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PM R 8 (2016) 161-168


Narrative Review

Fascial Disorders: Implications for Treatment

Antonio Stecco, MD, Robert Stern, MD, Ilaria Fantoni, MD, Raffaele De Caro, MD,
Carla Stecco, MD


In the past 15 years, multiple articles have appeared that target fascia as an important component of treatment in the field of
physical medicine and rehabilitation. To better understand the possible actions of fascial treatments, there is a need to clarify the
definition of fascia and how it interacts with various other structures: muscles, nerves, vessels, organs. Fascia is a tissue that
occurs throughout the body. However, different kinds of fascia exist. In this narrative review, we demonstrate that symptoms
related to dysfunction of the lymphatic system, superficial vein system, and thermoregulation are closely related to dysfunction
involving superficial fascia. Dysfunction involving alterations in mechanical coordination, proprioception, balance, myofascial
pain, and cramps are more related to deep fascia and the epimysium. Superficial fascia is obviously more superficial than the
other types and contains more elastic tissue. Consequently, effective treatment can probably be achieved with light massage or
with treatment modalities that use large surfaces that spread the friction in the first layers of the subcutis. The deep fasciae and
the epymisium require treatment that generates enough pressure to reach the surface of muscles. For this reason, the use of small
surface tools and manual deep friction with the knuckles or elbows are indicated. Due to different anatomical locations and to the
qualities of the fascial tissue, it is important to recognize that different modalities of approach have to be taken into consid-
eration when considering treatment options.

Introduction and the individuals who perform research in fascial

In the past 15 years, multiple articles have appeared Fascia is a tissue that occurs throughout the body.
that target fascia as an important component of treat- However, different kinds of fasciae exist (Table 2). In
ment in the field of physical medicine and rehabilitation any general classification system, it is important to
[1,2]. The current research was performed on PubMed recognize a superficial fascia, a deep (or muscular)
databases using keywords that contain the word fascia, and a visceral fascia (Figures 1-3). Numerous
fascia related to various noninvasive treatments. The authors [3-5] recognize, in addition, the existence of
research included articles published between 2000 and the epimysium and perimysium within deep fasciae.
2015 (Table 1). A total of 79 articles were surveyed. Each category of fascia has specific anatomical and
These studies varied immensely in quality. Moreover, histological features that interact with the aforemen-
there were no clear indications for relating symptoms to tioned structures in a very precise manner. These must
specific fascial treatment modalities. This is a very be separated from each other and compared.
important issue that demands clarification, for the sake
of the clinical specialty, for patients, and for Literature Search Strategy
The purpose of this narrative review is to clarify the The current research was performed by A.S. on arti-
physiology of fascia and its disorders to better correlate cles available only in PubMed databases using keywords
fascial symptoms with specific therapeutic approaches. that contain the word fascia. Key words are listed in
The review includes articles, found in the PubMed da- Table 1. Articles involved various noninvasive treat-
tabases in the last decade, with a clear focus in fascial ments with a level of evidence of II-3 or above. The
anatomy and pathology. This review will facilitate dis- research included articles published between 2000 and
cussions between clinicians and also between clinicians 2015 (Table 1). A total of 79 articles were surveyed.

1934-1482/$ - see front matter 2016 by the American Academy of Physical Medicine and Rehabilitation
162 Fascial Disorders: Implications for Treatment

