O | |
4.3 O | |
years O | |
( O | |
interquartile O | |
range O | |
, O | |
8.5 O | |
) O | |
. O | |
Inferior O | |
SVASD O | |
was O | |
present O | |
in O | |
24 O | |
patients O | |
( O | |
17 O | |
% O | |
) O | |
. O | |
A O | |
single O | |
autologous O | |
untreated O | |
pericardial O | |
patch O | |
was O | |
used O | |
for O | |
114 O | |
patients O | |
( O | |
79 O | |
% O | |
) O | |
, O | |
a O | |
two O | |
- O | |
patch O | |
technique O | |
for O | |
20 O | |
patients O | |
( O | |
14 O | |
% O | |
, O | |
last O | |
performed O | |
in O | |
2000 B-DATE | |
) O | |
, O | |
and O | |
a O | |
Warden O | |
procedure O | |
in O | |
10 O | |
patients O | |
( O | |
7 O | |
% O | |
) O | |
. O | |
Median O | |
length O | |
of O | |
stay O | |
was O | |
4 O | |
days O | |
( O | |
interquartile O | |
range O | |
, O | |
2 O | |
) O | |
. O | |
On O | |
echocardiogram O | |
follow O | |
- O | |
up O | |
, O | |
no O | |
patient O | |
had O | |
pulmonary O | |
vein O | |
stenosis O | |
. O | |
One O | |
patient O | |
who O | |
had O | |
the O | |
Warden O | |
procedure O | |
required O | |
a O | |
balloon O | |
dilation O | |
of O | |
the O | |
superior O | |
caval O | |
vein O | |
2 O | |
years O | |
postoperatively O | |
and O | |
a O | |
stent O | |
3 O | |
years O | |
later O | |
. O | |
Two O | |
- O | |
patch O | |
patients O | |
were O | |
substantially O | |
less O | |
likely O | |
to O | |
be O | |
in O | |
normal O | |
sinus O | |
rhythm O | |
( O | |
41 O | |
% O | |
) O | |
on O | |
postoperative O | |
electrocardiograms O | |
compared O | |
with O | |
the O | |
other O | |
two O | |
techniques O | |
( O | |
81 O | |
% O | |
one O | |
- O | |
patch O | |
and O | |
89 O | |
% O | |
Warden O | |
, O | |
P O | |
= O | |
.02 O | |
) O | |
. O | |
Conclusions O | |
The O | |
great O | |
majority O | |
of O | |
patients O | |
with O | |
sinus O | |
venosus O | |
atrial O | |
septal O | |
defects O | |
can O | |
be O | |
successfully O | |
repaired O | |
with O | |
a O | |
single O | |
patch O | |
of O | |
autologous O | |
pericardium O | |
. O | |
We O | |
transitioned O | |
to O | |
using O | |
either O | |
a O | |
single O | |
pericardial O | |
patch O | |
or O | |
the O | |
Warden O | |
procedure O | |
, O | |
resulting O | |
in O | |
a O | |
higher O | |
frequency O | |
of O | |
normal O | |
sinus O | |
rhythm O | |
on O | |
postoperative O | |
electrocardiograms O | |
. O | |
Background O | |
Antiretroviral O | |
chemoprophylaxis O | |
before O | |
exposure O | |
is O | |
a O | |
promising O | |
approach O | |
for O | |
the O | |
prevention O | |
of O | |
human O | |
immunodeficiency O | |
virus O | |
( O | |
HIV O | |
) O | |
acquisition O | |
. O | |
Methods O | |
We O | |
randomly O | |
assigned O | |
2499 O | |
HIV O | |
- O | |
seronegative O | |
men B-SEX | |
or O | |
transgender O | |
women B-SEX | |
who O | |
have O | |
sex O | |
with O | |
men B-SEX | |
to O | |
receive O | |
a O | |
combination O | |
of O | |
two O | |
oral O | |
antiretroviral O | |
drugs O | |
, O | |
emtricitabine O | |
and O | |
tenofovir O | |
disoproxil O | |
fumarate O | |
( O | |
FTC O | |
- O | |
TDF O | |
) O | |
, O | |
or O | |
placebo O | |
once O | |
daily O | |
. O | |
All O | |
subjects O | |
received O | |
HIV O | |
testing O | |
, O | |
risk O | |
- O | |
reduction O | |
counseling O | |
, O | |
condoms O | |
, O | |
and O | |
management O | |
of O | |
sexually O | |
transmitted O | |
infections O | |
. O | |
Results O | |
The O | |
study O | |
subjects O | |
were O | |
followed O | |
for O | |
3324 O | |
person O | |
- O | |
years O | |
( O | |
median O | |
, O | |
1.2 O | |
years O | |
; O | |
maximum O | |
, O | |
2.8 O | |
years O | |
) O | |
. O | |
Of O | |
these O | |
subjects O | |
, O | |
10 O | |
were O | |
found O | |
to O | |
have O | |
been O | |
infected O | |
with O | |
HIV O | |
at O | |
enrollment O | |
, O | |
and O | |
100 O | |
became O | |
infected O | |
during O | |
follow O | |
- O | |
up O | |
( O | |
36 O | |
in O | |
the O | |
FTC O | |
- O | |
TDF O | |
group O | |
and O | |
64 O | |
in O | |
the O | |
placebo O | |
group O | |
) O | |
, O | |
indicating O | |
a O | |
44 O | |
% O | |
reduction O | |
in O | |
the O | |
incidence B-EPI | |
of O | |
HIV O | |
( O | |
95 O | |
% O | |
confidence O | |
interval O | |
, O | |
15 O | |
to O | |
63 O | |
; O | |
P=0.005 O | |
) O | |
. O | |
In O | |
the O | |
FTC O | |
- O | |
TDF O | |
group O | |
, O | |
the O | |
study O | |
drug O | |
was O | |
detected O | |
in O | |
22 O | |
of O | |
43 O | |
of O | |
seronegative O | |
subjects O | |
( O | |
51 O | |
% O | |
) O | |
and O | |
in O | |
3 O | |
of O | |
34 O | |
HIV O | |
- O | |
infected O | |
subjects O | |
( O | |
9 O | |
% O | |
) O | |
( O | |
P<0.001 O | |
) O | |
. O | |
Nausea O | |
was O | |
reported O | |
more O | |
frequently O | |
during O | |
the O | |
first O | |
4 O | |
weeks O | |
in O | |
the O | |
FTC O | |
- O | |
TDF O | |
group O | |
than O | |
in O | |
the O | |
placebo O | |
group O | |
( O | |
P<0.001 O | |
) O | |
. O | |
The O | |
two O | |
groups O | |
had O | |
similar O | |
rates O | |
of O | |
serious O | |
adverse O | |
events O | |
( O | |
P=0.57 O | |
) O | |
. O | |
Conclusions O | |
Oral O | |
FTC O | |
- O | |
TDF O | |
provided O | |
protection O | |
against O | |
the O | |
acquisition O | |
of O | |
HIV O | |
infection O | |
among O | |
the O | |
subjects O | |
. O | |
Detectable O | |
blood O | |
levels O | |
strongly O | |
correlated O | |
with O | |
the O | |
prophylactic O | |
effect O | |
. O | |
( O | |
Funded O | |
by O | |
the O | |
National O | |
Institutes O | |
of O | |
Health O | |
and O | |
the O | |
Bill O | |
and O | |
Melinda O | |
Gates O | |
Foundation O | |
; O | |
ClinicalTrials.gov O | |
number O | |
, O | |
NCT00458393 O | |
. O | |
Coronavirus O | |
2019 O | |
( O | |
COVID-19 O | |
) O | |
is O | |
responsible O | |
for O | |
the O | |
current O | |
pandemic O | |
which O | |
has O | |
already O | |
resulted O | |
in O | |
considerable O | |
mortality O | |
worldwide B-LOC | |
. O | |
This O | |
systematic O | |
review O | |
was O | |
conducted O | |
to O | |
summarize O | |
the O | |
results O | |
of O | |
the O | |
published O | |
articles O | |
assessing O | |
the O | |
incidence B-EPI | |
of O | |
heart O | |
diseases O | |
in O | |
patients O | |
infected O | |
with O | |
COVID-19 O | |
. O | |
The O | |
electronic O | |
databases O | |
Scopus O | |
, O | |
Web O | |
of O | |
Science O | |
, O | |
Pubmed O | |
, O | |
Science O | |
Direct O | |
, O | |
and O | |
ProQuest O | |
were O | |
used O | |
to O | |
search O | |
for O | |
potentially O | |
relevant O | |
articles O | |
. O | |
Articles O | |
published O | |
from O | |
Dec B-DATE | |
2019 I-DATE | |
to I-DATE | |
April I-DATE | |
2020 I-DATE | |
were O | |
included O | |
. O | |
All O | |
cross O | |
- O | |
sectional O | |
, O | |
retrospective O | |
or O | |
prospective O | |
observational O | |
cohort O | |
and O | |
case O | |
- O | |
control O | |
studies O | |
were O | |
selected O | |
which O | |
reported O | |
the O | |
incidence B-EPI | |
or O | |
prevalence B-EPI | |
of O | |
myocardial O | |
injury O | |
, O | |
myocardial O | |
infarction O | |
, O | |
or O | |
cardiovascular O | |
disease O | |
in O | |
patients O | |
with O | |
confirmed O | |
COVID-19 O | |
infection O | |
. O | |
Based O | |
on O | |
the O | |
inclusion O | |
criteria O | |
, O | |
12 O | |
articles O | |
were O | |
selected O | |
. O | |
The O | |
incidence B-EPI | |
of O | |
cardiac O | |
injury O | |
was O | |
reported O | |
in O | |
8 O | |
articles O | |
and O | |
8 O | |
articles O | |
focused O | |
on O | |
the O | |
cardiovascular O | |
outcomes O | |
of O | |
COVID-19 O | |
infection O | |
. O | |
The O | |
incidence B-EPI | |
of O | |
new O | |
cardiac O | |
injury O | |
was O | |
reported O | |
to O | |
be O | |
7.2 O | |
- O | |
77 O | |
% O | |
in O | |
live O | |
and O | |
dead O | |
patients O | |
, O | |
respectively O | |
. O | |
The O | |
results O | |
showed O | |
that O | |
patients O | |
with O | |
cardiac O | |
injury O | |
had O | |
worse O | |
outcomes O | |
including O | |
higher O | |
mortality O | |
than O | |
those O | |
without O | |
cardiac O | |
injury O | |
. O | |
The O | |
most O | |
common O | |
cardiac O | |
injury O | |
outcomes O | |
were O | |
shock O | |
and O | |
malignant O | |
arrhythmias O | |
. O | |
The O | |
most O | |
common O | |
radiographic O | |
findings O | |
in O | |
patients O | |
with O | |
cardiac O | |
injury O | |
were O | |
multiple O | |
mottling O | |
and O | |
ground O | |
- O | |
glass O | |
opacities O | |
in O | |
the O | |
lungs O | |
( O | |
64.6 O | |
% O | |
) O | |
. O | |
A O | |
significant O | |
number O | |
of O | |
patients O | |
with O | |
cardiac O | |
injury O | |
required O | |
noninvasive O | |
mechanical O | |
ventilation O | |
( O | |
46.3 O | |
% O | |
) O | |
or O | |
invasive O | |
mechanical O | |
ventilation O | |
( O | |
22.0 O | |
% O | |
) O | |
. O | |
Acute O | |
respiratory O | |
distress O | |
syndrome O | |
was O | |
seen O | |
in O | |
58.5 O | |
% O | |
, O | |
acute O | |
kidney O | |
injury O | |
in O | |
8.5 O | |
% O | |
, O | |
electrolyte O | |
disturbances O | |
in O | |
15.9 O | |
% O | |
, O | |
hypoproteinemia O | |
in O | |
13.4 O | |
% O | |
, O | |
and O | |
coagulation O | |
disorders O | |
in O | |
7.3 O | |
% O | |
of O | |
patients O | |
with O | |
cardiac O | |
injuries O | |
. O | |
In O | |
addition O | |
, O | |
survival O | |
days O | |
were O | |
negatively O | |
correlated O | |
with O | |
cardiac O | |
troponin O | |
I O | |
levels O | |
( O | |
r O | |
= O | |
-0.42 O | |
, O | |
95 O | |
% O | |
, O | |
p O | |
= O | |
0.005 O | |
) O | |
. O | |
The O | |
results O | |
of O | |
this O | |
review O | |
showed O | |
that O | |
myocardial O | |
injury O | |
in O | |
patients O | |
with O | |
COVID O | |
19 O | |
has O | |
a O | |
poor O | |
prognosis O | |
. O | |
Hence O | |
, O | |
cardiac O | |
investigation O | |
and O | |
management O | |
in O | |
these O | |
patients O | |
are O | |
crucial O | |
. O | |
Diarrhoea O | |
lasting O | |
longer O | |
than O | |
14 O | |
days O | |
and O | |
failing O | |
to O | |
respond O | |
to O | |
conventional O | |
management O | |
is O | |
defined O | |
as O | |
severe O | |
and O | |
protracted O | |
diarrhoea O | |
( O | |
SD O | |
) O | |
. O | |
In O | |
this O | |
study O | |
, O | |
we O | |
investigated O | |
the O | |
prevalence B-EPI | |
, O | |
pathogens O | |
and O | |
prognosis O | |
of O | |
SD O | |
in O | |
primary O | |
immunodeficiency O | |
diseases O | |
( O | |
PIDs O | |
) O | |
. O | |
Among O | |
246 O | |
patients O | |
with O | |
predominantly O | |
paediatric O | |
- O | |
onset O | |
PIDs O | |
from O | |
2003 B-DATE | |
- I-DATE | |
2015 I-DATE | |
, O | |
21 O | |
[ O | |
Btk O | |
( O | |
six O | |
) O | |
, O | |
IL2RG O | |
( O | |
four O | |
) O | |
, O | |
WASP O | |
, O | |
CD40L O | |
, O | |
gp91 O | |
( O | |
three O | |
each O | |
) O | |
, O | |
gp47 O | |
, O | |
RAG2 O | |
( O | |
one O | |
each O | |
) O | |
] O | |
and O | |
five O | |
[ O | |
CVID O | |
( O | |
four O | |
) O | |
, O | |
SCID O | |
( O | |
one O | |
) O | |
] O | |
without O | |
identified O | |
mutations O | |
had O | |
SD O | |
before O | |
prophylactic O | |
treatment O | |
. O | |
Detectable O | |
pathogens O | |
included O | |
pseudomonas O | |
, O | |
salmonella O | |
( O | |
six O | |
each O | |
) O | |
, O | |
E. O | |
coli O | |
, O | |
cytomegalovirus O | |
, O | |
coxsackie O | |
virus O | |
and O | |
cryptosporidium O | |
( O | |
one O | |
each O | |
) O | |
, O | |
all O | |
of O | |
whom O | |
improved O | |
after O | |
a O | |
mean O | |
17 O | |
days O | |
of O | |
antibiotics O | |
and/or O | |
IVIG O | |
treatment O | |
. O | |
Seven O | |
( O | |
7/26 O | |
; O | |
27.0 O | |
% O | |
) O | |
patients O | |
died O | |
[ O | |
respiratory O | |
failure O | |
( O | |
four O | |
) O | |
, O | |
lymphoma O | |
, O | |
sepsis O | |
and O | |
intracranial O | |
haemorrhage O | |
( O | |
one O | |
each O | |
) O | |
] O | |
. O | |
The O | |
patients O | |
with O | |
WAS O | |
, O | |
CGD O | |
and O | |
CD40L O | |
and O | |
SD O | |
had O | |
a O | |
higher O | |
mortality O | |
rate O | |
than O | |
those O | |
without O | |
. O | |
Another O | |
five O | |
males B-SEX | |
with O | |
mutant O | |
XIAP O | |
, O | |
STAT1 O | |
, O | |
FOXP3 O | |
( O | |
one O | |
each O | |
) O | |
and O | |
STAT3 O | |
( O | |
two O | |
) O | |
had O | |
undetectable O | |
- O | |
pathogenic O | |
refractory O | |
diarrhoea O | |
( O | |
RD O | |
) O | |
that O | |
persisted O | |
> O | |
21 O | |
days O | |
despite O | |
aggressive O | |
antibiotic O | |
/ O | |
steroid O | |
treatment O | |
and O | |
directly O | |
resulted O | |
in O | |
mortality O | |
. O | |
For O | |
the O | |
patients O | |
with O | |
RD O | |
without O | |
anti O | |
- O | |
inflammatory O | |
optimization O | |
, O | |
those O | |
with O | |
mutant O | |
XIAP O | |
and O | |
FOXP3 O | |
died O | |
of O | |
Crohn's O | |
- O | |
like O | |
colitis O | |
and O | |
electrolyte O | |
exhaustion O | |
in O | |
awaiting O | |
transplantation O | |
, O | |
while O | |
transplantation O | |
cured O | |
the O | |
STAT1 O | |
patient O | |
. O | |
Background O | |
Hereditary O | |
cancer O | |
susceptibility O | |
syndrome O | |
( O | |
HCSS O | |
) O | |
contributes O | |
to O | |
the O | |
cancer O | |
predisposition O | |
at O | |
an O | |
early O | |
age O | |
, O | |
therefore O | |
, O | |
identification O | |
of O | |
HCSS O | |
has O | |
found O | |
to O | |
be O | |
crucial O | |
for O | |
surveillance O | |
, O | |
managing O | |
therapeutic O | |
interventions O | |
and O | |
refer O | |
the O | |
patients O | |
and O | |
their O | |
families O | |
for O | |
genetic O | |
counselling O | |
. O | |
The O | |
study O | |
aimed O | |
to O | |
identify O | |
ALL O | |
patients O | |
who O | |
meet O | |
the O | |
American B-ETHN | |
College O | |
of O | |
Medical O | |
Genetics O | |
( O | |
ACMG O | |
) O | |
criteria O | |
and O | |
refer O | |
them O | |
for O | |
the O | |
genetic O | |
testing O | |
for O | |
HCSS O | |
as O | |
hereditary O | |
leukemia O | |
and O | |
hematologic O | |
malignancy O | |
syndrome O | |
, O | |
and O | |
to O | |
elucidate O | |
the O | |
significance O | |
of O | |
high O | |
consanguinity O | |
with O | |
the O | |
prevalence B-EPI | |
of O | |
inherited O | |
leukemia O | |
in O | |
Pakistani B-ETHN | |
population O | |
. O | |
Methods O | |
A O | |
total O | |
of O | |
300 O | |
acute O | |
lymphoblastic O | |
leukemia O | |
patients O | |
were O | |
recruited O | |
from O | |
the O | |
Children O | |
's O | |
Hospital O | |
, O | |
Lahore B-LOC | |
, I-LOC | |
Pakistan B-LOC | |
from O | |
December B-DATE | |
2018 I-DATE | |
to I-DATE | |
September I-DATE | |
2019 I-DATE | |
. O | |
A O | |
structured O | |
self O | |
- O | |
reporting O | |
questionnaire O | |
based O | |
on O | |
family O | |
and O | |
medical O | |
history O | |
of O | |
the O | |
disease O | |
was O | |
utilized O | |
for O | |
the O | |
data O | |
collection O | |
. O | |
Results O | |
In O | |
our O | |
cohort O | |
, O | |
60.40 O | |
% O | |
of O | |
ALL O | |
patients O | |
were O | |
identified O | |
to O | |
meet O | |
ACMG O | |
criteria O | |
. O | |
Among O | |
them O | |
, O | |
a O | |
large O | |
number O | |
of O | |
patients O | |
( O | |
40.65 O | |
% O | |
) O | |
solely O | |
fulfil O | |
the O | |
criteria O | |
due O | |
to O | |
the O | |
presence O | |
of O | |
parental O | |
consanguinity O | |
. O | |
However O | |
, O | |
parental O | |
consanguinity O | |
showed O | |
protective O | |
impact O | |
on O | |
the O | |
onset O | |
at O | |
early O | |
age O | |
of O | |
disease O | |
[ O | |
OD O | |
= O | |
0.44 O | |
( O | |
0.25 O | |
- O | |
0.77 O | |
) O | |
, O | |
p O | |
- O | |
value O | |
= O | |
0.00 O | |
] O | |
while O | |
, O | |
a O | |
family O | |
history O | |
of O | |
cancer O | |
increased O | |
the O | |
risk O | |
of O | |
cardiotoxicity O | |
[ O | |
OD O | |
= O | |
2.46 O | |
( O | |
1.15 O | |
- O | |
5.24 O | |
) O | |
, O | |
p O | |
- O | |
value O | |
= O | |
0.02 O | |
] O | |
. O | |
Parental O | |
consanguinity O | |
shows O | |
no O | |
significant O | |
impact O | |
on O | |
the O | |
family O | |
history O | |
of O | |
cancer O | |
and O | |
the O | |
number O | |
of O | |
relatives O | |
with O | |
cancer O | |
. O | |
Conclusions O | |
More O | |
than O | |
50 O | |
% O | |
of O | |
the O | |
ALL O | |
patients O | |
were O | |
considered O | |
the O | |
strong O | |
candidates O | |
' O | |
for O | |
genetic O | |
testing O | |
of O | |
HCSS O | |
in O | |
the O | |
Pakistani B-ETHN | |
population O | |
, O | |
and O | |
parental O | |
consanguinity O | |
was O | |
the O | |
leading O | |
criteria O | |
fulfilled O | |
by O | |
the O | |
individuals O | |
when O | |
assessed O | |
through O | |
ACMG O | |
guidelines O | |
. O | |
Our O | |
study O | |
suggests O | |
revisiting O | |
ACMG O | |
guidelines O | |
, O | |
especially O | |
for O | |
the O | |
criterion O | |
of O | |
parental O | |
consanguinity O | |
, O | |
and O | |
formulating O | |
the O | |
score O | |
based O | |
criteria O | |
based O | |
on O | |
; O | |
genetic O | |
research O | |
, O | |
the O | |
toxicology O | |
profile O | |
, O | |
physical O | |
features O | |
, O | |
personal O | |
and O | |
family O | |
history O | |
of O | |
cancer O | |
for O | |
the O | |
identification O | |
of O | |
patients O | |
for O | |
the O | |
genetic O | |
testing O | |
. O | |
Background O | |
The O | |
majority O | |
of O | |
active O | |
tuberculosis O | |
( O | |
TB O | |
) O | |
cases O | |
develop O | |
from O | |
latent O | |
tuberculosis O | |
infection O | |
( O | |
LTBI O | |
) O | |
. O | |
Since O | |
the O | |
risk O | |
of O | |
TB O | |
in O | |
hemodialysis O | |
( O | |
HD O | |
) O | |
patients O | |
is O | |
particularly O | |
high O | |
, O | |
interferon O | |
- O | |
gamma O | |
release O | |
assay O | |
( O | |
IGRA O | |
) O | |
for O | |
LTBI O | |
screening O | |
in O | |
HD O | |
patients O | |
is O | |
considered O | |
important O | |
. O | |
However O | |
, O | |
the O | |
prevalence B-EPI | |
and O | |
characteristics O | |
of O | |
LTBI O | |
in O | |
Japanese B-ETHN | |
HD O | |
patients O | |
remain O | |
obscure O | |
. O | |
Methods O | |
We O | |
performed O | |
an O | |
observational O | |
cross O | |
- O | |
sectional O | |
study O | |
of O | |
LTBI O | |
using O | |
IGRA O | |
QFT-3 O | |
G O | |
tests O | |
in O | |
118 O | |
HD O | |
outpatients O | |
enrolled O | |
at O | |
3 O | |
hospitals O | |
of O | |
varying O | |
location O | |
and O | |
function O | |
. O | |
Results O | |
Of O | |
the O | |
118 O | |
patients O | |
, O | |
96 O | |
were O | |
QFT O | |
negative O | |
, O | |
7 O | |
were O | |
QFT O | |
indeterminate O | |
, O | |
14 O | |
were O | |
QFT O | |
positive O | |
, O | |
and O | |
1 O | |
was O | |
QFT O | |
judgment O | |
impossible O | |
. O | |
No O | |
patient O | |
had O | |
active O | |
TB O | |
. O | |
Confirmed O | |
( O | |
QFT O | |
positive O | |
) O | |
and O | |
possible O | |
( O | |
QFT O | |
positive O | |
+ O | |
indeterminate O | |
) O | |
LTBI O | |
patients O | |
totaled O | |
14 O | |
( O | |
11.9 O | |
% O | |
) O | |
and O | |
21 O | |
( O | |
17.8 O | |
% O | |
) O | |
, O | |
respectively O | |
. O | |
The O | |
LTBI O | |
possible O | |
group O | |
was O | |
significantly O | |
older O | |
and O | |
had O | |
a O | |
significantly O | |
higher O | |
rate O | |
of O | |
nephrosclerosis O | |
versus O | |
the O | |
QFT O | |
- O | |
negative O | |
group O | |
. O | |
The O | |
indeterminate O | |
group O | |
had O | |
a O | |
significantly O | |
longer O | |
HD O | |
period O | |
. O | |
The O | |
QFT O | |
results O | |
were O | |
not O | |
remarkably O | |
affected O | |
by O | |
other O | |
clinical O | |
data O | |
, O | |
including O | |
hospital O | |
characteristics O | |
. O | |
The O | |
possible O | |
LTBI O | |
rate O | |
increased O | |
age O | |
- O | |
dependently O | |
, O | |
with O | |
higher O | |
values O | |
from O | |
60 O | |
years O | |
of O | |
age O | |
. O | |
Conclusions O | |
The O | |
prevalence B-EPI | |
of O | |
LTBI O | |
is O | |
high O | |
in O | |
Japanese B-ETHN | |
HD O | |
patients O | |
, O | |
especially O | |
from O | |
the O | |
age O | |
of O | |
60 O | |
years O | |
. O | |
Older O | |
age O | |
was O | |
a O | |
significant O | |
risk O | |
factor O | |
for O | |
LTBI O | |
, O | |
with O | |
prediction O | |
difficult O | |
using O | |
other O | |
clinical O | |
data O | |
. O | |
Extended O | |
HD O | |
may O | |
mask O | |
IGRA O | |
results O | |
. O | |
Therefore O | |
, O | |
aggressive O | |
screening O | |
for O | |
LTBI O | |
is O | |
advised O | |
in O | |
all O | |
HD O | |
patients O | |
regardless O | |
of O | |
hospital O | |
region O | |
or O | |
type O | |
, O | |
especially O | |
in O | |
patients O | |
over O | |
60 O | |
years O | |
of O | |
age O | |
or O | |
newly O | |
commencing O | |
HD O | |
. O | |
In O | |
the O | |
year O | |
2000 B-DATE | |
, O | |
the O | |
discovery O | |
of O | |
OPA1 O | |
mutations O | |
as O | |
causative O | |
for O | |
dominant O | |
optic O | |
atrophy O | |
( O | |
DOA O | |
) O | |
was O | |
pivotal O | |
to O | |
rapidly O | |
expand O | |
the O | |
field O | |
of O | |
mitochondrial O | |
dynamics O | |
and O | |
describe O | |
the O | |
complex O | |
machinery O | |
governing O | |
this O | |
pathway O | |
, O | |
with O | |
a O | |
multitude O | |
of O | |
other O | |
genes O | |
and O | |
encoded O | |
proteins O | |
involved O | |
in O | |
neurodegenerative O | |
disorders O | |
of O | |
the O | |
optic O | |
nerve O | |
. O | |
OPA1 O | |
turned O | |
out O | |
to O | |
be O | |
a O | |
much O | |
more O | |
complex O | |
protein O | |
than O | |
initially O | |
envisaged O | |
, O | |
connecting O | |
multiple O | |
pathways O | |
beyond O | |
its O | |
strict O | |
role O | |
in O | |
mitochondrial O | |
fusion O | |
, O | |
such O | |
as O | |
sensing O | |
of O | |
OXPHOS O | |
needs O | |
and O | |
mitochondrial O | |
DNA O | |
maintenance O | |
. O | |
As O | |
a O | |
consequence O | |
, O | |
an O | |
increasing O | |
need O | |
to O | |
investigate O | |
OPA1 O | |
functions O | |
at O | |
multiple O | |
levels O | |
has O | |
imposed O | |
the O | |
development O | |
of O | |
multiple O | |
tools O | |
and O | |
models O | |
that O | |
are O | |
here O | |
reviewed O | |
. O | |
Translational O | |
mitochondrial O | |
medicine O | |
, O | |
with O | |
the O | |
ultimate O | |
objective O | |
of O | |
translating O | |
basic O | |
science O | |
necessary O | |
to O | |
understand O | |
pathogenic O | |
mechanisms O | |
into O | |
therapeutic O | |
strategies O | |
, O | |
requires O | |
disease O | |
modeling O | |
at O | |
multiple O | |
levels O | |
: O | |
from O | |
the O | |
simplest O | |
, O | |
like O | |
in O | |
yeast O | |
, O | |
to O | |
cell O | |
models O | |
, O | |
including O | |
the O | |
increasing O | |
use O | |
of O | |
reprogrammed O | |
stem O | |
cells O | |
( O | |
iPSCs O | |
) O | |
from O | |
patients O | |
, O | |
to O | |
animal O | |
models O | |
. O | |
In O | |
the O | |
present O | |
review O | |
, O | |
we O | |
thoroughly O | |
examine O | |
and O | |
provide O | |
the O | |
state O | |
of O | |
the O | |
art O | |
of O | |
all O | |
these O | |
approaches O | |
. O | |
Sexual O | |
activity O | |
during O | |
adolescence O | |
can O | |
lead O | |
to O | |
unwanted O | |
pregnancy O | |
, O | |
which O | |
in O | |
turn O | |
can O | |
result O | |
in O | |
serious O | |
maternal O | |
and O | |
fetal O | |
complications O | |
. O | |
The O | |
present O | |
study O | |
aimed O | |
to O | |
evaluate O | |
the O | |
complications O | |
related O | |
to O | |
adolescent O | |
pregnancy O | |
, O | |
through O | |
a O | |
systematic O | |
review O | |
using O | |
the O | |
Medical O | |
Subject O | |
Headings O | |
: O | |
pregnancy O | |
complication O | |
AND O | |
adolescent O | |
OR O | |
pregnancy O | |
in O | |
adolescence O | |
. O | |
Only O | |
full O | |
original O | |
articles O | |
in O | |
English B-ETHN | |
or O | |
Portuguese B-ETHN | |
with O | |
a O | |
clearly O | |
described O | |
methodology O | |
, O | |
were O | |
included O | |
. O | |
No O | |
qualitative O | |
studies O | |
, O | |
reviews O | |
or O | |
meta O | |
- O | |
analyses O | |
, O | |
editorials O | |
, O | |
case O | |
series O | |
, O | |
or O | |
case O | |
reports O | |
were O | |
included O | |
. O | |
The O | |
sample O | |
consisted O | |
of O | |
15 O | |
articles O | |
; O | |
in O | |
that O | |
10 O | |
were O | |
cross O | |
- O | |
sectional O | |
and O | |
5 O | |
were O | |
cohort O | |
studies O | |
. O | |
The O | |
overall B-EPI | |
prevalence I-EPI | |
of O | |
adolescent O | |
pregnancy O | |
was O | |
10 O | |
% O | |
, O | |
and O | |
among O | |
the O | |
Brazilian B-ETHN | |
studies O | |
, O | |
the O | |
adolescent O | |
pregnancy O | |
rate O | |
was O | |
26 O | |
% O | |
. O | |
The O | |
cesarean O | |
delivery O | |
rate O | |
was O | |
lower O | |
than O | |
that O | |
reported O | |
in O | |
the O | |
general O | |
population O | |
. O | |
The O | |
main O | |
maternal O | |
and O | |
neonatal O | |
complications O | |
were O | |
hypertensive O | |
disorders O | |
of O | |
pregnancy O | |
, O | |
prematurity O | |
and O | |
low O | |
birth O | |
weight O | |
, O | |
respectively O | |
. O | |
Adolescent O | |
pregnancy O | |
is O | |
related O | |
to O | |
increased O | |
frequency O | |
of O | |
neonatal O | |
and O | |
maternal O | |
complications O | |
and O | |
lower O | |
prevalence B-EPI | |
of O | |
cesarean O | |
delivery O | |
. O | |
Excessive O | |
daytime O | |
sleepiness O | |
( O | |
EDS O | |
) O | |
is O | |
a O | |
highly O | |
prevalent B-EPI | |
condition O | |
that O | |
is O | |
associated O | |
with O | |
significant O | |
morbidity O | |
. O | |
The O | |
causes O | |
of O | |
EDS O | |
are O | |
varied O | |
, O | |
and O | |
include O | |
inadequate O | |
sleep O | |
, O | |
sleep O | |
disordered O | |
breathing O | |
, O | |
circadian O | |
rhythm O | |
sleep O | |
- O | |
wake O | |
disorders O | |
, O | |
and O | |
central O | |
disorders O | |
of O | |
hypersomnolence O | |
( O | |
narcolepsy O | |
, O | |
idiopathic O | |
hypersomnia O | |
, O | |
and O | |
Kleine O | |
- O | |
Levin O | |
syndrome O | |
) O | |
. O | |
Additionally O | |
, O | |
EDS O | |
could O | |
represent O | |
a O | |
symptom O | |
of O | |
an O | |
underlying O | |
medical O | |
or O | |
psychiatric O | |
disorder O | |
. O | |
Assessment O | |
of O | |
EDS O | |
includes O | |
a O | |
thorough O | |
sleep O | |
, O | |
medical O | |
, O | |
and O | |
psychiatric O | |
history O | |
, O | |
targeted O | |
clinical O | |
examination O | |
, O | |
and O | |
appropriate O | |
use O | |
of O | |
actigraphy O | |
to O | |
measure O | |
sleep O | |
duration O | |
and O | |
sleep O | |
- O | |
wake O | |
patterns O | |
, O | |
polysomnography O | |
to O | |
assess O | |
for O | |
associated O | |
conditions O | |
such O | |
as O | |
sleep O | |
- O | |
related O | |
breathing O | |
disorders O | |
or O | |
other O | |
factors O | |
that O | |
might O | |
disrupt O | |
nighttime O | |
sleep O | |
, O | |
multiple O | |
sleep O | |
latency O | |
testing O | |
to O | |
ascertain O | |
objective O | |
sleepiness O | |
and O | |
diagnose O | |
central O | |
disorders O | |
of O | |
hypersomnolence O | |
, O | |
and O | |
measurement O | |
of O | |
cerebrospinal O | |
fluid O | |
hypocretin-1 O | |
concentration O | |
. O | |
Treatment O | |
of O | |
EDS O | |
secondary O | |
to O | |
central O | |
disorders O | |
of O | |
hypersomnolence O | |
is O | |
primarily O | |
pharmacologic O | |
with O | |
wakefulness O | |
- O | |
promoting O | |
agents O | |
such O | |
as O | |
modafinil O | |
, O | |
stimulants O | |
such O | |
as O | |
methylphenidate O | |
and O | |
amphetamines O | |
, O | |
and O | |
newer O | |
agents O | |
specifically O | |
designed O | |
to O | |
improve O | |
wakefulness O | |
; O | |
behavioral O | |
interventions O | |
can O | |
provide O | |
a O | |
useful O | |
adjunct O | |
to O | |
pharmacologic O | |
treatment O | |
. O | |
When O | |
excessive O | |
sleepiness O | |
is O | |
secondary O | |
to O | |
other O | |
conditions O | |
, O | |
the O | |
treatment O | |
should O | |
focus O | |
on O | |
targeting O | |
the O | |
primary O | |
disorder O | |
. O | |
This O | |
review O | |
discusses O | |
current O | |
epidemiology O | |
, O | |
provides O | |
guidance O | |
on O | |
clinical O | |
assessments O | |
and O | |
testing O | |
, O | |
and O | |
discusses O | |
the O | |
latest O | |
treatment O | |
options O | |
. O | |
For O | |
this O | |
review O | |
, O | |
we O | |
collated O | |
the O | |
latest O | |
evidence O | |
using O | |
the O | |
search O | |
terms O | |
excessive O | |
sleepiness O | |
, O | |
hypersomnia O | |
, O | |
hypersomnolence O | |
, O | |
treatment O | |
from O | |
PubMed O | |
and O | |
MEDLINE O | |
and O | |
the O | |
latest O | |
practice O | |
parameters O | |
from O | |
the O | |
American B-ETHN | |
Academy O | |
of O | |
Sleep O | |
Medicine O | |
. O | |
Aim O | |
To O | |
evaluate O | |
the O | |
risk O | |
factors O | |
and O | |
incidence B-EPI | |
of O | |
Asherman O | |
Syndrome O | |
in O | |
women B-SEX | |
with O | |
post O | |
- O | |
abortion O | |
uterine O | |
evacuation O | |
and O | |
curettage O | |
. O | |
Methods O | |
A O | |
total O | |
of O | |
2546 O | |
patients O | |
