<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">JBM</journal-id><journal-title-group><journal-title>Journal of Biosciences and Medicines</journal-title></journal-title-group><issn pub-type="epub">2327-5081</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/jbm.2017.53013</article-id><article-id pub-id-type="publisher-id">JBM-74899</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biomedical&amp;Life Sciences</subject></subj-group></article-categories><title-group><article-title>
 
 
  Qi Gong and Heart Rate Variability: A Systematic Review
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Carla</surname><given-names>Cristina Ramos</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Elias</surname><given-names>de França</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Thatiana</surname><given-names>Lacerda Nobre</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Jeferson</surname><given-names>Oliveira Santana</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Diana</surname><given-names>Madureira</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Cesar</surname><given-names>Augustus Sousa Zocoler</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bruno</surname><given-names>Rodrigues</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ronaldo</surname><given-names>V. T. Santos</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Iris</surname><given-names>Calado Sanches</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Erico</surname><given-names>Caperuto</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib></contrib-group><aff id="aff1"><addr-line>Gepame-Human Movement Laboratory, S&amp;amp;atilde;o Judas Tadeu University, S&amp;amp;atilde;o Paulo, Brazil</addr-line></aff><aff id="aff2"><addr-line>Unicamp-Physical Education College, S&amp;amp;atilde;o Paulo, Brazil</addr-line></aff><aff id="aff3"><addr-line>Unifesp-Campus Santos, S&amp;amp;atilde;o Paulo, Brazil</addr-line></aff><pub-date pub-type="epub"><day>10</day><month>03</month><year>2017</year></pub-date><volume>05</volume><issue>03</issue><fpage>120</fpage><lpage>127</lpage><history><date date-type="received"><day>October</day>	<month>15,</month>	<year>2016</year></date><date date-type="rev-recd"><day>Accepted:</day>	<month>March</month>	<year>24,</year>	</date><date date-type="accepted"><day>March</day>	<month>27,</month>	<year>2017</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  Q&#236; Gōng is a type of exercise that involves meditation and is used for health. With a background from the martial arts, it is known also as an auto healing exercise with three main elements according to Traditional Chinese Medicine (TCM): body focus (posture and movement), breathing and mind focus (meditative elements). Heart rate variability is a tool that allows us to measure the autonomic system velocity to detect and respond to unexpected stimuli. So our goal was to build a systematic review of Qi Gong and Heart rate variability. PUBMED, EBSCO and Science Direct data bases were searched. Key terms (MeSH) were Heart Rate Variability and Ch’i Kung OR Qi Gong with a 10-year filter. Four independent reviewers analyzed all articles and excluded duplicated articles, articles in Chinese and articles with no adherence to the subject. The end result was 5 studies selected. Our results showed no significant improvements in HRV with the practice of Q&#236; Gōng, probably because of data heterogeneity. We found 5 types of Q&#236; Gōng, 3 different instruments and different time intervals to measure HRV and 2 different age groups in the studies. We can conclude that there is evidence that Q&#236; Gōng can improve HRV but studies that would use the same parameters are needed to further confirm that.
 
</p></abstract><kwd-group><kwd>Qi Gong</kwd><kwd> Heart Rate Variability</kwd><kwd> Meditation Exercises</kwd><kwd> Exercise Physiology</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>Ancient China knowledge is deeply present in its Medicine. Some of its pillars are adequate nutrition, phytotherapy, acupuncture, massage and regular physical exercise. One of these pillars is Q&#236; Gōng.</p><p>Q&#236; Gōng is a physical exercise that involves meditation and is widely used for health. With a background from the martial arts, it is known also as an auto healing exercise with three main elements according to Traditional Chinese Me- dicine (TCM): body focus (posture and movement), breathing and mind focus (meditative elements).</p><p>Q&#236; Gōng means “vital energy work”, where Q&#236; is everything that controls our body, our vital energy and Gōng is work, the work that might improve and cultivate this energy. It’s understood as a traditional biofeedback therapy and the Qi activation can be reached by breathing control and the achievement of a special mental state [<xref ref-type="bibr" rid="scirp.74899-ref1">1</xref>] . Wang et al., (2014) divided Q&#236; Gōng in some categories: static, dynamic, internal (nei qi) and external (wei qi) and states that it can be practiced in several ways, for example, standing or seated [<xref ref-type="bibr" rid="scirp.74899-ref2">2</xref>] .