Table 1 Deep Fascia

Key words used and numbers of PubMed articles surveyed
Key Words Articles (n) The term deep fascia refers to all of the well-
Fascia treatment 2 organized, dense, fibrous layers that interpenetrate
Fascial treatment 2 and surround muscles, bones, nerves and blood vessels,
Fascia therapy 7 binding all of these structures together into a firm,
Fascial therapy 2
compact, continuous mass. Over bones it is termed the
Fascia technique 0
Fascial technique 2 periosteum; around tendons it forms the paratendon;
Fascia method 0 and around vessels and nerves it forms the neuro-
Fascial method 2 vascular sheath. Around joints it strengthens the
Fascia manipulation 2 capsules and ligaments. So, we can consider the para-
Fascial manipulation 3
tendon, the neurovascular sheath, and the periosteum
Fascia relase 0
Fascial release 4 as particular specializations of deep fascia, not only
Myofascial therapy 18 because they are in continuity with deep fascia but also
Myofascial treatment 16 because they have the same histological features. It is
Myofascial release 19 possible to distinguish 2 major types of muscular fascia,
Total 79
according to their thickness and to their relationships
with underlying muscles: the aponeurotic fasciae and
Fascial Anatomy the epimysial fasciae. The aponeurotic fasciae contain
collagen fiber bundles that are aligned all along the
Superficial Fascia main axis of the limbs. Consequently, in both longitu-
dinal and oblique directions, the deep fasciae function
According to the Italian and German schools of like a tendon, allowing force transmission along the
thought, the superficial fascia is a fibrous layer that limbs. Another important characteristic of the aponeu-
divides the subcutis into a superficial and deep, loosely rotic fascia is its ability to adapt to volume variations of
organized adipose-rich layer. It is formed by loosely the underlying muscles during contraction. In the
packed interwoven collagen fibers admixed with abun- transverse direction, collagen fiber bundles are less
dant elastic fibers. Superficial fascia is present compact and, due to the presence of loose connective
throughout the body and, according to Abu-Hijleh et al tissue, are easily separated from each other. This
[6], has arrangements and thickness that vary according increased motion of the collagen fiber bundles allows
to the region of the body, to the body surface, and also to the aponeurotic fasciae to adapt to the volume varia-
differences that exist between genders. It is thicker in the tions of the underlying muscles, particularly since they
lower than in the upper extremities, on the posterior than contain so few elastic fibers.
on the anterior aspect of the body, and in females It is apparent that the adaptability of aponeurotic
compared with males. Macroscopically, the superficial fascia is based on its unique relationship with loose
fascia appears as a well-defined membrane and can be connective tissue. Several studies demonstrate that the
dissected with scalpels. Microscopically, its structure is aponeurotic fasciae are richly innervated (mean volume
better described as multi-lamellar, or like a tightly fraction, 1.2%). Abundant free and encapsulated nerve
packed honeycomb. The superficial fascia is tightly con- endings (including Ruffini and Pacinian corpuscles) have
nected with superficial veins and with lymphatic vessels. been found in the thoracolumbar fascia, the bicipital
Inside the superficial fascia, the subcutaneous plexus is aponeurosis, and the various retinacula [7-12]. Nerve
present, which functions in thermoregulation. fibers, particularly numerous around blood vessels, are

Table 2
Description of different fascia types
Fascia Type Anatomy Neural Properties Depth Load Transmission Treatment Profile
Superficial Loosely packed, interwoven Pacini Rufini corpuscle From a few millimeters Low effect Light massage with a
collagen fibers admixed and free ending below the skin to the large surface
with abundant elastic fibers nerves middle of the
Deep Well-organized, dense, Pacini Rufini corpuscle Inferior to the High effect Deep manipulation
fibrous layers and free ending hypodermal over the with a small surface
nerves epimysium for a limited amount
of gliding
Epimysial Fibrous laminae composed of Relation with muscle Over the muscles High effect in Deep manipulation
type I and III collagen fibers spindles combination with with a small surface
and elastic fibers the adherent for a limit amount of
muscle gliding
A. Stecco et al. / PM R 8 (2016) 161-168 163

Figure 3. Ultrasonography of the lumbar area.