who O | |
had O | |
surgical O | |
abortion O | |
( O | |
uterine O | |
evacuation O | |
and O | |
curettage O | |
) O | |
before O | |
the O | |
20th O | |
gestational O | |
week O | |
with O | |
indications O | |
of O | |
missed O | |
abortion O | |
, O | |
anembryonic O | |
pregnancy O | |
, O | |
incomplete O | |
abortion O | |
, O | |
and O | |
elective O | |
curettage O | |
in O | |
a O | |
tertiary O | |
antenatal O | |
care O | |
center O | |
were O | |
recruited O | |
. O | |
The O | |
patients O | |
were O | |
called O | |
and O | |
surveyed O | |
for O | |
their O | |
symptoms O | |
; O | |
including O | |
infertility O | |
, O | |
oligo O | |
- O | |
amenorrhea O | |
and O | |
recurrent O | |
pregnancy O | |
loss O | |
, O | |
preterm O | |
birth O | |
and O | |
intrauterine O | |
growth O | |
retardation O | |
and O | |
abnormal O | |
placentation O | |
as O | |
criteria O | |
of O | |
Asherman O | |
Syndrome O | |
. O | |
Diagnostic O | |
( O | |
office O | |
) O | |
hysteroscopy O | |
was O | |
performed O | |
for O | |
177 O | |
who O | |
had O | |
one O | |
of O | |
those O | |
complaints O | |
. O | |
Results O | |
The O | |
incidence B-EPI | |
of O | |
Asherman O | |
Syndrome O | |
was O | |
1.6 O | |
% O | |
( O | |
n O | |
= O | |
43/2546 O | |
) O | |
. O | |
History O | |
of O | |
≥3 O | |
abortions O | |
was O | |
the O | |
main O | |
factor O | |
that O | |
increased O | |
the O | |
risk O | |
of O | |
Asherman O | |
Syndrome O | |
for O | |
by O | |
4.6 O | |
times O | |
. O | |
Use O | |
of O | |
vacuum O | |
aspiration O | |
or O | |
sharp O | |
curettage O | |
, O | |
premedication O | |
for O | |
cervical O | |
priming O | |
, O | |
and O | |
having O | |
a O | |
pregnancy O | |
> O | |
10th O | |
gestational O | |
weeks O | |
were O | |
not O | |
risk O | |
factors O | |
for O | |
Asherman O | |
Syndrome O | |
. O | |
Conclusion O | |
When O | |
the O | |
diagnosis O | |
was O | |
based O | |
on O | |
presence O | |
of O | |
symptoms O | |
who O | |
underwent O | |
uterine O | |
instrumentation O | |
, O | |
the O | |
incidence B-EPI | |
of O | |
Asherman O | |
Syndrome O | |
was O | |
found O | |
to O | |
be O | |
1.6 O | |
% O | |
. O | |
Repeated O | |
abortions O | |
were O | |
the O | |
main O | |
risk O | |
factor O | |
for O | |
Asherman O | |
Syndrome O | |
and O | |
avoiding O | |
from O | |
repeated O | |
uterine O | |
instrumentations O | |
may O | |
have O | |
a O | |
role O | |
in O | |
prevention O | |
. O | |
Background O | |
Xanthogranulomatous O | |
pyelonephritis O | |
( O | |
XGP O | |
) O | |
is O | |
an O | |
inflammatory O | |
condition O | |
of O | |
the O | |
kidney O | |
and O | |
its O | |
treatment O | |
most O | |
often O | |
involves O | |
a O | |
combination O | |
of O | |
antibiotics O | |
and O | |
nephrectomy O | |
. O | |
This O | |
study O | |
aimed O | |
to O | |
define O | |
the O | |
clinical O | |
features O | |
and O | |
management O | |
of O | |
XGP O | |
, O | |
focusing O | |
on O | |
microbiological O | |
aspects O | |
and O | |
antibiotic O | |
therapy O | |
. O | |
Methods O | |
We O | |
performed O | |
a O | |
retrospective O | |
study O | |
of O | |
27 O | |
cases O | |
of O | |
XGP O | |
diagnosed O | |
between B-DATE | |
January I-DATE | |
2001 I-DATE | |
and I-DATE | |
January I-DATE | |
2020 I-DATE | |
to O | |
analyse O | |
their O | |
clinical O | |
and O | |
management O | |
characteristics O | |
. O | |
In O | |
addition O | |
, O | |
a O | |
literature O | |
review O | |
was O | |
conducted O | |
of O | |
XGP O | |
case O | |
series O | |
covering O | |
the O | |
period O | |
from O | |
2000 B-DATE | |
- I-DATE | |
2020 I-DATE | |
. O | |
We O | |
searched O | |
PubMed O | |
for O | |
case O | |
series O | |
through O | |
April I-DATE | |
2020 I-DATE | |
without O | |
language O | |
restrictions O | |
. O | |
Studies O | |
reporting O | |
case O | |
series O | |
of O | |
XGP O | |
( O | |
more O | |
than O | |
ten O | |
cases O | |
) O | |
were O | |
included O | |
if O | |
they O | |
were O | |
relevant O | |
to O | |
this O | |
study O | |
. O | |
Results O | |
Twenty O | |
- O | |
seven O | |
patients O | |
were O | |
diagnosed O | |
with O | |
XGP O | |
, O | |
and O | |
26 O | |
of O | |
them O | |
were O | |
histologically O | |
proven O | |
to O | |
have O | |
XGP O | |
. O | |
A O | |
total O | |
of O | |
81.5 O | |
% O | |
of O | |
the O | |
patients O | |
were O | |
female B-SEX | |
and O | |
the O | |
mean O | |
age O | |
was O | |
59.6 O | |
years O | |
( O | |
SD O | |
19.2 O | |
) O | |
. O | |
The O | |
most O | |
frequent O | |
symptoms O | |
were O | |
flank O | |
pain O | |
( O | |
70.4 O | |
% O | |
) O | |
and O | |
fever O | |
( O | |
59.3 O | |
% O | |
) O | |
, O | |
while O | |
77.8 O | |
% O | |
of O | |
patients O | |
had O | |
renal O | |
stones O | |
. O | |
Proteus O | |
mirabilis O | |
was O | |
detected O | |
in O | |
the O | |
urine O | |
culture O | |
in O | |
18.5 O | |
% O | |
of O | |
patients O | |
, O | |
followed O | |
by O | |
detection O | |
of O | |
Escherichia O | |
coli O | |
in O | |
14.8 O | |
% O | |
of O | |
patients O | |
. O | |
The O | |
computed O | |
tomography O | |
( O | |
CT O | |
) O | |
findings O | |
included O | |
perirenal O | |
( O | |
29.6 O | |
% O | |
) O | |
or O | |
pararenal O | |
( O | |
29.6 O | |
% O | |
) O | |
involvement O | |
in O | |
the O | |
majority O | |
of O | |
patients O | |
. O | |
Twenty O | |
- O | |
six O | |
patients O | |
underwent O | |
nephrectomy O | |
. O | |
Piperacillin O | |
/ O | |
tazobactam O | |
and O | |
ceftriaxone O | |
were O | |
the O | |
most O | |
commonly O | |
prescribed O | |
antibiotics O | |
for O | |
treatment O | |
. O | |
The O | |
reported O | |
piperacillin O | |
/ O | |
tazobactam O | |
and O | |
ceftriaxone O | |
resistance O | |
rates O | |
were O | |
14.3 O | |
% O | |
and O | |
16.6 O | |
% O | |
, O | |
respectively O | |
. O | |
Twenty O | |
- O | |
six O | |
case O | |
series O | |
were O | |
included O | |
in O | |
the O | |
literature O | |
review O | |
, O | |
reporting O | |
693 O | |
cases O | |
in O | |
total O | |
. O | |
Conclusion O | |
We O | |
found O | |
well O | |
- O | |
established O | |
characteristics O | |
of O | |
XGP O | |
patients O | |
among O | |
series O | |
in O | |
terms O | |
of O | |
previous O | |
history O | |
, O | |
clinical O | |
, O | |
laboratory O | |
and O | |
imaging O | |
findings O | |
, O | |
and O | |
operative O | |
and O | |
postoperative O | |
outcomes O | |
. O | |
It O | |
is O | |
important O | |
to O | |
know O | |
the O | |
clinical O | |
presentation O | |
and O | |
potential O | |
severity O | |
of O | |
XGP O | |
, O | |
as O | |
well O | |
as O | |
the O | |
most O | |
frequently O | |
involved O | |
microorganisms O | |
and O | |
their O | |
antibiotic O | |
resistance O | |
profiles O | |
, O | |
to O | |
select O | |
the O | |
most O | |
appropriate O | |
antibiotic O | |
therapy O | |
. O | |
Introduction O | |
Cardiac O | |
rehabilitation O | |
( O | |
CR O | |
) O | |
is O | |
a O | |
proven O | |
therapy O | |
for O | |
reducing O | |
cardiovascular O | |
death O | |
and O | |
hospitalization O | |
. O | |
Whether O | |
CR O | |
participation O | |
is O | |
associated O | |
with O | |
improved O | |
outcomes O | |
in O | |
patients O | |
with O | |
chronic O | |
kidney O | |
disease O | |
( O | |
CKD O | |
) O | |
is O | |
unknown O | |
. O | |
Methods O | |
We O | |
obtained O | |
data O | |
on O | |
all O | |
adult O | |
patients O | |
in O | |
Calgary B-LOC | |
, O | |
Alberta B-LOC | |
, O | |
Canada B-LOC | |
with O | |
angiographically O | |
proven O | |
coronary O | |
artery O | |
disease O | |
from O | |
1996 B-DATE | |
to I-DATE | |
2016 I-DATE | |
referred O | |
to O | |
CR O | |
from O | |
The O | |
Alberta B-LOC | |
Provincial O | |
Project O | |
for O | |
Outcome O | |
Assessment O | |
in O | |
Coronary O | |
Heart O | |
Disease O | |
and O | |
TotalCardiology O | |
Rehabilitation O | |
. O | |
An O | |
estimated O | |
glomerular O | |
filtration O | |
rate O | |
( O | |
eGFR O | |
) O | |
< O | |
60 O | |
ml O | |
/ O | |
min/1.73 O | |
m O | |
2 O | |
or O | |
kidney O | |
replacement O | |
therapy O | |
defined O | |
CKD O | |
. O | |
Predictors O | |
of O | |
CR O | |
use O | |
were O | |
estimated O | |
with O | |
multinomial O | |
logistic O | |
regression O | |
. O | |
The O | |
association O | |
between O | |
starting O | |
versus O | |
not O | |
starting O | |
and O | |
completion O | |
versus O | |
noncompletion O | |
of O | |
CR O | |
and O | |
clinical O | |
outcomes O | |
were O | |
estimated O | |
using O | |
multivariable O | |
Cox O | |
proportional O | |
hazards O | |
models O | |
. O | |
Results O | |
Of O | |
23,215 O | |
patients O | |
referred O | |
to O | |
CR O | |
, O | |
12,084 O | |
were O | |
eligible O | |
for O | |
inclusion O | |
. O | |
Participants O | |
with O | |
CKD O | |
( O | |
N O | |
= O | |
1322 O | |
) O | |
were O | |
older O | |
, O | |
had O | |
more O | |
comorbidity O | |
, O | |
lower O | |
exercise O | |
capacity O | |
on O | |
graded O | |
treadmill O | |
testing O | |
, O | |
and O | |
took O | |
longer O | |
to O | |
be O | |
referred O | |
and O | |
to O | |
start O | |
CR O | |
than O | |
those O | |
without O | |
CKD O | |
. O | |
CKD O | |
predicted O | |
not O | |
starting O | |
CR O | |
: O | |
odds O | |
ratio O | |
0.73 O | |
( O | |
95 O | |
% O | |
confidence O | |
interval O | |
[ O | |
CI O | |
] O | |
0.64 O | |
- O | |
0.83 O | |
) O | |
. O | |
Over O | |
a O | |
median O | |
1 O | |
year O | |
follow O | |
- O | |
up O | |
, O | |
there O | |
were O | |
146 O | |
deaths O | |
, O | |
40 O | |
( O | |
0.3 O | |
% O | |
) O | |
from O | |
CKD O | |
and O | |
106 O | |
( O | |
1.0 O | |
% O | |
) O | |
not O | |
from O | |
CKD O | |
. O | |
Similar O | |
to O | |
those O | |
without O | |
CKD O | |
, O | |
the O | |
risk O | |
of O | |
death O | |
was O | |
lower O | |
in O | |
CR O | |
completers O | |
( O | |
hazard O | |
ratio O | |
[ O | |
HR O | |
] O | |
0.24 O | |
[ O | |
95 O | |
% O | |
CI O | |
0.06 O | |
- O | |
0.91 O | |
) O | |
and O | |
starters O | |
( O | |
HR O | |
0.56 O | |
[ O | |
95 O | |
% O | |
CI O | |
0.29- O | |
1.10 O | |
] O | |
) O | |
with O | |
CKD O | |
. O | |
Conclusion O | |
CR O | |
participation O | |
was O | |
associated O | |
with O | |
comparable O | |
benefits O | |
in O | |
people O | |
with O | |
moderate O | |
CKD O | |
as O | |
those O | |
without O | |
who O | |
survived O | |
to O | |
CR O | |
. O | |
Lower O | |
rates O | |
of O | |
CR O | |
attendance O | |
in O | |
this O | |
high O | |
- O | |
risk O | |
population O | |
suggest O | |
that O | |
strategies O | |
to O | |
increase O | |
CR O | |
utilization O | |
are O | |
needed O | |
. O | |
Background O | |
Lichen O | |
scrofulosorum O | |
( O | |
LS O | |
) O | |
represents O | |
immunologic O | |
reaction O | |
to O | |
the O | |
Mycobacterium O | |
tuberculosis O | |
antigen O | |
and O | |
presents O | |
with O | |
subtle O | |
, O | |
asymptomatic O | |
, O | |
grouped O | |
follicular O | |
papules O | |
over O | |
the O | |
trunk O | |
and O | |
shows O | |
good O | |
therapeutic O | |
response O | |
to O | |
antitubercular O | |
drugs O | |
. O | |
Objective O | |
To O | |
study O | |
the O | |
clinical O | |
and O | |
epidemiological O | |
characteristics O | |
of O | |
patients O | |
diagnosed O | |
with O | |
LS O | |
. O | |
Materials O | |
and O | |
methods O | |
A O | |
single O | |
- O | |
center O | |
retrospective O | |
review O | |
of O | |
patients O | |
diagnosed O | |
with O | |
LS O | |
from O | |
1997 B-DATE | |
to I-DATE | |
2018 I-DATE | |
was O | |
conducted O | |
. O | |
The O | |
data O | |
pertained O | |
to O | |
clinico O | |
- O | |
epidemiological O | |
profile O | |
, O | |
BCG O | |
vaccination O | |
, O | |
Mantoux O | |
positivity O | |
, O | |
laboratory O | |
investigations O | |
, O | |
coexistent O | |
focus O | |
of O | |
tuberculosis O | |
, O | |
and O | |
response O | |
to O | |
antitubercular O | |
treatment O | |
( O | |
ATT O | |
) O | |
. O | |
Results O | |
LS O | |
cases O | |
constituted O | |
15.2 O | |
% O | |
( O | |
221/1458 O | |
) O | |
of O | |
all O | |
the O | |
patients O | |
diagnosed O | |
with O | |
cutaneous O | |
tuberculosis O | |
( O | |
CTB O | |
) O | |
. O | |
Of O | |
these O | |
, O | |
156 O | |
( O | |
70.5 O | |
% O | |
) O | |
were O | |
pediatric O | |
patients O | |
. O | |
All O | |
patients O | |
presented O | |
with O | |
multiple O | |
follicular O | |
and O | |
perifollicular O | |
grouped O | |
papules O | |
. O | |
The O | |
trunk O | |
was O | |
the O | |
most O | |
common O | |
site O | |
involved O | |
( O | |
98.6 O | |
% O | |
) O | |
, O | |
followed O | |
by O | |
lower O | |
limb O | |
( O | |
25.33 O | |
% O | |
) O | |
, O | |
upper O | |
limb O | |
( O | |
15.83 O | |
% O | |
) O | |
, O | |
face O | |
( O | |
5 O | |
% O | |
) O | |
, O | |
and O | |
external O | |
genitalia O | |
( O | |
3.6 O | |
% O | |
) O | |
. O | |
Evidence O | |
of O | |
BCG O | |
vaccination O | |
and O | |
Mantoux O | |
test O | |
positivity O | |
was O | |
observed O | |
in O | |
52.03 O | |
and O | |
83.2 O | |
% O | |
, O | |
respectively O | |
. O | |
Coexistent O | |
TB O | |
focus O | |
was O | |
detected O | |
in O | |
134 O | |
( O | |
60.6 O | |
% O | |
) O | |
patients O | |
in O | |
lymph O | |
nodes O | |
, O | |
lungs O | |
, O | |
abdomen O | |
, O | |
and O | |
unusual O | |
sites O | |
such O | |
as O | |
intracranial O | |
, O | |
endometrium O | |
, O | |
and O | |
eye O | |
. O | |
Twenty O | |
- O | |
eight O | |
patients O | |
( O | |
12.66 O | |
% O | |
) O | |
had O | |
coexistent O | |
other O | |
clinical O | |
forms O | |
of O | |
CTB O | |
. O | |
Clinical O | |
diagnosis O | |
of O | |
LS O | |
was O | |
confirmed O | |
on O | |
histology O | |
that O | |
revealed O | |
chiefly O | |
periappendageal O | |
epithelioid O | |
cell O | |
granuloma O | |
. O | |
Response O | |
to O | |
ATT O | |
was O | |
good O | |
with O | |
complete O | |
resolution O | |
of O | |
lesion O | |
in O | |
8 O | |
- O | |
12 O | |
weeks O | |
. O | |
Conclusion O | |
LS O | |
appears O | |
to O | |
be O | |
an O | |
underdiagnosed O | |
entity O | |
. O | |
Subtle O | |
and O | |
asymptomatic O | |
lesions O | |
of O | |
LS O | |
are O | |
often O | |
missed O | |
, O | |
thereby O | |
necessitating O | |
a O | |
high O | |
index O | |
of O | |
suspicion O | |
and O | |
appropriate O | |
evaluation O | |
of O | |
the O | |
underlying O | |
TB O | |
focus O | |
. O | |
Coagulation O | |
factor O | |
X O | |
( O | |
F10 O | |
) O | |
amplifies O | |
the O | |
clotting O | |
reaction O | |
in O | |
the O | |
middle O | |
of O | |
the O | |
coagulation O | |
cascade O | |
, O | |
and O | |
thus O | |
F10 O | |
deficiency O | |
leads O | |
to O | |
a O | |
bleeding O | |
tendency O | |
. O | |
Isolated O | |
acquired O | |
F10 O | |
deficiency O | |
is O | |
widely O | |
recognized O | |
in O | |
patients O | |
with O | |
immunoglobulin O | |
light O | |
- O | |
chain O | |
amyloidosis O | |
or O | |
plasma O | |
cell O | |
dyscrasias O | |
. O | |
However O | |
, O | |
its O | |
occurrence B-EPI | |
as O | |
an O | |
autoimmune O | |
disorder O | |
is O | |
extremely O | |
rare O | |
. O | |
The O | |
Japanese B-ETHN | |
Collaborative O | |
Research O | |
Group O | |
has O | |
been O | |
conducting O | |
a O | |
nationwide O | |
survey O | |
on O | |
autoimmune O | |
coagulation O | |
factor O | |
deficiencies O | |
( O | |
AiCFDs O | |
) O | |
starting O | |
in O | |
the O | |
last O | |
decade O | |
; O | |
we O | |
recently O | |
identified O | |
three O | |
patients O | |
with O | |
autoimmune O | |
F10 O | |
deficiency O | |
( O | |
AiF10D O | |
) O | |
. O | |
Furthermore O | |
, O | |
an O | |
extensive O | |
literature O | |
search O | |
was O | |
performed O | |
, O | |
confirming O | |
26 O | |
AiF10D O | |
and O | |
28 O | |
possible O | |
cases O | |
. O | |
Our O | |
study O | |
revealed O | |
that O | |
AiF10D O | |
patients O | |
were O | |
younger O | |
than O | |
patients O | |
with O | |
other O | |
AiCFDs O | |
; O | |
AiF10D O | |
patients O | |
included O | |
children O | |
and O | |
were O | |
predominantly O | |
male B-SEX | |
. O | |
AiF10D O | |
was O | |
confirmed O | |
as O | |
a O | |
severe O | |
type O | |
of O | |
bleeding O | |
diathesis O | |
, O | |
although O | |
its O | |
mortality O | |
rate O | |
was O | |
not O | |
high O | |
. O | |
As O | |
AiF10D O | |
patients O | |
showed O | |
only O | |
low O | |
F10 O | |
inhibitor O | |
titers O | |
, O | |
they O | |
were O | |
considered O | |
to O | |
have O | |
nonneutralizing O | |
anti O | |
- O | |
F10 O | |
autoantibodies O | |
rather O | |
than O | |
their O | |
neutralizing O | |
counterparts O | |
. O | |
Accordingly O | |
, O | |
immunological O | |
anti O | |
- O | |
F10 O | |
antibody O | |
detection O | |
is O | |
highly O | |
recommended O | |
. O | |
Hemostatic O | |
and O | |
immunosuppressive O | |
therapies O | |
may O | |
help O | |
arrest O | |
bleeding O | |
and O | |
eliminate O | |
anti O | |
- O | |
F10 O | |
antibodies O | |
, O | |
leading O | |
to O | |
a O | |
high O | |
recovery O | |
rate O | |
. O | |
However O | |
, O | |
further O | |
investigation O | |
is O | |
necessary O | |
to O | |
understand O | |
the O | |
basic O | |
characteristics O | |
and O | |
proper O | |
management O | |
of O | |
AiF10D O | |
owing O | |
to O | |
the O | |
limited O | |
number O | |
of O | |
patients O | |
. O | |
Herpes O | |
simplex O | |
virus O | |
( O | |
HSV O | |
) O | |
1 O | |
and O | |
HSV-2 O | |
infections O | |
are O | |
highly O | |
prevalent B-EPI | |
worldwide B-LOC | |
and O | |
are O | |
characterized O | |
by O | |
establishing O | |
lifelong O | |
infection O | |
with O | |
periods O | |
of O | |
latency O | |
interspersed O | |
with O | |
periodic O | |
episodes O | |
of O | |
reactivation O | |
. O | |
Acquisition O | |
of O | |
HSV O | |
by O | |
an O | |
infant O | |
during O | |
the O | |
peripartum O | |
or O | |
postpartum O | |
period O | |
results O | |
in O | |
neonatal O | |
HSV O | |
disease O | |
, O | |
a O | |
rare O | |
but O | |
significant O | |
infection O | |
that O | |
can O | |
be O | |
associated O | |
with O | |
severe O | |
morbidity O | |
and O | |
mortality O | |
, O | |
especially O | |
if O | |
there O | |
is O | |
dissemination O | |
or O | |
central O | |
nervous O | |
system O | |
involvement O | |
. O | |
Diagnostic O | |
and O | |
therapeutic O | |
advances O | |
have O | |
led O | |
to O | |
improvements O | |
in O | |
mortality O | |
and O | |
, O | |
to O | |
a O | |
lesser O | |
extent O | |
, O | |
neurodevelopmental O | |
outcomes O | |
, O | |
but O | |
room O | |
exists O | |
for O | |
further O | |
improvement O | |
. O | |
Q O | |
fever O | |
is O | |
a O | |
zoonotic O | |
disease O | |
caused O | |
by O | |
Coxiella O | |
burnetii O | |
which O | |
has O | |
a O | |
worldwide B-LOC | |
distribution O | |
. O | |
Pneumonia O | |
occurs B-EPI | |
in O | |
almost O | |
half O | |
of O | |
the O | |
patients O | |
who O | |
have O | |
an O | |
acute O | |
C. O | |
burnetii O | |
infection O | |
. O | |
Less O | |
than O | |
5 O | |
- O | |
6 O | |
% O | |
of O | |
community O | |
acquired O | |
pneumonia O | |
( O | |
CAP O | |
) O | |
is O | |
found O | |
to O | |
be O | |
caused O | |
by O | |
this O | |
organism O | |
. O | |
Endemicity O | |
of O | |
C. O | |
burnetii O | |
infection O | |
has O | |
been O | |
recorded O | |
in O | |
various O | |
studies O | |
carried O | |
out O | |
in O | |
our O | |
country O | |
. O | |
However O | |
there O | |
is O | |
no O | |
mention O | |
about O | |
Q O | |
fever O | |
as O | |
a O | |
cause O | |
of O | |
CAP O | |
in O | |
the O | |
various O | |
studies O | |
done O | |
to O | |
identify O | |
the O | |
aetiological O | |
agent O | |
. O | |
We O | |
report O | |
a O | |
case O | |
of O | |
acute O | |
Q O | |
fever O | |
related O | |
pneumonia O | |
and O | |
this O | |
appears O | |
to O | |
be O | |
the O | |
first O | |
reported O | |
case O | |
of O | |
pneumonia O | |
due O | |
to O | |
C. O | |
burnetii O | |
infection O | |
in O | |
India B-LOC | |
. O | |
Objective O | |
To O | |
investigate O | |
the O | |
prevalence B-EPI | |
of O | |
mutations O | |
in O | |
domain O | |
V O | |
of O | |
Mycoplasma O | |
pneumoniae O | |
( O | |
MP O | |
) O | |
23S O | |
ribosomal O | |
RNA O | |
( O | |
rRNA O | |
) O | |
and O | |
the O | |
clinical O | |
characteristics O | |
of O | |
pediatric O | |
MP O | |
pneumonia O | |
( O | |
MPP O | |
) O | |
in O | |
Nanjing B-LOC | |
, I-LOC | |
China I-LOC | |
. O | |
Methods O | |
Domain O | |
V O | |
of O | |
23S O | |
rRNA O | |
was O | |
sequenced O | |
in O | |
MP O | |
strains O | |
collected O | |
from O | |
children O | |
diagnosed O | |
with O | |
MPP O | |
in O | |
Nanjing B-LOC | |
. O | |
Clinical O | |
and O | |
laboratory O | |
data O | |
were O | |
obtained O | |
. O | |
Results O | |
Among O | |
the O | |
276 O | |
MP O | |
strains O | |
, O | |
255 O | |
( O | |
92.39 O | |
% O | |
) O | |
harbored O | |
mutations O | |
, O | |
primarily O | |
A2063 O | |
G O | |
in O | |
domain O | |
V O | |
of O | |
MP O | |
23S O | |
rRNA O | |
. O | |
When O | |
children O | |
were O | |
stratified O | |
according O | |
to O | |
the O | |
presence O | |
or O | |
absence O | |
of O | |
mutations O | |
, O | |
no O | |
significant O | |
differences O | |
were O | |
found O | |
in O | |
sex O | |
, O | |
age O | |
, O | |
the O | |
MP O | |
DNA O | |
load O | |
at O | |
enrollment O | |
, O | |
lymphocyte O | |
counts O | |
, O | |
pulmonary O | |
complications O | |
, O | |
immunomodulator O | |
levels O | |
, O | |
fever O | |
duration O | |
, O | |
the O | |
duration O | |
of O | |
fever O | |
after O | |
macrolide O | |
therapy O | |
, O | |
and O | |
hospital O | |
stay O | |
. O | |
The O | |
prevalence B-EPI | |
of O | |
refractory O | |
MPP O | |
in O | |
the O | |
two O | |
groups O | |
was O | |
similar O | |
. O | |
Children O | |
with O | |
refractory O | |
MPP O | |
exhibited O | |
higher O | |
MP O | |
DNA O | |
loads O | |
than O | |
those O | |
with O | |
non O | |
- O | |
refractory O | |
MPP O | |
. O | |
Conclusions O | |
Despite O | |
the O | |
high O | |
prevalence B-EPI | |
of O | |
the O | |
A2063 O | |
G O | |
mutation O | |
in O | |
domain O | |
V O | |
of O | |
MP O | |
23S O | |
rRNA O | |
, O | |
mutations O | |
were O | |
not O | |
associated O | |
with O | |
the O | |
clinical O | |
characteristics O | |
of O | |
MPP O | |
. O | |
The O | |
MP O | |
DNA O | |
load O | |
significantly O | |
differed O | |
between O | |
refractory O | |
and O | |
non O | |
- O | |
refractory O | |
MPP O | |
. O | |
The O | |
MBTPS2 O | |
gene O | |
on O | |
the O | |
X O | |
- O | |
chromosome O | |
encodes O | |
the O | |
membrane O | |
- O | |
bound O | |
transcription O | |
factor O | |
protease O | |
, O | |
site-2 O | |
( O | |
MBTPS2 O | |
) O | |
or O | |
site-2 O | |
protease O | |
( O | |
S2P O | |
) O | |
which O | |
cleaves O | |
and O | |
activates O | |
several O | |
signaling O | |
and O | |
regulatory O | |
proteins O | |
from O | |
the O | |
membrane O | |
. O | |
The O | |
MBTPS2 O | |
is O | |
critical O | |
for O | |
a O | |
myriad O | |
of O | |
cellular O | |
processes O | |
, O | |
ranging O | |
from O | |
the O | |
regulation O | |
of O | |
cholesterol O | |
homeostasis O | |
to O | |
unfolded O | |
protein O | |
responses O | |
. O | |
While O | |
its O | |
functional O | |
role O | |
has O | |
become O | |
much O | |
clearer O | |
in O | |
the O | |
recent O | |
years O | |
, O | |
how O | |
mutations O | |
in O | |
the O | |
MBTPS2 O | |
gene O | |
lead O | |
to O | |
several O | |
human O | |
disorders O | |
with O | |
different O | |
phenotypes O | |
including O | |
Ichthyosis O | |
Follicularis O | |
, O | |
Atrichia O | |
and O | |
Photophobia O | |
syndrome O | |
( O | |
IFAP O | |
) O | |
with O | |
or O | |
without O | |
BRESHECK O | |
syndrome O | |
, O | |
Keratosis O | |
Follicularis O | |
Spinulosa O | |
Decalvans O | |
( O | |
KFSD O | |
) O | |
, O | |
Olmsted O | |
syndrome O | |
, O | |
and O | |
Osteogenesis O | |
Imperfecta O | |
type O | |
XIX O | |
remains O | |
obscure O | |
. O | |
This O | |
review O | |
presents O | |
the O | |
biological O | |
role O | |
of O | |
MBTPS2 O | |
in O | |
development O | |
, O | |
summarizes O | |
its O | |
mutations O | |
and O | |
implicated O | |
disorders O | |
, O | |
and O | |
discusses O | |
outstanding O | |
unanswered O | |
questions O | |
. O | |
Group O | |
B O | |
Streptococcus O | |
, O | |
a O | |
common O | |
commensal O | |
in O | |
the O | |
gut O | |
of O | |
humans O | |
and O | |
in O | |
the O | |
lower O | |
genital O | |
tract O | |
in O | |
women B-SEX | |
, O | |
remains O | |
an O | |
important O | |
cause O | |
of O | |
neonatal O | |
mortality O | |
and O | |
morbidity O | |
. O | |
The O | |
incidence B-EPI | |
of O | |
early O | |
onset O | |
disease O | |
has O | |
fallen O | |
markedly O | |
in O | |
countries O | |
that O | |
test O | |
women B-SEX | |
for O | |
carriage O | |
at O | |
35 O | |
- O | |
37 O | |
weeks O | |
of O | |
pregnancy O | |
and O | |
then O | |
offer O | |
intrapartum O | |
prophylaxis O | |
with O | |
penicillin O | |
during O | |
labour O | |
. O | |
Countries O | |
that O | |
do O | |
not O | |
test O | |
, O | |
but O | |
instead O | |
employ O | |
a O | |
risk O | |
factor O | |
approach O | |
, O | |
have O | |
not O | |
seen O | |
a O | |
similar O | |
fall O | |
. O | |
There O | |
are O | |
concerns O | |
about O | |
the O | |
effect O | |
on O | |
the O | |
neonatal O | |
microbiome O | |
of O | |
widespread O | |
use O | |
of O | |
antibiotic O | |
prophylaxis O | |
during O | |
labour O | |
, O | |
but O | |
so O | |
far O | |
the O | |
effects O | |
seem O | |
minor O | |
and O | |
temporary O | |
. O | |
Vaccination O | |
against O | |
GBS O | |
would O | |
be O | |
acceptable O | |
to O | |
most O | |
women B-SEX | |
and O | |
GBS O | |
vaccines O | |
are O | |
in O | |
the O | |
early O | |
stages O | |
of O | |
development O | |
. O | |
Tweetable O | |
abstract O | |
: O | |
Group O | |
B O | |
Strep O | |
is O | |
a O | |
key O | |
cause O | |
of O | |
infection O | |
, O | |
death O | |
and O | |
disability O | |
in O | |
young O | |
babies O | |
. O | |
Antibiotics O | |
given O | |
in O | |
labour O | |
remain O | |
the O | |
mainstay O | |
of O | |
prevention O | |
, O | |
until O | |
a O | |
vaccine O | |
is O | |
available O | |
. O | |
BACKGROUND O | |
: O | |
Adrenocortical O | |
carcinoma O | |
( O | |
ACC O | |
) O | |
is O | |
a O | |
rare O | |
endocrine O | |
malignancy O | |
, O | |
often O | |
with O | |
an O | |
unfavorable O | |
prognosis O | |
. O | |
Radical O | |
adrenalectomy O | |
is O | |
the O | |
gold O | |
standard O | |
of O | |
treatment O | |
of O | |
localized O | |
disease O | |
. O | |
CASE O | |
DESCRIPTION O | |
: O | |
We O | |
report O | |
a O | |
case O | |
of O | |
a O | |
23 O | |
- O | |
year O | |
- O | |
old O | |
male B-SEX | |
patient O | |
who O | |
presented O | |
with O | |
persistent O | |
left O | |
flank O | |
pain O | |
and O | |
urticaria O | |
for O | |
3 O | |
months O | |
. O | |
Imaging O | |
studies O | |
confirmed O | |
the O | |
presence O | |
of O | |
a O | |
large O | |
left O | |
adrenal O | |
mass O | |
with O | |
malignant O | |
features O | |
. O | |
The O | |
biochemical O | |
workup O | |
was O | |
unremarkable O | |
. O | |
Open O | |
left O | |
radical O | |
adrenalectomy O | |
was O | |
performed O | |
, O | |
the O | |
final O | |
pathologic O | |
examination O | |
showed O | |
ACC O | |
with O | |
negative O | |
surgical O | |
margins O | |
. O | |
The O | |
patient O | |
remained O | |
disease O | |
- O | |
free O | |
for O | |
eighteen O | |
months O | |
period O | |
of O | |
follow O | |
up O | |
after O | |
surgery O | |
. O | |
DISCUSSION O | |
: O | |
ACC O | |
is O | |
a O | |
rare O | |
neoplasm O | |
with O | |
poor O | |
prognosis O | |
and O | |
with O | |
an O | |
incidence B-EPI | |
of O | |
one B-STAT | |
in I-STAT | |
one I-STAT | |
million I-STAT | |
population I-STAT | |
. O | |
There O | |
is O | |
a O | |
slight O | |
female B-SEX | |
predilection O | |
. O | |
The O | |
ACC O | |
may O | |
be O | |
functional O | |
with O | |
a O | |
clinically O | |
pure O | |
endocrine O | |
syndrome O | |
like O | |
Cushing O | |
syndrome O | |
. O | |
Most O | |
of O | |
patients O | |
with O | |
ACC O | |
present O | |
with O | |
symptoms O | |
and O | |
signs O | |
of O | |
hormonal O | |
secretion O | |
. O | |
Adrenal O | |
computed O | |
tomography O | |
( O | |
CT O | |
) O | |
scanning O | |
and O | |
magnetic O | |
resonance O | |
imaging O | |
( O | |
MRI O | |
) O | |
are O | |
the O | |
imaging O | |
studies O | |
of O | |
choice O | |
in O | |
ACC O | |
. O | |
When O | |
feasible O | |
, O | |
total O | |
resection O | |
remains O | |
the O | |
treatment O | |
of O | |
choice O | |
for O | |
the O | |
definitive O | |
treatment O | |
of O | |
ACC O | |
. O | |
The O | |
benefit O | |
of O | |
the O | |
use O | |
of O | |
mitotane O | |
as O | |
an O | |
adjuvant O | |
treatment O | |
has O | |
been O | |
considered O | |
controversial O | |
. O | |
Adjuvant O | |
mitotane O | |
significantly O | |
decreases O | |
the O | |
recurrence O | |
and O | |
mortality O | |
rate O | |
after O | |
resection O | |
of O | |
ACC O | |
in O | |
patients O | |
without O | |
distant O | |
metastasis O | |
as O | |
proved O | |
by O | |
some O | |
studies O | |
, O | |
but O | |
these O | |
findings O | |
