Alternative

Selama pengembangan, transkripsional dan pasca-tran-

jaringan naskah diatur secara terkoordinasi
pendarahan organ pematangan Penyambungan splicing alternatif-
Dengan memproduksi protein khusus temporal iso-
formulir. Kami sebelumnya menemukan gen yang dialaminya
transisi splicing selama jantung tikus postnatal
pengembangan diperkaya untuk perdagangan vesikular
dan fungsi dinamika membran. Ini, kami tunjukkan
isoform perdagangan orang dewasa juga dinyatakan dalam
otot rangka dewasa dan berhipotesis yang lurik
Otot menggunakan splicing alternatif untuk menghasilkan spe-
Forma spesifik yang diperlukan untuk fungsi jaringan dewasa.
Kami memberikan morpholinos ke dalamnya
fleksor digitorum brevis
otot pada tikus dewasa untuk mengarahkan splicing empat
gen trafficking ke isoform janin. Splicing
beralih hasil dalam multiplestructural dan fungsional de-
fek, termasuk tubulus transversal (T-tubule) disrup-
tion dan dihydropyridine reseptor alpha (DHPR) dan
Ryr1 mislocalization, mengganggu eksitasi-contrac-
kopling, penanganan kalsium, dan genera-
tion. Hasilnya menunjukkan sebelumnya tidak jelas-
Peran nirlaba untuk fungsi perdagangan manusia pada otot dewasa
homeostasis jaringan dan kebutuhan spesifik untuk
varian sambatan orang dewasa
Pentingnya proses yang disebutkan di atas dalam lurik
Otot disorot oleh banyaknya mutasi manusia pada gen dinamika perdagangan dan membran yang
menyebabkan penyakit otot dan jantung. Dalam karya ini, kami menghubungkan tiga bidang
penelitian: perdagangan manusia, AS,
dan fisiologi otot lurik. Penelitian genome-wide miliki
secara konsisten menunjukkan pentingnya transkripsi dan post-
mekanisme pengaturan transkripsi dalam struktur organ dan jaringan
opment dan diferensiasi sel (
Wang et al., 2008; Bland et al.,
2010; Ellis dkk., 2012; Merkin et al., 2012; Dillman et al., 2013;
Giudice et al., 2014; Singh et al., 2014
). Peran trafficking
dan dinamika membran pada fisiologi otot lurik normal
dan penyakit juga terdokumentasi dengan baik. Namun fungsinya
dari sejumlah besar protein trafiking di otot belum
telah dieksplorasi Hal ini penting karena saat ini ada
banyak gangguan otot dengan penyebab yang tidak diketahui. Meskipun
signifikansi fisiologis peraturan AS tentang perdagangan manusia
dan proses dinamika membrane adalah underex-
bidang plored, karya sebelumnya pasti mengisyaratkan pentingnya.
Misalnya, baru-baru ini, AS salah mengatur saluran natrium
SCN5A telah terbukti berkontribusi terhadap konduksi jantung
keterlambatan dan aritmia pada tikus, sama dengan yang diamati pada
distrofi myotonic
Freyermuth et al., 2016
). Sebelumnya, mis-
AS dari Bin1 pada tikus telah dikaitkan dengan perubahan tubulus T
dan kelemahan otot rangka, ciri utama myoto-
dystrophy nic
Fugier dkk., 2011
).
Di sini, kami menyelidiki dampak fisiologis AS terhadap empat orang
gen trafficking in vivo: Snap23, Trip10, Cltc, dan Tmed2.
Keempat kejadian ini belum pernah diteliti secara fisik-
konteks iologis Tidak ada mutasi manusia yang dilaporkan dalam hal ini
gen kecuali dua mutasi yang baru saja diidentifikasi
CLTC
gen
yang menyebabkan kerusakan perkembangan parah (
DeMari et al., 2016
).