</p><p>The autonomic nervous system is divided in 2 parts that act in a balanced way, the sympathetic nervous system and the parasympathetic nervous system. The balance of these systems results in homeostasis [<xref ref-type="bibr" rid="scirp.74899-ref3">3</xref>] .</p><p>As Q&#236; Gōng is an active meditative strategy, it helps to balance the autonomic nervous system and all the structures controlled by it. For example, theautonomic nervous system influences the cardiovascular system in two ways, tonic and reflexively and there are some elements that might interfere positively in this control such as Q&#236; Gōng or negatively as daily stress, posture changes and involuntary breathing control [<xref ref-type="bibr" rid="scirp.74899-ref4">4</xref>] .</p><p>Heart Rate Variability (HRV) assessment helps to understand how the cardiovascular system adapts to the changes caused by the environment, and to mea- sure the autonomic system velocity to detect and respond to unexpected stimuli [<xref ref-type="bibr" rid="scirp.74899-ref5">5</xref>] .</p><p>Autonomic control assessment by HRVin Q&#236; Gōng practice has been made in some studies. But because of different variables considered, different age groups and different measuring techniques, there are several aspects of this phenomenon that need to be further investigated.</p></sec><sec id="s2"><title>2. Objective</title><p>The objective of this study is to further understand the effects of Q&#236; Gōng on autonomic control, especially on its sympathetic and parasympathetic system branches, through a systematic literature review.</p></sec><sec id="s3"><title>3. Methods</title><p>We searched PUBMED, EBSCO and Science Direct.</p><p>In all databases we used the following key terms (MeSH): 1) “Heart Rate Variability”; 2) “Ch'i Kung” OR “Qi Gong” and 3) “Heart Rate Variability” plus “Ch’i Kung” OR “Qi Gong”, all searches were did with a 10 years filter (2006-2016).</p><p>Two independent reviewers read all articles titles and abstracts and as excluding criteria we used duplicated articles, articles that were only in Chinese (most common language on the topic), because we understand that Chinese is an important, but local language or articles that didn’t have any relationship of HRV and Qi gong although the keywords were in the title or abstract. The end result was 7 studies that were initially selected.</p><p>After a more detailed investigation, 2 more articles were excluded. The first one mentioned HRV, but didn’t have any results about it and the second one used only HR and not HRV as an assessment tool. <xref ref-type="fig" rid="fig1">Figure 1</xref> below shows the articles search and selection fluxogram.</p></sec><sec id="s4"><title>4. Results</title><p>Of the 5 remaining studies, we found a total number of 334 participants. From the 5 studies, one had only one experimental group of Q&#236; Gōng while the others had two groups, one is experimental and other control group. The 5 studies can be seen in <xref ref-type="table" rid="table1">Table 1</xref>.</p></sec><sec id="s5"><title>5. Discussion</title><p>All studies used Internal Q&#236; Gōng. Amongits many types we found the following: Q&#236; Gōng: BāDu&#224;nJĭn (8 Pieces of Brocade), Dharma Drum (Dharma drum),</p><fig id="fig1"  position="float"><label><xref ref-type="fig" rid="fig1">Figure 1</xref></label><caption><title> Article search and selection in all database</title></caption><graphic mimetype="image"   position="float"  xlink:type="simple"  xlink:href="http://html.scirp.org/file/9-2150289x2.png"/></fig><table-wrap-group id="1"><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Articles selected to compose the systematic review. (&#233;= increase; &#234; = decrease</title></caption><table-wrap id="1_1"><table><tbody><thead><tr><th align="center" valign="middle" >Author/year</th><th align="center" valign="middle" >Objective</th><th align="center" valign="middle" >Intervention</th><th align="center" valign="middle" >Method</th><th align="center" valign="middle" >Variables</th><th align="center" valign="middle" >Results</th></tr></thead><tr><td align="center" valign="middle" >Li, R. et al./2014</td><td align="center" valign="middle" >Effects of 16 weeks of Qigong Baduanjin to fitness and health</td><td align="center" valign="middle" >Ba DuanJin Qi gong</td><td align="center" valign="middle" >GC-55 sedentary subjects; GE-55 trained individuals-(learned Qigong 2 weeks before the start); 34.2 years 16 weeks of Qi gong Ba DuanJin 3x/week 30 to 60 minutes</td><td align="center" valign="middle" >Total cholesterol (TC); Serum Triglycerides, LDL, HDL, SDS (depression scale) Body fat percentage; Flexibility; BMI and circumferences; Blood pressure; HRV, Vital capacity, O2 consumption, Max HR, Max Ventilation; sit and reach.