need O | |
further O | |
validation O | |
. O | |
CONCLUSION O | |
: O | |
ACC O | |
is O | |
a O | |
rare O | |
neoplasm O | |
characterized O | |
by O | |
a O | |
high O | |
risk O | |
of O | |
recurrence O | |
after O | |
surgical O | |
resection O | |
. O | |
The O | |
high O | |
prevalence B-EPI | |
of O | |
hearing O | |
loss O | |
among O | |
older O | |
adults O | |
creates O | |
a O | |
perception O | |
that O | |
it O | |
is O | |
simply O | |
a O | |
benign O | |
consequence O | |
of O | |
aging O | |
, O | |
which O | |
leads O | |
to O | |
unaddressed O | |
communication O | |
needs O | |
. O | |
Strategies O | |
to O | |
address O | |
hearing O | |
loss O | |
as O | |
part O | |
of O | |
routine O | |
clinical O | |
care O | |
are O | |
pertinent O | |
to O | |
the O | |
geriatric O | |
care O | |
setting O | |
where O | |
hearing O | |
loss O | |
is O | |
prevalent B-EPI | |
in O | |
two B-STAT | |
out I-STAT | |
of O | |
every I-STAT | |
three I-STAT | |
patients O | |
70 O | |
years O | |
and O | |
older O | |
. O | |
Our O | |
objectives O | |
are O | |
to O | |
briefly O | |
discuss O | |
the O | |
pathophysiology O | |
of O | |
hearing O | |
loss O | |
, O | |
describe O | |
the O | |
epidemiologic O | |
prevalence B-EPI | |
and O | |
impact O | |
, O | |
identify O | |
statutory O | |
barriers O | |
facing O | |
older O | |
adults O | |
in O | |
accessing O | |
hearing O | |
care O | |
, O | |
discuss O | |
current O | |
progress O | |
on O | |
legislation O | |
to O | |
address O | |
accessibility O | |
issues O | |
, O | |
and O | |
provide O | |
actionable O | |
strategies O | |
for O | |
addressing O | |
hearing O | |
loss O | |
as O | |
a O | |
barrier O | |
to O | |
effective O | |
communication O | |
. O | |
Simple O | |
steps O | |
can O | |
be O | |
taken O | |
to O | |
improve O | |
hearing O | |
care O | |
accessibility O | |
for O | |
older O | |
adults O | |
with O | |
hearing O | |
loss O | |
and O | |
can O | |
optimize O | |
understanding O | |
in O | |
daily O | |
communication O | |
, O | |
re O | |
- O | |
engage O | |
patients O | |
in O | |
being O | |
actively O | |
involved O | |
in O | |
their O | |
care O | |
, O | |
and O | |
promote O | |
patient O | |
autonomy O | |
in O | |
informed O | |
decision- O | |
making O | |
. O | |
In O | |
recent O | |
years O | |
the O | |
number O | |
of O | |
disorders O | |
known O | |
to O | |
affect O | |
amino O | |
acid O | |
synthesis O | |
has O | |
grown O | |
rapidly O | |
. O | |
Nor O | |
is O | |
it O | |
just O | |
the O | |
number O | |
of O | |
disorders O | |
that O | |
has O | |
increased O | |
: O | |
the O | |
associated O | |
clinical O | |
phenotypes O | |
have O | |
also O | |
expanded O | |
spectacularly O | |
, O | |
primarily O | |
due O | |
to O | |
the O | |
advances O | |
of O | |
next O | |
generation O | |
sequencing O | |
diagnostics O | |
. O | |
In O | |
contrast O | |
to O | |
the O | |
classical O | |
inborn O | |
errors O | |
of O | |
metabolism O | |
in O | |
catabolic O | |
pathways O | |
, O | |
in O | |
which O | |
elevated O | |
levels O | |
of O | |
metabolites O | |
are O | |
easily O | |
detected O | |
in O | |
body O | |
fluids O | |
, O | |
synthesis O | |
defects O | |
present O | |
with O | |
low O | |
values O | |
of O | |
metabolites O | |
or O | |
, O | |
confusingly O | |
, O | |
even O | |
completely O | |
normal O | |
levels O | |
of O | |
amino O | |
acids O | |
. O | |
This O | |
makes O | |
the O | |
biochemical O | |
diagnosis O | |
of O | |
this O | |
relatively O | |
new O | |
group O | |
of O | |
metabolic O | |
diseases O | |
challenging O | |
. O | |
Defects O | |
in O | |
the O | |
synthesis O | |
pathways O | |
of O | |
serine O | |
metabolism O | |
, O | |
glutamine O | |
, O | |
proline O | |
and O | |
, O | |
recently O | |
, O | |
asparagine O | |
have O | |
all O | |
been O | |
reported O | |
. O | |
Although O | |
these O | |
amino O | |
acid O | |
synthesis O | |
defects O | |
are O | |
in O | |
unrelated O | |
metabolic O | |
pathways O | |
, O | |
they O | |
do O | |
share O | |
many O | |
clinical O | |
features O | |
. O | |
In O | |
children O | |
the O | |
central O | |
nervous O | |
system O | |
is O | |
primarily O | |
affected O | |
, O | |
giving O | |
rise O | |
to O | |
( O | |
congenital O | |
) O | |
microcephaly O | |
, O | |
early O | |
onset O | |
seizures O | |
and O | |
varying O | |
degrees O | |
of O | |
mental O | |
disability O | |
. O | |
The O | |
brain O | |
abnormalities O | |
are O | |
accompanied O | |
by O | |
skin O | |
disorders O | |
such O | |
as O | |
cutis O | |
laxa O | |
in O | |
defects O | |
of O | |
proline O | |
synthesis O | |
, O | |
collodion O | |
- O | |
like O | |
skin O | |
and O | |
ichthyosis O | |
in O | |
serine O | |
deficiency O | |
, O | |
and O | |
necrolytic O | |
erythema O | |
in O | |
glutamine O | |
deficiency O | |
. O | |
Hypomyelination O | |
with O | |
accompanying O | |
loss O | |
of O | |
brain O | |
volume O | |
and O | |
gyration O | |
defects O | |
can O | |
be O | |
observed O | |
on O | |
brain O | |
MRI O | |
in O | |
all O | |
synthesis O | |
disorders O | |
. O | |
In O | |
adults O | |
with O | |
defects O | |
in O | |
serine O | |
or O | |
proline O | |
synthesis O | |
, O | |
spastic O | |
paraplegia O | |
and O | |
several O | |
forms O | |
of O | |
polyneuropathy O | |
with O | |
or O | |
without O | |
intellectual O | |
disability O | |
appear O | |
to O | |
be O | |
the O | |
major O | |
symptoms O | |
in O | |
these O | |
late O | |
- O | |
presenting O | |
forms O | |
of O | |
amino O | |
acid O | |
disorders O | |
. O | |
This O | |
review O | |
provides O | |
a O | |
comprehensive O | |
overview O | |
of O | |
the O | |
disorders O | |
in O | |
amino O | |
acid O | |
synthesis O | |
. O | |
Congenital O | |
lung O | |
agenesis O | |
is O | |
an O | |
extremely O | |
rare O | |
condition O | |
with O | |
an O | |
estimated B-EPI | |
prevalence I-EPI | |
of O | |
34 B-STAT | |
in I-STAT | |
1,000,000 I-STAT | |
live I-STAT | |
births I-STAT | |
. O | |
It O | |
is O | |
often O | |
associated O | |
with O | |
other O | |
congenital O | |
malformations O | |
of O | |
the O | |
skeletal O | |
, O | |
cardiovascular O | |
, O | |
urogenital O | |
, O | |
and O | |
gastrointestinal O | |
systems O | |
. O | |
We O | |
discuss O | |
the O | |
case O | |
of O | |
a O | |
5 O | |
- O | |
month O | |
- O | |
old O | |
who O | |
presented O | |
with O | |
increasing O | |
stridor O | |
over O | |
1 O | |
month O | |
. O | |
Imaging O | |
revealed O | |
right O | |
lung O | |
agenesis O | |
, O | |
complete O | |
dextromalposition O | |
of O | |
heart O | |
, O | |
and O | |
compression O | |
of O | |
distal O | |
trachea O | |
. O | |
An O | |
intrathoracic O | |
saline O | |
tissue O | |
expander O | |
was O | |
placed O | |
which O | |
marked O | |
improved O | |
distal O | |
tracheal O | |
stenosis O | |
. O | |
In O | |
patients O | |
who O | |
are O | |
symptomatic O | |
it O | |
becomes O | |
imperative O | |
to O | |
perform O | |
surgeries O | |
to O | |
increase O | |
survival O | |
as O | |
was O | |
the O | |
case O | |
in O | |
this O | |
patient O | |
. O | |
Childhood O | |
wasting O | |
is O | |
among O | |
the O | |
most O | |
prevalent B-EPI | |
forms O | |
of O | |
undernutrition O | |
globally B-LOC | |
. O | |
The O | |
Southeast B-LOC | |
Asia I-LOC | |
region O | |
is O | |
home O | |
to O | |
many O | |
wasted O | |
children O | |
, O | |
but O | |
wasting O | |
is O | |
not O | |
recognized O | |
as O | |
a O | |
public O | |
health O | |
problem O | |
and O | |
its O | |
epidemiology O | |
is O | |
yet O | |
to O | |
be O | |
fully O | |
examined O | |
. O | |
This O | |
analysis O | |
aimed O | |
to O | |
determine O | |
the O | |
burden O | |
of O | |
wasting O | |
, O | |
its O | |
predictors O | |
, O | |
and O | |
the O | |
level O | |
of O | |
wasting O | |
and O | |
stunting O | |
concurrence O | |
. O | |
Datasets O | |
from O | |
Demographic O | |
and O | |
Health O | |
Surveys O | |
and O | |
Multiple O | |
Indicator O | |
Cluster O | |
Surveys O | |
in O | |
six O | |
countries O | |
in O | |
the O | |
region O | |
were O | |
analyzed O | |
. O | |
The O | |
pooled O | |
weighted O | |
prevalence I-EPI | |
for O | |
wasting O | |
and O | |
concurrent O | |
wasting O | |
and O | |
stunting O | |
among O | |
children O | |
0 O | |
- O | |
59 O | |
months O | |
in O | |
the O | |
six O | |
countries O | |
was O | |
8.9 O | |
% O | |
, O | |
95 O | |
% O | |
CI O | |
( O | |
8.0 O | |
- O | |
9.9 O | |
) O | |
and O | |
1.6 O | |
% O | |
, O | |
95 O | |
% O | |
CI O | |
( O | |
1.5 O | |
- O | |
1.8 O | |
) O | |
, O | |
respectively O | |
. O | |
This O | |
prevalence B-EPI | |
is O | |
approximately O | |
12 O | |
- O | |
fold O | |
higher O | |
than O | |
the O | |
0.7 B-STAT | |
% I-STAT | |
prevalence B-EPI | |
of O | |
high O | |
- O | |
income O | |
countries O | |
; O | |
and O | |
translated O | |
into O | |
an O | |
absolute O | |
number O | |
of O | |
1,088,747 O | |
children O | |
affected O | |
by O | |
wasting O | |
and O | |
272,563 O | |
concurrent O | |
wasting O | |
and O | |
stunting O | |
. O | |
Wasting O | |
prevalence B-EPI | |
was O | |
50 O | |
percent O | |
higher O | |
in O | |
the O | |
0 O | |
- O | |
23 O | |
- O | |
month O | |
age O | |
group O | |
. O | |
Predictors O | |
for O | |
wasting O | |
included O | |
source O | |
of O | |
drinking O | |
water O | |
, O | |
wealth O | |
index O | |
, O | |
urban O | |
residence O | |
, O | |
child O | |
's O | |
age O | |
and O | |
history O | |
of O | |
illness O | |
and O | |
mother O | |
's O | |
body O | |
mass O | |
index O | |
. O | |
In O | |
conclusion O | |
, O | |
our O | |
analysis O | |
showed O | |
that O | |
wasting O | |
is O | |
a O | |
serious O | |
public O | |
health O | |
problem O | |
in O | |
the O | |
region O | |
that O | |
should O | |
be O | |
addressed O | |
urgently O | |
using O | |
both O | |
preventive O | |
and O | |
curative O | |
approaches O | |
. O | |
Q O | |
fever O | |
is O | |
a O | |
disease O | |
of O | |
high O | |
zoonotic O | |
potential O | |
, O | |
but O | |
interest O | |
in O | |
its O | |
causative O | |
agent O | |
is O | |
rather O | |
low O | |
although O | |
it O | |
causes O | |
some O | |
public O | |
health O | |
problems O | |
in O | |
Hungary B-LOC | |
. O | |
The O | |
prevalence B-EPI | |
of O | |
Q O | |
fever O | |
is O | |
highly O | |
variable O | |
by O | |
country O | |
. O | |
The O | |
main O | |
reservoirs O | |
of O | |
the O | |
disease O | |
are O | |
the O | |
same O | |
domestic O | |
ruminant O | |
species O | |
everywhere O | |
, O | |
but O | |
the O | |
epidemiological O | |
profile O | |
depends O | |
on O | |
the O | |
features O | |
of O | |
the O | |
specific O | |
reservoir O | |
. O | |
The O | |
aim O | |
of O | |
this O | |
large O | |
- O | |
scale O | |
study O | |
was O | |
to O | |
demonstrate O | |
the O | |
importance O | |
of O | |
Q O | |
fever O | |
in O | |
different O | |
species O | |
as O | |
a O | |
possible O | |
source O | |
for O | |
human O | |
infection O | |
in O | |
most O | |
regions O | |
of O | |
Hungary B-LOC | |
. O | |
A O | |
total O | |
of O | |
851 O | |
serum O | |
samples O | |
from O | |
44 O | |
dairy O | |
farms O | |
, O | |
16 O | |
sheep O | |
flocks O | |
, O | |
4 O | |
goat O | |
farms O | |
and O | |
3 O | |
zoos O | |
located O | |
in O | |
different O | |
parts O | |
of O | |
Hungary B-LOC | |
were O | |
tested O | |
. O | |
The O | |
presence O | |
of O | |
antibodies O | |
to O | |
Coxiella O | |
burnetii O | |
was O | |
surveyed O | |
in O | |
dairy O | |
cattle O | |
( O | |
n O | |
= O | |
547 O | |
) O | |
, O | |
goats O | |
( O | |
n O | |
= O | |
71 O | |
) O | |
, O | |
sheep O | |
( O | |
n O | |
= O | |
200 O | |
) O | |
and O | |
zoo O | |
animals O | |
( O | |
n O | |
= O | |
33 O | |
) O | |
. O | |
The O | |
animal O | |
species O | |
tested O | |
in O | |
Hungary B-LOC | |
showed O | |
different O | |
seroprevalence O | |
values O | |
of O | |
C. O | |
burnetii O | |
infection O | |
. O | |
Seropositivity O | |
by O | |
the O | |
enzyme O | |
- O | |
linked O | |
immunosorbent O | |
assay O | |
was O | |
found O | |
in O | |
258 O | |
out O | |
of O | |
547 O | |
( O | |
47.2 O | |
% O | |
) O | |
cows O | |
and O | |
in O | |
69 O | |
out O | |
of O | |
271 O | |
( O | |
25.5 O | |
% O | |
) O | |
small O | |
ruminants O | |
, O | |
among O | |
them O | |
in O | |
47 O | |
out O | |
of O | |
200 O | |
( O | |
23.5 O | |
% O | |
) O | |
sheep O | |
and O | |
in O | |
22 O | |
out O | |
of O | |
71 O | |
( O | |
31.0 O | |
% O | |
) O | |
goats O | |
. O | |
Antibodies O | |
to O | |
C. O | |
burnetii O | |
were O | |
not O | |
detected O | |
in O | |
zoo O | |
animals O | |
. O | |
Seropositivity O | |
was O | |
demonstrated O | |
in O | |
44 O | |
out O | |
of O | |
44 O | |
( O | |
100 O | |
% O | |
) O | |
dairy O | |
cattle O | |
farms O | |
, O | |
with O | |
at O | |
least O | |
one O | |
serum O | |
sample O | |
found O | |
to O | |
be O | |
positive O | |
on O | |
each O | |
farm O | |
. O | |
The O | |
seropositivity O | |
rate O | |
of O | |
small O | |
ruminant O | |
farms O | |
was O | |
55.0 O | |
% O | |
( O | |
11 O | |
positive O | |
out O | |
of O | |
20 O | |
tested O | |
) O | |
, O | |
with O | |
9 O | |
out O | |
of O | |
16 O | |
( O | |
56.3 O | |
% O | |
) O | |
sheep O | |
flocks O | |
and O | |
2 O | |
out O | |
of O | |
4 O | |
( O | |
50.0 O | |
% O | |
) O | |
goat O | |
herds O | |
showing O | |
seropositivity O | |
. O | |
Microcephaly O | |
is O | |
a O | |
prevalent B-EPI | |
phenotype O | |
in O | |
patients O | |
with O | |
neurodevelopmental O | |
problems O | |
, O | |
often O | |
with O | |
genetic O | |
causes O | |
. O | |
We O | |
comprehensively O | |
investigated O | |
the O | |
clinical O | |
phenotypes O | |
and O | |
genetic O | |
background O | |
of O | |
microcephaly O | |
in O | |
40 O | |
Korean B-ETHN | |
patients O | |
. O | |
We O | |
analyzed O | |
their O | |
clinical O | |
phenotypes O | |
and O | |
radiologic O | |
images O | |
and O | |
conducted O | |
whole O | |
exome O | |
sequencing O | |
( O | |
WES O | |
) O | |
and O | |
analysis O | |
of O | |
copy O | |
number O | |
variation O | |
( O | |
CNV O | |
) O | |
. O | |
Infantile O | |
hypotonia O | |
and O | |
developmental O | |
delay O | |
were O | |
present O | |
in O | |
all O | |
patients O | |
. O | |
Thirty O | |
- O | |
four O | |
patients O | |
( O | |
85 O | |
% O | |
) O | |
showed O | |
primary O | |
microcephaly O | |
. O | |
The O | |
diagnostic O | |
yield O | |
from O | |
the O | |
WES O | |
and O | |
CNV O | |
analyses O | |
was O | |
47.5 O | |
% O | |
. O | |
With O | |
WES O | |
, O | |
we O | |
detected O | |
pathogenic O | |
or O | |
likely O | |
pathogenic O | |
variants O | |
that O | |
were O | |
previously O | |
associated O | |
with O | |
microcephaly O | |
in O | |
12 O | |
patients O | |
( O | |
30 O | |
% O | |
) O | |
; O | |
nine O | |
of O | |
these O | |
were O | |
de O | |
novo O | |
variants O | |
with O | |
autosomal O | |
dominant O | |
inheritance O | |
. O | |
Two O | |
unrelated O | |
patients O | |
had O | |
mutations O | |
in O | |
the O | |
KMT2A O | |
gene O | |
. O | |
In O | |
10 O | |
other O | |
patients O | |
, O | |
we O | |
found O | |
mutations O | |
in O | |
the O | |
GNB1 O | |
, O | |
GNAO1 O | |
, O | |
TCF4 O | |
, O | |
ASXL1 O | |
, O | |
SMC1A O | |
, O | |
VPS13B O | |
, O | |
ACTG1 O | |
, O | |
EP300 O | |
, O | |
and O | |
KMT2D O | |
genes O | |
. O | |
Seven O | |
patients O | |
( O | |
17.5 O | |
% O | |
) O | |
were O | |
diagnosed O | |
with O | |
pathogenic O | |
CNVs O | |
. O | |
Korean B-ETHN | |
patients O | |
with O | |
microcephaly O | |
show O | |
a O | |
genetic O | |
spectrum O | |
that O | |
is O | |
different O | |
from O | |
that O | |
of O | |
patients O | |
with O | |
microcephaly O | |
of O | |
other O | |
ethnicities O | |
. O | |
WES O | |
along O | |
with O | |
CNV O | |
analysis O | |
represents O | |
an O | |
effective O | |
approach O | |
for O | |
diagnosis O | |
of O | |
the O | |
underlying O | |
causes O | |
of O | |
microcephaly O | |
. O | |
Renal O | |
and O | |
hepatic O | |
functions O | |
are O | |
often O | |
mingled O | |
through O | |
both O | |
the O | |
existence O | |
of O | |
associated O | |
primary O | |
organ O | |
diseases O | |
and O | |
hemodynamic O | |
co O | |
- O | |
relationship O | |
. O | |
The O | |
primary O | |
objective O | |
of O | |
this O | |
study O | |
was O | |
to O | |
sum O | |
up O | |
the O | |
relationship O | |
between O | |
autoimmune O | |
hepatitis O | |
( O | |
AIH O | |
) O | |
on O | |
renal O | |
tubular O | |
acidosis O | |
( O | |
RTA O | |
) O | |
and O | |
the O | |
stages O | |
of O | |
the O | |
disease O | |
. O | |
A O | |
systematic O | |
review O | |
was O | |
performed O | |
for O | |
24 O | |
trials O | |
. O | |
A O | |
total O | |
of O | |
3687 O | |
patients O | |
were O | |
included O | |
. O | |
The O | |
incidence B-EPI | |
of O | |
RTA O | |
occurring O | |
and O | |
short O | |
- O | |
term O | |
mortality O | |
reduction O | |
was O | |
seen O | |
in O | |
two O | |
groups O | |
; O | |
for O | |
an O | |
overall O | |
effect O | |
: O | |
Z O | |
= O | |
2.85 O | |
( O | |
P O | |
= O | |
0.004 O | |
) O | |
a O | |
total O | |
95 O | |
% O | |
CI O | |
of O | |
0.53 O | |
[ O | |
0.34 O | |
, O | |
0.82 O | |
] O | |
. O | |
Only O | |
one O | |
patient O | |
with O | |
alcoholic O | |
liver O | |
cirrhosis O | |
was O | |
found O | |
to O | |
have O | |
an O | |
incomplete O | |
type O | |
of O | |
RTA O | |
. O | |
Test O | |
for O | |
overall O | |
effect O | |
: O | |
Z O | |
= O | |
2.28 O | |
( O | |
P O | |
= O | |
0.02 O | |
) O | |
95 O | |
% O | |
CI O | |
of O | |
2.83 O | |
[ O | |
1.16 O | |
, O | |
6.95 O | |
] O | |
. O | |
A O | |
reduction O | |
in O | |
fatal O | |
infections O | |
with O | |
dual O | |
therapy O | |
of O | |
corticosteroid O | |
plus O | |
N O | |
- O | |
acetylcysteine O | |
( O | |
NAC O | |
) O | |
test O | |
for O | |
overall O | |
effect O | |
: O | |
Z O | |
= O | |
3.07 O | |
( O | |
P O | |
= O | |
0.002 O | |
) O | |
with O | |
95 O | |
% O | |
CI O | |
of O | |
0.45 O | |
[ O | |
0.27 O | |
, O | |
0.75 O | |
] O | |
. O | |
Autoimmune O | |
diseases O | |
are O | |
the O | |
most O | |
frequent O | |
underlying O | |
cause O | |
of O | |
secondary O | |
RTA O | |
in O | |
adults O | |
. O | |
The O | |
primary O | |
renal O | |
disease O | |
must O | |
be O | |
actively O | |
excluded O | |
in O | |
all O | |
patients O | |
with O | |
hepatic O | |
failure O | |
by O | |
aggressive O | |
clinical O | |
and O | |
laboratory O | |
evaluations O | |
. O | |
Rhabdomyosarcoma O | |
( O | |
RMS O | |
) O | |
is O | |
the O | |
most O | |
common O | |
soft O | |
- O | |
tissue O | |
sarcoma O | |
in O | |
children O | |
, O | |
yet O | |
little O | |
is O | |
known O | |
about O | |
its O | |
etiology O | |
. O | |
Studies O | |
that O | |
examine O | |
either O | |
environmental O | |
exposures O | |
or O | |
germline O | |
genetic O | |
predisposition O | |
in O | |
RMS O | |
have O | |
begun O | |
to O | |
identify O | |
factors O | |
that O | |
contribute O | |
to O | |
this O | |
malignancy O | |
. O | |
Here O | |
, O | |
we O | |
summarize O | |
epidemiological O | |
reports O | |
of O | |
RMS O | |
incidence B-EPI | |
in O | |
terms O | |
of O | |
several O | |
factors O | |
, O | |
including O | |
age O | |
at O | |
diagnosis O | |
, O | |
biological O | |
sex O | |
, O | |
and O | |
geographic O | |
location O | |
. O | |
We O | |
then O | |
describe O | |
findings O | |
from O | |
association O | |
studies O | |
, O | |
which O | |
explore O | |
the O | |
role O | |
of O | |
parental O | |
exposures O | |
, O | |
birth O | |
and O | |
perinatal O | |
characteristics O | |
, O | |
and O | |
childhood O | |
exposures O | |
in O | |
RMS O | |
. O | |
Further O | |
, O | |
we O | |
discuss O | |
RMS O | |
predisposition O | |
syndromes O | |
and O | |
large O | |
- O | |
scale O | |
sequencing O | |
studies O | |
that O | |
have O | |
further O | |
identified O | |
RMS O | |
- O | |
associated O | |
genes O | |
. O | |
Finally O | |
, O | |
we O | |
propose O | |
future O | |
directions O | |
of O | |
study O | |
, O | |
which O | |
aim O | |
to O | |
advance O | |
our O | |
understanding O | |
of O | |
the O | |
origin O | |
of O | |
RMS O | |
and O | |
can O | |
provide O | |
knowledge O | |
for O | |
novel O | |
RMS O | |
therapies O | |
. O | |
Objective O | |
: O | |
To O | |
analyze O | |
the O | |
prevalence B-EPI | |
and O | |
the O | |
related O | |
factors O | |
of O | |
dyslipidemia O | |
in O | |
21 O | |
- O | |
hydroxylase O | |
deficiency O | |
( O | |
21 O | |
- O | |
OHD O | |
) O | |
patients O | |
. O | |
Methods O | |
: O | |
A O | |
total O | |
of O | |
205 O | |
patients O | |
with O | |
21 O | |
- O | |
OHD O | |
were O | |
recruited O | |
in O | |
Peking B-LOC | |
Union I-LOC | |
Medical I-LOC | |
College I-LOC | |
Hospital O | |
from O | |
January B-DATE | |
2016 I-DATE | |
to I-DATE | |
January I-DATE | |
2018 I-DATE | |
. O | |
The O | |
basic O | |
information O | |
, O | |
glucocorticoid O | |
replacement O | |
therapy O | |
, O | |
and O | |
laboratory O | |
examination O | |
results O | |
of O | |
patients O | |
were O | |
obtained O | |
from O | |
medical O | |
records O | |
. O | |
The O | |
genotypes O | |
of O | |
CYP21A2 O | |
were O | |
identified O | |
by O | |
Sanger O | |
sequencing O | |
and O | |
multiplex O | |
ligation O | |
dependent O | |
probe O | |
amplification O | |
. O | |
The O | |
prevalence B-EPI | |
of O | |
dyslipidemia O | |
among O | |
21 O | |
- O | |
OHD O | |
patients O | |
, O | |
basic O | |
information O | |
and O | |
related O | |
hormone O | |
levels O | |
of O | |
21 O | |
- O | |
OHD O | |
patients O | |
with O | |
different O | |
status O | |
of O | |
blood O | |
lipid O | |
were O | |
described O | |
. O | |
Logistic O | |
regression O | |
model O | |
was O | |
used O | |
to O | |
analyze O | |
the O | |
related O | |
factors O | |
of O | |
dyslipidemia O | |
in O | |
21 O | |
- O | |
OHD O | |
patients O | |
. O | |
Results O | |
: O | |
The O | |
age O | |
of O | |
subjects O | |
was O | |
17.0 O | |
( O | |
8.3 O | |
, O | |
25.0 O | |
) O | |
years O | |
old O | |
, O | |
including O | |
51 O | |
males B-SEX | |
( O | |
24.9 O | |
% O | |
) O | |
. O | |
According O | |
to O | |
CYP21A2 O | |
genotypes O | |
, O | |
there O | |
were O | |
16 O | |
cases O | |
in O | |
Null O | |
group O | |
, O | |
26 O | |
cases O | |
in O | |
Group O | |
A O | |
, O | |
105 O | |
cases O | |
in O | |
group O | |
B O | |
, O | |
27 O | |
cases O | |
in O | |
group O | |
C O | |
, O | |
and O | |
31 O | |
cases O | |
in O | |
group O | |
D. O | |
The O | |
incidence B-EPI | |
of O | |
dyslipidemia O | |
was O | |
29.3 O | |
% O | |
( O | |
60/205 O | |
) O | |
, O | |
among O | |
which O | |
37.3 O | |
% O | |
( O | |
19/51 O | |
) O | |
in O | |
male B-SEX | |
and O | |
26.6 O | |
% O | |
( O | |
41/154 O | |
) O | |
in O | |
female B-SEX | |
patients O | |
, O | |
respectively O | |
. O | |
The O | |
M O | |
( O | |
Q O | |
1 O | |
, O | |
Q O | |
3 O | |
) O | |
of O | |
total O | |
cortisol O | |
level O | |
( O | |
nmol O | |
/ O | |
L O | |
) O | |
and O | |
body O | |
mass O | |
index O | |
( O | |
kg O | |
/ O | |
m O | |
2 O | |
) O | |
of O | |
male B-SEX | |
21 O | |
- O | |
OHD O | |
patients O | |
with O | |
dyslipidemia O | |
were O | |
0.17 O | |
( O | |
0.06 O | |
, O | |
0.35 O | |
) O | |
and O | |
25.76 O | |
( O | |
17.01 O | |
, O | |
30.45 O | |
) O | |
, O | |
respectively O | |
, O | |
which O | |
were O | |
higher O | |
than O | |
those O | |
with O | |
ortholiposis O | |
[ O | |
0.04 O | |
( O | |
0.02 O | |
, O | |
0.21 O | |
) O | |
and O | |
18.83 O | |
( O | |
16.53 O | |
, O | |
23.88 O | |
) O | |
] O | |
( O | |
all O | |
P O | |
0.05 O | |
) O | |
. O | |
The O | |
M O | |
( O | |
Q O | |
1 O | |
, O | |
Q O | |
3 O | |
) O | |
of O | |
progesterone O | |
level O | |
( O | |
nmol O | |
/ O | |
L O | |
) O | |
, O | |
body O | |
mass O | |
index O | |
( O | |
kg O | |
/ O | |
m O | |
2 O | |
) O | |
and O | |
age O | |
( O | |
years O | |
) O | |
of O | |
female B-SEX | |
21 O | |
- O | |
OHD O | |
patients O | |
with O | |
dyslipidemia O | |
were O | |
74.40 O | |
( O | |
50.97 O | |
, O | |
98.52 O | |
) O | |
, O | |
23.09 O | |
( O | |
21.78 O | |
, O | |
27.78 O | |
) O | |
and O | |
23.00 O | |
( O | |
16.50 O | |
, O | |
28.00 O | |
) O | |
, O | |
respectively O | |
, O | |
which O | |
were O | |
higher O | |
than O | |
those O | |
with O | |
ortholiposis O | |
[ O | |
52.81 O | |
( O | |
33.41 O | |
, O | |
68.85 O | |
) O | |
, O | |
21.55 O | |
( O | |
18.63 O | |
, O | |
25.71 O | |
) O | |
and O | |
18.00 O | |
( O | |
9.50 O | |
, O | |
25.00 O | |
) O | |
] O | |
( O | |
all O | |
P O | |
0.05 O | |
) O | |
. O | |
The O | |
risk O | |
of O | |
dyslipidemia O | |
increased O | |
by O | |
5.0 O | |
% O | |
[ O | |
OR O | |
( O | |
95 O | |
% O | |
CI O | |
): O | |
1.05 O | |
( O | |
1.01 O | |
, O | |
1.09 O | |
) O | |
] O | |
for O | |
every O | |
1 O | |
nmol O | |
/ O | |
L O | |
increase O | |
of O | |
progesterone O | |
. O | |
Conclusion O | |
: O | |
The O | |
incidence B-EPI | |
of O | |
dyslipidemia O | |
is O | |
high O | |
in O | |
21 O | |
- O | |
OHD O | |
patients O | |
, O | |
and O | |
progesterone O | |
level O | |
is O | |
positively O | |
correlated O | |
with O | |
dyslipidemia O | |
. O | |
Lysosomal O | |
disorders O | |
are O | |
diseases O | |
that O | |
involve O | |
mutations O | |
in O | |
genes O | |
responsible O | |
for O | |
the O | |
coding O | |
of O | |
lysosomal O | |
enzymes O | |
, O | |
transport O | |
proteins O | |
, O | |
activator O | |
proteins O | |
and O | |
protein O | |
processing O | |
enzymes O | |
. O | |
These O | |
defects O | |
lead O | |
to O | |
the O | |
storage O | |
of O | |
specific O | |
metabolites O | |
within O | |
lysosomes O | |
resulting O | |
in O | |
a O | |
great O | |
variety O | |
of O | |
clinical O | |
features O | |
depending O | |
on O | |
the O | |
tissues O | |
with O | |
the O | |
storage O | |
, O | |
the O | |
storage O | |
products O | |
and O | |
the O | |
extent O | |
of O | |
the O | |
storage O | |
. O | |
The O | |
methods O | |
for O | |
rapidly O | |
diagnosing O | |
patients O | |
started O | |
in O | |
the O | |
late O | |
1960 B-DATE | |
's O | |
when O | |
the O | |
enzyme O | |
defects O | |
were O | |
identified O | |
eliminating O | |
the O | |
need O | |
for O | |
tissue O | |
biopsies O | |
. O | |
The O | |
first O | |
requests O | |
for O | |
diagnostic O | |
help O | |
in O | |
this O | |
laboratory O | |
came O | |
in O | |
1973 B-DATE | |
. O | |
In O | |
that O | |
year O | |
, O | |
patients O | |
with O | |
Krabbe O | |
disease O | |
and O | |
Niemann O | |
- O | |
Pick O | |
type O | |
A O | |
were O | |
diagnosed O | |
. O | |
Since O | |
that O | |
time O | |
samples O | |
from O | |
about O | |
62000.0 O | |
individuals O | |
have O | |
been O | |
received O | |
for O | |
diagnostic O | |
studies O | |
, O | |
and O | |
4900 O | |
diagnoses O | |
have O | |
been O | |
made O | |
. O | |
The O | |
largest O | |
number O | |
of O | |
diagnosed O | |
individuals O | |
had O | |
metachromatic O | |
leukodystrophy O | |
and O | |
Krabbe O | |
disease O | |
because O | |
of O | |
our O | |
research O | |
interest O | |
in O | |
leukodystrophies O | |
. O | |
A O | |
number O | |
of O | |
new O | |
disorders O | |
were O | |
identified O | |
and O | |
the O | |
primary O | |
defects O | |
in O | |
other O | |
disorders O | |
were O | |
clarified O | |
. O | |
With O | |
new O | |
methods O | |
for O | |
diagnosis O | |
, O | |
including O | |
newborn O | |
screening O | |
, O | |
molecular O | |
analysis O | |
, O | |
microarrays O | |
, O | |
there O | |
is O | |
still O | |
a O | |
need O | |
for O | |
biochemical O | |
confirmation O | |
before O | |
treatment O | |
is O | |
considered O | |
. O | |
With O | |
new O | |
treatments O | |
, O | |
including O | |
gene O | |
therapy O | |
, O | |
stem O | |
cell O | |
transplantation O | |
, O | |
enzyme O | |
replacement O | |
used O | |
alone O | |
or O | |
in O | |
combination O | |
becoming O | |
more O | |
available O | |
, O | |
the O | |
need O | |
for O | |
rapid O | |
, O | |
accurate O | |
diagnosis O | |
is O | |
critical O | |
. O | |
Background O | |
and O | |
aims O | |
one O | |
of O | |
the O | |
health O | |
concerns O | |
for O | |
any O | |
society O | |
is O | |
to O | |
have O | |
its O | |
own O | |
standard O | |
of O | |
growth O | |
. O | |
The O | |
aim O | |
of O | |
this O | |
study O | |
was O | |
to O | |
provide O | |
the O | |
age- O | |
and O | |
sex O | |
- O | |
specific O | |
percentile O | |
values O | |
of O | |
anthropometric O | |
measures O | |
for O | |
adolescents O | |
of O | |
developing O | |
countries O | |
. O | |
The O | |
use O | |
of O | |
global O | |
percentiles O | |
in O | |
developing O | |
countries O | |
overestimates O | |
underweight O | |
and O | |
stunting O | |
while O | |
underestimates O | |
overweight O | |
and O | |
obesity O | |
. O | |
Methods O | |
The O | |
data O | |
were O | |
obtained O | |
from O | |
the O | |
Global O | |
School O | |
- O | |
based O | |
Student O | |
Health O | |
Survey O | |
( O | |
GSHS O | |
) O | |
. O | |
This O | |
study O | |
was O | |
conducted O | |
on O | |
school O | |
students O | |
, O | |
selected O | |
by O | |
multistage O | |
random O | |
cluster O | |