Menggunakan morfin, kami dialihkan AS sedemikian rupa sehingga sebagian besar
Isoform pendek (lazim pada neonatus) diekspresikan pada orang dewasa
otot. Bila hanya isoform pendek yang diungkapkan, kalsium
Pelepasan dikurangi serta generasi kekuatan otot (
Ara-
ures 2
A dan 2B). Regulator utama kontraktil otot skeletal
Fungsi adalah jaringan T-tubule dan SR yang terorganisir dengan tepat.
Detreminants
Kerusakan otot pernafasan telah semakin terkontaminasi-
nized sebagai kontributor patofisiologis independen untuk disor-
hal yang mempengaruhi populasi anak-anak. Anak-anak dengan kistik
fibrosis (CF)
1-3
dan penyakit neuromuskular
4
berisiko tinggi
Kelelahan otot pernafasan. Orang gemuk mengalami gangguan
fungsi otot pernapasan dibandingkan dengan kontrol karena
peningkatan beban mekanis otot pernafasan.
5
Fungsi otot pernafasan yang terganggu telah diidentifikasi sebagai
prediktor independen hasil ekstubasi pada anak-anak.
6
Bulu-
thermore, antropometri,
7
polimorfisme genetik,
8
dan aerobik
olahraga
9,10
juga berkontribusi terhadap fungsi otot pernapasan di
anak-anak.
Kekuatan otot pernafasan bisa ditentukan secara noninvasif
dengan pengukuran tekanan inspirasi maksimal (P
Imax
)
dan tekanan ekspirasi maksimal (P
Emax
).
11
Meski P
Imax
dan
P
Emax
menggambarkan gambaran kinerja otot pernafasan pada a
titik waktu tertentu, fungsi otot pernapasan dan risikonya
Kelelahan otot bisa lebih dinilai dengan baik oleh indeks tambahan
gambarkan beban pernafasan, yang terdiri dari dinding dada dan
beban elastis paru ditambah beban resistif. Indeks seperti itu adalah
Indeks ketegangan-waktu non-invasif otot inspirasi
(TTI
mus
).
12
TTI
mus
adalah indeks berdimensi komposit yang incor-
pengukuran pengukuran tekanan dan waktu dan menggambarkan
Efisiensi total pekerjaan yang dilakukan oleh pernafasan
otot.
13
Nilai TTI lebih tinggi
mus
adalah indikasi tidak efisien
fungsi otot inspirasi dan peningkatan risiko inspirasi
kelelahan otot dan gagal napas.
12,13
Penilaian klinis risiko relatif otot inspirasi
Keletihan dan kegagalan pernafasan pada anak bisa memudahkan
keputusan yang ditujukan untuk menerapkan modalitas pengobatan seperti ventilasi noninvasive
dan latihan otot inspirasi atau imple-
Menting strategi untuk menyapih dari ventilasi mekanis.
Sepengetahuan kami, penelitian melaporkan nilai TTI
mus
di
Anak-anak yang sehat jarang,
7
dan data dan data pasien
Dari subjek berventilasi akan terpengaruh oleh distorsi paru-paru
mekanika. Dalam penelitian ini kami menggambarkan pola perubahan
TTI
mus
pada anak sehat dan melaporkan demografi dan
parameter antropometri yang berkontribusi terhadap perubahan
Fungsi otot inspirasi dalam populasi ini Ninety-six healthy children without respiratory problems
who were able to perform reproducible maximal respiratory
maneuvers were prospectively recruited. They were studied in
the outpatient department of the University Hospital of Patras,
Greece. Their age ranged from 6 to18 years. The subjects were
healthy children recruited from the community and siblings of
children attending the outpatient department. Children with
pre-existing respiratory conditions such as asthma or CF, chil-
dren with genetic disorders such as thalassemia, and children
who were unwell were excluded from the study. Children younger
than 6 years of age were excluded because they could not
reliably execute reproducible maneuvers requiring a maximal
effort. Suitability of inclusion was assessed by questionnaire.
All respiratory and nutrition measurements were performed
by the same examiner (TD).