</td><td align="center" valign="middle" >Flexibility improvement (improves coordination, muscle Power, speed and physical skills); improves body mind coordination; no significant difference in the SDS (self rating depression scale), significant decrease in the body fat percentage; no significant variation on blood pressure, HRV, vital capacity, max O<sub>2</sub> consumption and max ventilation.</td></tr><tr><td align="center" valign="middle" >Chang, M-Y/2014</td><td align="center" valign="middle" >Effects of 12 weeks of qi gong (8 moves) on HRV and perypheral vasomotor response.</td><td align="center" valign="middle" >8 moves Dharma Drum’s-Qi gong</td><td align="center" valign="middle" >Pre and Post test 77 subjects 47-EQG (experimental qi gong) &#177; 62.98 years 30 CG (control group) &#177; 65.07 years 12 weeks 30’ qi gong-3x week</td><td align="center" valign="middle" >HRV-SDNN, low frequency, high frequency and total Power. PVR (peripheral vasomotor response)</td><td align="center" valign="middle" >&#233; sdnn &#233; low frequency &#233; high frequency &#233; total power</td></tr><tr><td align="center" valign="middle" >Chang, C; Tsai, G &amp; Hsieh, C-J/2013</td><td align="center" valign="middle" >Laughing Qigong effects on psychological, immunological and physiological systems and to make LQP a standard method to simulate laughing interventions.</td><td align="center" valign="middle" >Laughing Qi Gong Program (LQP) and Facial Scale before and after each session of LQP</td><td align="center" valign="middle" >Quantitative and qualitative study Control and experimental groups (CG and EG), 67 teenagers = 34 (EG) (16 male and 18 female) and 33 (CG) (18 male and 15 female) 2 months, 8 sessions of 45 minutes (LQP) and 15 min (data collection) CG (reading or doing homework for 1 hour)</td><td align="center" valign="middle" >Rosemberg’s scale for self steem (RSE), chinese humor scale (CHS), subscales from CHS (HC humor creativity), (HT humor trend), facial scale (FS); Blood pressure (BP), Heart rate variability (HRV); Salivar cortisol analysis</td><td align="center" valign="middle" >EG showed significant improvement in CHS &#233;, specifically for HC &#233;; Humor state improved in the FS; cortisol &#234;, HRV showed significant difference when compared to CG.</td></tr><tr><td align="center" valign="middle" >Goshvarpour, A. e Goshvarpour, A./2012</td><td align="center" valign="middle" >To analyze and compare the contribution of the quadratic phase of HRV during 2 different meditation models.</td><td align="center" valign="middle" >Chinese Qi gong and Kundalini Yoga</td><td align="center" valign="middle" >Qi gong Group (5 male and 3 female &#177; 29 years) Kundalini Yoga Group (2 male and 2 female &#177; 33 years) Qi gong (1 - 3 months of practice before data collection)-1 hour of Qi gong meditation. Kundalini Yoga (meditation advanced training level)-1 hour of Kundalini meditation</td><td align="center" valign="middle" >Heart rate signals-Holter monitor- HOS-higher order spectra QG-holter 10 hours during DLA, 5 hours of recording from the 1 hour practices. KY-holter-1:30 hr and 15 min of easy breathing before 1 hour of meditation. For both the sample rate was 360 Hz.</td><td align="center" valign="middle" >Different forms of meditation could change specific components of HRV signals and the can have specific health benefits.</td></tr></tbody></table></table-wrap><table-wrap id="1_2"><table><tbody><thead><tr><th align="center" valign="middle" >Kuan, S-C, et al./2012</th><th align="center" valign="middle" >To test the effects of 12 weeks of a Qigong exercise program n psychological and physiological health in wheelchair older adults.</th><th align="center" valign="middle" >Qigong Ho-gong</th><th align="center" valign="middle" >72 older subjects, Wheel chair users of similar problems-65 years or more with cognitive integrity; CG-38 subjects without qigong, yoga or tai chi chuan for at least 3 months); EG-34 subjects for Qigong Ho-gong classes. 