sampling O | |
from O | |
73 O | |
developing O | |
countries O | |
. O | |
A O | |
parametric O | |
method O | |
was O | |
used O | |
for O | |
constructing O | |
age O | |
- O | |
specific O | |
reference O | |
intervals O | |
( O | |
normal O | |
ranges O | |
) O | |
. O | |
Results O | |
In O | |
general O | |
, O | |
210,045 O | |
11 O | |
- O | |
18 O | |
years O | |
- O | |
old O | |
schoolchildren O | |
( O | |
14.38 O | |
± O | |
1.39 O | |
) O | |
from O | |
73 O | |
developing O | |
countries O | |
between B-DATE | |
2003 I-DATE | |
and I-DATE | |
2014 I-DATE | |
were O | |
included O | |
in O | |
this O | |
study O | |
, O | |
among O | |
which O | |
103,080 O | |
( O | |
49.08 O | |
% O | |
) O | |
were O | |
male B-SEX | |
and O | |
106,965 O | |
( O | |
50.92 O | |
% O | |
) O | |
were O | |
female B-SEX | |
. O | |
Calculation O | |
of O | |
body O | |
mass O | |
index O | |
( O | |
BMI O | |
) O | |
percentile O | |
showed O | |
that O | |
for O | |
all O | |
BMI O | |
percentile O | |
curves O | |
of O | |
both O | |
sexes O | |
, O | |
there O | |
was O | |
a O | |
gradual O | |
increase O | |
up O | |
to O | |
the O | |
age O | |
of O | |
around O | |
15 O | |
years O | |
, O | |
and O | |
then O | |
remain O | |
stable O | |
( O | |
except O | |
for O | |
95th O | |
percentile O | |
) O | |
. O | |
Moreover O | |
in O | |
all O | |
weight O | |
percentile O | |
curves O | |
of O | |
boys B-SEX | |
, O | |
except O | |
90th O | |
and O | |
above O | |
, O | |
there O | |
was O | |
a O | |
slight O | |
rise O | |
until O | |
the O | |
age O | |
of O | |
18 O | |
years O | |
. O | |
In O | |
10th O | |
height O | |
percentile O | |
curves O | |
and O | |
above O | |
in O | |
boys B-SEX | |
, O | |
there O | |
was O | |
a O | |
sharp O | |
increase O | |
up O | |
to O | |
the O | |
age O | |
of O | |
17 O | |
, O | |
followed O | |
by O | |
a O | |
decline O | |
. O | |
Similarly O | |
, O | |
this O | |
pattern O | |
was O | |
found O | |
for O | |
50th O | |
height O | |
percentile O | |
and O | |
above O | |
in O | |
girls B-SEX | |
. O | |
Conclusion O | |
The O | |
use O | |
of O | |
global O | |
percentiles O | |
in O | |
developing O | |
countries O | |
overestimates O | |
underweight O | |
and O | |
stunting O | |
while O | |
underestimates O | |
overweight O | |
and O | |
obesity O | |
. O | |
Premature O | |
loss O | |
of O | |
ovarian O | |
activity O | |
before O | |
40 O | |
years O | |
of O | |
age O | |
is O | |
known O | |
as O | |
primary O | |
ovarian O | |
insufficiency O | |
( O | |
POI O | |
) O | |
and O | |
occurs B-EPI | |
in O | |
~ O | |
1.0 B-STAT | |
% I-STAT | |
of O | |
women B-SEX | |
. O | |
A O | |
more O | |
subtle O | |
decline O | |
in O | |
ovarian O | |
activity O | |
, O | |
known O | |
as O | |
premature O | |
ovarian O | |
ageing O | |
( O | |
POA O | |
) O | |
, O | |
occurs B-EPI | |
in O | |
~ O | |
10.0 B-STAT | |
% I-STAT | |
of O | |
women B-SEX | |
. O | |
Despite O | |
the O | |
high O | |
prevalence B-EPI | |
of O | |
POA O | |
, O | |
very O | |
little O | |
is O | |
known O | |
regarding O | |
its O | |
genetic O | |
causation O | |
. O | |
Senataxin O | |
( O | |
SETX O | |
) O | |
is O | |
an O | |
RNA O | |
/ O | |
DNA O | |
helicase O | |
involved O | |
in O | |
repair O | |
of O | |
oxidative O | |
stress O | |
- O | |
induced O | |
DNA O | |
damage O | |
. O | |
Homozygous O | |
mutation O | |
of O | |
SETX O | |
leads O | |
to O | |
the O | |
neurodegenerative O | |
disorder O | |
, O | |
ataxia O | |
oculomotor O | |
apraxia O | |
type O | |
2 O | |
( O | |
AOA2 O | |
) O | |
. O | |
There O | |
have O | |
been O | |
reports O | |
of O | |
POI O | |
in O | |
AOA2 O | |
females B-SEX | |
suggesting O | |
a O | |
link O | |
between O | |
SETX O | |
and O | |
ovarian O | |
ageing O | |
. O | |
Here O | |
, O | |
we O | |
studied O | |
female B-SEX | |
mice O | |
lacking O | |
either O | |
one O | |
( O | |
Setx+/- O | |
) O | |
or O | |
both O | |
( O | |
Setx-/- O | |
) O | |
copies O | |
of O | |
SETX O | |
over O | |
a O | |
12- O | |
to O | |
14 O | |
- O | |
month O | |
period O | |
. O | |
We O | |
find O | |
that O | |
DNA O | |
damage O | |
is O | |
increased O | |
in O | |
oocytes O | |
from O | |
8 O | |
- O | |
month O | |
- O | |
old O | |
Setx+/- O | |
and O | |
Setx-/- O | |
females B-SEX | |
compared O | |
with O | |
Setx+/+ O | |
oocytes O | |
leading O | |
to O | |
a O | |
marked O | |
reduction O | |
in O | |
all O | |
classes O | |
of O | |
ovarian O | |
follicles O | |
at O | |
least O | |
4 O | |
months O | |
earlier O | |
than O | |
typically O | |
occurs O | |
in O | |
female B-SEX | |
mice O | |
. O | |
Furthermore O | |
, O | |
during O | |
a O | |
12 O | |
- O | |
month O | |
long O | |
mating O | |
trial O | |
, O | |
Setx+/- O | |
and O | |
Setx-/- O | |
females B-SEX | |
produced O | |
significantly O | |
fewer O | |
pups O | |
than O | |
Setx+/+ O | |
females B-SEX | |
from O | |
7 O | |
months O | |
of O | |
age O | |
onwards O | |
. O | |
These O | |
data O | |
show O | |
that O | |
SETX O | |
is O | |
critical O | |
for O | |
preventing O | |
POA O | |
in O | |
mice O | |
, O | |
likely O | |
by O | |
preserving O | |
DNA O | |
integrity O | |
in O | |
oocytes O | |
. O | |
Intriguingly O | |
, O | |
heterozygous O | |
Setx O | |
loss O | |
causes O | |
an O | |
equally O | |
severe O | |
impact O | |
on O | |
ovarian O | |
ageing O | |
as O | |
homozygous O | |
Setx O | |
loss O | |
. O | |
Because O | |
heterozygous O | |
SETX O | |
disruption O | |
is O | |
less O | |
likely O | |
to O | |
produce O | |
systemic O | |
effects O | |
, O | |
SETX O | |
compromise O | |
could O | |
underpin O | |
some O | |
cases O | |
of O | |
insidious O | |
POA O | |
. O | |
Objectives O | |
The O | |
objective O | |
of O | |
our O | |
study O | |
was O | |
to O | |
conduct O | |
a O | |
systematic O | |
literature O | |
review O | |
of O | |
estimates O | |
of O | |
costs O | |
of O | |
illness O | |
of O | |
spinal O | |
muscular O | |
atrophy O | |
( O | |
SMA O | |
) O | |
. O | |
Methods O | |
We O | |
searched O | |
MEDLINE O | |
( O | |
through O | |
PubMed O | |
) O | |
, O | |
CINAHL O | |
, O | |
Embase O | |
, O | |
Web O | |
of O | |
Science O | |
, O | |
National O | |
Health O | |
Service O | |
Economic O | |
Evaluation O | |
Database O | |
, O | |
and O | |
the O | |
National O | |
Health O | |
Service O | |
Health O | |
Technology O | |
Assessment O | |
Database O | |
for O | |
studies O | |
published O | |
from O | |
inception O | |
up O | |
until O | |
31 B-DATE | |
August I-DATE | |
, I-DATE | |
2020 I-DATE | |
, O | |
reporting O | |
direct O | |
medical O | |
, O | |
direct O | |
non O | |
- O | |
medical O | |
, O | |
and/or O | |
indirect O | |
costs O | |
of O | |
any O | |
phenotype O | |
of O | |
SMA O | |
. O | |
Two O | |
reviewers O | |
independently O | |
screened O | |
records O | |
for O | |
eligibility O | |
, O | |
extracted O | |
the O | |
data O | |
, O | |
and O | |
assessed O | |
studies O | |
for O | |
risk O | |
of O | |
bias O | |
using O | |
the O | |
Newcastle B-LOC | |
- O | |
Ottawa B-LOC | |
Scale O | |
. O | |
Costs O | |
were O | |
adjusted O | |
and O | |
converted O | |
to O | |
2018 O | |
US O | |
dollars O | |
. O | |
Results O | |
The O | |
search O | |
identified O | |
14 O | |
studies O | |
from O | |
eight O | |
countries O | |
( O | |
Australia B-LOC | |
, O | |
France B-LOC | |
, O | |
Germany B-LOC | |
, O | |
Italy B-LOC | |
, O | |
Spain B-LOC | |
, O | |
Sweden B-LOC | |
, O | |
the O | |
UK B-LOC | |
, O | |
and O | |
the O | |
USA B-LOC | |
) O | |
. O | |
The O | |
mean O | |
per O | |
- O | |
patient O | |
annual O | |
direct O | |
medical O | |
cost O | |
of O | |
illness O | |
was O | |
estimated O | |
at O | |
between O | |
$ O | |
3320 O | |
( O | |
SMA O | |
type O | |
III O | |
, O | |
Italy B-LOC | |
) O | |
and O | |
$ O | |
324,410 O | |
( O | |
SMA O | |
type O | |
I O | |
, O | |
USA B-LOC | |
) O | |
, O | |
mean O | |
per O | |
- O | |
patient O | |
annual O | |
direct O | |
non O | |
- O | |
medical O | |
cost O | |
between O | |
$ O | |
25,880 O | |
( O | |
SMA O | |
types O | |
I O | |
- O | |
III O | |
, O | |
Spain O | |
) O | |
and O | |
$ O | |
136,800 O | |
( O | |
SMA O | |
type O | |
I O | |
, O | |
Sweden B-LOC | |
) O | |
, O | |
and O | |
mean O | |
per O | |
- O | |
patient O | |
annual O | |
indirect O | |
cost O | |
between O | |
$ O | |
9440 O | |
( O | |
SMA O | |
type O | |
I O | |
, O | |
Germany B-LOC | |
) O | |
and O | |
$ O | |
74,910 O | |
( O | |
SMA O | |
type O | |
II O | |
, O | |
Australia B-LOC | |
) O | |
. O | |
Most O | |
studies O | |
exhibited O | |
a O | |
risk O | |
of O | |
bias O | |
. O | |
Conclusions O | |
The O | |
current O | |
body O | |
of O | |
evidence O | |
of O | |
costs O | |
of O | |
illness O | |
of O | |
SMA O | |
is O | |
relatively O | |
scarce O | |
and O | |
characterized O | |
by O | |
considerable O | |
variability O | |
across O | |
geographical O | |
settings O | |
and O | |
disease O | |
phenotypes O | |
. O | |
Our O | |
review O | |
provides O | |
data O | |
pertaining O | |
to O | |
the O | |
economic O | |
impact O | |
of O | |
SMA O | |
, O | |
which O | |
is O | |
of O | |
particular O | |
relevance O | |
in O | |
light O | |
of O | |
emerging O | |
treatments O | |
and O | |
ongoing O | |
research O | |
in O | |
this O | |
field O | |
, O | |
and O | |
underscores O | |
the O | |
substantial O | |
unmet O | |
medical O | |
need O | |
in O | |
this O | |
patient O | |
population O | |
. O | |
Background O | |
Dominant O | |
optic O | |
atrophy O | |
( O | |
DOA O | |
) O | |
is O | |
an O | |
inherited O | |
optic O | |
neuropathy O | |
that O | |
mainly O | |
affects O | |
visual O | |
acuity O | |
, O | |
central O | |
visual O | |
fields O | |
and O | |
color O | |
vision O | |
due O | |
to O | |
a O | |
progressive O | |
loss O | |
of O | |
retinal O | |
ganglion O | |
cells O | |
and O | |
their O | |
axons O | |
that O | |
form O | |
the O | |
optic O | |
nerve O | |
. O | |
Approximately O | |
45 O | |
- O | |
90 O | |
% O | |
of O | |
affected O | |
individuals O | |
with O | |
DOA O | |
harbor O | |
pathogenic O | |
variants O | |
in O | |
the O | |
OPA1 O | |
gene O | |
. O | |
The O | |
mutation O | |
spectrum O | |
of O | |
OPA1 O | |
comprises O | |
nonsense O | |
, O | |
canonical O | |
and O | |
non O | |
- O | |
canonical O | |
splice O | |
site O | |
, O | |
frameshift O | |
and O | |
missense O | |
as O | |
well O | |
as O | |
copy O | |
number O | |
variants O | |
, O | |
but O | |
intragenic O | |
inversions O | |
have O | |
not O | |
been O | |
reported O | |
so O | |
far O | |
. O | |
Case O | |
presentation O | |
We O | |
report O | |
a O | |
33 O | |
- O | |
year O | |
- O | |
old O | |
male B-SEX | |
with O | |
characteristic O | |
clinical O | |
features O | |
of O | |
DOA O | |
. O | |
Whole O | |
- O | |
genome O | |
sequencing O | |
identified O | |
a O | |
structural O | |
variant O | |
of O | |
2.4 O | |
kb O | |
comprising O | |
an O | |
inversion O | |
of O | |
937 O | |
bp O | |
at O | |
the O | |
OPA1 O | |
locus O | |
. O | |
Fine O | |
mapping O | |
of O | |
the O | |
breakpoints O | |
to O | |
single O | |
nucleotide O | |
level O | |
revealed O | |
that O | |
the O | |
structural O | |
variation O | |
was O | |
an O | |
inversion O | |
flanked O | |
by O | |
two O | |
deletions O | |
. O | |
As O | |
this O | |
rearrangement O | |
inverts O | |
the O | |
entire O | |
first O | |
exon O | |
of O | |
OPA1 O | |
, O | |
it O | |
was O | |
classified O | |
as O | |
likely O | |
pathogenic O | |
. O | |
Conclusions O | |
We O | |
report O | |
the O | |
first O | |
DOA O | |
case O | |
harboring O | |
an O | |
inversion O | |
in O | |
the O | |
OPA1 O | |
gene O | |
. O | |
Our O | |
study O | |
demonstrates O | |
that O | |
copy O | |
- O | |
neutral O | |
genomic O | |
rearrangements O | |
have O | |
to O | |
be O | |
considered O | |
as O | |
a O | |
possible O | |
cause O | |
of O | |
disease O | |
in O | |
DOA O | |
cases O | |
. O | |
Introduction O | |
/ O | |
background O | |
Bladder O | |
exstrophy O | |
patients O | |
have O | |
a O | |
high O | |
prevalence B-EPI | |
of O | |
inguinal O | |
hernia O | |
that O | |
often O | |
become O | |
clinically O | |
evident O | |
following O | |
bladder O | |
closure O | |
. O | |
Understanding O | |
when O | |
the O | |
bladder O | |
exstrophy O | |
patient O | |
is O | |
under O | |
greatest O | |
risk O | |
of O | |
developing O | |
an O | |
inguinal O | |
hernia O | |
following O | |
bladder O | |
closure O | |
is O | |
important O | |
, O | |
since O | |
incarceration O | |
resulting O | |
in O | |
strangulation O | |
of O | |
intra O | |
- O | |
abdominal O | |
contents O | |
can O | |
lead O | |
to O | |
significant O | |
morbidity O | |
if O | |
not O | |
addressed O | |
in O | |
a O | |
timely O | |
fashion O | |
. O | |
Although O | |
the O | |
incidence B-EPI | |
and O | |
risk O | |
factors O | |
of O | |
inguinal O | |
hernia O | |
have O | |
been O | |
reported O | |
, O | |
the O | |
timing O | |
of O | |
occurrence B-EPI | |
is O | |
not O | |
well O | |
understood O | |
. O | |
Objective O | |
The O | |
primary O | |
objective O | |
of O | |
this O | |
study O | |
was O | |
to O | |
assess O | |
the O | |
timing O | |
of O | |
inguinal O | |
hernia O | |
following O | |
complete O | |
primary O | |
repair O | |
of O | |
bladder O | |
exstrophy O | |
( O | |
CPRE O | |
) O | |
. O | |
In O | |
addition O | |
, O | |
we O | |
aimed O | |
to O | |
evaluate O | |
possible O | |
risk O | |
factors O | |
associated O | |
with O | |
inguinal O | |
hernia O | |
, O | |
including O | |
sex O | |
, O | |
age O | |
at O | |
bladder O | |
closure O | |
and O | |
iliac O | |
osteotomy O | |
status O | |
. O | |
Study O | |
design O | |
A O | |
multi O | |
- O | |
institutional O | |
retrospective O | |
review O | |
identified O | |
patients O | |
with O | |
bladder O | |
exstrophy O | |
repaired O | |
by O | |
CPRE O | |
under O | |
6 O | |
months O | |
of O | |
age O | |
while O | |
excluding O | |
those O | |
who O | |
underwent O | |
inguinal O | |
hernia O | |
repair O | |
before O | |
or O | |
during O | |
bladder O | |
closure O | |
. O | |
Timing O | |
of O | |
inguinal O | |
hernia O | |
following O | |
bladder O | |
closure O | |
was O | |
evaluated O | |
using O | |
Kaplan O | |
- O | |
Meier O | |
methods O | |
. O | |
Cox O | |
proportional O | |
hazards O | |
model O | |
was O | |
used O | |
to O | |
investigate O | |
association O | |
of O | |
sex O | |
, O | |
age O | |
at O | |
bladder O | |
closure O | |
, O | |
and O | |
osteotomy O | |
on O | |
the O | |
risk O | |
of O | |
developing O | |
of O | |
inguinal O | |
hernia O | |
while O | |
clustering O | |
for O | |
institution O | |
. O | |
Results O | |
91 O | |
subjects O | |
were O | |
included O | |
in O | |
our O | |
analysis O | |
with O | |
median O | |
follow O | |
- O | |
up O | |
time O | |
of O | |
6.5 O | |
years O | |
. O | |
34 O | |
of O | |
53 O | |
males B-SEX | |
( O | |
64.2 O | |
% O | |
) O | |
and O | |
2 O | |
of O | |
38 O | |
females B-SEX | |
( O | |
5.3 O | |
% O | |
) O | |
underwent O | |
inguinal O | |
hernia O | |
repair O | |
. O | |
The O | |
median O | |
time O | |
to O | |
inguinal O | |
hernia O | |
was O | |
4.7 O | |
months O | |
following O | |
closure O | |
. O | |
The O | |
greatest O | |
hazard O | |
of O | |
inguinal O | |
hernia O | |
was O | |
within O | |
the O | |
first O | |
six O | |
months O | |
following O | |
closure O | |
. O | |
In O | |
multivariate O | |
analysis O | |
, O | |
male B-SEX | |
sex O | |
was O | |
strongly O | |
associated O | |
with O | |
inguinal O | |
hernia O | |
( O | |
HR O | |
= O | |
19.00 O | |
, O | |
p O | |
= O | |
0.0038 O | |
) O | |
. O | |
Osteotomy O | |
and O | |
delay O | |
in O | |
closure O | |
were O | |
not O | |
significantly O | |
associated O | |
with O | |
inguinal O | |
hernia O | |
. O | |
7 O | |
of O | |
36 O | |
patients O | |
( O | |
19.4 O | |
% O | |
) O | |
who O | |
underwent O | |
inguinal O | |
hernia O | |
repair O | |
presented O | |
with O | |
recurrence O | |
on O | |
the O | |
ipsilateral O | |
side O | |
. O | |
Discussion O | |
Our O | |
results O | |
suggest O | |
that O | |
the O | |
greatest O | |
risk O | |
of O | |
inguinal O | |
hernia O | |
is O | |
within O | |
the O | |
first O | |
six O | |
months O | |
following O | |
bladder O | |
closure O | |
. O | |
The O | |
decreased O | |
risk O | |
of O | |
inguinal O | |
hernia O | |
after O | |
one O | |
year O | |
of O | |
follow O | |
- O | |
up O | |
may O | |
reflect O | |
anatomic O | |
stability O | |
that O | |
is O | |
reached O | |
following O | |
major O | |
reconstruction O | |
of O | |
the O | |
pelvis O | |
. O | |
While O | |
male B-SEX | |
bladder O | |
exstrophy O | |
patients O | |
are O | |
significantly O | |
more O | |
susceptible O | |
to O | |
inguinal O | |
hernias O | |
following O | |
CPRE O | |
, O | |
osteotomy O | |
and O | |
delayed O | |
bladder O | |
closure O | |
do O | |
not O | |
appear O | |
to O | |
be O | |
protective O | |
factors O | |
for O | |
inguinal O | |
hernia O | |
development O | |
following O | |
initial O | |
bladder O | |
closure O | |
. O | |
Conclusions O | |
There O | |
is O | |
a O | |
heightened O | |
risk O | |
of O | |
inguinal O | |
hernia O | |
in O | |
the O | |
first O | |
six O | |
months O | |
following O | |
closure O | |
. O | |
The O | |
rate O | |
of O | |
recurrence O | |
following O | |
inguinal O | |
hernia O | |
repair O | |
is O | |
significantly O | |
elevated O | |
compared O | |
to O | |
the O | |
general O | |
pediatric O | |
population O | |
. O | |
Background O | |
Little O | |
is O | |
known O | |
about O | |
the O | |
prognosis O | |
regarding O | |
shunt O | |
revision O | |
and O | |
mortality O | |
among O | |
hydrocephalus O | |
patients O | |
below O | |
2 O | |
years O | |
of O | |
age O | |
. O | |
The O | |
aims O | |
of O | |
this O | |
study O | |
were O | |
to O | |
investigate O | |
( O | |
1 O | |
) O | |
the O | |
cumulative O | |
risks O | |
of O | |
shunt O | |
revision O | |
( O | |
SR O | |
) O | |
and O | |
mortality O | |
and O | |
( O | |
2 O | |
) O | |
the O | |
potential O | |
associations O | |
between O | |
prematurity O | |
, O | |
low O | |
weight O | |
for O | |
gestational O | |
age O | |
( O | |
LWGA O | |
) O | |
, O | |
underlying O | |
aetiology O | |
, O | |
sex O | |
, O | |
age O | |
of O | |
the O | |
child O | |
at O | |
shunt O | |
placement O | |
, O | |
and O | |
the O | |
risk O | |
of O | |
SR O | |
. O | |
Method O | |
This O | |
was O | |
a O | |
purely O | |
register O | |
- O | |
based O | |
cohort O | |
study O | |
including O | |
all O | |
shunted O | |
hydrocephalic O | |
infants O | |
in O | |
Denmark B-LOC | |
1996 B-DATE | |
- I-DATE | |
2015 I-DATE | |
. O | |
The O | |
cumulative O | |
risks O | |
of O | |
SR O | |
and O | |
mortality O | |
were O | |
estimated O | |
using O | |
the O | |
Aalen O | |
- O | |
Johansen O | |
and O | |
Kaplan O | |
- O | |
Meier O | |
estimators O | |
, O | |
respectively O | |
. O | |
A O | |
multivariable O | |
Cox O | |
- O | |
regression O | |
model O | |
was O | |
used O | |
to O | |
estimate O | |
hazard O | |
ratios O | |
( O | |
HRs O | |
) O | |
for O | |
SR O | |
according O | |
to O | |
the O | |
listed O | |
patient O | |
- O | |
related O | |
risk O | |
factors O | |
. O | |
Results O | |
Among O | |
374 O | |
shunted O | |
infantile O | |
hydrocephalus O | |
patients O | |
accounting O | |
for O | |
1047 O | |
SRs O | |
, O | |
the O | |
3 O | |
- O | |
month O | |
and O | |
1 O | |
- O | |
year O | |
cumulative O | |
risks O | |
of O | |
SR O | |
were O | |
36 O | |
% O | |
and O | |
50 O | |
% O | |
, O | |
respectively O | |
. O | |
The O | |
overall O | |
10 O | |
- O | |
year O | |
cumulative O | |
mortality O | |
was O | |
12 O | |
% O | |
, O | |
and O | |
for O | |
non O | |
- O | |
tumour O | |
subgroups O | |
7 O | |
- O | |
16 O | |
% O | |
( O | |
isolated O | |
hydrocephalus O | |
7 O | |
% O | |
) O | |
. O | |
The O | |
10 O | |
- O | |
year O | |
cumulative O | |
mortality O | |
for O | |
children O | |
born O | |
with O | |
LWGA O | |
was O | |
21 O | |
% O | |
. O | |
Except O | |
for O | |
aetiology O | |
, O | |
we O | |
observed O | |
no O | |
strong O | |
overall O | |
associations O | |
between O | |
the O | |
investigated O | |
risk O | |
factors O | |
and O | |
the O | |
risk O | |
of O | |
SR O | |
but O | |
interaction O | |
analyses O | |
for O | |
aetiology O | |
showed O | |
that O | |
patients O | |
with O | |
Dandy O | |
- O | |
Walker O | |
malformation O | |
born O | |
with O | |
LWGA O | |
had O | |
a O | |
higher O | |
risk O | |
of O | |
SR O | |
compared O | |
to O | |
patients O | |
of O | |
similar O | |
aetiology O | |
with O | |
normal O | |
WGA O | |
( O | |
HR O | |
2.47 O | |
, O | |
95 O | |
% O | |
CI O | |
: O | |
1.39 O | |
- O | |
4.40 O | |
) O | |
. O | |
Conclusions O | |
We O | |
found O | |
very O | |
high O | |
cumulative O | |
risks O | |
of O | |
SR O | |
and O | |
mortality O | |
among O | |
this O | |
youngest O | |
group O | |
of O | |
hydrocephalus O | |
patients O | |
, O | |
disregarding O | |
aetiology O | |
, O | |
but O | |
none O | |
of O | |
them O | |
were O | |
strongly O | |
related O | |
to O | |
the O | |
investigated O | |
risk O | |
factors O | |
. O | |
Objective O | |
This O | |
study O | |
aimed O | |
to O | |
examine O | |
the O | |
application O | |
of O | |
the O | |
Objective O | |
Structured O | |
Clinical O | |
Examination O | |
( O | |
OSCE O | |
) O | |
to O | |
the O | |
assessment O | |
of O | |
competency O | |
among O | |
child O | |
and O | |
adolescent O | |
psychiatry O | |
( O | |
CAP O | |
) O | |
residents O | |
and O | |
to O | |
analyze O | |
the O | |
feedback O | |
from O | |
the O | |
residents O | |
and O | |
the O | |
examiners O | |
. O | |
Methods O | |
The O | |
OSCE O | |
was O | |
administered O | |
to O | |
53 O | |
CAP O | |
residents O | |
based O | |
on O | |
three O | |
seniority O | |
levels O | |
over O | |
a O | |
14 O | |
- O | |
year O | |
period O | |
. O | |
The O | |
results O | |
of O | |
147 O | |
OSCEs O | |
applied O | |
to O | |
residents O | |
and O | |
the O | |
feedback O | |
received O | |
were O | |
evaluated O | |
. O | |
OSCE O | |
scores O | |
were O | |
calculated O | |
based O | |
on O | |
the O | |
scores O | |
given O | |
by O | |
the O | |
examiners O | |
and O | |
standardized O | |
patients O | |
( O | |
SPs O | |
) O | |
. O | |
Results O | |
Examiners O | |
' O | |
communication O | |
skills O | |
scores O | |
were O | |
significantly O | |
higher O | |
than O | |
examiners O | |
' O | |
task O | |
performance O | |
scores O | |
but O | |
were O | |
not O | |
significantly O | |
different O | |
than O | |
the O | |
SPs O | |
' O | |
scores O | |
. O | |
Intraclass O | |
correlation O | |
coefficients O | |
indicated O | |
that O | |
examiners O | |
and O | |
SPs O | |
were O | |
very O | |
consistent O | |
in O | |
their O | |
assessments O | |
among O | |
themselves O | |
. O | |
The O | |
scores O | |
given O | |
by O | |
the O | |
examiners O | |
and O | |
the O | |
SPs O | |
were O | |
not O | |
different O | |
between O | |
genders O | |
except O | |
for O | |
female B-SEX | |
residents O | |
' O | |
communication O | |
skills O | |
scores O | |
given O | |
by O | |
SPs O | |
in O | |
the O | |
OSCE O | |
- O | |
senior O | |
. O | |
With O | |
regard O | |
to O | |
the O | |
feedback O | |
on O | |
the O | |
OSCE O | |
, O | |
it O | |
was O | |
determined O | |
that O | |
examiners O | |
gave O | |
significantly O | |
higher O | |
scores O | |
than O | |
residents O | |
on O | |
every O | |
item O | |
except O | |
for O | |
neutrality O | |
of O | |
the O | |
examiners O | |
. O | |
Conclusions O | |
A O | |
standard O | |
OSCE O | |
including O | |
different O | |
station O | |
types O | |
was O | |
structured O | |
to O | |
assess O | |
the O | |
progressive O | |
clinical O | |
skills O | |
of O | |
residents O | |
over O | |
the O | |
years O | |
. O | |
Using O | |
the O | |
OSCE O | |
contributed O | |
to O | |
CAP O | |
residency O | |
training O | |
far O | |
beyond O | |
assessment O | |
, O | |
creating O | |
a O | |
useful O | |
educational O | |
experience O | |
for O | |
both O | |
the O | |
trainers O | |
and O | |
the O | |
residents O | |
. O | |
Despite O | |
the O | |
challenge O | |
experienced O | |
related O | |
to O | |
SPs O | |
, O | |
the O | |
OSCE O | |
was O | |
found O | |
to O | |
be O | |
useful O | |
in O | |
improving O | |
training O | |
programs O | |
. O | |
Maintaining O | |
proper O | |
eye O | |
alignment O | |
is O | |
necessary O | |
to O | |
generate O | |
a O | |
cohesive O | |
visual O | |
image O | |
. O | |
This O | |
involves O | |
the O | |
coordination O | |
of O | |
complex O | |
neural O | |
networks O | |
, O | |
which O | |
can O | |
become O | |
impaired O | |
by O | |
various O | |
neurodegenerative O | |
diseases O | |
. O | |
When O | |
the O | |
vergence O | |
system O | |
is O | |
affected O | |
, O | |
this O | |
can O | |
result O | |
in O | |
strabismus O | |
and O | |
disorienting O | |
diplopia O | |
. O | |
While O | |
previous O | |
studies O | |
have O | |
detailed O | |
the O | |
effect O | |
of O | |
these O | |
disorders O | |
on O | |
other O | |
eye O | |
movements O | |
, O | |
such O | |
as O | |
saccades O | |
, O | |
relatively O | |
little O | |
is O | |
known O | |
about O | |
strabismus O | |
. O | |
Here O | |
, O | |
we O | |
focus O | |
on O | |
the O | |
prevalence B-EPI | |
, O | |
clinical O | |
characteristics O | |
, O | |
and O | |
treatment O | |
of O | |
strabismus O | |
and O | |
disorders O | |
of O | |
vergence O | |
in O | |
Parkinson O | |
's O | |
disease O | |
, O | |
spinocerebellar O | |
ataxia O | |
, O | |
Huntington O | |
disease O | |
, O | |
and O | |
multiple O | |
system O | |
atrophy O | |
. O | |
We O | |
find O | |
that O | |
vergence O | |
abnormalities O | |
may O | |
be O | |
more O | |
common O | |
in O | |
these O | |
disorders O | |
than O | |
previously O | |
thought O | |
. O | |
In O | |
Parkinson O | |
's O | |
disease O | |
, O | |
the O | |
evidence O | |
suggests O | |
that O | |
strabismus O | |
is O | |
related O | |
to O | |
convergence O | |
insufficiency O | |
; O | |
however O | |
, O | |
it O | |
is O | |
responsive O | |
to O | |
dopamine O | |
replacement O | |
therapy O | |
and O | |
can O | |
, O | |
therefore O | |
, O | |
fluctuate O | |
with O | |
medication O | |
on O | |
and O | |
off O | |
periods O | |
throughout O | |
the O | |
day O | |
. O | |
Diplopia O | |
is O | |
also O | |
established O | |
as O | |
a O | |
side O | |
effect O | |
of O | |
deep O | |
brain O | |
stimulation O | |
and O | |
is O | |
thought O | |
to O | |
be O | |
related O | |
to O | |
stimulation O | |
of O | |
the O | |
subthalamic O | |
nucleus O | |
and O | |
extraocular O | |
motor O | |
nucleus O | |
among O | |
other O | |
structures O | |
. O | |
In O | |
regards O | |
to O | |
the O | |
spinocerebellar O | |
ataxias O | |
, O | |
oculomotor O | |
symptoms O | |
are O | |
common O | |
in O | |
many O | |
subtypes O | |
, O | |
but O | |
diplopia O | |
is O | |
most O | |
common O | |
in O | |
SCA3 O | |
also O | |
known O | |
as O | |
Machado O | |
- O | |
Joseph O | |
disease O | |
. O | |
Ophthalmoplegia O | |
and O | |
vergence O | |
insufficiency O | |
have O | |
both O | |
been O | |
implicated O | |
in O | |
strabismus O | |
in O | |
these O | |
patients O | |
, O | |
but O | |
can O | |
not O | |
fully O | |
explain O | |
the O | |
properties O | |
of O | |
the O | |
strabismus O | |
, O | |
suggesting O | |
the O | |
involvement O | |
of O | |
other O | |
structures O | |
as O | |
well O | |
. O | |
Strabismus O | |
has O | |
not O | |
been O | |
reported O | |
as O | |
a O | |
common O | |
finding O | |
in O | |
Huntington O | |
disease O | |
or O | |
atypical O | |
parkinsonian O | |
syndromes O | |
and O | |
more O | |
studies O | |
are O | |
needed O | |
to O | |
determine O | |
how O | |
these O | |
disorders O | |
affect O | |
binocular O | |
alignment O | |
. O | |
Background O | |
Lipodystrophy O | |
syndromes O | |
are O | |
a O | |
group O | |
of O | |
disorders O | |
characterized O | |
by O | |
a O | |
loss O | |
of O | |
adipose O | |
tissue O | |
once O | |
other O | |
situations O | |
of O | |
nutritional O | |
deprivation O | |
or O | |
exacerbated O | |
catabolism O | |
have O | |
been O | |
ruled O | |
out O | |
. O | |
With O | |
the O | |
exception O | |
of O | |
the O | |
HIV O | |
- O | |
associated O | |
lipodystrophy O | |
, O | |
they O | |
have O | |
a O | |
very O | |
low O | |
prevalence B-EPI | |
, O | |
which O | |
together O | |
with O | |
their O | |
large O | |
phenotypic O | |
heterogeneity O | |
makes O | |
their O | |
identification O | |
difficult O | |
, O | |
even O | |
for O | |
endocrinologists O | |
and O | |
pediatricians O | |
. O | |
This O | |
leads O | |
to O | |
significant O | |
delays O | |
in O | |
diagnosis O | |
or O | |
even O | |
to O | |
misdiagnosis O | |
. O | |
Our O | |
group O | |
has O | |
developed O | |
an O | |
algorithm O | |
that O | |
identifies O | |
the O | |
more O | |
than O | |
40 O | |
rare O | |
lipodystrophy O | |
subtypes O | |
described O | |
to O | |
date O | |
. O | |
This O | |
algorithm O | |
has O | |
been O | |
implemented O | |
in O | |
a O | |
free O | |
mobile O | |
application O | |
, O | |
LipoDDx O | |
. O | |
Our O | |
aim O | |
was O | |
to O | |
establish O | |
the O | |
effectiveness O | |
of O | |
LipoDDx O | |