Figure 1. CT scan of the lumbar area. mainly reflect the progression of muscular fibers, forming
a dense lamina that continues into the tendon of the
distributed throughout the fibrous components of their muscle. One of the most important features of the epi-
respective fascia. The capsules of the corpuscles and mysial fasciae is their tight adherence to underlying
free nerve endings (mechanoreceptors) are closely muscles via multiple fibrous septa that originate from
connected to the surrounding collagen fibers and fibrous their inner aspect and penetrate the muscle. For this
stroma that make up the fascia. Deising et al [13] find a reason, it is impossible to separate the functions and
dense neuronal innervation with nonpeptidergic nerve features of the epimysial fascia and underlying muscle.
fiber endings and encapsulated mechano-receptors in Various authors [17-19] have demonstrated how 30%-40%
muscle fascia. Stecco et al [12] have also demonstrated of the force generated by these muscle is transmitted not
the presence of autonomic nerve fibers in deep fasciae. along the tendon but, rather, by the connective tissue
Tesarz et al [14] confirmed the dense sensory innerva- surrounding the muscle.
tion of the thoracolumbar fascia. For these reason, The presence of a constant basal tone of these muscle
authors have considered the thoracolumbar fascia an fibers maintains the epimysial fasciae in a state of
important link in nonspecified low back pain. permanent more or less increased tension. Many muscle
fibers do not necessarily extend from origin to insertion
Epimysial Fascia (non-spanning muscles) but have tapered ends in the
middle of the muscle belly and end within the muscle
Epimysial fascia comprises fibrous laminae with a belly. These muscles can transmit force between adja-
mean thickness of 150 to 200 mm. They are composed of cent muscle fibers only via their common perimysium,
type I and III collagen fibers [15] as well as many elastic emphasizing the concept that force transmission can
fibers (w15%). In fusiform muscles (ie, biceps brachii), occur by pathways other than through myotendinous
the collagen fibers have an angle of incidence of 55 with routes [20]. These extratendinous transmission forces
respect to the path of the muscle fibers at rest [16]. In may also be used for stabilization of the joint. The force
pennate muscles (ie, rectus femoris) the epimysial fascia expressed by a muscle depends not only on its anatomical
structure but also by the angle at which its fibers are
attached to the intramuscular connective tissue and their
relation with the epimysium and deep fasciae [21].
The epimysial fasciae have free nerve endings that
are neither Pacini nor Ruffini corpuscles. The free nerve
endings are particularly numerous surrounding vessels,
but are also distributed homogeneously throughout their
fibrous components. In addition, the epimysial fasciae
make a connection with another type of nervous
receptor: the muscle spindles. Indeed, the capsule of
the muscle spindles corresponds to the perimysium,
epimysium, or fascial septae [22,23].
Strasmann et al [24], analyzing the septum of the
supinator muscle, affirm that a great number of muscle
spindles are inserted directly into the connective tissue
Figure 2. MRI of the lumbar area. of the septum. Also, examining the evolution of the
164 Fascial Disorders: Implications for Treatment

locomotor system, it becomes evident that the muscle because of their hyperechogenicity. Furthermore, they
spindles are firmly connected with the fascia, as has are composed of interwoven connective tissue fibers
been demonstrated in the lamprey [25]. Muscle spindles emerging directly from the saphenous adventitia. The
are sensory receptors within the belly of a muscle that evaluation of serially sectioned specimens reveals that
primarily detect changes in the length of this muscle. these strands form two continuous laminae. Such a
The sensitive fibers of the muscle spindle are stimulated double-laminar ligament can also be demonstrated
by minimal stretching, the threshold corresponding to a using anatomic or surgical preparations, especially if
tension of 3 g. For this reason, the epimysial fascia plays care is taken to preserve the planar arrangement of the
a fundamental role. The spindles can be shortened, connective framework of the hypodermis.
responding to the gamma stimulus only if the perimy- Schweighofer et al [30] describe the same structure
sium is elastic and adaptable. for the small saphenous vein, and the dissections of