The study protocol was approved by the Research Ethics
Committee of the University Hospital of Patras. Parents or legal
guardians provided informed written consent prior to the study,
and children provided informed assen
Our study demonstrated that inspiratory muscle function is
enhanced in regularly exercising children compared with
nonexercising ones. We reported that TTI
mus
values are normal
in healthy children and are negatively related to height, weight,
age, and muscular state. Furthermore, we calculated predictive
regression equations for TTI
mus
in male and female children.
TTI
mus
in our study attained comparable values to previously
published data for nonventilated children.
1–4,7
Assessment of
respiratory muscle function by means of TTI
mus
has demon-
strated that measurement of TTI
mus
can accurately predict extu-
bation outcome in ventilated children.
6
Children with CF
exhibit increased TTI
mus
values, signaling compromised respi-
ratory muscle function, which is determined by a combination
of increased load and decreased strength owing to airway
obstruction and malnutrition, respectively.
1–3,20
Children with
neuromuscular disorders also attain higher TTI
mus
values,
mainly secondary to decreased respiratory muscle strength as a
direct consequence of the disease.
4
Obese individuals exhibit
increased TTI
mus
values as a result of the excessive mechanical
load imposed on the respiratory muscles.
5
Our study recon-
firmed the range of values of TTI
mus
reported in previous studies
and complemented the literature with novel, previously unre-
ported parameters that determine TTI
mus
, such as the state of
skeletal muscularity and the effect of aerobic exercise on the
respiratory muscles in healthy children. Given the reported
impact of genetic polymorphisms on respiratory muscle
function,
8
another strength of our study is that it is the first to
report normal values of TTI
mus
in healthy southern European,
predominantly Greek, children.
Male children exhibited lower values of TTI
mus
in our study
compared with age-matched females. Male muscles are known
to generate a higher maximum power output than female
muscles. The mechanisms behind gender-related differences in skeletal muscle function are not
known, but they are likely a
consequence of different sex hormonal status.
21
Respiratory muscle function in children can be affected by
increased respiratory load, decreased muscle strength, or a
combination of both. Hence, TTI
mus
is an index ideally equipped
to describe and assess this compromise. Furthermore, TTI
mus
is
a global inspiratory muscle index that does not preferentially
assess diaphragm function, and it is also noninvasive and simple
to perform. Other methods have been utilized to assess respi-
ratory muscle function, such as diaphragmatic electromyography
22
or sniff nasal inspiratory pressure (SNIP).
23
However, surface
diaphragmatic electromyography in children would be consid-
erably affected by electrical noise from neighboring muscle
groups, whereas nostril occlusion for measurement of SNIP
might be poorly tolerated in young children, and SNIP values
might vary substantively for anatomic reasons in children of
different ethnic backgrounds.
24
Our study reported values of P
0.1
that decrease with age.
P
0.1
is a reproducible index
25
that was introduced to assess
respiratory drive in children with chronic intrinsic loaded
breathing.
11,26
Although it is perceived that the timing of the P
0.1
is such that it is independent of lung compliance and airway
resistance, the age-related decrease in P
0.1
in our study might
reflect developmental changes, which is consistent with the
tendency of lung compliance to increase through childhood into
early adult life.
27
In our study P
Imax
increased with age; this probably reflects a
maturation process related to increasing muscle mass and body
growth.
28
Values of P
Imax
have been previously reported in
children.
23
Our study reports values for maximal respiratory
pressures similar to previously published data from healthy
children.
7,29-32
Both P
Imax
and P
Emax
positively correlated with
increasing age and anthropometric indices that describe mus-
cular state; given that respiratory muscles are skeletal muscles,
this is a logical finding.