. O | |
Forty O | |
clinical O | |
records O | |
of O | |
patients O | |
with O | |
a O | |
diagnosis O | |
of O | |
certainty O | |
of O | |
most O | |
lipodystrophy O | |
subtypes O | |
were O | |
analyzed O | |
, O | |
including O | |
subjects O | |
without O | |
lipodystrophy O | |
. O | |
The O | |
medical O | |
records O | |
, O | |
blinded O | |
for O | |
diagnosis O | |
, O | |
were O | |
evaluated O | |
by O | |
13 O | |
physicians O | |
, O | |
1 O | |
biochemist O | |
and O | |
1 O | |
dentist O | |
. O | |
Each O | |
evaluator O | |
first O | |
gave O | |
his O | |
/ O | |
her O | |
results O | |
based O | |
on O | |
his O | |
/ O | |
her O | |
own O | |
criteria O | |
. O | |
Then O | |
, O | |
a O | |
second O | |
diagnosis O | |
was O | |
given O | |
using O | |
LipoDDx O | |
. O | |
The O | |
results O | |
were O | |
analysed O | |
based O | |
on O | |
a O | |
score O | |
table O | |
according O | |
to O | |
the O | |
complexity O | |
of O | |
each O | |
case O | |
and O | |
the O | |
prevalence B-EPI | |
of O | |
the O | |
disease O | |
. O | |
Results O | |
LipoDDx O | |
provides O | |
a O | |
user O | |
- O | |
friendly O | |
environment O | |
, O | |
based O | |
on O | |
usually O | |
dichotomous O | |
questions O | |
or O | |
choice O | |
of O | |
clinical O | |
signs O | |
from O | |
drop O | |
- O | |
down O | |
menus O | |
. O | |
The O | |
final O | |
result O | |
provided O | |
by O | |
this O | |
app O | |
for O | |
a O | |
particular O | |
case O | |
can O | |
be O | |
a O | |
low O | |
/ O | |
high O | |
probability O | |
of O | |
suffering O | |
a O | |
particular O | |
lipodystrophy O | |
subtype O | |
. O | |
Without O | |
using O | |
LipoDDx O | |
the O | |
success O | |
rate O | |
was O | |
17 O | |
± O | |
20 O | |
% O | |
, O | |
while O | |
with O | |
LipoDDx O | |
the O | |
success O | |
rate O | |
was O | |
79 O | |
± O | |
20 O | |
% O | |
( O | |
p O | |
< O | |
0.01 O | |
) O | |
. O | |
Conclusions O | |
LipoDDx O | |
is O | |
a O | |
free O | |
app O | |
that O | |
enables O | |
the O | |
identification O | |
of O | |
subtypes O | |
of O | |
rare O | |
lipodystrophies O | |
, O | |
which O | |
in O | |
this O | |
small O | |
cohort O | |
has O | |
around O | |
80 O | |
% O | |
effectiveness O | |
, O | |
which O | |
will O | |
be O | |
of O | |
help O | |
to O | |
doctors O | |
who O | |
are O | |
not O | |
experts O | |
in O | |
this O | |
field O | |
. O | |
However O | |
, O | |
it O | |
will O | |
be O | |
necessary O | |
to O | |
analyze O | |
more O | |
cases O | |
in O | |
order O | |
to O | |
obtain O | |
a O | |
more O | |
accurate O | |
efficiency O | |
value O | |
. O | |
Pierson O | |
syndrome O | |
, O | |
an O | |
autosomal O | |
recessive O | |
disorder O | |
caused O | |
by O | |
a O | |
mutation O | |
in O | |
laminin O | |
ß2 O | |
( O | |
LAMB2 O | |
) O | |
gene O | |
, O | |
is O | |
characterized O | |
by O | |
congenital O | |
nephrotic O | |
syndrome O | |
and O | |
various O | |
ocular O | |
abnormalities O | |
. O | |
The O | |
ocular O | |
findings O | |
in O | |
Pierson O | |
syndrome O | |
are O | |
not O | |
well O | |
understood O | |
, O | |
because O | |
the O | |
incidence B-EPI | |
of O | |
this O | |
syndrome O | |
is O | |
very O | |
rare O | |
. O | |
We O | |
report O | |
ocular O | |
findings O | |
in O | |
a O | |
5 O | |
- O | |
month O | |
- O | |
old O | |
boy B-SEX | |
with O | |
Pierson O | |
syndrome O | |
with O | |
a O | |
novel O | |
mutation O | |
in O | |
LAMB2 O | |
. O | |
We O | |
performed O | |
a O | |
pupilloplasty O | |
for O | |
his O | |
microcoria O | |
. O | |
Ophthalmic O | |
examinations O | |
after O | |
surgery O | |
revealed O | |
that O | |
he O | |
had O | |
cataract O | |
, O | |
severe O | |
retinal O | |
degeneration O | |
, O | |
and O | |
high O | |
myopia O | |
. O | |
Optical O | |
coherence O | |
tomography O | |
showed O | |
the O | |
collapse O | |
of O | |
retinal O | |
layer O | |
structures O | |
and O | |
a O | |
marked O | |
decrease O | |
of O | |
choroidal O | |
thickness O | |
. O | |
Immunohistochemistry O | |
and O | |
electron O | |
microscopy O | |
examinations O | |
revealed O | |
abnormal O | |
iris O | |
differentiation O | |
and O | |
thinning O | |
or O | |
defect O | |
of O | |
basal O | |
membranes O | |
. O | |
These O | |
results O | |
suggest O | |
that O | |
the O | |
development O | |
of O | |
the O | |
iris O | |
, O | |
lens O | |
, O | |
retina O | |
, O | |
and O | |
choroid O | |
are O | |
affected O | |
in O | |
this O | |
type O | |
of O | |
mutation O | |
. O | |
Thiamine O | |
responsive O | |
megaloblastic O | |
anemia O | |
syndrome O | |
, O | |
an O | |
autosomal O | |
recessive O | |
inherited O | |
disorder O | |
characterized O | |
by O | |
a O | |
triad O | |
of O | |
anemia O | |
, O | |
diabetes O | |
mellitus O | |
and O | |
sensorineural O | |
deafness O | |
is O | |
caused O | |
by O | |
a O | |
deficiency O | |
of O | |
a O | |
thiamine O | |
transporter O | |
protein O | |
. O | |
The O | |
disorder O | |
is O | |
rare O | |
and O | |
has O | |
not O | |
been O | |
reported O | |
from O | |
our O | |
community O | |
which O | |
has O | |
high O | |
background O | |
of O | |
consanguinity O | |
. O | |
We O | |
report O | |
a O | |
six O | |
years O | |
old O | |
girl B-SEX | |
who O | |
presented O | |
with O | |
diabetes O | |
mellitus O | |
which O | |
remitted O | |
after O | |
thiamine O | |
replacement O | |
. O | |
The O | |
girl B-SEX | |
in O | |
addition O | |
had O | |
sensorineural O | |
deafness O | |
, O | |
reinopathy O | |
, O | |
atrial O | |
septal O | |
defect O | |
and O | |
megaloblastic O | |
anemia O | |
which O | |
responded O | |
to O | |
high O | |
doses O | |
of O | |
thymine O | |
. O | |
This O | |
is O | |
the O | |
first O | |
case O | |
reported O | |
from O | |
Kashmir B-LOC | |
valley I-LOC | |
and O | |
third O | |
from O | |
India B-LOC | |
. O | |
The O | |
presentation O | |
and O | |
management O | |
in O | |
such O | |
cases O | |
is O | |
discussed O | |
. O | |
Background O | |
Obstructive O | |
sleep O | |
apnea O | |
( O | |
OSA O | |
) O | |
is O | |
prevalent B-EPI | |
in O | |
individuals O | |
with O | |
Osteogenesis O | |
imperfecta O | |
( O | |
OI O | |
) O | |
. O | |
To O | |
date O | |
, O | |
no O | |
study O | |
has O | |
investigated O | |
treatment O | |
of O | |
OSA O | |
in O | |
adult O | |
individuals O | |
with O | |
OI O | |
using O | |
positive O | |
airway O | |
pressure O | |
( O | |
PAP O | |
) O | |
. O | |
This O | |
observational O | |
pilot O | |
study O | |
examined O | |
the O | |
adherence O | |
of O | |
adults O | |
with O | |
OI O | |
to O | |
treatment O | |
of O | |
OSA O | |
with O | |
PAP O | |
therapy O | |
, O | |
and O | |
the O | |
evolution O | |
of O | |
self O | |
- O | |
experienced O | |
sleepiness O | |
and O | |
depression O | |
symptoms O | |
before O | |
and O | |
after O | |
treatment O | |
. O | |
Methods O | |
We O | |
included O | |
20 O | |
patients O | |
, O | |
with O | |
a O | |
mean O | |
age O | |
of O | |
51 O | |
years O | |
, O | |
who O | |
represented O | |
varying O | |
severity O | |
of O | |
OI O | |
and O | |
displayed O | |
an O | |
apnea O | |
and O | |
hypopnea O | |
index O | |
≥ O | |
5 O | |
/sleeping O | |
hour O | |
as O | |
recorded O | |
by O | |
an O | |
overnight O | |
polysomnography O | |
. O | |
PAP O | |
therapy O | |
was O | |
proposed O | |
to O | |
all O | |
patients O | |
. O | |
Epworth O | |
Sleepiness O | |
Scale O | |
( O | |
ESS O | |
) O | |
questionnaire O | |
to O | |
evaluate O | |
daytime O | |
sleepiness O | |
, O | |
and O | |
a O | |
validated O | |
self O | |
- O | |
rating O | |
depression O | |
questionnaire O | |
to O | |
identify O | |
possible O | |
depression O | |
, O | |
were O | |
completed O | |
prior O | |
to O | |
PAP O | |
therapy O | |
and O | |
repeated O | |
after O | |
a O | |
minimum O | |
of O | |
one O | |
year O | |
. O | |
The O | |
datasets O | |
supporting O | |
the O | |
conclusions O | |
of O | |
this O | |
article O | |
are O | |
included O | |
within O | |
the O | |
article O | |
. O | |
Results O | |
From O | |
the O | |
20 O | |
patients O | |
, O | |
15 O | |
initiated O | |
PAP O | |
therapy O | |
, O | |
and O | |
two O | |
patients O | |
later O | |
interrupted O | |
it O | |
. O | |
The O | |
mean O | |
PAP O | |
follow O | |
- O | |
up O | |
period O | |
was O | |
1230 O | |
days O | |
. O | |
At O | |
baseline O | |
, O | |
an O | |
abnormally O | |
high O | |
ESS O | |
score O | |
was O | |
reported O | |
by O | |
29 O | |
% O | |
of O | |
the O | |
respondents O | |
, O | |
and O | |
an O | |
abnormally O | |
high O | |
number O | |
of O | |
symptoms O | |
suggesting O | |
depression O | |
by O | |
29 O | |
% O | |
. O | |
Follow O | |
- O | |
up O | |
questionnaires O | |
were O | |
completed O | |
by O | |
60 O | |
% O | |
of O | |
the O | |
patients O | |
, O | |
of O | |
whom O | |
83 O | |
% O | |
were O | |
adherent O | |
to O | |
PAP O | |
treatment O | |
. O | |
ESS O | |
score O | |
and O | |
depression O | |
symptoms O | |
did O | |
not O | |
decrease O | |
significantly O | |
with O | |
PAP O | |
therapy O | |
. O | |
Conclusions O | |
Patients O | |
with O | |
OI O | |
accepted O | |
well O | |
PAP O | |
therapy O | |
and O | |
remained O | |
compliant O | |
. O | |
Sleepiness O | |
and O | |
depression O | |
persisted O | |
unaltered O | |
despite O | |
good O | |
PAP O | |
adherence O | |
. O | |
These O | |
unexpectedly O | |
poor O | |
improvements O | |
in O | |
symptoms O | |
by O | |
PAP O | |
therapy O | |
may O | |
be O | |
due O | |
to O | |
subjective O | |
depression O | |
symptoms O | |
and O | |
the O | |
complexity O | |
of O | |
factors O | |
underlying O | |
persisting O | |
sleepiness O | |
in O | |
OI O | |
. O | |
Further O | |
research O | |
is O | |
needed O | |
to O | |
confirm O | |
this O | |
novel O | |
finding O | |
. O | |
Objective O | |
Tarsal O | |
coalition O | |
is O | |
known O | |
to O | |
cause O | |
abnormal O | |
talocrural O | |
stress O | |
, O | |
hindfoot O | |
malalignment O | |
, O | |
and O | |
ankle O | |
sprains O | |
. O | |
These O | |
can O | |
all O | |
be O | |
associated O | |
with O | |
osteochondritis O | |
dissecans O | |
( O | |
OCD O | |
) O | |
of O | |
the O | |
talar O | |
dome O | |
. O | |
We O | |
present O | |
the O | |
first O | |
detailed O | |
description O | |
of O | |
a O | |
series O | |
of O | |
talar O | |
OCDs O | |
occurring O | |
in O | |
patients O | |
with O | |
tarsal O | |
coalition O | |
, O | |
with O | |
the O | |
goal O | |
of O | |
determining O | |
whether O | |
there O | |
is O | |
an O | |
increased O | |
prevalence B-EPI | |
of O | |
OCDs O | |
among O | |
patients O | |
with O | |
tarsal O | |
coalition O | |
. O | |
Materials O | |
and O | |
methods O | |
We O | |
studied O | |
ankle O | |
MRIs O | |
in O | |
57 O | |
patients O | |
with O | |
tarsal O | |
coalitions O | |
, O | |
excluding O | |
those O | |
with O | |
a O | |
reported O | |
inciting O | |
traumatic O | |
event O | |
. O | |
The O | |
MRIs O | |
were O | |
performed O | |
on O | |
magnetic O | |
field O | |
strengths O | |
ranging O | |
from O | |
0.3 O | |
to O | |
1.5 O | |
T O | |
and O | |
included O | |
axial O | |
, O | |
coronal O | |
, O | |
and O | |
sagittal O | |
T1 O | |
and O | |
T2 O | |
or O | |
PD O | |
fat O | |
- O | |
suppressed O | |
sequences O | |
. O | |
We O | |
evaluated O | |
the O | |
morphology O | |
and O | |
location O | |
of O | |
classically O | |
described O | |
OCDs O | |
in O | |
these O | |
patients O | |
, O | |
type O | |
and O | |
location O | |
of O | |
concomitant O | |
tarsal O | |
coalition O | |
, O | |
and O | |
, O | |
when O | |
available O | |
, O | |
the O | |
presence O | |
of O | |
pes O | |
planus O | |
and O | |
hindfoot O | |
valgus O | |
on O | |
weight O | |
- O | |
bearing O | |
radiographs O | |
. O | |
Chi O | |
- O | |
squared O | |
analysis O | |
was O | |
used O | |
to O | |
compare O | |
categorical O | |
variables O | |
and O | |
a O | |
Student O | |
's O | |
t O | |
test O | |
was O | |
used O | |
for O | |
parametric O | |
continuous O | |
variables O | |
. O | |
Additionally O | |
, O | |
logistic O | |
regression O | |
was O | |
used O | |
to O | |
compute O | |
the O | |
odds O | |
ratio O | |
of O | |
talar O | |
OCD O | |
associated O | |
with O | |
patient O | |
age O | |
, O | |
gender O | |
, O | |
laterality O | |
, O | |
pes O | |
planus O | |
status O | |
, O | |
hindfoot O | |
valgus O | |
status O | |
, O | |
and O | |
coalition O | |
type O | |
. O | |
Results O | |
Eighty O | |
- O | |
nine O | |
percent O | |
of O | |
tarsal O | |
coalitions O | |
were O | |
non O | |
- O | |
osseous O | |
coalitions O | |
and O | |
the O | |
calcaneonavicular O | |
space O | |
was O | |
the O | |
most O | |
common O | |
site O | |
of O | |
abnormal O | |
tarsal O | |
connection O | |
( O | |
54.4 O | |
% O | |
) O | |
. O | |
In O | |
the O | |
29 O | |
patients O | |
with O | |
tarsal O | |
coalitions O | |
and O | |
talar O | |
OCDs O | |
, O | |
OCDs O | |
commonly O | |
occurred O | |
medially O | |
( O | |
75.9 O | |
% O | |
) O | |
. O | |
In O | |
the O | |
sagittal O | |
plane O | |
, O | |
talar O | |
OCDs O | |
occurred O | |
centrally O | |
, O | |
with O | |
only O | |
one O | |
case O | |
sparing O | |
the O | |
central O | |
talar O | |
dome O | |
. O | |
The O | |
mean O | |
surface O | |
area O | |
of O | |
the O | |
29 O | |
OCDs O | |
was O | |
89.7 O | |
mm O | |
2 O | |
. O | |
Both O | |
osseous O | |
coalition O | |
and O | |
hindfoot O | |
valgus O | |
were O | |
associated O | |
with O | |
smaller O | |
talar O | |
OCD O | |
mean O | |
surface O | |
area O | |
( O | |
p O | |
= O | |
0.015 O | |
and O | |
p O | |
= O | |
0.0001 O | |
, O | |
respectively O | |
) O | |
. O | |
There O | |
was O | |
no O | |
association O | |
between O | |
depth O | |
and O | |
surface O | |
area O | |
of O | |
talar O | |
OCD O | |
with O | |
either O | |
coalition O | |
location O | |
or O | |
presence O | |
of O | |
pes O | |
planus O | |
( O | |
coalition O | |
location O | |
: O | |
p O | |
= O | |
0.455 O | |
for O | |
depth O | |
and O | |
p O | |
= O | |
0.295 O | |
for O | |
surface O | |
area O | |
; O | |
presence O | |
of O | |
pes O | |
planus O | |
: O | |
p O | |
= O | |
0.593 O | |
for O | |
depth O | |
and O | |
p O | |
= O | |
0.367 O | |
for O | |
surface O | |
area O | |
) O | |
. O | |
Conclusion O | |
Talar O | |
OCD O | |
prevalence B-EPI | |
is O | |
higher O | |
in O | |
patients O | |
with O | |
tarsal O | |
coalition O | |
than O | |
that O | |
reported O | |
for O | |
the O | |
general O | |
population O | |
. O | |
This O | |
occurrence B-EPI | |
may O | |
relate O | |
to O | |
altered O | |
biomechanics O | |
and O | |
repetitive O | |
talocrural O | |
stress O | |
owing O | |
to O | |
altered O | |
subtalar O | |
motion O | |
, O | |
particularly O | |
given O | |
the O | |
findings O | |
of O | |
increased O | |
odds O | |
of O | |
talar O | |
OCD O | |
in O | |
older O | |
patients O | |
, O | |
as O | |
well O | |
as O | |
weak O | |
associations O | |
between O | |
OCD O | |
surface O | |
area O | |
and O | |
both O | |
non O | |
- O | |
osseous O | |
coalition O | |
and O | |
hindfoot O | |
alignment O | |
. O | |
However O | |
, O | |
we O | |
did O | |
not O | |
find O | |
any O | |
specific O | |
OCD O | |
morphologic O | |
features O | |
attributable O | |
to O | |
the O | |
precise O | |
location O | |
of O | |
the O | |
tarsal O | |
coalition O | |
. O | |
Gyrate O | |
Atrophy O | |
( O | |
GA O | |
) O | |
of O | |
the O | |
choroid O | |
and O | |
retina O | |
( O | |
MIM O | |
# O | |
258870 O | |
) O | |
is O | |
an O | |
autosomal O | |
recessive O | |
disorder O | |
due O | |
to O | |
mutations O | |
of O | |
the O | |
OAT O | |
gene O | |
encoding O | |
ornithine O | |
- O | |
delta O | |
- O | |
aminotransferase O | |
( O | |
OAT O | |
) O | |
, O | |
associated O | |
with O | |
progressive O | |
retinal O | |
deterioration O | |
and O | |
blindness O | |
. O | |
The O | |
disease O | |
has O | |
a O | |
theoretical O | |
global B-LOC | |
incidence B-EPI | |
of O | |
approximately B-STAT | |
1:1,500,000 I-STAT | |
. O | |
OAT O | |
is O | |
mainly O | |
involved O | |
in O | |
ornithine O | |
catabolism O | |
in O | |
adults O | |
, O | |
thus O | |
explaining O | |
the O | |
hyperornithinemia O | |
as O | |
hallmark O | |
of O | |
the O | |
disease O | |
. O | |
Patients O | |
are O | |
treated O | |
with O | |
an O | |
arginine O | |
- O | |
restricted O | |
diet O | |
, O | |
to O | |
limit O | |
ornithine O | |
load O | |
, O | |
or O | |
the O | |
administration O | |
of O | |
Vitamin O | |
B6 O | |
, O | |
a O | |
precursor O | |
of O | |
the O | |
OAT O | |
coenzyme O | |
pyridoxal O | |
phosphate O | |
. O | |
Although O | |
the O | |
clinical O | |
and O | |
genetic O | |
aspects O | |
of O | |
GA O | |
are O | |
known O | |
for O | |
many O | |
years O | |
, O | |
the O | |
enzymatic O | |
phenotype O | |
of O | |
pathogenic O | |
variants O | |
and O | |
their O | |
response O | |
to O | |
Vitamin O | |
B6 O | |
, O | |
as O | |
well O | |
as O | |
the O | |
molecular O | |
mechanisms O | |
explaining O | |
retinal O | |
damage O | |
, O | |
are O | |
poorly O | |
clarified O | |
. O | |
Herein O | |
, O | |
we O | |
provide O | |
an O | |
overview O | |
of O | |
the O | |
current O | |
knowledge O | |
on O | |
the O | |
biochemical O | |
properties O | |
of O | |
human O | |
OAT O | |
and O | |
on O | |
the O | |
molecular O | |
, O | |
cellular O | |
, O | |
and O | |
clinical O | |
aspects O | |
of O | |
GA O | |
. O | |
As O | |
the O | |
HIV O | |
epidemic O | |
in O | |
sub B-LOC | |
- I-LOC | |
Saharan I-LOC | |
Africa I-LOC | |
matures O | |
, O | |
evidence O | |
about O | |
the O | |
age O | |
distribution O | |
of O | |
new O | |
HIV O | |
infections O | |
and O | |
how O | |
this O | |
distribution O | |
has O | |
changed O | |
over O | |
the O | |
epidemic O | |
is O | |
needed O | |
to O | |
guide O | |
HIV O | |
prevention O | |
. O | |
We O | |
aimed O | |
to O | |
assess O | |
trends O | |
in O | |
age O | |
- O | |
specific O | |
HIV O | |
incidence B-EPI | |
in O | |
six O | |
population O | |
- O | |
based O | |
cohort O | |
studies O | |
in O | |
eastern B-LOC | |
and I-LOC | |
southern I-LOC | |
Africa I-LOC | |
, O | |
reporting O | |
changes O | |
in O | |
mean O | |
age O | |
at O | |
infection O | |
, O | |
age O | |
distribution O | |
of O | |
new O | |
infections O | |
, O | |
and O | |
birth B-EPI | |
cohort I-EPI | |
cumulative B-EPI | |
incidence I-EPI | |
. O | |
We O | |
used O | |
a O | |
Bayesian O | |
model O | |
to O | |
reconstruct O | |
age O | |
- O | |
specific O | |
HIV O | |
incidence B-EPI | |
from O | |
repeated O | |
observations O | |
of O | |
individuals O | |
' O | |
HIV O | |
serostatus O | |
and O | |
survival O | |
collected O | |
among O | |
population O | |
HIV O | |
cohorts O | |
in O | |
rural O | |
Malawi B-LOC | |
, O | |
South B-LOC | |
Africa I-LOC | |
, O | |
Tanzania B-LOC | |
, O | |
Uganda B-LOC | |
, O | |
and O | |
Zimbabwe B-LOC | |
, O | |
in O | |
a O | |
collaborative O | |
analysis O | |
of O | |
the O | |
ALPHA O | |
network O | |
. O | |
We O | |
modelled O | |
HIV O | |
incidence B-EPI | |
rates I-EPI | |
by O | |
age O | |
, O | |
time O | |
, O | |
and O | |
sex O | |
using O | |
smoothing O | |
splines O | |
functions O | |
. O | |
We O | |
estimated B-EPI | |
incidence B-EPI | |
trends O | |
separately O | |
by O | |
sex O | |
and O | |
study O | |
. O | |
We O | |
used O | |
estimated B-EPI | |
incidence I-EPI | |
and O | |
prevalence B-EPI | |
results O | |
for O | |
2000 B-DATE | |
- I-DATE | |
17 I-DATE | |
, O | |
standardised O | |
to O | |
study O | |
population O | |
distribution O | |
, O | |
to O | |
estimate O | |
mean O | |
age O | |
at O | |
infection O | |
and O | |
proportion O | |
of O | |
new O | |
infections O | |
by O | |
age O | |
. O | |
We O | |
also O | |
estimated O | |
cumulative B-EPI | |
incidence I-EPI | |
( O | |
lifetime O | |
risk O | |
of O | |
infection O | |
) O | |
by O | |
birth O | |
cohort O | |
. O | |
Age B-EPI | |
- O | |
specific I-EPI | |
incidence B-EPI | |
declined O | |
at O | |
all O | |
ages O | |
, O | |
although O | |
the O | |
timing O | |
and O | |
pattern O | |
of O | |
decline O | |
varied O | |
by O | |
study O | |
. O | |
The O | |
mean O | |
age O | |
at O | |
infection O | |
was O | |
higher O | |
in O | |
men B-SEX | |
( O | |
cohort O | |
mean O | |
27·8 O | |
- O | |
34·6 O | |
years O | |
) O | |
than O | |
in O | |
women B-SEX | |
( O | |
24·8 O | |
- O | |
29·6 O | |
years O | |
) O | |
. O | |
Between B-DATE | |
2000 I-DATE | |
and I-DATE | |
2017 I-DATE | |
, O | |
the O | |
mean O | |
age O | |
at O | |
infection O | |
per O | |
cohort O | |
increased O | |
slightly O | |
: O | |
0·5 O | |
to O | |
2·8 O | |
years O | |
among O | |
men B-SEX | |
and O | |
-0·2 O | |
to O | |
2·5 O | |
years O | |
among O | |
women B-SEX | |
. O | |
Across O | |
studies O | |
, O | |
between O | |
38 O | |
% O | |
and O | |
63 O | |
% O | |
( O | |
cohort O | |
medians O | |
) O | |
of O | |
the O | |
infections O | |
in O | |
women B-SEX | |
were O | |
among O | |
those O | |
aged O | |
15 O | |
- O | |
24 O | |
years O | |
and O | |
between O | |
30 O | |
% O | |
and O | |
63 O | |
% O | |
of O | |
infections O | |
in O | |
men B-SEX | |
were O | |
in O | |
those O | |
aged O | |
20 O | |
- O | |
29 O | |
years O | |
. O | |
Lifetime O | |
risk O | |
of O | |
HIV O | |
declined O | |
for O | |
successive O | |
birth O | |
cohorts O | |
. O | |
HIV O | |
incidence B-EPI | |
declined O | |
in O | |
all O | |
age O | |
groups O | |
and O | |
shifted O | |
slightly O | |
to O | |
older O | |
ages O | |
. O | |
Disproportionate O | |
new O | |
HIV O | |
infections O | |
occur O | |
among O | |
women B-SEX | |
aged O | |
15 O | |
- O | |
24 O | |
years O | |
and O | |
men B-SEX | |
aged O | |
20 O | |
- O | |
29 O | |
years O | |
, O | |
supporting O | |
focused O | |
prevention O | |
in O | |
these O | |
groups O | |
. O | |
However O | |
, O | |
40 O | |
- O | |
60 O | |
% O | |
of O | |
infections O | |
were O | |
outside O | |
these O | |
ages O | |
, O | |
emphasising O | |
the O | |
importance O | |
of O | |
providing O | |
appropriate O | |
HIV O | |
prevention O | |
to O | |
adults O | |
of O | |
all O | |
ages O | |
. O | |
Bill O | |
& O | |
Melinda O | |
Gates O | |
Foundation O | |
. O | |
Over O | |
260,000 O | |
( O | |
2013 B-DATE | |
) O | |
new O | |
oral O | |
squamous O | |
cell O | |
carcinoma O | |
( O | |
OSCC O | |
) O | |
cases O | |
are O | |
reported O | |
annually O | |
worldwide B-LOC | |
. O | |
Despite O | |
development O | |
in O | |
OSCC O | |
management O | |
, O | |
the O | |
outcome O | |
is O | |
still O | |
unsatisfactory O | |
. O | |
Identification O | |
of O | |
new O | |
molecular O | |
markers O | |
may O | |
be O | |
of O | |
use O | |
in O | |
prevention O | |
, O | |
prognosis O | |
, O | |
and O | |
choice O | |
of O | |
an O | |
appropriate O | |
therapy O | |
. O | |
The O | |
intracellular O | |
molecular O | |
signalling O | |
pathway O | |
of O | |
phosphatidyl O | |
- O | |
inositol-3 O | |
- O | |
kinase O | |
is O | |
involved O | |
in O | |
the O | |
process O | |
of O | |
cell O | |
growth O | |
, O | |
differentiation O | |
, O | |
migration O | |
, O | |
and O | |
survival O | |
. O | |
The O | |
main O | |
components O | |
of O | |
this O | |
pathway O | |
: O | |
PIK3CA O | |
( O | |
phosphatidylinositol-4,5 O | |
- O | |
bisphosphate-3 O | |
- O | |
kinase O | |
catalytic O | |
subunit O | |
[alpha] O | |
) O | |
, O | |
PTEN O | |
( O | |
phosphatase O | |
and O | |
tensin O | |
homologue O | |
deleted O | |
on O | |
chromosome O | |
10 O | |
) O | |
, O | |
and O | |
AKT O | |
( O | |
serine O | |
- O | |
threonine O | |
kinase O | |
) O | |
are O | |
potential O | |
objects O | |
of O | |
research O | |
when O | |
introducing O | |
new O | |
therapeutic O | |
agents O | |
. O | |
The O | |
aim O | |
of O | |
this O | |
paper O | |
is O | |
to O | |
evaluate O | |
the O | |
PIK3CA O | |
, O | |
PTEN O | |
, O | |
and O | |
AKT O | |
gene O | |
mutations O | |
as O | |
prognostic O | |
factors O | |
in O | |
OSCC O | |
and O | |
to O | |
describe O | |
their O | |
role O | |
in O | |
aggressive O | |
disease O | |
progression O | |
. O | |
This O | |
is O | |
crucial O | |
for O | |
oral O | |
cancer O | |
biology O | |
understanding O | |
and O | |
for O | |
indicating O | |
which O | |
direction O | |
new O | |
clinical O | |
treatments O | |
should O | |
take O | |
. O | |
Gastrointestinal O | |
symptoms O | |
are O | |
among O | |
the O | |
most O | |
common O | |
complaints O | |
in O | |
patients O | |
with O | |
postural O | |
tachycardia O | |
syndrome O | |
( O | |
POTS O | |
) O | |
. O | |
In O | |
some O | |
cases O | |
, O | |
they O | |
dominate O | |
the O | |
clinical O | |
presentation O | |
and O | |
cause O | |
substantial O | |
disabilities O | |
, O | |
including O | |
significant O | |
weight O | |
loss O | |
and O | |
malnutrition O | |
, O | |
that O | |
require O | |
the O | |
use O | |
of O | |
invasive O | |
treatment O | |
to O | |
support O | |
caloric O | |
intake O | |
. O | |
Multiple O | |
cross O | |
- O | |
sectional O | |
studies O | |
have O | |
reported O | |
a O | |
high O | |
prevalence B-EPI | |
of O | |
gastrointestinal O | |
symptoms O | |
in O | |
POTS O | |
patients O | |
with O | |
connective O | |
tissue O | |
diseases O | |
, O | |
such O | |
as O | |
Ehlers O | |
- O | |
Danlos O | |
, O | |
hypermobile O | |
type O | |
, O | |
and O | |
in O | |
patients O | |
with O | |
evidence O | |
of O | |
autonomic O | |
neuropathy O | |
. O | |
Previous O | |
studies O | |
that O | |
evaluated O | |
gastric O | |
motility O | |
in O | |
these O | |
patients O | |
reported O | |
a O | |
wide O | |
range O | |
of O | |
abnormalities O | |
, O | |
particularly O | |
delayed O | |
gastric O | |
emptying O | |
. O | |
The O | |
pathophysiology O | |
of O | |
gastrointestinal O | |
symptoms O | |
in O | |
POTS O | |
is O | |
likely O | |
multifactorial O | |
and O | |
probably O | |
depends O | |
on O | |
the O | |
co O | |
- O | |
morbid O | |
conditions O | |
. O | |
In O | |
patients O | |
with O | |
POTS O | |
and O | |
Ehlers O | |
- O | |
Danlos O | |
syndromes O | |
, O | |
structural O | |
and O | |
functional O | |
abnormalities O | |
in O | |
the O | |
gastrointestinal O | |
connective O | |
tissue O | |
may O | |
play O | |
a O | |
significant O | |
role O | |
, O | |
whereas O | |
in O | |
neuropathic O | |
POTS O | |
, O | |
the O | |
gastrointestinal O | |
tract O | |
motility O | |
and O | |
gut O | |
hormonal O | |
secretion O | |
may O | |
be O | |
directly O | |
impaired O | |
due O | |
to O | |
localized O | |
autonomic O | |
denervation O | |
. O | |
In O | |
patients O | |
with O | |
normal O | |
gastrointestinal O | |
motility O | |
but O | |
persistent O | |
gastrointestinal O | |
symptoms O | |
, O | |
gastrointestinal O | |
functional O | |
disorders O | |
should O | |
be O | |
considered O | |
. O | |
We O | |
performed O | |
a O | |
systematic O | |
review O | |
of O | |
the O | |
literature O | |
related O | |
to O | |
POTS O | |
and O | |
gastrointestinal O | |
symptoms O | |
have O | |
proposed O | |
possible O | |
mechanisms O | |
and O | |
discussed O | |
diagnosis O | |
and O | |
treatment O | |
approaches O | |
for O | |
delayed O | |
gastric O | |
emptying O | |
, O | |
the O | |
most O | |
common O | |
gastrointestinal O | |
abnormality O | |
reported O | |
in O | |
patients O | |
with O | |
POTS O | |
. O | |
Background O | |
We O | |
evaluated O | |
the O | |
association O | |
between O | |
maternal O | |
antiretrovirals O | |
( O | |
ARVs O | |
) O | |
during O | |
pregnancy O | |
and O | |
infant O | |
congenital O | |
anomalies O | |
( O | |
CAs O | |
) O | |
, O | |
utilizing O | |
data O | |
from O | |
the O | |
National O | |
Institute O | |
of O | |
Child O | |
Health O | |
and O | |
Human O | |
Development O | |
International O | |
Site O | |
Development O | |
Initiative O | |
Perinatal O | |
Study O | |
. O | |
Methods O | |
The O | |
study O | |
population O | |
consisted O | |
of O | |
first O | |
singleton O | |
pregnancies O | |
on O | |
study O | |
, O | |
> O | |
or O | |
= O | |
20 O | |
weeks O | |
gestation O | |
, O | |
among O | |
women B-SEX | |
enrolled O | |
in O | |
NISDI B-LOC | |
from O | |
Argentina B-LOC | |
and O | |
Brazil B-LOC | |
who O | |
delivered O | |
between B-DATE | |
September I-DATE | |
2002 I-DATE | |
and I-DATE | |
October I-DATE | |
2007 I-DATE | |
. O | |
CAs O | |
were O | |
defined O | |
as O | |
any O | |
major O | |
structural O | |
or O | |
chromosomal O | |
abnormality O | |
, O | |
or O | |
a O | |
cluster O | |
of O | |
2 O | |
or O | |
more O | |
minor O | |
abnormalities O | |
, O | |
according O | |
to O | |
the O | |
conventions O | |
of O | |
the O | |
Antiretroviral O | |
Pregnancy O | |
Registry O | |
. O | |
CAs O | |
were O | |
identified O | |
from O | |
fetal O | |
ultrasound O | |
, O | |
study O | |
visit O | |
, O | |
and O | |
death O | |
reports O | |
. O | |
Prevalence B-EPI | |
rates I-EPI | |
[ O | |
number O | |
of O | |
CAs O | |
per I-STAT | |
100 I-STAT | |
live I-STAT | |
births I-STAT | |
( O | |
LBs I-STAT | |
) O | |
] O | |
were O | |
calculated O | |
for O | |
specific O | |
ARVs O | |
, O | |
classes O | |
of O | |
ARVs O | |
, O | |
and O | |
overall O | |
exposure O | |
to O | |
ARVs O | |
. O | |
Results O | |
Of O | |
1229 O | |