Stecco et al [31] confirm that all the major superficial
Disorders of the Superficial Fascia veins of the inferior limbs are enveloped by a splitting of
the superficial fascia along their entire length. This
Fasciae and Lymphedema strong anatomic relationship between the saphenous
veins and the superficial fascia may have an important
Knowing the strong relationships between lymph role both in daily clinical practice and in the patho-
vessels and superficial fascia, it can be can postulated physiology of varicose disease. First, the tension of the
not only that an alteration in the superficial fascia can superficial fascia strongly influences the saphenous vein
cause lymphedema, but also that a patient with lym- caliber and consequently modulates the blood flow
phedema probably has an alteration of the superficial within it. Second, the superficial fascia may prevent the
fascia. Any treatment that involves superficial fascia saphenous vein from excessive pathological dilatation,
should improve the symptoms related to lymphedema. acting as a kind of of mechanical shield. These anatomic
This hypothesis is supported by a number of studies. findings can also explain why greater dilation and tor-
According to Tassenoy et al [26], in the case of lym- tuosity occur in the saphenous tributaries in primary
phedema, the adipose tissue, inferior to the superficial varicosities. Finally, the superficial fascia could be
fascia, has a honeycomb appearance, as established by considered a major marker for the correct identification
magnetic resonance imaging (MRI). This corresponds and stripping of the saphenous vein.
to fluid associated with the fibrosis. In particular, the
skin septa (or fibrous retinacula cutis) increase their Thermoregulation and Skin Tropism
thickness, the area and perimeter of fat cells is signifi-
cantly increased (P < .05), and fluid is associated with or All the subcutaneous arteries participate in the for-
close to the muscle fascia. In addition, Marotel et al [27] mation of 2 subcutaneous plexi: the subpapillary
find that with CT scans in patients with lymphedema, plexus, just under the papillaris dermis (top layer of the
there occurs, in order of frequency skin thickening, in- skin), and the deep plexus, inside the superficial fascia.
crease in the subcutaneous tissues area, muscular fascia The 2 plexi freely communicate. Only one-fifth of the
thickening, fat infiltration, lines parallel and perpen- capillaries are necessary for skin vascularization,
dicular to the skin (corresponding to fibrous retinacula whereas all of the others function in thermoregulation.
cutis), and areas of edema along deep fascia. The arteries of the deep plexus present multiple artero-
We suggest that the disposition of the collagen and venous connections. These provide shunts that control
elastic fibers inside the superficial fascia could guide blood flow to the skin and consequently control body
lymphatic flux in the correct direction. Indeed, Hauck temperature. The dilation and narrowing of the sub-
and Castenholz [28] demonstrate the existence of a cutaneous arteries determines both skin temperature
low-resistance pathway along connective tissue fibers and skin color in the light-skinned races/ethnicities.
for the transinterstitial fluid movement, from the pil- Marked skin pallor of the skin, seen in acute shock,
laries to the initial lymphatics. If the superficial fascia is results from vasoconstriction in the arterial plexus of
altered, the lymphatic drainage becomes compromised. the hypodermis. It is possible for a change in the
superficial fascia to cause a change in skin color or even
Fasciae and Venous Pathologies chronic ischemia of the skin. We can hypothesize that a
fibrotic superficial fascia can restrict or choke the
The superficial fascia is strongly associated with the arteries inside it, thereby reducing skin vascularization.
superficial veins. In particular, Caggiati [29] shows that If the arterio-venous shunts become deficient, an
stereo-microscopy of cross-sectioned specimens dem- alteration of thermoregulation may occur, resulting in
onstrates two thick strands originating from the outer sensations of excessively hot or cold skin. According to
adventitia of the long saphenous vein and anchoring it Distler et al [32], chronic ischemia can result in fibrosis
to the opposite faces of the compartment. These by creating a pathological path that decreases skin
strands are also easily recognized by ultrasonography vascularization.
A. Stecco et al. / PM R 8 (2016) 161-168 165