In terms of clinical significance, our data demonstrate that
TTI
mus
in children is influenced by gender, anthropometry,
indices of muscularity, and aerobic exercise. Incorporating this
information into clinical practice could enhance the use of
TTI
mus
as an objective monitoring parameter of inspiratory
muscle function in children and could assist in predicting respi-
ratory muscle fatigue in conjunction with clinical and pulmo-
nary function data. Early recognition of impending respiratory
failure would allow for timely application of treatment modali-
ties such as noninvasive ventilation, inspiratory muscle train-
ing, and mechanical ventilation. The protective role of aerobic
exercise in maintaining inspiratory muscle strength is rein-
forced by our results
Conclusion
This study demonstrated that inspiratory muscle function
in healthy children is determined by height and that aerobic
exercise might enhance respiratory muscle strength. This
knowledge is essential to assess the respiratory muscles and to
monitor respiratory muscle dysfunction and disease progres-
sion in children.

Wirst motion
Simulator fisiologis menciptakan kinematik dan kinetik con-
persimpangan pergelangan tangan alami secara in vitro dengan menerapkan beban tarik
untuk tendon spesimen kadaver (
Erhart dkk., 2012; Werner
et al., 1996
). Hal ini memungkinkan identifikasi variabel-variabel kunci mempengaruhi-
Dengan biomekanik, dengan implikasi langsung untuk rekonstruksi bedah-
tions dan / atau prosedur rehabilitasi. Dalam kasus pergelangan tangan
rehabilitasi, satu protokol standar yang diusulkan mencakup penempatan
lengan bawah pada orientasi horizontal dengan pronasi netral
(
Fess dan Moran, 1981
), diikuti dengan kinerja yang ditentukan
latihan
Williams et al., 2001
). Namun, beberapa rehabilitasi pro-
tocols terdiri dari rangkaian gerak pergelangan tangan yang lebih besar dengan variasi
rotasi forearm dan orientasi tangan (
Pandian dan Narayan,
2012
). Oleh karena itu, penting untuk mengukur efek lengan bawah
rotasi dan orientasi tangan pada biomekanika pergelangan tangan, terutama
karena mereka diketahui mempengaruhi faktor kunci seperti kekuatan pegangan, sementara
menilai kemajuan rehabilitasi pergelangan tangan (
Richards dkk.,
1996
). Meskipun efek dari berbagai pronasi forearm-
Sudut supinasi pada otot pergelangan tangan telah dipelajari
secara in vitro
Farr et al., 2013
), semua simulator pergelangan tangan yang dilaporkan dalam liter-
ature telah menghitung biomekanika pergelangan tangan hanya di vertikal ori-
entasi tangan
Erhart dkk., 2012; Werner et al., 1996
);
efek dari berbagai orientasi tangan pada otot pergelangan tangan
belum dieksplorasi Selain itu, sementara simulasi func-
Gerakan gerak pergelangan tangan, hanya salah satu arah circum-
duksi telah dianalisis pada simulator pergelangan tangan (
Werner dkk.,
1996, 2010
); efek perubahan arah pengelupasan
Pada otot pergelangan tangan belum dianalisis.
Untuk mensimulasikan gerakan pergelangan tangan planar dan kompleks secara in vitro
menggunakan simulator fisiologis, resolusi beban distribu-
Di antara tendon sangat penting, karena tak tentu
masalah aktuasi otot berlebihan, yang timbul akibat
Kehadiran enam otot primer mengendalikan dua derajat n previous work, hybrid control and
cascade control – two novel control strategies combining position
and force feedback – were implemented on a functional replica of
the human forearm and hand, and resulted in more accurate kine-
matics and more physiologic muscle forces as compared to the
conventional position and force control strategies (
Shah and
Kedgley, 2016
).
Therefore, the first objective of this study was to test the robust-
ness and repeatability of these novel control strategies in recreat-
ing simple and complex wrist motions in cadaveric specimens.
The second objective of this study was to quantify the effects of
varying hand orientations on wrist biomechanics, with the hypoth-
esis that wrist muscle forces would be higher for the horizontal ori-
entation. The third objective of this study was to quantify the
muscle forces during wrist circumduction, with the hypothesis
that the direction of motion would significantly affect the magni-
tude of the forces

Results
Both hybrid and cascade control resulted in accurate joint kine-
matics (
Fig. 2
), with low in-plane and out-of-plane kinematic
errors for the planar motions FE-30 and RUD-10, as well as low
kinematic errors for complex motions DTM, CCD
cw
and CCD
acw
(
Appendix A.1
). Repeatable muscle forces were obtained using
both hybrid and cascade control for all six muscles (
Appendix A.2
).