women B-SEX | |
enrolled O | |
, O | |
995 O | |
pregnancy O | |
outcomes O | |
( O | |
974 O | |
LBs O | |
) O | |
met O | |
the O | |
inclusion O | |
criteria O | |
. O | |
Of O | |
these O | |
, O | |
60 O | |
infants O | |
( O | |
59 O | |
LBs O | |
and O | |
1 O | |
stillbirth O | |
) O | |
had O | |
at O | |
least O | |
1 O | |
CA O | |
. O | |
The O | |
overall B-EPI | |
prevalence I-EPI | |
of O | |
CAs O | |
( O | |
per I-STAT | |
100 I-STAT | |
LBs I-STAT | |
) O | |
was O | |
6.2 B-STAT | |
[ O | |
95 O | |
% O | |
confidence O | |
interval O | |
( O | |
CI O | |
) O | |
4.6 O | |
to O | |
7.7 O | |
] O | |
. O | |
The O | |
prevalence B-EPI | |
of O | |
CAs O | |
after O | |
first O | |
trimester O | |
ARVs O | |
( O | |
6.2 O | |
; O | |
95 O | |
% O | |
CI O | |
3.1 O | |
to O | |
9.3 O | |
) O | |
was O | |
similar O | |
to O | |
that O | |
after O | |
second O | |
( O | |
6.8 O | |
; O | |
95 O | |
% O | |
CI O | |
4.5 O | |
to O | |
9.0 O | |
) O | |
or O | |
third O | |
trimester O | |
( O | |
4.3 O | |
; O | |
95 O | |
% O | |
CI O | |
1.5 O | |
to O | |
7.2 O | |
) O | |
exposure O | |
. O | |
The O | |
rate O | |
of O | |
CAs O | |
identified O | |
within O | |
7 O | |
days O | |
of O | |
delivery O | |
was O | |
2.36 O | |
( O | |
95 O | |
% O | |
CI O | |
1.4 O | |
to O | |
3.3 O | |
) O | |
. O | |
Conclusions O | |
The O | |
prevalence B-EPI | |
of O | |
CAs O | |
after O | |
first O | |
trimester O | |
exposure O | |
to O | |
ARVs O | |
was O | |
similar O | |
to O | |
that O | |
after O | |
second O | |
or O | |
third O | |
trimester O | |
exposure O | |
. O | |
Continued O | |
surveillance O | |
for O | |
CAs O | |
among O | |
children O | |
exposed O | |
to O | |
ARVs O | |
during O | |
gestation O | |
is O | |
needed O | |
. O | |
The O | |
zoonosis O | |
Q O | |
fever O | |
is O | |
caused O | |
by O | |
the O | |
obligate O | |
intracellular O | |
bacterium O | |
Coxiella O | |
burnetii O | |
. O | |
Besides O | |
the O | |
main O | |
transmission O | |
route O | |
via O | |
inhalation O | |
of O | |
contaminated O | |
aerosols O | |
, O | |
ticks O | |
are O | |
discussed O | |
as O | |
vectors O | |
since O | |
the O | |
first O | |
isolation O | |
of O | |
the O | |
pathogen O | |
from O | |
a O | |
Dermacentor O | |
andersonii O | |
tick O | |
. O | |
The O | |
rare O | |
detection O | |
of O | |
C. O | |
burnetii O | |
in O | |
ticks O | |
and O | |
the O | |
difficult O | |
differentiation O | |
of O | |
C. O | |
burnetii O | |
from O | |
Coxiella O | |
-like O | |
endosymbionts O | |
( O | |
CLEs O | |
) O | |
are O | |
questioning O | |
the O | |
relevance O | |
of O | |
ticks O | |
in O | |
the O | |
epidemiology O | |
of O | |
Q O | |
fever O | |
. O | |
In O | |
this O | |
review O | |
, O | |
literature O | |
databases O | |
were O | |
systematically O | |
searched O | |
for O | |
recent O | |
prevalence B-EPI | |
studies O | |
concerning O | |
C. O | |
burnetii O | |
in O | |
ticks O | |
in O | |
Europe B-LOC | |
and O | |
experimental O | |
studies O | |
evaluating O | |
the O | |
vector O | |
competence O | |
of O | |
tick O | |
species O | |
. O | |
A O | |
total O | |
of O | |
72 O | |
prevalence B-EPI | |
studies O | |
were O | |
included O | |
and O | |
evaluated O | |
regarding O | |
DNA O | |
detection O | |
methods O | |
and O | |
collection O | |
methods O | |
, O | |
country O | |
, O | |
and O | |
tested O | |
tick O | |
species O | |
. O | |
Specimens O | |
of O | |
more O | |
than O | |
25 O | |
different O | |
tick O | |
species O | |
were O | |
collected O | |
in O | |
23 O | |
European O | |
countries O | |
. O | |
Overall O | |
, O | |
an O | |
average B-EPI | |
prevalence I-EPI | |
of O | |
4.8 B-STAT | |
% I-STAT | |
was O | |
determined O | |
. O | |
However O | |
, O | |
in O | |
half O | |
of O | |
the O | |
studies O | |
, O | |
no O | |
Coxiella O | |
-DNA O | |
was O | |
detected O | |
. O | |
In O | |
Southern B-LOC | |
European I-LOC | |
countries I-LOC | |
, O | |
a O | |
significantly O | |
higher O | |
prevalence B-EPI | |
was O | |
observed O | |
, O | |
possibly O | |
related O | |
to O | |
the O | |
abundance O | |
of O | |
different O | |
tick O | |
species O | |
here O | |
, O | |
namely O | |
Hyalomma O | |
spp O | |
. O | |
and O | |
Rhipicephalus O | |
spp O | |
. O | |
In O | |
comparison O | |
, O | |
a O | |
similar O | |
proportion O | |
of O | |
studies O | |
used O | |
ticks O | |
sampled O | |
by O | |
flagging O | |
and O | |
dragging O | |
or O | |
tick O | |
collection O | |
from O | |
animals O | |
, O | |
under O | |
30 O | |
% O | |
of O | |
the O | |
total O | |
tick O | |
samples O | |
derived O | |
from O | |
the O | |
latter O | |
. O | |
There O | |
was O | |
no O | |
significant O | |
difference O | |
in O | |
the O | |
various O | |
target O | |
genes O | |
used O | |
for O | |
the O | |
molecular O | |
test O | |
. O | |
In O | |
most O | |
of O | |
the O | |
studies O | |
, O | |
no O | |
distinction O | |
was O | |
made O | |
between O | |
C. O | |
burnetii O | |
and O | |
CLEs O | |
. O | |
The O | |
application O | |
of O | |
specific O | |
detection O | |
methods O | |
and O | |
the O | |
confirmation O | |
of O | |
positive O | |
results O | |
are O | |
crucial O | |
to O | |
determine O | |
the O | |
role O | |
of O | |
ticks O | |
in O | |
Q O | |
fever O | |
transmission O | |
. O | |
Only O | |
two O | |
studies O | |
were O | |
available O | |
, O | |
which O | |
assessed O | |
the O | |
vector O | |
competence O | |
of O | |
ticks O | |
for O | |
C. O | |
burnetii O | |
in O | |
the O | |
last O | |
20 O | |
years O | |
, O | |
demonstrating O | |
the O | |
need O | |
for O | |
further O | |
research O | |
. O | |
Background O | |
Wilson O | |
disease O | |
( O | |
WD O | |
) O | |
is O | |
an O | |
autosomal O | |
recessive O | |
disorder O | |
caused O | |
by O | |
mutations O | |
in O | |
the O | |
ATP7B O | |
gene O | |
. O | |
In O | |
1984 B-DATE | |
, O | |
Scheinberg B-LOC | |
and O | |
Sternlieb B-LOC | |
estimated O | |
the O | |
prevalence B-EPI | |
of O | |
WD O | |
to O | |
be O | |
1:30,000 B-STAT | |
. O | |
However O | |
, O | |
recent O | |
epidemiological O | |
studies O | |
have O | |
reported O | |
increasing O | |
prevalence B-EPI | |
rates I-EPI | |
in O | |
different O | |
populations O | |
. O | |
The O | |
carrier O | |
frequency O | |
of O | |
ATP7B O | |
variants O | |
and O | |
the O | |
prevalence B-EPI | |
of O | |
WD O | |
in O | |
the O | |
Japanese B-ETHN | |
population O | |
have O | |
not O | |
been O | |
reported O | |
using O | |
multiple O | |
databases O | |
. O | |
Methods O | |
Multiple O | |
public O | |
databases O | |
were O | |
used O | |
. O | |
First O | |
, O | |
we O | |
included O | |
mutations O | |
in O | |
the O | |
ATP7B O | |
gene O | |
that O | |
were O | |
registered O | |
in O | |
the O | |
Human O | |
Gene O | |
Mutation O | |
Database O | |
( O | |
HGMD O | |
) O | |
Professional O | |
, O | |
where O | |
885 O | |
ATP7B O | |
variants O | |
were O | |
identified O | |
as O | |
pathogenic O | |
. O | |
Next O | |
, O | |
we O | |
investigated O | |
the O | |
allele O | |
frequencies O | |
of O | |
these O | |
885 O | |
variants O | |
in O | |
Japanese B-ETHN | |
individuals O | |
using O | |
the O | |
Human O | |
Genetic O | |
Variation O | |
Database O | |
( O | |
HGVD O | |
) O | |
and O | |
the O | |
Japanese B-ETHN | |
Multi O | |
Omics O | |
Reference O | |
Panel O | |
( O | |
jMorp O | |
) O | |
. O | |
Results O | |
Of O | |
the O | |
885 O | |
variants O | |
of O | |
ATP7B O | |
, O | |
7 O | |
and O | |
12 O | |
missense O | |
and O | |
nonsense O | |
variants O | |
, O | |
0 O | |
and O | |
3 O | |
splicing O | |
variants O | |
, O | |
and O | |
0 O | |
and O | |
2 O | |
small O | |
deletions O | |
were O | |
found O | |
in O | |
the O | |
HGVD O | |
and O | |
in O | |
jMorp O | |
, O | |
respectively O | |
. O | |
The O | |
total O | |
allele O | |
frequencies O | |
of O | |
the O | |
ATP7B O | |
mutations O | |
were O | |
0.011 O | |
in O | |
the O | |
HGVD O | |
and O | |
0.014 O | |
in O | |
the O | |
jMorp O | |
. O | |
According O | |
to O | |
these O | |
data O | |
, O | |
the O | |
carrier O | |
frequencies O | |
were O | |
0.022 O | |
( O | |
2.2 O | |
% O | |
) O | |
and O | |
0.028 O | |
( O | |
2.8 O | |
% O | |
) O | |
, O | |
respectively O | |
, O | |
and O | |
patient O | |
frequencies O | |
were O | |
0.000121 B-STAT | |
( O | |
1.21/10,000 B-STAT | |
individuals I-STAT | |
) O | |
and O | |
0.000196 B-STAT | |
( O | |
1.96/10,000 B-STAT | |
individuals I-STAT | |
) O | |
, O | |
respectively O | |
. O | |
Conclusion O | |
This O | |
is O | |
the O | |
first O | |
study O | |
to O | |
report O | |
the O | |
carrier O | |
frequency O | |
of O | |
ATP7B O | |
variants O | |
and O | |
the O | |
prevalence B-EPI | |
of O | |
WD O | |
in O | |
Japan B-LOC | |
using O | |
multiple O | |
databases O | |
. O | |
The O | |
calculated B-EPI | |
prevalence I-EPI | |
of O | |
WD O | |
was O | |
comparatively O | |
higher O | |
than O | |
that O | |
of O | |
previous O | |
reports O | |
, O | |
indicating O | |
previous O | |
underdiagnosis O | |
or O | |
the O | |
existence O | |
of O | |
less O | |
severe O | |
phenotypes O | |
. O | |
Purpose O | |
of O | |
review O | |
In O | |
this O | |
review O | |
, O | |
we O | |
report O | |
on O | |
the O | |
state O | |
of O | |
knowledge O | |
about O | |
human O | |
Q O | |
fever O | |
in O | |
Brazil B-LOC | |
and O | |
on O | |
the O | |
Guiana B-LOC | |
Shield I-LOC | |
, O | |
an O | |
Amazonian B-LOC | |
region O | |
located O | |
in O | |
northeastern B-LOC | |
South I-LOC | |
America I-LOC | |
. O | |
There O | |
is O | |
a O | |
contrast O | |
between O | |
French B-LOC | |
Guiana I-LOC | |
, O | |
where O | |
the O | |
incidence B-EPI | |
of O | |
this O | |
disease O | |
is O | |
the O | |
highest O | |
in O | |
the O | |
world O | |
, O | |
and O | |
other O | |
countries O | |
where O | |
this O | |
disease O | |
is O | |
practically O | |
non O | |
- O | |
existent O | |
. O | |
Recent O | |
findings O | |
Recent O | |
findings O | |
are O | |
essentially O | |
in O | |
French B-LOC | |
Guiana I-LOC | |
where O | |
a O | |
unique O | |
strain O | |
MST17 O | |
has O | |
been O | |
identified O | |
; O | |
it O | |
is O | |
probably O | |
more O | |
virulent O | |
than O | |
those O | |
usually O | |
found O | |
with O | |
a O | |
particularly O | |
marked O | |
pulmonary O | |
tropism O | |
, O | |
a O | |
mysterious O | |
animal O | |
reservoir O | |
, O | |
a O | |
geographical O | |
distribution O | |
that O | |
raises O | |
questions O | |
. O | |
Summary O | |
Q O | |
fever O | |
is O | |
a O | |
bacterial O | |
zoonosis O | |
due O | |
to O | |
Coxiella O | |
burnetii O | |
that O | |
has O | |
been O | |
reported O | |
worldwide B-LOC | |
. O | |
On O | |
the O | |
Guiana B-LOC | |
Shield I-LOC | |
, O | |
a O | |
region O | |
mostly O | |
covered O | |
by O | |
Amazonian O | |
forest O | |
, O | |
which O | |
encompasses O | |
the O | |
Venezuelan B-ETHN | |
State I-LOC | |
of O | |
Bolivar B-LOC | |
, O | |
Guyana B-LOC | |
, O | |
Suriname B-LOC | |
, O | |
French B-LOC | |
Guiana I-LOC | |
, O | |
and O | |
the O | |
Brazilian B-ETHN | |
State I-LOC | |
of O | |
Amapá B-LOC | |
, O | |
the O | |
situation O | |
is O | |
very O | |
heterogeneous O | |
. O | |
While O | |
French B-LOC | |
Guiana I-LOC | |
is O | |
the O | |
region O | |
reporting O | |
the O | |
highest O | |
incidence B-EPI | |
of O | |
this O | |
disease O | |
in O | |
the O | |
world O | |
, O | |
with O | |
a O | |
single O | |
infecting O | |
clone O | |
( O | |
MST O | |
117 O | |
) O | |
and O | |
a O | |
unique O | |
epidemiological O | |
cycle O | |
, O | |
it O | |
has O | |
hardly O | |
ever O | |
been O | |
reported O | |
in O | |
other O | |
countries O | |
in O | |
the O | |
region O | |
. O | |
This O | |
absence O | |
of O | |
cases O | |
raises O | |
many O | |
questions O | |
and O | |
is O | |
probably O | |
due O | |
to O | |
massive O | |
under O | |
- O | |
diagnosis O | |
. O | |
Studies O | |
should O | |
estimate O | |
comprehensively O | |
the O | |
true O | |
burden O | |
of O | |
this O | |
disease O | |
in O | |
the O | |
region O | |
. O | |
Background O | |
& O | |
methods O | |
Blastocystis O | |
sp O | |
. O | |
is O | |
one O | |
of O | |
the O | |
most O | |
prevalent B-EPI | |
unicellular O | |
eukaryote O | |
of O | |
the O | |
human O | |
large O | |
intestine O | |
in O | |
Chile B-LOC | |
and O | |
worldwide B-LOC | |
. O | |
It O | |
is O | |
classified O | |
in O | |
subtypes O | |
( O | |
STs O | |
) O | |
, O | |
where O | |
using O | |
the O | |
polymorphic O | |
sequences O | |
of O | |
its O | |
18S O | |
rRNA O | |
genes O | |
currently O | |
recognizes O | |
22 O | |
. O | |
STs O | |
1 O | |
- O | |
9 O | |
and O | |
ST12 O | |
have O | |
been O | |
reported O | |
in O | |
humans O | |
. O | |
It O | |
has O | |
been O | |
hypothesized O | |
that O | |
different O | |
STs O | |
of O | |
Blastocystis O | |
sp O | |
. O | |
differentially O | |
affect O | |
the O | |
clinical O | |
severity O | |
of O | |
the O | |
digestive O | |
disease O | |
in O | |
Irritable O | |
Bowel O | |
Syndrome O | |
( O | |
IBS O | |
) O | |
patients O | |
, O | |
but O | |
more O | |
studies O | |
ar4e O | |
needed O | |
to O | |
establish O | |
this O | |
statement O | |
. O | |
To O | |
contribute O | |
in O | |
the O | |
elucidation O | |
of O | |
the O | |
potential O | |
relationship O | |
between O | |
Blastocystis O | |
sp O | |
. O | |
subtypes O | |
and O | |
IBS O | |
severity O | |
, O | |
37 O | |
IBS O | |
patient O | |
fecal O | |
samples O | |
were O | |
collected O | |
at O | |
hospitals O | |
in O | |
Santiago B-LOC | |
( O | |
Chile B-LOC | |
) O | |
and O | |
were O | |
screened O | |
for O | |
the O | |
presence O | |
of O | |
vacuolated O | |
forms O | |
of O | |
Blastocystis O | |
sp O | |
. O | |
by O | |
using O | |
conventional O | |
microscopy O | |
. O | |
Positive O | |
samples O | |
were O | |
submitted O | |
to O | |
PCR O | |
and O | |
sequencing O | |
for O | |
determining O | |
STs O | |
. O | |
The O | |
same O | |
procedure O | |
was O | |
performed O | |
in O | |
fecal O | |
samples O | |
from O | |
five O | |
non O | |
- O | |
IBS O | |
Blastocystis O | |
sp O | |
. O | |
carriers O | |
for O | |
preliminary O | |
comparative O | |
purpose O | |
. O | |
Results O | |
and O | |
discussion O | |
Four O | |
out O | |
of O | |
the O | |
37 O | |
samples O | |
from O | |
the O | |
IBS O | |
patients O | |
were O | |
found O | |
positive O | |
for O | |
Blastocystis O | |
sp O | |
. O | |
( O | |
10.81 O | |
% O | |
) O | |
by O | |
using O | |
microscopy O | |
. O | |
The O | |
presence O | |
of O | |
this O | |
microorganism O | |
in O | |
these O | |
four O | |
samples O | |
were O | |
confirmed O | |
by O | |
PCR O | |
and O | |
sequencing O | |
. O | |
Subtypes O | |
and O | |
their O | |
respective O | |
closest O | |
match O | |
alleles O | |
were O | |
searched O | |
and O | |
the O | |
ST1 O | |
, O | |
ST2 O | |
and O | |
ST4 O | |
subtypes O | |
were O | |
found O | |
in O | |
these O | |
patients O | |
. O | |
ST4 O | |
subtype O | |
is O | |
scarcely O | |
detected O | |
in O | |
South B-LOC | |
America I-LOC | |
countries O | |
, O | |
being O | |
reported O | |
previously O | |
only O | |
in O | |
Colombia B-LOC | |
and O | |
Brazil B-LOC | |
. O | |
In O | |
this O | |
ST4 O | |
subtype O | |
we O | |
determined O | |
the O | |
allele O | |
42 O | |
which O | |
is O | |
the O | |
most O | |
frequent O | |
allele O | |
observed O | |
in O | |
human O | |
Blastocystis O | |
isolates O | |
. O | |
In O | |
the O | |
non O | |
- O | |
IBS O | |
individuals O | |
' O | |
carriers O | |
, O | |
three O | |
subtypes O | |
were O | |
found O | |
: O | |
ST1 O | |
, O | |
ST2 O | |
and O | |
ST3 O | |
, O | |
even O | |
belonging O | |
to O | |
the O | |
same O | |
family O | |
group O | |
. O | |
Closest O | |
match O | |
alleles O | |
: O | |
2 O | |
, O | |
12 O | |
and O | |
34 O | |
here O | |
detected O | |
were O | |
also O | |
commonly O | |
reported O | |
globally O | |
. O | |
Instead O | |
of O | |
the O | |
small O | |
number O | |
of O | |
IBS O | |
patients O | |
studied O | |
here O | |
, O | |
the O | |
frequency O | |
of O | |
blastocystosis O | |
detected O | |
( O | |
10.81 O | |
% O | |
) O | |
was O | |
lower O | |
than O | |
the O | |
prevalence B-EPI | |
of O | |
Blastocystis O | |
sp O | |
. O | |
infections O | |
described O | |
for O | |
the O | |
Chilean B-ETHN | |
general O | |
population O | |
( O | |
30.4 O | |
% O | |
) O | |
. O | |
In O | |
Chile B-LOC | |
, O | |
clear O | |
correlation O | |
of O | |
Blastocystis O | |
sp O | |
. O | |
subtypes O | |
and O | |
IBS O | |
severity O | |
is O | |
still O | |
lacking O | |
with O | |
this O | |
study O | |
but O | |
it O | |
may O | |
lead O | |
and O | |
contribute O | |
to O | |
a O | |
better O | |
understanding O | |
of O | |
its O | |
pathogenicity O | |
and O | |
worldwide O | |
epidemiology O | |
. O | |
Introduction O | |
: O | |
Charcot O | |
- O | |
Marie O | |
- O | |
Tooth O | |
disease O | |
( O | |
CMT O | |
) O | |
and O | |
related O | |
neuropathies O | |
represent O | |
the O | |
most O | |
prevalent B-EPI | |
inherited O | |
neuromuscular O | |
disorders O | |
. O | |
Nonetheless O | |
, O | |
there O | |
is O | |
still O | |
no O | |
pharmacological O | |
treatment O | |
available O | |
for O | |
any O | |
CMT O | |
type O | |
. O | |
However O | |
, O | |
the O | |
landscape O | |
is O | |
rapidly O | |
evolving O | |
and O | |
several O | |
novel O | |
approaches O | |
are O | |
providing O | |
encouraging O | |
results O | |
in O | |
preclinical O | |
studies O | |
and O | |
leading O | |
to O | |
clinical O | |
trials O | |
. O | |
Areas O | |
covered O | |
: O | |
The O | |
authors O | |
review O | |
the O | |
most O | |
promising O | |
therapies O | |
under O | |
study O | |
and O | |
the O | |
ongoing O | |
/ O | |
planned O | |
clinical O | |
trials O | |
. O | |
Several O | |
approaches O | |
to O | |
address O | |
PMP22 O | |
overexpression O | |
underlying O | |
CMT1A O | |
, O | |
the O | |
most O | |
frequent O | |
subtype O | |
, O | |
are O | |
being O | |
tested O | |
. O | |
Gene O | |
silencing O | |
, O | |
targeting O | |
PMP22 O | |
, O | |
and O | |
gene O | |
therapy O | |
, O | |
to O | |
introduce O | |
specific O | |
genes O | |
or O | |
to O | |
substitute O | |
or O | |
modulate O | |
defective O | |
ones O | |
, O | |
are O | |
being O | |
experimented O | |
in O | |
animal O | |
models O | |
. O | |
Compounds O | |
acting O | |
on O | |
ER O | |
stress O | |
, O | |
unfolded O | |
protein O | |
response O | |
, O | |
neuregulin O | |
pathways O | |
, O | |
phosphoinositides O | |
metabolism O | |
, O | |
axonal O | |
transport O | |
and O | |
degeneration O | |
, O | |
inflammation O | |
, O | |
polyol O | |
pathway O | |
, O | |
deoxysphingolipid O | |
metabolism O | |
, O | |
purine O | |
nucleotide O | |
pool O | |
are O | |
potential O | |
therapeutic O | |
candidates O | |
for O | |
different O | |
forms O | |
of O | |
CMT O | |
and O | |
related O | |
neuropathies O | |
. O | |
Expert O | |
opinion O | |
: O | |
We O | |
are O | |
getting O | |
closer O | |
to O | |
find O | |
effective O | |
therapies O | |
for O | |
CMT O | |
, O | |
but O | |
are O | |
far O | |
behind O | |
the O | |
exciting O | |
examples O | |
of O | |
other O | |
genetic O | |
neuromuscular O | |
disorders O | |
. O | |
The O | |
authors O | |
analyze O | |
the O | |
possible O | |
reasons O | |
for O | |
this O | |
gap O | |
and O | |
the O | |
way O | |
to O | |
fill O | |
it O | |
. O | |
Preclinical O | |
and O | |
clinical O | |
research O | |
is O | |
ongoing O | |
with O | |
coordinated O | |
efforts O | |
and O | |
they O | |
are O | |
confident O | |
that O | |
in O | |
the O | |
next O | |
few O | |
years O | |
we O | |
will O | |
see O | |
the O | |
first O | |
effective O | |
treatments O | |
. O | |
Over O | |
90 O | |
years O | |
ago O | |
, O | |
Otto O | |
Warburg O | |
's O | |
seminal O | |
discovery O | |
of O | |
aerobic O | |
glycolysis O | |
established O | |
metabolic O | |
reprogramming O | |
as O | |
one O | |
of O | |
the O | |
first O | |
distinguishing O | |
characteristics O | |
of O | |
cancer O | |
1 O | |
. O | |
The O | |
field O | |
of O | |
cancer O | |
metabolism O | |
subsequently O | |
revealed O | |
additional O | |
metabolic O | |
alterations O | |
in O | |
cancer O | |
by O | |
focusing O | |
on O | |
central O | |
carbon O | |
metabolism O | |
, O | |
including O | |
the O | |
citric O | |
acid O | |
cycle O | |
and O | |
pentose O | |
phosphate O | |
pathway O | |
. O | |
Recent O | |
reports O | |
have O | |
, O | |
however O | |
, O | |
uncovered O | |
substantial O | |
non O | |
- O | |
carbon O | |
metabolism O | |
contributions O | |
to O | |
cancer O | |
cell O | |
viability O | |
and O | |
growth O | |
. O | |
Amino O | |
acids O | |
, O | |
nutrients O | |
vital O | |
to O | |
the O | |
survival O | |
of O | |
all O | |
cell O | |
types O | |
, O | |
experience O | |
reprogrammed O | |
metabolism O | |
in O | |
cancer O | |
. O | |
This O | |
review O | |
outlines O | |
the O | |
diverse O | |
roles O | |
of O | |
amino O | |
acids O | |
within O | |
the O | |
tumor O | |
and O | |
in O | |
the O | |
tumor O | |
microenvironment O | |
. O | |
Beyond O | |
their O | |
role O | |
in O | |
biosynthesis O | |
, O | |
they O | |
serve O | |
as O | |
energy O | |
sources O | |
and O | |
help O | |
maintain O | |
redox O | |
balance O | |
. O | |
In O | |
addition O | |
, O | |
amino O | |
acid O | |
derivatives O | |
contribute O | |
to O | |
epigenetic O | |
regulation O | |
and O | |
immune O | |
responses O | |
linked O | |
to O | |
tumorigenesis O | |
and O | |
metastasis O | |
. O | |
Furthermore O | |
, O | |
in O | |
discussing O | |
the O | |
transporters O | |
and O | |
transaminases O | |
that O | |
mediate O | |
amino O | |
acid O | |
uptake O | |
and O | |
synthesis O | |
, O | |
we O | |
identify O | |
potential O | |
metabolic O | |
liabilities O | |
as O | |
targets O | |
for O | |
therapeutic O | |
intervention O | |
. O | |
Objective O | |
Non O | |
- O | |
operative O | |
management O | |
of O | |
blunt O | |
splenic O | |
injury O | |
in O | |
adults O | |
has O | |
been O | |
applied O | |
increasingly O | |
at O | |
the O | |
end O | |
of O | |
the O | |
last O | |
century O | |
. O | |
Therefore O | |
, O | |
the O | |
lifelong O | |
risk O | |
of O | |
overwhelming O | |
post O | |
- O | |
splenectomy O | |
infection O | |
has O | |
been O | |
the O | |
major O | |
impetus O | |
for O | |
preservation O | |
of O | |
the O | |
spleen O | |
. O | |
However O | |
, O | |
the O | |
prevalence B-EPI | |
of O | |
posttraumatic O | |
infection O | |
after O | |
splenectomy O | |
in O | |
contrast O | |
to O | |
a O | |
conservative O | |
management O | |
is O | |
still O | |
unknown B-STAT | |
. O | |
Objective O | |
was O | |
to O | |
determine O | |
if O | |
splenectomy O | |
is O | |
an O | |
independent O | |
risk O | |
factor O | |
for O | |
the O | |
development O | |
of O | |
posttraumatic O | |
sepsis O | |
and O | |
multi O | |
- O | |
organ O | |
failure O | |
. O | |
Methods O | |
13,433 O | |
patients O | |
from O | |
113 O | |
hospitals O | |
were O | |
prospective O | |
collected O | |
from O | |
1993 B-DATE | |
to I-DATE | |
2005 I-DATE | |
. O | |
Patients O | |
with O | |
an O | |
injury O | |
severity O | |
score O | |
> O | |
16 O | |
, O | |
no O | |
isolated O | |
head O | |
injury O | |
, O | |
primary O | |
admission O | |
to O | |
a O | |
trauma O | |
center O | |
and O | |
splenic O | |
injury O | |
were O | |
included O | |
. O | |
Data O | |
were O | |
allocated O | |
according O | |
to O | |
the O | |
operative O | |
management O | |
into O | |
2 O | |
groups O | |
( O | |
splenectomy O | |
( O | |
I O | |
) O | |
and O | |
conservative O | |
managed O | |
patients O | |
( O | |
II O | |
) O | |
) O | |
. O | |
Results O | |
From O | |
1,630 O | |
patients O | |
with O | |
splenic O | |
injury O | |
758 O | |
patients O | |
undergoing O | |
splenectomy O | |
compared O | |
with O | |
872 O | |
non O | |
- O | |
splenectomized O | |
patients O | |
. O | |
96 O | |
( O | |
18.3 O | |
% O | |
) O | |
of O | |
the O | |
patients O | |
with O | |
splenectomy O | |
and O | |
102 O | |
( O | |
18.5 O | |
% O | |
) O | |
without O | |
splenectomy O | |
had O | |
apparent O | |
infection O | |
after O | |
operation O | |
. O | |
Additionally O | |
, O | |
there O | |
was O | |
no O | |
difference O | |
in O | |
mortality O | |
( O | |
24.8 O | |
% O | |
versus O | |
22.2 O | |
% O | |
) O | |
in O | |
both O | |
groups O | |
. O | |
After O | |
massive O | |
transfusion O | |
of O | |
red O | |
blood O | |
cells O | |
( O | |
> O | |
10 O | |
) O | |
non O | |
- O | |
splenectomy O | |
patients O | |
showed O | |
a O | |
significant O | |
increase O | |
of O | |
multi O | |
- O | |
organ O | |
failure O | |
( O | |
46 O | |
% O | |
vs. O | |
40 O | |
% O | |
) O | |
and O | |
sepsis O | |
( O | |
38 O | |
% O | |
vs. O | |
25 O | |
% O | |
) O | |
. O | |
Conclusions O | |
Non O | |
- O | |
operative O | |
management O | |
leads O | |
to O | |
lower O | |
systemic O | |
infection O | |
rates O | |
and O | |
mortality O | |
in O | |
adult O | |
patients O | |
with O | |
moderate O | |
blunt O | |
splenic O | |
injury O | |
( O | |
grade O | |
1 O | |
- O | |
3 O | |
) O | |
and O | |
should O | |
therefore O | |
be O | |
advocated O | |
. O | |
Patients O | |
with O | |
grade O | |
4 O | |
and O | |
5 O | |
injury O | |
, O | |
patients O | |
with O | |
massive O | |
transfusion O | |
of O | |
red O | |
blood O | |
cells O | |
and O | |
unstable O | |
patients O | |
should O | |
be O | |
managed O | |
operatively O | |
. O | |
Background O | |
Adrenocortical O | |
carcinoma O | |
( O | |
ACC O | |
) O | |
is O | |
a O | |
rare O | |
endocrine O | |
carcinoma O | |
with O | |
poor O | |
5 O | |
- O | |
year O | |
survival O | |
rates O | |
of O | |
< O | |
40 O | |
% O | |
. O | |
According O | |
to O | |
the O | |
literature O | |
, O | |
ACC O | |
is O | |
rarely O | |
an O | |
incidental O | |
imaging O | |
finding O | |
. O | |
However O | |
, O | |
presentation O | |
, O | |
treatment O | |
and O | |
outcome O | |
may O | |
differ O | |
in O | |
modern O | |
series O | |
. O | |
Design O | |
and O | |
methods O | |
We O | |
studied O | |
all O | |
patients O | |
( O | |
n O | |
= O | |
47 O | |
, O | |
four O | |
children O | |
) O | |
from O | |
a O | |
single O | |
centre O | |
during O | |
years O | |
2002 B-DATE | |
- I-DATE | |
2018 I-DATE | |
. O | |
We O | |
re O | |
- O | |
evaluated O | |
radiologic O | |
and O | |
histopathological O | |
findings O | |
and O | |
assessed O | |
treatments O | |
and O | |
outcome O | |
. O | |
We O | |
searched O | |
for O | |
possible O | |
TP53 O | |
gene O | |
defects O | |
and O | |
assessed O | |
nationwide O | |
incidence B-EPI | |
of O | |
ACC O | |
. O | |
Results O | |
In O | |
adults O | |
, O | |
incidental O | |
radiologic O | |
finding O | |
led O | |
to O | |
diagnosis O | |
in O | |
79 O | |
% O | |
at O | |
median O | |
age O | |
of O | |
61 O | |
years O | |
. O | |
ENSAT O | |
stage O | |
I O | |
, O | |
II O | |
, O | |
III O | |
and O | |
IV O | |
was O | |
19 O | |
% O | |
, O | |
40 O | |
% O | |
, O | |
19 O | |
% O | |
and O | |
21 O | |
% O | |
, O | |
respectively O | |
. O | |
Nonenhanced O | |
CT O | |
demonstrated O | |
> O | |
20 O | |
Hounsfield O | |
Units O | |
( O | |
HU O | |
) O | |
for O | |
all O | |
tumours O | |
( O | |
median O | |
34 O | |
( O | |
21 O | |
- O | |
45 O | |
) O | |
) O | |
, O | |
median O | |
size O | |
92 O | |
mm O | |
( O | |
20 O | |
- O | |
196 O | |
) O | |
, O | |
Ki67 O | |
17 O | |
% O | |
( O | |
1 O | |
- O | |
40 O | |
% O | |
) O | |
, O | |
Weiss O | |
score O | |
7 O | |
( O | |
4 O | |
- O | |
9 O | |
) O | |
and O | |
Helsinki O | |
score O | |
24 O | |
( O | |
4 O | |
- O | |
48 O | |
) O | |
. O | |
ACC O | |
was O | |
more O | |
often O | |
found O | |
in O | |
the O | |
left O | |
than O | |
the O | |
right O | |
adrenal O | |
( O | |
p O | |
< O | |
0.05 O | |
) O | |
. O | |
One O | |
child O | |
had O | |
Beckwith O | |
- O | |
Wiedemann O | |
and O | |
one O | |
a O | |
TP53 O | |
mutation O | |
. O | |
In O | |
adults O | |
, O | |
the O | |
primary O | |
tumour O | |
was O | |
resected O | |
in O | |
88 O | |
and O | |
79 O | |
% O | |
received O | |
adjuvant O | |
mitotane O | |
therapy O | |
. O | |
Median O | |
hospital O | |
stay O | |
was O | |
significantly O | |
shorter O | |
in O | |
the O | |
laparoscopic O | |
vs. O | |
open O | |
surgery O | |
group O | |
( O | |
4 O | |
( O | |
3 O | |
- O | |
7 O | |
) O | |
vs. O | |
8 O | |
( O | |
5 O | |
- O | |
38 O | |
) O | |
days O | |
, O | |
respectively O | |
; O | |
p O | |
< O | |
0.001 O | |
) O | |
. O | |
In O | |
3/4 O | |
patients O | |
, O | |
prolonged O | |
remission O | |
of O | |
> O | |
5 O | |
to O | |
> O | |
10 O | |
years O | |
was O | |
achieved O | |
after O | |
repeated O | |
surgery O | |
of O | |
metastases O | |
. O | |
Overall O | |
5 O | |
- O | |
year O | |
survival O | |
was O | |
67 O | |
% O | |
, O | |
and O | |
96 O | |
% O | |
vs. O | |
26 O | |
% O | |
for O | |
ENSAT O | |
stage O | |
I O | |
- O | |
II O | |
vs. O | |
III O | |
- O | |
IV O | |
( O | |
p O | |
< O | |
0.0001 O | |
) O | |
. O | |
ENSAT O | |
stage O | |
and O | |
Ki67 O | |
predicted O | |
survival O | |
, O | |
type O | |
of O | |
surgery O | |
did O | |
not O | |