According to Storkebaum and Carmeliet [33], the echogenicity, trunk flexion range of motion, and trunk
regulation of peripheral resistance arteries is essential extension. This demonstrates the importance of altered
for several physiological processes, including control of sliding of the thoracolumbar fascial layers in low back
blood pressure, thermoregulation, and increase in blood pain.
flow to the central nervous system and to the heart More recently, Stecco et al [37] documented a corre-
under stress conditions, such as occurs in severe hyp- lation between a decrease in range of motion and an in-
oxia. For these authors, defects in control of peripheral crease in neck deep fasciae thickness. In particular, a
resistances lead to disorders such as hypertension, value of 0.15 mm of the sternocleidomastoid fascia is
orthostatic hypotension, Raynaud phenomenon, defec- proposed as a cut-off value that allows the clinician to
tive thermoregulation, hand-foot syndrome, migraine, make a diagnosis of myofascial disease in subjects with
headaches, and congestive heart failure. chronic neck pain. Apparently, from this study, variations
of thickness in fascia correlate with increases in quantity
Disorders of the Deep Fascia of its loose connective tissue, but not with fibrous tissue.

Myofascial Pain Alterations in Proprioception

Some recent studies have been published that address The first to suggest a possible role of the deep fasciae
the possible role of the deep fascia in myofascial pain. in proprioception were Viladot et al [38]. These authors
Deising et al [13] injected nerve growth factor into the affirmed that because the ankle retinacula (which
fascia of the erector spinae muscles at the lumbar level represent specialization of the deep fascia) are thin and
and observed a long-lasting sensitization to mechanical flexible, they have a modest effect on the mechanical
pressure and to chemical stimulation. Sensitization was stability of the joint, whereas they have a far more
confined to deeper tissues, but did not reach the skin. important role in proprioception. Pisani [39] concludes
This suggests that sensitization of fascial nociceptors to that the histological features of the retinacula are more
mechanical and chemical stimuli may contribute to the suggestive of a perceptive function, whereas the tendons
pathophysiology of chronic musculoskeletal pain. and ligaments are structured for a mechanical role. The
Schilder et al [34] have also demonstrated that injections retinacula are the most highly innervated fascial tissues.
of hypertonic saline into the thoracolumbar fascia result They are rich in free nerve endings, Ruffini and Pacini
in a significantly protracted time of pain intensity, corpuscles, Golgi-Mazzoni, and rare spherical clubs [12].
compared to injections into the subcutis or into muscle. The retinacula cannot be considered merely as passive
Also, pain intensity and pain radiation evoked by injec- stabilizers but, rather, as specialized proprioceptive
tion into fascia was significantly greater compared to organs to better perceive joint movements [40,41].
injection into muscle or the subcutis. The description of Sanchis-Alfonso and Rosello-Sastre [11] demonstrate an
pain after fascia injection, as reported by volunteers, increase in free nerve endings and nerve in-growth in the
were burning, throbbing, and stinging. This suggests an shortened compressed lateral retinaculum in patients
innervation by both A- and C-fiber nociceptors. For this with patellofemoral malalignment and anterior knee
reason the authors support the supposition that the pain. Samples of lateral knee retinacula were excised at
thoracolumbar fascia is a prime candidate for contribu- the time of proximal realignment or isolated lateral
tion to nonspecific lower back pain. retinacular release. Stecco et al [40] demonstrate, with
Changes in innervation can also occur pathologically MRI and static posturography, damages to ankle reti-
in fascia. Sanchis-Alfonso and Rosello-Sastre [11] report nacula (adherences, formation of new fibrous bundles
the ingrowth of nociceptive fibers and an immuno- into the deep fasciae of the foot, interruption of the
reaction to substance P in the lateral knee retinaculum retinacula) in patients with alterations of proprioception
of patients with patello-femoral alignment problems. and functional ankle instability after ankle sprain.
Bednar et al [35] found an alteration in both the histo- Damage to the retinacula and their embedded pro-
logical structure (inflammation and microcalcifications) prioceptors result in inaccurate proprioceptive affer-
and the degree of innervation of the thoracolumbar entation. This may result in poorly coordinated joint
fascia in patients with chronic lumbalgia, indicating a movement and eventual inflammation and activation of
possible role of fascia in lumbar pain. In particular, nociceptors. A treatment focused on restoring normal
these authors noted a loss of nerve fibers in the thoa- fascial tension may improve the outcome of ankle sprain.
columber fascia of back pain patients.
A recent work by Langevin et al [36] focuses attention Fascia and Diabetes
on the sliding capability of fascial sublayers. These au-
thors found significant correlations in male participants Duffin et al [42] demonstrate that patients with type I
with chronic low back pain between shear strain capa- diabetes have a plantar fascia that is significantly
bility of the thoracolumbar fascia and with the following thicker compared to that of normal controls. Also, Li
variables: perimuscular connective tissue thickness, et al [43] show that collagen cross-linking by advanced
166 Fascial Disorders: Implications for Treatment