No differences were observed between kinematic errors in wrist
motions simulated with the hand in the vertically upward and
downward orientations (
p
-value of the vertically upward orienta-
tion compared to the vertically downward orientation (
p
UD
)
> 0.169); however, the horizontal orientation resulted in higher
out-of-plane errors in both FE-30 and RUD-10 compared to the ver-
tically upward and downward orientations (
p
-value of the horizon-
tal orientation compared to the vertically upward orientation
(
p
HU
) < 0.007,
p
-value of the horizontal orientation compared to
the vertically downward orientation (
p
HD
) < 0.005) (
Table 1
). The
extensor force (sum of ECRL, ECRB, ECU) was higher for the hand
in the horizontal orientation throughout the range of motion in
FE and RUD (
p
HU
< 0.017,
p
HD
< 0.017), except at small angles dur-
ing extension (
p
HU
> 0.028,
p
HD
> 0.059) (
Fig. 3
). No differences
A physiologic wrist simulator was developed to replicate
motions of the intact human wrist in cadaveric specimens. One
of the main advantages of employing an optical motion capture
system to track joint angles was the use of light, passive markers,
which did not appreciably add to the mass of the body segments.
Hybrid and cascade control, which combined both position and
force feedback simultaneously, resulted in accurate (
Appendix
A.1
) and repeatable (
Appendix A.2
) wrist motions in vitro, thus
supporting our hypothesis. However, owing to higher cycle times
(
Appendix A.1
), lower repeatability (
Appendix A.2
) and large mus-
cle forces (
Appendix A.3
) in cascade control, hybrid control was
preferred over cascade control. One of the limitations of the simu-
lator was the exclusion of the extrinsic muscles of the fingers and
the thumb. Although these muscles pass through the wrist, and are
therefore expected to affect wrist biomechanics, their inclusion
would have further added to the complexity of the control strate-
gies. Another limitation of the study was the fixation of the ulna
relative to the radius, which prevented forearm pronation-
supination or ulnar length variation during wrist motions

Jadi, saat tangan dipegang di hor-

Orientasi izontal, tergantung pada arah gravitasi mana yang beraksi
(palmar, dorsal, radial atau ulnar), fungsi fungsional mus-
kelompok cle (ekstensor, fleksor, deviator ulnaris atau deviator radial)
kemungkinan akan kelebihan beban, konsisten dengan hipotesis kita. Lebih lanjut-
lebih banyak lagi, kesalahan kinematis out-of-plane lebih tinggi untuk tangan
dalam orientasi horizontal dari dua orientasi vertikal
(
Tabel 1
), menunjukkan bahwa lebih sulit mengendalikan pergelangan tangan
di tingkat sekunder kebebasan sebagai pengaruh eksternal
kekuatan meningkat, seperti juga dilaporkan dalam kontrol robot manip-
ulos (
Raibert dan Craig, 1981
). Saat membandingkan dua vertikal
orientasi, gaya fleksor lebih tinggi pada vertikal down-
orientasi lingkungan untuk sudut fleksi yang lebih tinggi (
hal
UD
<0.009) (
Gambar 3
Sebuah)
untuk menangkal gravitasi akting di bagian punggung, sedangkan gaya ekstensor
lebih tinggi pada orientasi vertikal ke atas untuk fleksi yang lebih tinggi
Sudut untuk melawan gravitasi bertindak palmarly, meski berbeda-
ences tidak signifikan
hal
UD
> 0,017). Pengamatan ini bisa dilakukan
dukung penempatan lengan bawah secara vertikal ke atas ori-
entasi, berlawanan dengan orientasi horizontal yang diusulkan (
Fess
dan Moran, 1981
), selama pelaksanaan rehabilitasi pergelangan tangan-
protokol.