. O | |
Mitotane O | |
associated O | |
with O | |
better O | |
survival O | |
. O | |
Conclusions O | |
Contemporary O | |
ACC O | |
predominantly O | |
presents O | |
as O | |
an O | |
incidental O | |
imaging O | |
finding O | |
, O | |
characterised O | |
by O | |
HU O | |
> O | |
20 O | |
on O | |
nonenhanced O | |
CT O | |
but O | |
variable O | |
tumour O | |
size O | |
( O | |
20 O | |
- O | |
196 O | |
mm O | |
) O | |
. O | |
Malignancy O | |
can O | |
not O | |
be O | |
ruled O | |
out O | |
by O | |
small O | |
tumour O | |
size O | |
only O | |
. O | |
The O | |
5 O | |
- O | |
year O | |
survival O | |
of O | |
96 O | |
% O | |
in O | |
ENSAT O | |
stage O | |
I O | |
- O | |
III O | |
compares O | |
favourably O | |
to O | |
previous O | |
studies O | |
. O | |
Study O | |
objectives O | |
The O | |
primary O | |
objective O | |
was O | |
to O | |
describe O | |
trends O | |
in O | |
the O | |
2 O | |
- O | |
year O | |
limited O | |
duration O | |
prevalence B-EPI | |
of O | |
narcolepsy O | |
from O | |
2013 B-DATE | |
- I-DATE | |
2016 I-DATE | |
in O | |
a O | |
large O | |
insured O | |
population O | |
with O | |
claims O | |
activity O | |
. O | |
Secondary O | |
objectives O | |
were O | |
to O | |
assess O | |
the O | |
prevalence B-EPI | |
of O | |
other O | |
sleep O | |
disorders O | |
and O | |
the O | |
frequency O | |
of O | |
diagnostic O | |
sleep O | |
testing O | |
. O | |
Methods O | |
Nationwide O | |
medical O | |
/ O | |
prescription O | |
claims O | |
( O | |
Symphony O | |
Health O | |
) O | |
were O | |
analyzed O | |
to O | |
estimate O | |
the O | |
annual B-EPI | |
prevalence I-EPI | |
per I-STAT | |
100,000 I-STAT | |
persons I-STAT | |
of O | |
narcolepsy O | |
and O | |
other O | |
sleep O | |
disorders O | |
( O | |
obstructive O | |
sleep O | |
apnea O | |
, O | |
idiopathic O | |
hypersomnia O | |
, O | |
rapid O | |
eye O | |
movement O | |
sleep O | |
behavior O | |
disorder O | |
, O | |
periodic O | |
limb O | |
movement O | |
disorder O | |
) O | |
and O | |
the O | |
frequency O | |
of O | |
diagnostic O | |
sleep O | |
testing O | |
. O | |
Prevalence B-EPI | |
was O | |
adjusted O | |
to O | |
the O | |
age O | |
/ O | |
sex O | |
distribution O | |
of O | |
the O | |
2016 B-DATE | |
US B-LOC | |
census O | |
estimates O | |
. O | |
Results O | |
The O | |
prevalence B-EPI | |
of O | |
narcolepsy O | |
per I-STAT | |
100,000 I-STAT | |
persons I-STAT | |
increased O | |
14 O | |
% O | |
from O | |
38.9 B-STAT | |
in O | |
2013 B-DATE | |
to I-DATE | |
44.3 I-STAT | |
in O | |
2016 I-DATE | |
. O | |
Obstructive O | |
sleep O | |
apnea O | |
prevalence B-EPI | |
increased O | |
41 O | |
% O | |
over O | |
the O | |
study O | |
period O | |
from O | |
2,429 B-STAT | |
to I-STAT | |
3,420 I-STAT | |
per I-STAT | |
100,000 I-STAT | |
. O | |
Large O | |
increases O | |
in O | |
prevalence B-EPI | |
were O | |
also O | |
seen O | |
for O | |
idiopathic O | |
hypersomnia O | |
( O | |
32 O | |
% O | |
) O | |
, O | |
periodic O | |
limb O | |
movement O | |
disorder O | |
( O | |
30 O | |
% O | |
) O | |
, O | |
and O | |
rapid O | |
eye O | |
movement O | |
sleep O | |
behavior O | |
disorder O | |
( O | |
64 O | |
% O | |
) O | |
. O | |
For O | |
each O | |
sleep O | |
disorder O | |
, O | |
prevalence B-EPI | |
was O | |
higher O | |
for O | |
those O | |
with O | |
commercial O | |
insurance O | |
versus O | |
Medicare O | |
/ O | |
Medicaid O | |
, O | |
and O | |
markedly O | |
lower O | |
prevalence B-EPI | |
was O | |
observed O | |
for O | |
the O | |
Northeast B-LOC | |
compared O | |
with O | |
the O | |
Midwest B-LOC | |
, O | |
South B-LOC | |
, O | |
and O | |
Western B-LOC | |
US I-LOC | |
regions O | |
. O | |
The O | |
frequency O | |
of O | |
multiple O | |
sleep O | |
latency O | |
/ O | |
maintenance O | |
of O | |
wakefulness O | |
testing O | |
declined O | |
by O | |
20 O | |
% O | |
, O | |
and O | |
polysomnography O | |
declined O | |
by O | |
15 O | |
% O | |
. O | |
Conversely O | |
, O | |
home O | |
sleep O | |
apnea O | |
testing O | |
increased O | |
by O | |
117 O | |
% O | |
. O | |
Conclusions O | |
The O | |
prevalence B-EPI | |
of O | |
narcolepsy O | |
, O | |
obstructive O | |
sleep O | |
apnea O | |
, O | |
and O | |
the O | |
other O | |
sleep O | |
disorders O | |
increased O | |
appreciably O | |
over O | |
the O | |
2013 B-DATE | |
- I-DATE | |
2016 I-DATE | |
period O | |
. O | |
It O | |
remains O | |
to O | |
be O | |
determined O | |
whether O | |
the O | |
trends O | |
seen O | |
in O | |
our O | |
analyses O | |
are O | |
due O | |
to O | |
increased O | |
incidence B-EPI | |
or O | |
increased O | |
awareness O | |
of O | |
these O | |
conditions O | |
. O | |
Most O | |
of O | |
the O | |
studies O | |
examining O | |
the O | |
impact O | |
of O | |
cannabis O | |
use O | |
in O | |
first O | |
episode O | |
psychosis O | |
( O | |
FEP O | |
) O | |
have O | |
been O | |
carried O | |
out O | |
in O | |
samples O | |
with O | |
adult O | |
- O | |
onset O | |
FEP O | |
. O | |
Data O | |
in O | |
persons O | |
with O | |
early O | |
onset O | |
psychosis O | |
( O | |
EOP O | |
) O | |
is O | |
scarce O | |
. O | |
The O | |
aims O | |
of O | |
the O | |
study O | |
were O | |
: O | |
To O | |
describe O | |
the O | |
prevalence B-EPI | |
of O | |
lifetime O | |
cannabis O | |
use O | |
, O | |
current O | |
use O | |
, O | |
and O | |
daily O | |
use O | |
in O | |
patients O | |
with O | |
EOP O | |
compared O | |
to O | |
healthy O | |
controls O | |
. O | |
To O | |
study O | |
the O | |
differences O | |
in O | |
clinical O | |
presentation O | |
between O | |
cannabis O | |
users O | |
and O | |
non O | |
- O | |
users O | |
. O | |
To O | |
examine O | |
the O | |
risk O | |
of O | |
presenting O | |
an O | |
EOP O | |
associated O | |
with O | |
cannabis O | |
use O | |
and O | |
the O | |
effect O | |
of O | |
doses O | |
and O | |
age O | |
of O | |
onset O | |
of O | |
use O | |
. O | |
An O | |
observational O | |
cross O | |
- O | |
sectional O | |
study O | |
was O | |
performed O | |
in O | |
90 O | |
EOP O | |
cases O | |
and O | |
62 O | |
healthy O | |
controls O | |
, O | |
aged O | |
between O | |
7 O | |
and O | |
17 O | |
years O | |
. O | |
Our O | |
results O | |
show O | |
a O | |
higher O | |
prevalence B-EPI | |
of O | |
lifetime O | |
use O | |
( O | |
p O | |
= O | |
0002 O | |
) O | |
, O | |
current O | |
use O | |
( O | |
p O | |
< O | |
0.001 O | |
) O | |
, O | |
and O | |
daily O | |
use O | |
( O | |
p O | |
< O | |
0.001 O | |
) O | |
in O | |
EOP O | |
cases O | |
in O | |
comparison O | |
with O | |
healthy O | |
controls O | |
. O | |
Regarding O | |
clinical O | |
presentation O | |
, O | |
we O | |
did O | |
not O | |
find O | |
significant O | |
differences O | |
in O | |
any O | |
subscale O | |
of O | |
the O | |
Positive O | |
and O | |
Negative O | |
Syndrome O | |
Scale O | |
( O | |
PANSS O | |
) O | |
. O | |
Non O | |
- O | |
user O | |
patients O | |
presented O | |
more O | |
severe O | |
depressive O | |
symptoms O | |
( O | |
p O | |
= O | |
0002 O | |
) O | |
and O | |
worse O | |
social O | |
functioning O | |
than O | |
cannabis O | |
users O | |
( O | |
p O | |
= O | |
0026 O | |
) O | |
. O | |
Compared O | |
with O | |
subjects O | |
who O | |
never O | |
used O | |
cannabis O | |
, O | |
the O | |
risk O | |
of O | |
an O | |
EOP O | |
was O | |
significantly O | |
higher O | |
for O | |
those O | |
with O | |
a O | |
lifetime O | |
use O | |
( O | |
OR O | |
= O | |
2.88 O | |
, O | |
p O | |
= O | |
0.002)current O | |
use O | |
( O | |
O.R O | |
= O | |
6.09 O | |
, O | |
p O | |
< O | |
0001 O | |
) O | |
, O | |
and O | |
especially O | |
in O | |
those O | |
with O | |
daily O | |
use O | |
( O | |
O.R O | |
= O | |
42.77 O | |
, O | |
p O | |
= O | |
< O | |
0001 O | |
) O | |
. O | |
We O | |
found O | |
a O | |
higher O | |
risk O | |
of O | |
EOP O | |
in O | |
patients O | |
that O | |
have O | |
used O | |
cannabis O | |
before O | |
15 O | |
years O | |
of O | |
age O | |
. O | |
In O | |
conclusion O | |
, O | |
it O | |
is O | |
necessary O | |
to O | |
develop O | |
early- O | |
detection O | |
and O | |
specific O | |
treatment O | |
programs O | |
for O | |
adolescents O | |
with O | |
cannabis O | |
use O | |
. O | |
Background O | |
The O | |
combination O | |
of O | |
esophageal O | |
atresia O | |
, O | |
congenital O | |
duodenal O | |
obstruction O | |
, O | |
and O | |
anorectal O | |
malformation O | |
has O | |
seldom O | |
been O | |
reported O | |
. O | |
We O | |
describe O | |
the O | |
largest O | |
series O | |
of O | |
patients O | |
with O | |
such O | |
association O | |
, O | |
which O | |
we O | |
summed O | |
up O | |
with O | |
the O | |
mnemonic O | |
acronym O | |
DATE O | |
[ O | |
D O | |
- O | |
duodenal O | |
obstruction O | |
, O | |
A O | |
- O | |
anorectal O | |
malformation O | |
( O | |
ARM O | |
) O | |
, O | |
and O | |
TE O | |
- O | |
tracheoesophageal O | |
fistula O | |
with O | |
esophageal O | |
atresia O | |
] O | |
. O | |
Methods O | |
This O | |
was O | |
a O | |
multicenter O | |
retrospective O | |
review O | |
of O | |
13 O | |
patients O | |
recruited O | |
from O | |
8 O | |
institutions O | |
over O | |
a O | |
nearly O | |
5 O | |
- O | |
decade O | |
period O | |
( O | |
1968 B-DATE | |
- I-DATE | |
2017 I-DATE | |
) O | |
. O | |
Information O | |
gathered O | |
included O | |
type O | |
of O | |
DATE O | |
malformations O | |
, O | |
other O | |
associated O | |
anomalies O | |
, O | |
type O | |
and O | |
timing O | |
of O | |
surgery O | |
, O | |
and O | |
clinical O | |
outcomes O | |
. O | |
Results O | |
The O | |
DATE O | |
association O | |
consisted O | |
of O | |
type O | |
C O | |
esophageal O | |
atresia O | |
( O | |
13 O | |
) O | |
, O | |
complete O | |
( O | |
9 O | |
) O | |
or O | |
incomplete O | |
( O | |
4 O | |
) O | |
congenital O | |
duodenal O | |
obstruction O | |
( O | |
CDO O | |
) O | |
, O | |
and O | |
high O | |
or O | |
intermediate O | |
( O | |
8) O | |
or O | |
low O | |
( O | |
5 O | |
) O | |
ARM O | |
. O | |
Eight O | |
patients O | |
had O | |
at O | |
least O | |
one O | |
additional O | |
component O | |
feature O | |
of O | |
VACTERL O | |
association O | |
. O | |
A O | |
total O | |
of O | |
6 O | |
patients O | |
died O | |
. O | |
Overall O | |
, O | |
9 O | |
patients O | |
achieved O | |
complete O | |
restoration O | |
of O | |
gastrointestinal O | |
continuity O | |
, O | |
7 O | |
of O | |
whom O | |
are O | |
alive O | |
at O | |
a O | |
median O | |
follow O | |
- O | |
up O | |
of O | |
4 O | |
Y O | |
( O | |
range O | |
, O | |
1 O | |
to O | |
9 O | |
) O | |
. O | |
Survivors O | |
received O | |
a O | |
median O | |
of O | |
6 O | |
major O | |
operations O | |
( O | |
range O | |
, O | |
4 O | |
to O | |
14 O | |
) O | |
to O | |
overcome O | |
their O | |
anomalies O | |
and O | |
surgical O | |
complications O | |
. O | |
Two O | |
incomplete O | |
duodenal O | |
obstructions O | |
were O | |
initially O | |
overlooked O | |
. O | |
All O | |
survivors O | |
with O | |
high O | |
or O | |
intermediate O | |
ARM O | |
defects O | |
required O | |
some O | |
form O | |
of O | |
bowel O | |
management O | |
to O | |
keep O | |
them O | |
clean O | |
. O | |
Conclusions O | |
The O | |
DATE O | |
association O | |
is O | |
a O | |
low O | |
- O | |
frequency O | |
entity O | |
, O | |
often O | |
occurring O | |
among O | |
the O | |
wider O | |
spectrum O | |
of O | |
VACTERL O | |
association O | |
. O | |
Functional O | |
outcomes O | |
largely O | |
depend O | |
on O | |
the O | |
severity O | |
of O | |
ARM O | |
or O | |
other O | |
major O | |
associated O | |
malformations O | |
. O | |
Awareness O | |
of O | |
the O | |
DATE O | |
association O | |
may O | |
avoid O | |
untoward O | |
diagnostic O | |
delays O | |
of O | |
subtler O | |
component O | |
features O | |
of O | |
the O | |
spectrum O | |
, O | |
such O | |
as O | |
an O | |
incomplete O | |
CDO O | |
. O | |
Background O | |
A O | |
preliminary O | |
safety O | |
signal O | |
for O | |
neural O | |
- O | |
tube O | |
defects O | |
was O | |
previously O | |
reported O | |
in O | |
association O | |
with O | |
dolutegravir O | |
exposure O | |
from O | |
the O | |
time O | |
of O | |
conception O | |
, O | |
which O | |
has O | |
affected O | |
choices O | |
of O | |
antiretroviral O | |
treatment O | |
( O | |
ART O | |
) O | |
for O | |
human O | |
immunodeficiency O | |
virus O | |
( O | |
HIV O | |
) O | |
- O | |
infected O | |
women B-SEX | |
of O | |
reproductive O | |
potential O | |
. O | |
The O | |
signal O | |
can O | |
now O | |
be O | |
evaluated O | |
with O | |
data O | |
from O | |
follow O | |
- O | |
up O | |
of O | |
additional O | |
pregnancies O | |
. O | |
Methods O | |
We O | |
conducted O | |
birth O | |
- O | |
outcomes O | |
surveillance O | |
at O | |
hospitals O | |
throughout O | |
Botswana B-LOC | |
, O | |
expanding O | |
from O | |
8 O | |
to O | |
18 O | |
sites O | |
in O | |
2018 B-DATE | |
. O | |
Trained O | |
midwives O | |
performed O | |
surface O | |
examinations O | |
of O | |
all O | |
live O | |
- O | |
born O | |
and O | |
stillborn O | |
infants O | |
. O | |
Research O | |
assistants O | |
photographed O | |
abnormalities O | |
after O | |
maternal O | |
consent O | |
was O | |
obtained O | |
. O | |
The O | |
prevalence B-EPI | |
of O | |
neural O | |
- O | |
tube O | |
defects O | |
and O | |
major O | |
external O | |
structural O | |
defects O | |
according O | |
to O | |
maternal O | |
HIV O | |
infection O | |
and O | |
ART O | |
exposure O | |
status O | |
was O | |
determined O | |
. O | |
In O | |
the O | |
primary O | |
analyses O | |
, O | |
we O | |
used O | |
the O | |
Newcombe O | |
method O | |
to O | |
evaluate O | |
differences O | |
in O | |
prevalence B-EPI | |
with O | |
95 O | |
% O | |
confidence O | |
intervals O | |
. O | |
Results O | |
From O | |
August B-DATE | |
2014 I-DATE | |
through I-DATE | |
March I-DATE | |
2019 I-DATE | |
, O | |
surveillance O | |
captured O | |
119,477 O | |
deliveries O | |
; O | |
119,033 O | |
( O | |
99.6 O | |
% O | |
) O | |
had O | |
an O | |
infant O | |
surface O | |
examination O | |
that O | |
could O | |
be O | |
evaluated O | |
, O | |
and O | |
98 O | |
neural O | |
- O | |
tube O | |
defects O | |
were O | |
identified O | |
( O | |
0.08 O | |
% O | |
of O | |
deliveries O | |
) O | |
. O | |
Among O | |
1683 O | |
deliveries O | |
in O | |
which O | |
the O | |
mother O | |
was O | |
taking O | |
dolutegravir O | |
at O | |
conception O | |
, O | |
5 O | |
neural O | |
- O | |
tube O | |
defects O | |
were O | |
found O | |
( O | |
0.30 O | |
% O | |
of O | |
deliveries O | |
) O | |
; O | |
the O | |
defects O | |
included O | |
two O | |
instances O | |
of O | |
myelomeningocele O | |
, O | |
one O | |
of O | |
anencephaly O | |
, O | |
one O | |
of O | |
encephalocele O | |
, O | |
and O | |
one O | |
of O | |
iniencephaly O | |
. O | |
In O | |
comparison O | |
, O | |
15 O | |
neural O | |
- O | |
tube O | |
defects O | |
were O | |
found O | |
among O | |
14,792 O | |
deliveries O | |
( O | |
0.10 O | |
% O | |
) O | |
in O | |
which O | |
the O | |
mother O | |
was O | |
taking O | |
any O | |
non O | |
- O | |
dolutegravir O | |
ART O | |
at O | |
conception O | |
, O | |
3 O | |
among O | |
7959 O | |
( O | |
0.04 O | |
% O | |
) O | |
in O | |
which O | |
the O | |
mother O | |
was O | |
taking O | |
efavirenz O | |
at O | |
conception O | |
, O | |
1 O | |
among O | |
3840 O | |
( O | |
0.03 O | |
% O | |
) O | |
in O | |
which O | |
the O | |
mother O | |
started O | |
dolutegravir O | |
treatment O | |
during O | |
pregnancy O | |
, O | |
and O | |
70 O | |
among O | |
89,372 O | |
( O | |
0.08 O | |
% O | |
) O | |
in O | |
HIV O | |
- O | |
uninfected O | |
mothers O | |
. O | |
The O | |
prevalence B-EPI | |
of O | |
neural O | |
- O | |
tube O | |
defects O | |
was O | |
higher O | |
in O | |
association O | |
with O | |
dolutegravir O | |
treatment O | |
at O | |
conception O | |
than O | |
with O | |
non O | |
- O | |
dolutegravir O | |
ART O | |
at O | |
conception O | |
( O | |
difference O | |
, O | |
0.20 O | |
percentage O | |
points O | |
; O | |
95 O | |
% O | |
confidence O | |
interval O | |
[ O | |
CI O | |
] O | |
, O | |
0.01 O | |
to O | |
0.59 O | |
) O | |
or O | |
with O | |
other O | |
types O | |
of O | |
ART O | |
exposure O | |
. O | |
Major O | |
external O | |
structural O | |
defects O | |
were O | |
found O | |
in O | |
0.95 O | |
% O | |
of O | |
deliveries O | |
among O | |
women B-SEX | |
exposed O | |
to O | |
dolutegravir O | |
at O | |
conception O | |
and O | |
0.68 O | |
% O | |
of O | |
those O | |
among O | |
women B-SEX | |
exposed O | |
to O | |
non O | |
- O | |
dolutegravir O | |
ART O | |
at O | |
conception O | |
( O | |
difference O | |
, O | |
0.27 O | |
percentage O | |
points O | |
; O | |
95 O | |
% O | |
CI O | |
, O | |
-0.13 O | |
to O | |
0.87 O | |
) O | |
. O | |
Conclusions O | |
The O | |
prevalence B-EPI | |
of O | |
neural O | |
- O | |
tube O | |
defects O | |
was O | |
slightly O | |
higher O | |
in O | |
association O | |
with O | |
dolutegravir O | |
exposure O | |
at O | |
conception O | |
than O | |
with O | |
other O | |
types O | |
of O | |
ART O | |
exposure O | |
at O | |
conception O | |
( O | |
3 B-STAT | |
per I-STAT | |
1000 I-STAT | |
deliveries I-STAT | |
vs. O | |
1 B-STAT | |
per I-STAT | |
1000 I-STAT | |
deliveries I-STAT | |
) O | |
. O | |
( O | |
Funded O | |
by O | |
the O | |
National O | |
Institutes O | |
of O | |
Health O | |
. O | |
) O | |
. O | |
Ataxia O | |
- O | |
telangiectasia O | |
is O | |
the O | |
second O | |
most O | |
common O | |
autosomal O | |
recessive O | |
hereditary O | |
ataxia O | |
, O | |
with O | |
an O | |
estimated B-EPI | |
incidence I-EPI | |
of O | |
1 B-STAT | |
in I-STAT | |
100,000 I-STAT | |
births I-STAT | |
. O | |
Besides O | |
ataxia O | |
and O | |
ocular O | |
telangiectasias O | |
, O | |
eye O | |
movement O | |
abnormalities O | |
have O | |
long O | |
been O | |
associated O | |
with O | |
this O | |
disorder O | |
and O | |
is O | |
frequently O | |
present O | |
in O | |
almost O | |
all O | |
patients O | |
. O | |
A O | |
handful O | |
of O | |
studies O | |
have O | |
described O | |
the O | |
phenomenology O | |
of O | |
ocular O | |
motor O | |
deficits O | |
in O | |
ataxia O | |
- O | |
telangiectasia O | |
. O | |
Contemporary O | |
literature O | |
linked O | |
their O | |
physiology O | |
to O | |
cerebellar O | |
dysfunction O | |
and O | |
secondary O | |
abnormalities O | |
at O | |
the O | |
level O | |
of O | |
brainstem O | |
. O | |
These O | |
studies O | |
, O | |
while O | |
providing O | |
a O | |
proof O | |
of O | |
concept O | |
of O | |
ocular O | |
motor O | |
physiology O | |
in O | |
disease O | |
, O | |
i.e. O | |
, O | |
ataxia O | |
- O | |
telangiectasia O | |
, O | |
also O | |
advanced O | |
our O | |
understanding O | |
of O | |
how O | |
the O | |
cerebellum O | |
works O | |
. O | |
Here O | |
, O | |
we O | |
will O | |
summarize O | |
the O | |
clinical O | |
abnormalities O | |
seen O | |
with O | |
ataxia O | |
- O | |
telangiectasia O | |
in O | |
each O | |
subtype O | |
of O | |
eye O | |
movements O | |
and O | |
subsequently O | |
describe O | |
the O | |
underlying O | |
pathophysiology O | |
. O | |
Finally O | |
, O | |
we O | |
will O | |
review O | |
how O | |
these O | |
deficits O | |
are O | |
linked O | |
to O | |
abnormal O | |
cerebellar O | |
function O | |
and O | |
how O | |
it O | |
allows O | |
better O | |
understanding O | |
of O | |
the O | |
cerebellar O | |
physiology O | |
. O | |
: O | |
The O | |
Bernard O | |
- O | |
Soulier O | |
syndrome O | |
( O | |
BSS O | |
) O | |
is O | |
a O | |
rare O | |
disease O | |
with O | |
a O | |
prevalence B-EPI | |
of O | |
1/1000000 B-STAT | |
; O | |
it O | |
is O | |
characterized O | |
by O | |
macrothrombocytopenia O | |
. O | |
BSS O | |
develops O | |
as O | |
a O | |
result O | |
of O | |
a O | |
defect O | |
in O | |
the O | |
glycoprotein O | |
GPIb O | |
- O | |
IX O | |
- O | |
V O | |
complex O | |
on O | |
the O | |
platelet O | |
surface O | |
. O | |
In O | |
this O | |
article O | |
, O | |
we O | |
present O | |
a O | |
pediatric O | |
patient O | |
with O | |
the O | |
novel O | |
mutation O | |
that O | |
has O | |
been O | |
identified O | |
for O | |
the O | |
first O | |
time O | |
in O | |
BSS O | |
. O | |
A O | |
13 O | |
- O | |
month O | |
- O | |
old O | |
male B-SEX | |
patient O | |
was O | |
admitted O | |
with O | |
severe O | |
thrombocytopenia O | |
unresponsive O | |
to O | |
intravenous O | |
immunoglobulin O | |
in O | |
the O | |
neonatal O | |
period O | |
and O | |
recurrent O | |
mucocutaneous O | |
bleeding O | |
which O | |
initiated O | |
at O | |
5 O | |
months O | |
of O | |
age O | |
. O | |
glycoprotein O | |
( O | |
GP O | |
) O | |
IX O | |
( O | |
CD42a O | |
) O | |
expression O | |
was O | |
normal O | |
as O | |
per O | |
flow O | |
cytometry O | |
results O | |
. O | |
Genetic O | |
analysis O | |
revealed O | |
a O | |
homozygous O | |
c.243C O | |
> O | |
A O | |
( O | |
p. O | |
Cys81 O | |
) O | |
( O | |
p. O | |
C81 O | |
) O | |
mutation O | |
. O | |
This O | |
novel O | |
mutation O | |
identified O | |
by O | |
us O | |
presents O | |
with O | |
severe O | |
thrombocytopenia O | |
and O | |
normal O | |
GPIX O | |
( O | |
CD42a O | |
) O | |
expression O | |
and O | |
is O | |
mistaken O | |
for O | |
immune O | |
thrombocytopenia O | |
in O | |
the O | |
neonatal O | |
period O | |
. O | |
This O | |
mutation O | |
creates O | |
an O | |
early O | |
stop O | |
codon O | |
and O | |
possibly O | |
leads O | |
to O | |
loss O | |
of O | |
function O | |
of O | |
the O | |
receptor O | |
. O | |
Scurvy O | |
is O | |
a O | |
disease O | |
caused O | |
by O | |
chronic O | |
vitamin O | |
C O | |
deficiency O | |
. O | |
The O | |
greater O | |
prevalence B-EPI | |
was O | |
found O | |
in O | |
the O | |
paediatric O | |
population O | |
with O | |
neurodevelopmental O | |
disorders O | |
such O | |
as O | |
autism O | |
spectrum O | |
disorders O | |
due O | |
to O | |
their O | |
restricted O | |
dietary O | |
intake O | |
. O | |
Our O | |
case O | |
reported O | |
a O | |
child O | |
with O | |
autism O | |
who O | |
presented O | |
with O | |
arthralgia O | |
and O | |
anaemia O | |
. O | |
Systemic O | |
lupus O | |
erythematosus O | |
was O | |
the O | |
first O | |
diagnostic O | |
impression O | |
, O | |
resulting O | |
in O | |
over O | |
investigation O | |
and O | |
delayed O | |
diagnosis O | |
of O | |
vitamin O | |
C O | |
deficiency O | |
. O | |
After O | |
the O | |
child O | |
was O | |
treated O | |
with O | |
ascorbic O | |
acid O | |
, O | |
the O | |
child O | |
's O | |
symptoms O | |
resolved O | |
. O | |
This O | |
case O | |
highlighted O | |
the O | |
importance O | |
of O | |
developmental O | |
and O | |
nutritional O | |
history O | |
taking O | |
in O | |
the O | |
paediatric O | |
population O | |
. O | |
Furthermore O | |
, O | |
parents O | |
and O | |
physicians O | |
should O | |
be O | |
concerned O | |
about O | |
nutritional O | |
status O | |
, O | |
especially O | |
in O | |
children O | |
with O | |
restrictive O | |
dietary O | |
intake O | |
. O | |
The O | |
hierarchical O | |
information O | |
flow O | |
through O | |
DNA O | |
- O | |
RNA O | |
- O | |
protein O | |
- O | |
metabolite O | |
collectively O | |
referred O | |
to O | |
as O | |
' O | |
molecular O | |
fingerprint O | |
' O | |
defines O | |
both O | |
health O | |
and O | |
disease O | |
. O | |
Environment O | |
and O | |
food O | |
( O | |
quality O | |
and O | |
quantity O | |
) O | |
are O | |
the O | |
key O | |
factors O | |
known O | |
to O | |
affect O | |
the O | |
health O | |
of O | |
an O | |
individual O | |
. O | |
The O | |
fundamental O | |
concepts O | |
are O | |
that O | |
the O | |
transition O | |
from O | |
a O | |
healthy O | |
condition O | |
to O | |
a O | |
disease O | |
phenotype O | |
must O | |
occur O | |
by O | |
concurrent O | |
alterations O | |
in O | |
the O | |
genome O | |
expression O | |
or O | |
by O | |
differences O | |
in O | |
protein O | |
synthesis O | |
, O | |
function O | |
and O | |
metabolites O | |
. O | |
In O | |
other O | |
words O | |
, O | |
the O | |
dietary O | |
components O | |
directly O | |
or O | |
indirectly O | |
modulate O | |
the O | |
molecular O | |
fingerprint O | |
and O | |
understanding O | |
of O | |
which O | |
is O | |
dealt O | |
with O | |
nutrigenomics O | |
. O | |
Although O | |
the O | |
fundamental O | |
principles O | |
of O | |
nutrigenomics O | |
remain O | |
similar O | |
to O | |
that O | |
of O | |
traditional O | |
research O | |
, O | |
a O | |
collection O | |
of O | |
comprehensive O | |
targeted O | |
/ O | |
untargeted O | |
data O | |
sets O | |
in O | |
the O | |
context O | |
of O | |
nutrition O | |
offers O | |
the O | |
unique O | |
advantage O | |
of O | |
understanding O | |
complex O | |
metabolic O | |
networks O | |
to O | |
provide O | |
a O | |
mechanistic O | |
understanding O | |
of O | |
data O | |
from O | |
epidemiological O | |
and O | |
intervention O | |
studies O | |
. O | |
In O | |
this O | |
review O | |
the O | |
challenges O | |
and O | |
opportunities O | |
of O | |
nutrigenomic O | |
tools O | |
in O | |
addressing O | |
the O | |
nutritional O | |
problems O | |
of O | |
public O | |
health O | |
importance O | |
are O | |
discussed O | |
. O | |
The O | |
application O | |
of O | |
nutrigenomic O | |
tools O | |
provided O | |
numerous O | |
leads O | |
on O | |
biomarkers O | |
of O | |
nutrient O | |
intake O | |
, O | |
undernutrition O | |
, O | |
metabolic O | |
syndrome O | |
and O | |
its O | |
complications O | |
. O | |
Importantly O | |
, O | |
nutrigenomic O | |
studies O | |
also O | |
led O | |
to O | |
the O | |
discovery O | |
of O | |
the O | |
association O | |
of O | |
multiple O | |
genetic O | |
polymorphisms O | |
in O | |
relation O | |
to O | |
the O | |
variability O | |
of O | |
micronutrient O | |
absorption O | |
and O | |
metabolism O | |
, O | |
providing O | |
a O | |
potential O | |
opportunity O | |
for O | |
further O | |
research O | |
toward O | |
setting O | |
personalized O | |
dietary O | |
recommendations O | |
for O | |
individuals O | |
and O | |
population O | |
subgroups O | |
. O | |
Background O | |
Neuromyelitis O | |
optica O | |
spectrum O | |
disorders O | |
( O | |
NMOSD O | |
) O | |
is O | |
an O | |
increasing O | |
diagnostic O | |
and O | |
therapeutic O | |
challenge O | |
in O | |
Latin B-LOC | |
America I-ETHN | |
( O | |
LATAM B-LOC | |
) O | |
. O | |
Despite O | |
the O | |
heterogeneity O | |
of O | |
this O | |
population O | |
, O | |
ethnic O | |
and O | |
socioeconomic O | |
commonalities O | |
exist O | |
, O | |
and O | |
epidemiologic O | |
studies O | |
from O | |
the O | |
region O | |
have O | |
had O | |
a O | |
limited O | |
geographic O | |
and O | |
population O | |
outreach O | |
. O | |
Identification O | |
of O | |
some O | |
aspects O | |
from O | |
the O | |
entire O | |
region O | |
are O | |
lacking O | |
. O | |
Objectives O | |
To O | |
determine O | |
ethnic O | |
, O | |
clinical O | |
characteristics O | |
, O | |
and O | |
utilization O | |
of O | |
diagnostic O | |
tools O | |
and O | |
types O | |
of O | |
therapy O | |
for O | |
patients O | |
with O | |
NMOSD O | |
in O | |
the O | |
entire O | |
Latin B-ETHN | |
American I-ETHN | |
region I-LOC | |
. O | |
Methods O | |
The O | |
Latin B-ETHN | |
American I-ETHN | |
Committee O | |
for O | |
Treatment O | |
and O | |
Research O | |
in O | |
MS O | |
( O | |
LACTRIMS O | |
) O | |
created O | |
an O | |
exploratory O | |
investigational O | |
survey O | |
addressed O | |
by O | |
Invitation O | |
to O | |
NMOSD O | |
Latin B-ETHN | |
American I-ETHN | |
experts O | |
identified O | |
through O | |
diverse O | |
sources O | |
. O | |
Data O | |
input O | |
closed O | |
after O | |
30 O | |
days O | |
from O | |
the O | |
initial O | |
invitation O | |
. O | |
The O | |
questionnaire O | |
allowed O | |
use O | |
of O | |
absolute O | |
numbers O | |
or O | |
percentages O | |
. O | |
Multiple O | |
option O | |
responses O | |
covering O | |
25 O | |
themes O | |
included O | |
definition O | |
of O | |
type O | |
of O | |
practice O | |
; O | |
number O | |
of O | |
NMOSD O | |
cases O | |
; O | |
ethnicity O | |
; O | |
utilization O | |
of O | |
the O | |
2015 B-DATE | |
International O | |
Panel O | |
criteria O | |
for O | |
the O | |
diagnosis O | |
of O | |
Neuromyelitis O | |
optica O | |
( O | |
IPDN O | |
) O | |
; O | |
clinical O | |
phenotypes O | |
; O | |
methodology O | |
utilized O | |
for O | |
determination O | |
of O | |
anti O | |
- O | |
Aquaporin-4 O | |
( O | |
anti- O | |
AQP4 O | |
) O | |
antibodies O | |
serological O | |
testing O | |
, O | |
and O | |
if O | |
this O | |
was O | |
performed O | |
locally O | |
or O | |
processed O | |
abroad O | |
; O | |
treatment O | |
of O | |
relapses O | |
, O | |
and O | |
long O | |
- O | |
term O | |
management O | |
were O | |
surveyed O | |
. O | |
Results O | |
We O | |
identified O | |
62 O | |
investigators O | |
from O | |
21 O | |
countries O | |
reporting O | |
information O | |
from O | |
2154 O | |
patients O | |
( O | |
utilizing O | |
the O | |
IPDN O | |
criteria O | |
in O | |
93.9 O | |
% O | |
of O | |
cases O | |
) O | |
, O | |
which O | |
were O | |
categorized O | |
in O | |
two O | |
geographical O | |
regions O | |
: O | |
North B-LOC | |
- I-LOC | |