glycation end-products alters the physical properties of Fascia and Peripheral Motor Coordination
collagen structures and tissue behavior, reduces tissue
stress relaxation (P < .01), with a concomitant increase The epimysial fasciae have free nerve endings, but
in tissue yield stress (P < .01), and ultimately failure lack Pacini and Ruffini corpuscles. Despite this, the
stress (P .036). Such collagens are also more suscep- epimysial fascia play a key role in proprioception and
tible to degradation by collagenases, and the panoply of peripheral motor coordination due to their close rela-
other matrix-metalloproteinases. tionship with muscle spindles. Indeed the muscle spin-
dles are localized in the perimysium and their capsule
Epimysial Fascia and Its Disorders connects to the epimysium and fascial septae
[23,47,48]. Strasmann et al [24] analyzing the septum of
Fascia and Immobilization the supinator muscle find that many muscle spindles are
inserted directly into the connective tissue of the
According to studies by Jarvinen et al [44], immobi- septum. Von During and Andrei [25], studying the evo-
lization results in a marked increase in the endo- and lution of the locomotor system, discovered that muscle
perimysial connective tissue. The majority of the spindles are strongly connected to the fascia. Due to
increased endomysial collagen is deposited directly on these connections, it is evident that tension developed
the sarcolemma of the muscle cells. Immobilization inside the deep fascia is also able to lengthen the
of the endomysium also results in a substantial increase muscle spindles connected with it, activating them by
in the number of perpendicularly oriented collagen fi- passive stretch. If epimysial fascia is overstretched, it is
bers that make contact with two adjacent muscle fibers. possible that the muscle spindles connected to this
Furthermore, immobilization clearly disturbs the normal portion of the fascia could become chronically stretched
structure of the endomysium, making it impossible to and overactivated. This implies that the associated
distinguish the various networks of fibers from one muscular fibers will be constantly stimulated to con-
another. In the perimysium, immobilization-induced tract. This could explain the increased amount of
changes are similar. The number of longitudinally ori- acetylcholine found in myofascial pain and, in partic-
ented collagen fibers increases, the connective tissue ular, in trigger points [49,50]. This passive stretch situ-
becomes very dense, the number of irregularly oriented ation could be responsible for muscular imbalances and
collagen fibers is markedly increased, and consequently recurrent cramps, and could result in incorrect move-
the different networks of collagen fibers cannot be ment of joints. This may represent a typical case in
distinguished from each other. Even the crimp angle of which there is limitation of joint range of motion and
the collagen fibers decreases more than 10% in all associated joint pain. The causation is often found in
muscles after the immobilizatio period. It is apparent the proximal muscles that move the joint. Palpation of
from the above-described quantitative and qualitative the proximal muscle belly will often reveal an area of a
changes in the intramuscular connective tissue that they painful localization of dense tissue. Another problem
significantly contribute to the decreased function and connected with the muscle spindles inside the epymisial
diminished biomechanical properties of immobilized fasciae is when the epimysial fascia is too rigid, and
skeletal muscle. consequently the muscle spindle are not activated
because they are embedded in a rigid structure. This
Fascia and Aging emphasizes the fact that normal muscular function is
dependent on normal well-hydrated, functioning fascia.
Gao et al [45] demonstrate that the epimysial fascia If the epimysial fascia is densified, some parts of a
from old rats is much stiffer than that of young rats. This muscle will not function normally during movement,
increased stiffness cannot be attributed to variations in causing an unbalanced movement of the joint, with
the thickness of the epimysial fasciae or in the size of resulting uncoordinated movement and eventual joint
the collagen fibrils. Microscopic analysis does not show pain. The epimysial fasciae could be considered as a key
any change in the arrangement or size of the collagen element in peripheral motor coordination.
fibrils of the epimysial fasciae in older rats [45]. It is
probable that the key element explaining this stiffness Discussion
is the composition of the extracellular matrix with
respect to the presence of hyaluronan. It is important to Only a better comprehension of the anatomy and
note that the space between the collagen fibers of the physiology of fasciae will permit us to answer common
epimysial fasciae is occupied by hyaluronan. This allows questions such as the following: Is it the superficial or
the collagen fibers to slide with less friction during deep fascia that generates these symptoms? What
movement [46]. Age-related increase in the stiffness of particular fascial treatment is useful for lymphedema?
the epimysial fasciae could play an important role in the What is the best approach for changes in proprioception?
muscular contraction and in the reduced elasticity that From this review, it is possible to conclude that
is often typical in older patients. symptoms related to dysfunction of the lymphatic
A. Stecco et al. / PM R 8 (2016) 161-168 167

system, superficial vein system, and thermoregulatory must be applied in relation to the types of fasciae that
system are more related to disorders of the superficial are involved.
fascia. Dysfunction such as alteration in mechanical This review is not designed to evaluate the literature
coordination, proprioception, balance, myofascial pain, on the treatment of fascial disorders. Other studies will
and cramps are more related to the deep fascia and be required to better understand the efficacy and
epimysium (Table 2). specificity of the different modalities of treatment for
Superficial fascia is obviously more superficial than specific fascial disorders.
the other types and contains more elastic tissue.
Consequently, effective treatment can probably be
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A.S. Sport Medicine Unit, Internal Medicine Department, University of Padova, R.D.C. Molecular Medicine Department, University of Padova, Padova, Italy
Padova, Italy. Address correspondence to: A.S.; Via Giustiniani 2, 35127 Padova, Disclosure: nothing to disclose
Italy; e-mail: antonio.stecco@gmail.com
Disclosure: nothing to disclose C.S. Molecular Medicine Department, University of Padova, Padova, Italy
Disclosure: nothing to disclose
R.S. Division of Basic Biomedical Sciences, Touro College of Osteopathic Medi-
Submitted for publication January 6, 2015; accepted June 7, 2015.
cine, New York, NY
Disclosure: nothing to disclose

I.F. Molecular Medicine Department, University of Padova, Padova, Italy

Disclosure: nothing to disclose