12 weeks-Qi gong Ho-gong practice (adapted to Wheel chairs) 5x/week-35 minutes</th><th align="center" valign="middle" >Blood pressure (BP), Heart Rare Variability (HRV); distant skin temperature (DST) and Brief Symptom Rating Scale (BSRS-5)</th><th align="center" valign="middle" >Systolic and diastolic pressures, distant skin temperature small increase (DST), no changes in the HRV, significant improvement in the psychological health;</th></tr></thead></tbody></table></table-wrap></table-wrap-group><p>Laughing Q&#236; Gōng Program (Smile Q&#236; Gōng), Chinese Q&#236; Gōng (there was no style specification, but it was reported that it was a practice of Q&#236; Gōng in the sitting position) and the Ho-gong (a type created for wheelchair users and elderly people). This type is acombination of some methods such as yi-ging-xi- sueygong (column adjustment method), yang shu sheng (method to nourish vital energy), dao yin shu (method of guidance and leadership) and Tu-na (breathing control method), and this combination of methods was intended to frail peo- ple to be practiced in any place and time with the objective of strengthening the Vital Energy, as well as all the other methods, types and/or styles of Q&#236; Gōng [<xref ref-type="bibr" rid="scirp.74899-ref6">6</xref>] .</p><p>The practice time ranged from 4 to 16 weeks, although we found 3 studies with 12 weeks of practice [<xref ref-type="bibr" rid="scirp.74899-ref6">6</xref>] [<xref ref-type="bibr" rid="scirp.74899-ref8">8</xref>] [<xref ref-type="bibr" rid="scirp.74899-ref9">9</xref>] used 16 weeks of practice between 30 and 60 minutes. In [<xref ref-type="bibr" rid="scirp.74899-ref8">8</xref>] there was an acute data collection after 1 hour of meditation, but the required practice time (participant experience) of Q&#236; Gōng to engage in the experiment was around 4 to 12 weeks.</p><p>The Qi Gong sessions had at least 30 minutes and a maximum of 60 minutes of duration, with two studies of 30 minutes [<xref ref-type="bibr" rid="scirp.74899-ref9">9</xref>] [<xref ref-type="bibr" rid="scirp.74899-ref10">10</xref>] . In [<xref ref-type="bibr" rid="scirp.74899-ref9">9</xref>] this time ranged from 30 to 60 minutes, meanwhile Chang, Tsai and Hsieh (2013) presented a variable time amount: 45 minutes to the group sessions and 60 minutes for the sessions done at home.</p><p>Weekly frequency ranged from 3&#215; a week (2 studies) [<xref ref-type="bibr" rid="scirp.74899-ref7">7</xref>] [<xref ref-type="bibr" rid="scirp.74899-ref9">9</xref>] ; 1 time [<xref ref-type="bibr" rid="scirp.74899-ref10">10</xref>] , 5 times [<xref ref-type="bibr" rid="scirp.74899-ref6">6</xref>] and an acute collection [<xref ref-type="bibr" rid="scirp.74899-ref8">8</xref>] .</p><p>The participants of the studies were heterogeneous regarding their ages. There were studies with teenagers (age not defined) [<xref ref-type="bibr" rid="scirp.74899-ref10">10</xref>] ; adults (29 to 34.2 years) [<xref ref-type="bibr" rid="scirp.74899-ref8">8</xref>] [<xref ref-type="bibr" rid="scirp.74899-ref9">9</xref>] ; elderly (62.98 or more) [<xref ref-type="bibr" rid="scirp.74899-ref6">6</xref>] in one study(with elderly people), the main feature was to be in a wheelchair.</p><p>When we analyze the HRV results, one study [<xref ref-type="bibr" rid="scirp.74899-ref9">9</xref>] (using a heart rate monitor, Polar RS 800CX, Polar Finland) with adults (~34.2 years) found no significant difference. They analyzed the RR interval, the very low frequency (VLF), low frequency (LF), high frequency (HF) and Total Power.</p><p>In the study of Goshvarpour and Goshvarpour (2013) [<xref ref-type="bibr" rid="scirp.74899-ref8">8</xref>] , used bispectrum magnitude analysis, estimated through three techniques, tendencious, parametric and direct (FFT). They found variations of different components of HRV in young adults (~29 years) with a significant decrease in the magnitude of the heart rate bispectrum. This type of analysis generates extra data that gives more information than the traditional power spectrum analysis.</p><p>That study was reinforced by another research with a meditation technique called Vipassana. The author analyzed LF and HF from adults (~43.8 years) after 10 days of an intensive course of the technique. Normalized HF data was significantly different and the authors believed that happened due to a decrease in LF values instead of an increase of HF itself [<xref ref-type="bibr" rid="scirp.74899-ref11">11</xref>] .</p><p>According to these authors, normalized data represents an advantage because it presents the measurement of the vagal output, not presented by other spectral analysis. These oscilating data (LF increase, HF increase or HF increase due to LF decrease) happens because meditation techniques have a slow breathing pattern that influences HRV components, as described in another study published by Leher (1992) [<xref ref-type="bibr" rid="scirp.74899-ref4">4</xref>] . Therefore, a careful analysis is needed when pure data is compared to normalized data in situations where the respiratory frequency might change the results [<xref ref-type="bibr" rid="scirp.74899-ref11">11</xref>] .