Central I-LOC | |
, O | |
including O | |
the O | |
Caribbean B-LOC | |
( O | |
NCC O | |
) O | |
, O | |
and O | |
South B-LOC | |
America I-LOC | |
( O | |
SA B-LOC | |
) O | |
. O | |
Ethnic O | |
identification O | |
disclosed O | |
Mestizos B-ETHN | |
61.4 O | |
% O | |
as O | |
the O | |
main O | |
group O | |
. O | |
The O | |
most O | |
common O | |
presenting O | |
symptoms O | |
were O | |
concomitant O | |
presence O | |
of O | |
optic O | |
neuritis O | |
and O | |
transverse O | |
myelitis O | |
in O | |
31.8 O | |
% O | |
( O | |
p=0.95 O | |
) O | |
; O | |
only O | |
optic O | |
neuritis O | |
in O | |
31.4 O | |
% O | |
( O | |
more O | |
common O | |
in O | |
SA O | |
) O | |
, O | |
p<0.001 O | |
) O | |
; O | |
involvement O | |
of O | |
the O | |
area O | |
postrema O | |
occurred O | |
in O | |
21.5 O | |
% O | |
and O | |
brain O | |
stem O | |
in O | |
8.3 O | |
% O | |
, O | |
both O | |
were O | |
more O | |
frequent O | |
in O | |
the O | |
South B-ETHN | |
American I-ETHN | |
cases O | |
( O | |
p<0.001 O | |
) O | |
. O | |
Anti O | |
- O | |
AQP4 O | |
antibodies O | |
were O | |
positive O | |
in O | |
63.9 O | |
% O | |
and O | |
anti O | |
- O | |
Myelin O | |
Oligodendrocyte O | |
Glycoprotein O | |
( O | |
MOG O | |
) O | |
antibodies O | |
in O | |
4.8 O | |
% O | |
of O | |
total O | |
cases O | |
. O | |
The O | |
specific O | |
laboratorial O | |
method O | |
employed O | |
was O | |
not O | |
known O | |
by O | |
23.8 O | |
% O | |
of O | |
the O | |
investigators O | |
. O | |
Acute O | |
relapses O | |
were O | |
identified O | |
in O | |
81.6 O | |
% O | |
of O | |
cases O | |
, O | |
and O | |
were O | |
treated O | |
in O | |
93.9 O | |
% O | |
of O | |
them O | |
with O | |
intravenous O | |
steroids O | |
( O | |
IVS O | |
) O | |
; O | |
62.1 O | |
% O | |
with O | |
plasma O | |
exchange O | |
( O | |
PE O | |
) O | |
, O | |
and O | |
40.9 O | |
% O | |
with O | |
intravenous O | |
immunoglobulin O | |
- O | |
G O | |
( O | |
IVIG O | |
) O | |
. O | |
Therapy O | |
was O | |
escalated O | |
in O | |
some O | |
cases O | |
due O | |
to O | |
suboptimal O | |
initial O | |
response O | |
. O | |
Respondents O | |
favored O | |
Rituximab O | |
as O | |
long O | |
- O | |
term O | |
therapy O | |
( O | |
86.3 O | |
% O | |
) O | |
, O | |
whereas O | |
azathioprine O | |
was O | |
also O | |
utilized O | |
on O | |
81.8 O | |
% O | |
of O | |
the O | |
cases O | |
, O | |
either O | |
agent O | |
used O | |
indistinctly O | |
by O | |
the O | |
investigators O | |
according O | |
to O | |
treatment O | |
accessibility O | |
or O | |
clinical O | |
judgement O | |
. O | |
There O | |
were O | |
no O | |
differences O | |
among O | |
the O | |
geographic O | |
regions O | |
. O | |
Conclusions O | |
This O | |
is O | |
the O | |
first O | |
study O | |
including O | |
all O | |
countries O | |
of O | |
LATAM B-LOC | |
and O | |
the O | |
largest O | |
cohort O | |
reported O | |
from O | |
a O | |
multinational O | |
specific O | |
world O | |
area O | |
. O | |
Ethnic O | |
distributions O | |
and O | |
phenotypic O | |
features O | |
of O | |
the O | |
disease O | |
in O | |
the O | |
region O | |
, O | |
challenges O | |
in O | |
access O | |
to O | |
diagnostic O | |
tools O | |
and O | |
therapy O | |
were O | |
identified O | |
. O | |
The O | |
Latin B-ETHN | |
American I-ETHN | |
neurological O | |
community O | |
should O | |
play O | |
a O | |
determinant O | |
role O | |
encouraging O | |
and O | |
advising O | |
local O | |
institutions O | |
and O | |
health O | |
officials O | |
in O | |
the O | |
availability O | |
of O | |
more O | |
sensitive O | |
and O | |
modern O | |
diagnostic O | |
methodology O | |
, O | |
in O | |
facilitating O | |
the O | |
the O | |
access O | |
to O | |
licensed O | |
medications O | |
for O | |
NMOSD O | |
, O | |
and O | |
addressing O | |
concerns O | |
on O | |
education O | |
, O | |
diagnosis O | |
and O | |
management O | |
of O | |
the O | |
disease O | |
in O | |
the O | |
community O | |
. O | |
Skeletal O | |
dysplasia O | |
( O | |
SD O | |
) O | |
, O | |
a O | |
heterogeneous O | |
disease O | |
group O | |
with O | |
rare O | |
incidence B-EPI | |
and O | |
various O | |
clinical O | |
manifestations O | |
, O | |
is O | |
associated O | |
with O | |
multiple O | |
causative O | |
genes O | |
. O | |
For O | |
clinicians O | |
, O | |
accurate O | |
diagnosis O | |
of O | |
SD O | |
is O | |
clinically O | |
and O | |
genetically O | |
difficult O | |
. O | |
The O | |
development O | |
of O | |
next O | |
- O | |
generation O | |
sequencing O | |
( O | |
NGS O | |
) O | |
has O | |
substantially O | |
aided O | |
in O | |
the O | |
genetic O | |
diagnosis O | |
of O | |
SD O | |
. O | |
In O | |
this O | |
study O | |
, O | |
we O | |
conducted O | |
a O | |
targeted O | |
NGS O | |
of O | |
437 O | |
genes O | |
- O | |
included O | |
in O | |
the O | |
nosology O | |
of O | |
SD O | |
published O | |
in O | |
2019 B-DATE | |
- O | |
in O | |
31 O | |
patients O | |
with O | |
a O | |
suspected O | |
SD O | |
. O | |
The O | |
clinical O | |
and O | |
genetic O | |
diagnoses O | |
were O | |
confirmed O | |
in O | |
16 O | |
out O | |
of O | |
the O | |
31 O | |
patients O | |
, O | |
and O | |
the O | |
diagnostic O | |
yield O | |
was O | |
51.9 O | |
% O | |
. O | |
In O | |
these O | |
patients O | |
, O | |
18 O | |
pathogenic O | |
variants O | |
were O | |
found O | |
in O | |
13 O | |
genes O | |
( O | |
COL2A1 O | |
, O | |
MYH3 O | |
, O | |
COMP O | |
, O | |
MATN3 O | |
, O | |
CTSK O | |
, O | |
EBP O | |
, O | |
CLCN7 O | |
, O | |
COL1A2 O | |
, O | |
EXT1 O | |
, O | |
TGFBR1 O | |
, O | |
SMAD3 O | |
, O | |
FIG4 O | |
, O | |
and O | |
ARID1B O | |
) O | |
, O | |
of O | |
which O | |
, O | |
four O | |
were O | |
novel O | |
variants O | |
. O | |
The O | |
diagnosis O | |
rate O | |
was O | |
very O | |
high O | |
in O | |
patients O | |
with O | |
a O | |
suspected O | |
familial O | |
SD O | |
and O | |
with O | |
radiological O | |
evidence O | |
indicating O | |
clinical O | |
SD O | |
( O | |
11 O | |
out O | |
of O | |
15 O | |
, O | |
73.3 O | |
% O | |
) O | |
. O | |
In O | |
patients O | |
with O | |
skeletal O | |
involvement O | |
and O | |
other O | |
clinical O | |
manifestations O | |
including O | |
dysmorphism O | |
or O | |
multiple O | |
congenital O | |
anomalies O | |
, O | |
and O | |
various O | |
degrees O | |
of O | |
developmental O | |
delay O | |
/ O | |
intellectual O | |
disability O | |
, O | |
the O | |
diagnosis O | |
rate O | |
was O | |
low O | |
( O | |
5 O | |
out O | |
of O | |
16 O | |
, O | |
31.2 O | |
% O | |
) O | |
but O | |
rare O | |
syndromic O | |
SD O | |
could O | |
be O | |
diagnosed O | |
. O | |
In O | |
conclusion O | |
, O | |
NGS O | |
- O | |
based O | |
gene O | |
panel O | |
sequencing O | |
can O | |
be O | |
helpful O | |
in O | |
diagnosing O | |
SD O | |
which O | |
has O | |
clinical O | |
and O | |
genetic O | |
heterogeneity O | |
. O | |
To O | |
increase O | |
the O | |
diagnostic O | |
yield O | |
of O | |
suspected O | |
SD O | |
patients O | |
, O | |
it O | |
is O | |
important O | |
to O | |
categorize O | |
patients O | |
based O | |
on O | |
the O | |
clinical O | |
features O | |
, O | |
family O | |
history O | |
, O | |
and O | |
radiographic O | |
evidence O | |
. O | |
Background O | |
The O | |
prevalence B-EPI | |
of O | |
perinatal O | |
infection O | |
from O | |
maternal O | |
exposure O | |
is O | |
increasing O | |
. O | |
The O | |
prevalence B-EPI | |
of O | |
acute O | |
maternal O | |
infections O | |
identifies O | |
cytomegalovirus O | |
, O | |
parvovirus O | |
B19 O | |
, O | |
toxoplasmosis O | |
, O | |
and O | |
varicella O | |
as O | |
the O | |
most O | |
common O | |
organisms O | |
and O | |
in O | |
the O | |
order O | |
of O | |
frequency O | |
. O | |
Maternal O | |
informed O | |
consent O | |
and O | |
understanding O | |
is O | |
required O | |
before O | |
intrauterine O | |
testing O | |
for O | |
fetal O | |
infectious O | |
and O | |
possible O | |
genetic O | |
risk O | |
assessment O | |
. O | |
Methods O | |
This O | |
structured O | |
review O | |
of O | |
the O | |
reproductive O | |
published O | |
literature O | |
focuses O | |
on O | |
the O | |
risks O | |
of O | |
amniocentesis O | |
and O | |
cordocentesis O | |
diagnostic O | |
procedure O | |
- O | |
related O | |
fetal O | |
loss O | |
rates O | |
and O | |
fetal O | |
vertical O | |
transmission O | |
( O | |
VT O | |
) O | |
rates O | |
from O | |
published O | |
infected O | |
pregnant O | |
cohorts O | |
. O | |
Results O | |
The O | |
total O | |
postprocedure O | |
fetal O | |
loss O | |
rate O | |
for O | |
diagnostic O | |
amniocentesis O | |
procedures O | |
, O | |
in O | |
limited O | |
infectious O | |
cohorts O | |
, O | |
is O | |
1.5 O | |
% O | |
and O | |
does O | |
not O | |
appear O | |
to O | |
be O | |
increased O | |
compared O | |
to O | |
noninfected O | |
amniocentesis O | |
cohorts O | |
using O | |
an O | |
estimated O | |
background O | |
spontaneous O | |
fetal O | |
loss O | |
rate O | |
( O | |
no O | |
procedure O | |
) O | |
of O | |
0.65 O | |
% O | |
. O | |
The O | |
pooled O | |
unintended O | |
fetal O | |
loss O | |
rate O | |
is O | |
from O | |
small O | |
infected O | |
population O | |
cohorts O | |
, O | |
but O | |
can O | |
be O | |
used O | |
for O | |
counseling O | |
purposes O | |
. O | |
Postcordocentesis O | |
fetal O | |
loss O | |
risk O | |
, O | |
in O | |
an O | |
infected O | |
cohort O | |
, O | |
is O | |
not O | |
possible O | |
to O | |
estimate O | |
due O | |
to O | |
limited O | |
data O | |
. O | |
The O | |
biological O | |
spontaneous O | |
fetal O | |
loss O | |
rate O | |
risk O | |
with O | |
a O | |
perinatal O | |
infection O | |
( O | |
positive O | |
or O | |
negative O | |
fetal O | |
anomalies O | |
) O | |
and O | |
no O | |
diagnostic O | |
procedure O | |
before O | |
20 O | |
weeks O | |
of O | |
gestation O | |
is O | |
reviewed O | |
. O | |
The O | |
risk O | |
of O | |
VT O | |
in O | |
acute O | |
infection O | |
cohorts O | |
as O | |
a O | |
result O | |
of O | |
the O | |
intra O | |
- O | |
amniotic O | |
diagnostic O | |
procedure O | |
is O | |
not O | |
found O | |
to O | |
be O | |
increased O | |
. O | |
Conclusion O | |
The O | |
unintended O | |
fetal O | |
loss O | |
rate O | |
after O | |
amniocentesis O | |
for O | |
perinatal O | |
infected O | |
cohorts O | |
is O | |
similar O | |
to O | |
that O | |
of O | |
noninfected O | |
cohorts O | |
, O | |
but O | |
the O | |
estimate O | |
is O | |
based O | |
on O | |
limited O | |
infected O | |
cohorts O | |
. O | |
There O | |
was O | |
no O | |
procedure O | |
- O | |
based O | |
risk O | |
of O | |
fetal O | |
VT O | |
in O | |
the O | |
infected O | |
cohorts O | |
, O | |
but O | |
identification O | |
of O | |
postprocedure O | |
maternal O | |
bleeding O | |
into O | |
the O | |
amniotic O | |
cavity O | |
increases O | |
the O | |
potential O | |
risk O | |
. O | |
Maternal O | |
knowledge O | |
translation O | |
and O | |
an O | |
informed O | |
consent O | |
process O | |
with O | |
risk O | |
- O | |
benefit O | |
maternal O | |
/ O | |
fetal O | |
risk O | |
counseling O | |
are O | |
required O | |
prior O | |
to O | |
any O | |
diagnostic O | |
amniocentesis O | |
procedure O | |
. O | |
Background O | |
Skin O | |
adnexal O | |
tumors O | |
( O | |
SAT O | |
) O | |
encompass O | |
wide O | |
spectrum O | |
of O | |
benign O | |
and O | |
malignant O | |
tumors O | |
that O | |
differentiate O | |
toward O | |
one O | |
or O | |
more O | |
adnexal O | |
structures O | |
found O | |
in O | |
normal O | |
skin O | |
. O | |
Overall B-EPI | |
incidence I-EPI | |
of O | |
SATs O | |
is O | |
low O | |
yet O | |
they O | |
can O | |
be O | |
challenging O | |
to O | |
diagnose O | |
. O | |
Aims O | |
The O | |
aim O | |
of O | |
this O | |
study O | |
is O | |
to O | |
study O | |
the O | |
spectrum O | |
and O | |
microscopic O | |
features O | |
of O | |
SATs O | |
. O | |
Materials O | |
and O | |
methods O | |
It O | |
was O | |
a O | |
retrospective O | |
cross O | |
- O | |
sectional O | |
, O | |
descriptive O | |
study O | |
conducted O | |
over O | |
a O | |
period O | |
of O | |
3 O | |
years O | |
. O | |
Formalin O | |
fixed O | |
, O | |
paraffin O | |
- O | |
embedded O | |
sections O | |
were O | |
stained O | |
with O | |
hematoxylin O | |
and O | |
eosin O | |
for O | |
histopathological O | |
analysis O | |
. O | |
Results O | |
Out O | |
of O | |
the O | |
total O | |
34,400 O | |
biopsies O | |
, O | |
110 O | |
cases O | |
were O | |
diagnosed O | |
as O | |
SATs O | |
comprising O | |
39.09 O | |
% O | |
of O | |
tumors O | |
with O | |
follicular O | |
differentiation O | |
followed O | |
by O | |
tumors O | |
showing O | |
sweat O | |
gland O | |
differentiation O | |
( O | |
37.27 O | |
% O | |
) O | |
, O | |
and O | |
sebaceous O | |
differentiation O | |
( O | |
23.63 O | |
% O | |
) O | |
. O | |
The O | |
age O | |
ranged O | |
from O | |
5 O | |
years O | |
to O | |
85 O | |
years O | |
and O | |
male B-SEX | |
: O | |
female B-SEX | |
ratio O | |
was O | |
1.03:1 O | |
. O | |
Most O | |
of O | |
the O | |
tumors O | |
were O | |
benign O | |
( O | |
82.73 O | |
% O | |
) O | |
while O | |
only O | |
17.27 O | |
% O | |
were O | |
malignant O | |
. O | |
Pilomatricoma O | |
( O | |
28.2 O | |
% O | |
) O | |
was O | |
the O | |
most O | |
common O | |
benign O | |
tumor O | |
while O | |
sebaceous O | |
carcinoma O | |
( O | |
11.8 O | |
% O | |
) O | |
was O | |
the O | |
most O | |
common O | |
malignant O | |
tumor O | |
. O | |
Conclusion O | |
Architectural O | |
features O | |
are O | |
of O | |
great O | |
importance O | |
in O | |
differentiating O | |
benign O | |
tumors O | |
from O | |
malignant O | |
. O | |
Objective O | |
To O | |
verify O | |
the O | |
prevalence B-EPI | |
of O | |
novel O | |
definitions O | |
of O | |
familial O | |
short O | |
stature O | |
on O | |
a O | |
cross O | |
- O | |
sectional O | |
cohort O | |
of O | |
children O | |
referred O | |
for O | |
short O | |
stature O | |
when O | |
their O | |
height O | |
and O | |
that O | |
of O | |
both O | |
parents O | |
were O | |
measured O | |
. O | |
Methods O | |
We O | |
consecutively O | |
enrolled O | |
65 O | |
individuals O | |
referred O | |
for O | |
short O | |
stature O | |
when O | |
both O | |
parents O | |
were O | |
present O | |
. O | |
We O | |
defined O | |
target O | |
height O | |
- O | |
related O | |
short O | |
stature O | |
( O | |
TH O | |
- O | |
SS O | |
) O | |
when O | |
child O | |
's O | |
height O | |
is O | |
≤ O | |
- O | |
2 O | |
SDS O | |
and O | |
included O | |
in O | |
the O | |
range O | |
of O | |
target O | |
height O | |
; O | |
suspected O | |
autosomal O | |
dominant O | |
short O | |
stature O | |
( O | |
AD O | |
- O | |
SS O | |
) O | |
when O | |
child O | |
height O | |
and O | |
at O | |
least O | |
one O | |
parent O | |
height O | |
are O | |
≤ O | |
- O | |
2 O | |
SDS O | |
; O | |
constitutional O | |
familial O | |
short O | |
stature O | |
( O | |
C O | |
- O | |
FSS O | |
) O | |
when O | |
a O | |
child O | |
with O | |
TH O | |
- O | |
SS O | |
does O | |
not O | |
have O | |
any O | |
parents O | |
with O | |
height O | |
≤ O | |
- O | |
2 O | |
SDS O | |
. O | |
Results O | |
Of O | |
65 O | |
children O | |
referred O | |
for O | |
SS O | |
, O | |
48 O | |
individuals O | |
had O | |
a O | |
height O | |
≤ O | |
- O | |
2 O | |
SDS O | |
. O | |
Based O | |
on O | |
the O | |
parents O | |
' O | |
measured O | |
heights O | |
, O | |
24 O | |
children O | |
had O | |
TH O | |
- O | |
SS O | |
, O | |
16 O | |
subjects O | |
AD O | |
- O | |
SS O | |
, O | |
and O | |
12 O | |
individuals O | |
C O | |
- O | |
FSS O | |
. O | |
If O | |
we O | |
had O | |
considered O | |
only O | |
the O | |
parents O | |
' O | |
reported O | |
height O | |
, O | |
3 O | |
of O | |
24 O | |
children O | |
with O | |
TH O | |
- O | |
SS O | |
, O | |
9 O | |
of O | |
16 O | |
with O | |
AD O | |
- O | |
SS O | |
, O | |
and O | |
10 O | |
of O | |
12 O | |
with O | |
C O | |
- O | |
FSS O | |
would O | |
have O | |
been O | |
lost O | |
. O | |
Conclusion O | |
We O | |
suggest O | |
novel O | |
definitions O | |
to O | |
adequately O | |
detect O | |
and O | |
approach O | |
the O | |
cases O | |
of O | |
FSS O | |
since O | |
C O | |
- O | |
FSS O | |
( O | |
25 O | |
% O | |
) O | |
might O | |
not O | |
need O | |
any O | |
specific O | |
investigation O | |
, O | |
while O | |
on O | |
the O | |
contrary O | |
, O | |
AD O | |
- O | |
SS O | |
( O | |
33 O | |
% O | |
) O | |
should O | |
undergo O | |
genetic O | |
evaluation O | |
. O | |
Moreover O | |
, O | |
this O | |
study O | |
underlines O | |
that O | |
adequate O | |
measurement O | |
and O | |
consideration O | |
of O | |
children O | |
's O | |
and O | |
parents O | |
' O | |
heights O | |
( O | |
individually O | |
and O | |
together O | |
) O | |
are O | |
crucial O | |
in O | |
the O | |
clinical O | |
evaluation O | |
of O | |
every O | |
child O | |
with O | |
short O | |
stature O | |
. O | |
The O | |
short O | |
telomere O | |
syndromes O | |
encompass O | |
a O | |
spectrum O | |
of O | |
clinical O | |
manifestations O | |
that O | |
present O | |
from O | |
infancy O | |
to O | |
late O | |
adulthood O | |
. O | |
They O | |
are O | |
caused O | |
by O | |
mutations O | |
in O | |
telomerase O | |
and O | |
other O | |
telomere O | |
maintenance O | |
genes O | |
and O | |
have O | |
a O | |
predominantly O | |
degenerative O | |
phenotype O | |
characterized O | |
by O | |
organ O | |
failure O | |
across O | |
multiple O | |
systems O | |
. O | |
They O | |
are O | |
collectively O | |
one O | |
of O | |
the O | |
most O | |
common O | |
inherited O | |
bone O | |
marrow O | |
failure O | |
syndromes O | |
; O | |
however O | |
, O | |
their O | |
most O | |
prevalent B-EPI | |
presentations O | |
are O | |
extrahematopoietic O | |
. O | |
This O | |
review O | |
focuses O | |
on O | |
these O | |
common O | |
nonhematologic O | |
complications O | |
, O | |
including O | |
pulmonary O | |
fibrosis O | |
, O | |
liver O | |
pathology O | |
, O | |
and O | |
immunodeficiency O | |
. O | |
The O | |
short O | |
telomere O | |
syndrome O | |
diagnosis O | |
informs O | |
clinical O | |
care O | |
, O | |
especially O | |
in O | |
guiding O | |
diagnostic O | |
evaluations O | |
as O | |
well O | |
as O | |
in O | |
the O | |
solid O | |
organ O | |
transplant O | |
setting O | |
. O | |
Early O | |
recognition O | |
allows O | |
an O | |
individualized O | |
approach O | |
to O | |
screening O | |
and O | |
management O | |
. O | |
This O | |
review O | |
illustrates O | |
a O | |
myriad O | |
of O | |
extrahematopoietic O | |
presentations O | |
of O | |
short O | |
telomere O | |
syndromes O | |
and O | |
how O | |
they O | |
impact O | |
clinical O | |
decisions O | |
. O | |
Second O | |
malignant O | |
neoplasms O | |
pose O | |
a O | |
concern O | |
for O | |
survivors O | |
of O | |
childhood O | |
cancer O | |
. O | |
We O | |
evaluated O | |
incidence B-EPI | |
, O | |
type O | |
and O | |
risk O | |
factors O | |
for O | |
second O | |
malignant O | |
neoplasms O | |
in O | |
patients O | |
included O | |
in O | |
Berlin O | |
- O | |
Frankfurt O | |
- O | |
Muenster O | |
protocols O | |
for O | |
childhood O | |
non O | |
- O | |
Hodgkin O | |
lymphoma O | |
. O | |
3590 O | |
patients O | |
< O | |
15 O | |
years O | |
of O | |
age O | |
at O | |
diagnosis O | |
registered O | |
between B-DATE | |
01/1981 I-DATE | |
and I-DATE | |
06/2010 I-DATE | |
were O | |
analyzed O | |
. O | |
Second O | |
malignant O | |
neoplasms O | |
were O | |
reported O | |
by O | |
the O | |
treating O | |
institutions O | |
and O | |
the O | |
German B-ETHN | |
Childhood O | |
Cancer O | |
Registry O | |
. O | |
After O | |
median O | |
follow O | |
- O | |
up O | |
of O | |
9.4 O | |
years O | |
( O | |
Quartile O | |
, O | |
Q1 O | |
6.7 O | |
and O | |
Q3 O | |
12.1 O | |
) O | |
95 O | |
second O | |
malignant O | |
neoplasms O | |
were O | |
registered O | |
( O | |
26 O | |
carcinomas O | |
including O | |
9 O | |
basal O | |
cell O | |
carcinomas O | |
, O | |
21 O | |
acute O | |
myeloid O | |
leukemias O | |
/ O | |
myelodysplastic O | |
syndromes O | |
, O | |
20 O | |
lymphoid O | |
malignancies O | |
, O | |
12 O | |
CNS O | |
- O | |
tumors O | |
, O | |
and O | |
16 O | |
other O | |
) O | |
. O | |
Cumulative B-EPI | |
incidence I-EPI | |
at O | |
20 O | |
years O | |
was O | |
5.7±0.7 O | |
% O | |
, O | |
standard O | |
incidence I-EPI | |
ratio O | |
excluding O | |
basal O | |
cell O | |
carcinomas O | |
was O | |
19.8 O | |
( O | |
95 O | |
% O | |
CI O | |
14.5 O | |
- O | |
26.5 O | |
) O | |
. O | |
Median O | |
time O | |
from O | |
initial O | |
diagnosis O | |
to O | |
second O | |
malignancy O | |
was O | |
8.7 O | |
years O | |
( O | |
range O | |
: O | |
0.2 O | |
- O | |
30.3 O | |
) O | |
. O | |
Acute O | |
- O | |
lymphoblastic O | |
- O | |
leukemia O | |
- O | |
type O | |
therapy O | |
, O | |
cumulative O | |
anthracycline O | |
dose O | |
, O | |
and O | |
cranial O | |
radiotherapy O | |
for O | |
brain O | |
tumor O | |
- O | |
development O | |
were O | |
significant O | |
risk O | |
factors O | |
in O | |
univariate O | |
analysis O | |
only O | |
. O | |
In O | |
multivariate O | |
analysis O | |
including O | |
risk O | |
factors O | |
significant O | |
in O | |
univariate O | |
analysis O | |
, O | |
female B-SEX | |
sex O | |
( O | |
HR O | |
1.87 O | |
, O | |
95 O | |
% O | |
CI O | |
1.23 O | |
- O | |
2.86 O | |
, O | |
p=0.004 O | |
) O | |
, O | |
CNS O | |
- O | |
involvement O | |
( O | |
HR O | |
2.24 O | |
, O | |
95 O | |
% O | |
CI O | |
1.03 O | |
- O | |
4.88 O | |
, O | |
p=0.042 O | |
) O | |
, O | |
lymphoblastic O | |
lymphoma O | |
( O | |
HR O | |
2.60 O | |
, O | |
95 O | |
% O | |
CI O | |
1.69 O | |
- O | |
3.97 O | |
, O | |
p<0.001 O | |
) O | |
, O | |
and O | |
cancer O | |
- O | |
predisposing O | |
condition O | |
( O | |
HR O | |
11.2 O | |
, O | |
95 O | |
% O | |
CI O | |
5.52 O | |
- O | |
22.75 O | |
, O | |
p<0.001 O | |
) O | |
retained O | |
an O | |
independent O | |
risk O | |
. O | |
Carcinomas O | |
were O | |
the O | |
most O | |
frequent O | |
second O | |
malignant O | |
neoplasms O | |
after O | |
non O | |
- O | |
Hodgkin O | |
lymphoma O | |
in O | |
childhood O | |
followed O | |
by O | |
acute O | |
myeloid O | |
leukemia O | |
and O | |
lymphoid O | |
malignancies O | |
. O | |
Female B-SEX | |
sex O | |
, O | |
lymphoblastic O | |
lymphoma O | |
, O | |
CNS O | |
- O | |
involvement O | |
, O | |
or O | |
/ O | |
and O | |
known O | |
cancer O | |
- O | |
predisposing O | |
condition O | |
were O | |
risk O | |
factors O | |
for O | |
second O | |
malignant O | |
neoplasm O | |
- O | |
development O | |
. O | |
Our O | |
findings O | |
set O | |
the O | |
basis O | |
for O | |
individualized O | |
long O | |
- O | |
term O | |
follow O | |
- O | |
up O | |
and O | |
risk O | |
assessment O | |
of O | |
new O | |
therapies O | |
. O | |
Background O | |
: O | |
Urticaria O | |
is O | |
a O | |
disorder O | |
affecting O | |
skin O | |
and O | |
mucosal O | |
tissues O | |
characterized O | |
by O | |
the O | |
occurrence B-EPI | |
of O | |
wheals O | |
, O | |
angioedema O | |
or O | |
both O | |
, O | |
the O | |
latter O | |
defining O | |
the O | |
urticaria O | |
- O | |
angioedema O | |
syndrome O | |
. O | |
It O | |
is O | |
estimated O | |
that O | |
12 O | |
- O | |
22 O | |
% O | |
of O | |
the O | |
general O | |
population O | |
has O | |
suffered O | |
at O | |
least O | |
one O | |
subtype O | |
of O | |
urticaria O | |
during O | |
life O | |
, O | |
but O | |
only O | |
a O | |
small O | |
percentage O | |
( O | |
estimated O | |
at O | |
7.6 O | |
- O | |
16 O | |
% O | |
) O | |
has O | |
acute O | |
urticaria O | |
, O | |
because O | |
it O | |
is O | |
usually O | |
self O | |
- O | |
limited O | |
and O | |
resolves O | |
spontaneously O | |
without O | |
requiring O | |
medical O | |
attention O | |
. O | |
This O | |
makes O | |
likely O | |
that O | |
its O | |
incidence B-EPI | |
is O | |
underestimated O | |
. O | |
The O | |
epidemiological O | |
data O | |
currently O | |
available O | |
on O | |
chronic O | |
urticaria O | |
in O | |
many O | |
cases O | |
are O | |
deeply O | |
discordant O | |
and O | |
not O | |
univocal O | |
, O | |
but O | |
a O | |
recent O | |
Italian B-ETHN | |
study O | |
, O | |
based O | |
on O | |
the O | |
consultation O | |
of O | |
a O | |
national O | |
registry O | |
, O | |
reports O | |
a O | |
prevalence B-EPI | |
of O | |
chronic O | |
spontaneous O | |
urticaria O | |
of O | |
0.02 B-STAT | |
% I-STAT | |
to I-STAT | |
0.4 I-STAT | |
% I-STAT | |
and O | |
an O | |
incidence B-EPI | |
of O | |
0.1 B-STAT | |
- I-STAT | |
1.5 I-STAT | |
cases/1000 I-STAT | |
inhabitants I-STAT | |
/ I-STAT | |
year I-STAT | |
. O | |
Methods O | |
: O | |
We O | |
reviewed O | |
the O | |
recent O | |
international O | |
guidelines O | |
about O | |
urticaria O | |
and O | |
we O | |
described O | |
a O | |
methodologic O | |
approach O | |
based O | |
on O | |
classification O | |
, O | |
pathophysiology O | |
, O | |
impact O | |
on O | |
quality O | |
of O | |
life O | |
, O | |
diagnosis O | |
and O | |
prognosis O | |
, O | |
differential O | |
diagnosis O | |
and O | |
management O | |
of O | |
all O | |
the O | |
types O | |
of O | |
urticaria O | |
. O | |
Conclusions O | |
: O | |
The O | |
aim O | |
of O | |
the O | |
present O | |
document O | |
from O | |
the O | |
Italian O | |
Society O | |
of O | |
Allergology O | |
, O | |
Asthma O | |
and O | |
Clinical O | |
Immunology O | |
( O | |
SIAAIC O | |
) O | |
and O | |
the O | |
Italian O | |
Society O | |
of O | |
Allergological O | |
, O | |
Occupational O | |
and O | |
Environmental O | |
Dermatology O | |
( O | |
SIDAPA O | |
) O | |
is O | |
to O | |
provide O | |
updated O | |
information O | |
to O | |
all O | |
physicians O | |
involved O | |
in O | |
diagnosis O | |
and O | |
management O | |
of O | |
urticaria O | |
and O | |
angioedema O | |
. O | |
Bullous O | |
pemphigoid O | |
( O | |
BP O | |
) O | |
is O | |
the O | |
most O | |
prevalent B-EPI | |
autoimmune O | |
blistering O | |
skin O | |
disease O | |
in O | |
the O | |
Western I-LOC | |
world I-LOC | |
affecting O | |
mainly O | |
the O | |
elderly O | |
population O | |
. O | |
The O | |
diagnosis O | |
is O | |
based O | |
on O | |
clinical O | |
assessment O | |
along O | |
with O | |
specific O | |
immunopathologic O | |
findings O | |
on O | |
skin O | |
biopsy O | |
. O | |
Risk O | |
factors O | |
include O | |
genetic O | |
factors O | |
, O | |
environmental O | |
exposures O | |
, O | |
and O | |
several O | |
infections O | |
including O | |
hepatitis O | |
B O | |
, O | |
hepatitis O | |
C O | |
, O | |
Helicobacter O | |
pylori O | |
, O | |
Toxoplasma O | |
gondi O | |
, O | |
and O | |
cytomegalovirus O | |
. O | |
A O | |
variety O | |
of O | |
drugs O | |
have O | |
been O | |
associated O | |
with O | |
BP O | |
including O | |
but O | |
not O | |
limited O | |
to O | |
dipeptidyl O | |
peptidase-4 O | |
inhibitors O | |
, O | |
loop O | |
diuretics O | |
, O | |
spironolactone O | |
, O | |
and O | |
neuroleptics O | |
. O | |
Associated O | |
neurologic O | |
disorders O | |
( O | |
dementia O | |
, O | |
Parkinson O | |
's O | |
disease O | |
, O | |
bipolar O | |
disorder O | |
, O | |
previous O | |
stroke O | |
history O | |
, O | |
and O | |
multiple O | |
sclerosis O | |
) O | |
have O | |
also O | |
been O | |
described O | |
. O | |
Common O | |
clinical O | |
presentation O | |
consists O | |
of O | |
extremely O | |
pruritic O | |
inflammatory O | |
plaques O | |
that O | |
resemble O | |
eczematous O | |
dermatitis O | |
or O | |
urticaria O | |
, O | |
followed O | |
by O | |
formation O | |
of O | |
tense O | |
bullae O | |
with O | |
subsequent O | |
erosions O | |
. O | |
Typical O | |
distribution O | |
involves O | |
the O | |
trunk O | |
and O | |
extremities O | |
. O | |
Mucosa O | |
is O | |
typically O | |
spared O | |
affecting O | |
only O | |
10 O | |
% O | |
to O | |
30 O | |
% O | |
of O | |
patients O | |
. O | |
Several O | |
unusual O | |
clinical O | |
presentations O | |
of O | |
BP O | |
have O | |
been O | |
described O | |
such O | |
as O | |
nonbullous O | |
forms O | |
with O | |
erythematous O | |
excoriated O | |
papules O | |
, O | |
plaques O | |
, O | |
and O | |
nodules O | |
. O | |
Other O | |
reported O | |
findings O | |
include O | |
urticarial O | |
lesions O | |
, O | |
prurigo O | |
- O | |
like O | |
nodules O | |
, O | |
multiple O | |
small O | |
vesicles O | |
resembling O | |
dermatitis O | |
herpetiformis O | |
or O | |
pompholyx O | |
, O | |
vegetating O | |
and O | |
purulent O | |
lesions O | |
localized O | |
in O | |
intertriginous O | |
areas O | |
, O | |
and O | |
even O | |
exfoliative O | |
erythroderma O | |
. O | |
Recognition O | |
and O | |
management O | |
of O | |
such O | |
cases O | |
can O | |
present O | |
a O | |
diagnostic O | |
challenge O | |
to O | |
clinicians O | |
. O | |
In O | |
this O | |
article O | |
, O | |
we O | |
describe O | |
another O | |
variant O | |
which O | |
to O | |
our O | |
knowledge O | |
is O | |
the O | |
first O | |
case O | |
to O | |
present O | |
with O | |
a O | |
cellulitis O | |
- O | |
like O | |
presentation O | |
in O | |
a O | |
patient O | |
with O | |
a O | |
known O | |
history O | |
of O | |
BP O | |
. O | |