</p><p>HF, LF and the low frequency/high frequency (LF/HF) ratio were analyzed in the teenager group doing the Smile Qi Gong. Although the authors didn’t specify the tool used to analyze this variable, there was a significant difference in the control group, with different results when compared to some other studies from the literature. That probably happened because the control group was submitted to stress relief activities such as reading and writing. Besides, the experimental group suffered cross contamination, they did not comply with the rules of pre- determined rest for the proper measurement of the variable, probably because of inadequate behavior related to their age.</p><p>The above results are in opposition with those obtained by [<xref ref-type="bibr" rid="scirp.74899-ref12">12</xref>] and [<xref ref-type="bibr" rid="scirp.74899-ref13">13</xref>] , they found gains in the parasympathetic nervous system modulation reflecting in a better HRV in teenagers. In the first study Sharma et al. (2015) [<xref ref-type="bibr" rid="scirp.74899-ref12">12</xref>] , the better HRV was associated to a larger estrogen concentration. This hormone, according to this study [<xref ref-type="bibr" rid="scirp.74899-ref12">12</xref>] , increases the parasympathetic system modulation, when female teenagers are compared to their counterparts (male teenagers). In the second study [<xref ref-type="bibr" rid="scirp.74899-ref13">13</xref>] when teenageathletes from both genders were compared, the difference found was not related to the gender, but to a better parasympathetic modulation imposed by physical training. In another gender and ethnic differences study, HRV was improved in black teenagers, especially those who did moderate cardiovascular activities [<xref ref-type="bibr" rid="scirp.74899-ref13">13</xref>] .</p><p>One of the studies analyzed HRV (BFM 5000 plus) with spectral analysis in the elderly, they analyzed SDNN, total power, HF, LF and the LF/HFratio. They found an increase of SDNN, total power, HF, LF and no significant difference in the LF/HF ratio. These results are in opposition to the findings of another study with Q&#236; Gōng and HRV (presented below).</p><p>Elderly individuals that were wheelchair users were also submitted to an adapted form of Q&#236; Gōng, so they could perform the movements. Their HRV was measured by a portable equipment manufactured by DailyCare. No significant differences were found for HRV [<xref ref-type="bibr" rid="scirp.74899-ref6">6</xref>] .</p><p>Lopes et al., (2007) [<xref ref-type="bibr" rid="scirp.74899-ref14">14</xref>] found in their study that strength training can improve HRV, especially in young people, but that was not seen in the elderly, since variability declines with the physiological process of aging because of depletion of the vagal tonus, increase in the sympathetic activity and the presence of diseases such as hypertension or heart failure.</p><p>Jandackova et al. (2016) [<xref ref-type="bibr" rid="scirp.74899-ref15">15</xref>] corroborates the notion that aging impairs HRV. They show that individuals present a decrease in autonomic control with a considerable reduction of heart rate variability. Therefore, the absence of results with the Qi Gong intervention in HRV is expected since different studies used different strategies with varied magnitudes.</p><p>We believe that meditative activities such as Q&#236; Gōng promote changes in the autonomic nervous system (ANS), depending on the level of concentration of the participant and that is improved when it is synchronized to a slow breathing rhythm.</p><p>However, because this practice has several types with different forms of Q&#236; Gōng presented in the studies used in this review, HRV analysis can be performed with different equipment, and finally the age differences of the experimental groups in the studies, studies with similar methods are needed to assure the Q&#236; Gōng positive effects in HRV pointed in this review.</p></sec><sec id="s6"><title>6. Conclusions</title><p>We concluded that Qi Gong promotes improvement in some of the Heart rate variability parameters, but there is no evidence to further detail this improvement.</p><p>Therefore, we suggest that further studies regarding both, longer time of practice and equal time interval and instruments used to analyze HRV are necessary to confirm such benefits.</p></sec><sec id="s7"><title>Cite this paper</title><p>Ramos, C.C., de Fran&#231;a, E., Nobre, T.L., Santana, J.O., Ma- dureira, D., Zocoler, C.A.S., Rodrigues, B., Santos, R.V.T., Sanches, I.C. and Caperuto, E. (2017) Qi Gong and Heart Rate Varia- bility: A Systematic Review. Journal of Bio- sciences and Medicines, 5, 120-127. https://doi.org/10.4236/jbm.2017.53013</p></sec></body><back><ref-list><title>References</title><ref id="scirp.74899-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Matos, L.C., Sousa, C.M., Gonalves, M., Gabriel, J., Machado, J. and Greten, H.J. 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