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From anatomic standardization analysis of perfusion SPECT data to perfusion pattern modeling: evidence of functional networks in healthy subjects and temporal lobe epilepsy patients.

From anatomic standardization analysis of perfusion SPECT data to perfusion pattern modeling: evidence of functional networks in healthy subjects and temporal lobe epilepsy patients.

Even if groups of statistically dependent anatomical structures were clearly exhibited from the analysis of both healthy subjects and MTLE patients, our results should be interpreted with caution, especially because of the limited number of SPECT data studied. Indeed, the proposed analysis may be spoiled by quantification errors caused by the spatial normalization step or by the perfusion measurement step. Those errors may thus artificially generate statistical dependencies between some perfusion measurements. As spatial resolution greatly affects the spatial range of statistical dependency between neighboring regions, we only considered reconstructed images with similar spatial resolution (i.e., F W HM = 12.2mm). The differences in dependencies seen between the two groups are therefore unlikely to be due to differences in spatial resolution. Moreover, as CA and HC performed on healthy subjects before and after scatter correction lead to similar results (results not shown), scatter can be assumed not
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A mechanism-based model for the population pharmacokinetics of free and bound aflibercept in healthy subjects.

A mechanism-based model for the population pharmacokinetics of free and bound aflibercept in healthy subjects.

18 data but were not retained as the final model of free aflibercept according to the statistical criteria. The next step of modelling was then to add bound aflibercept data, which serves as a marker of efficacy by representing the amount of VEGF bound to aflibercept. The mechanism of action of this drug suggested the use of TMDD model. Among several types, the MM approximation of TMDD model developed by Gibiansky et al proved the most appropriate to reflect the kinetics of aflibercept in our study as free aflibercept concentrations were much higher than target concentrations and their binding to VEGF resulted in a fully saturated target. The relatively low level of free circulating VEGF was confirmed by the range of 19-47 pg/ml of plasma VEGF levels observed in healthy subjects in a meta-analysis [17]. In order to model simultaneously both free and bound drug, the MM equation of bound aflbercept was added into the system of differential equations. Free aflibercept is therefore eliminated through two pathways: non saturable elimination from central compartment (k el ) and a specific and saturable binding to
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Assessment of myocardial and LV blood pool post-contrast T1 evolution: comparison between healthy subjects and patients with hypertrophic cardiomyopathy

Assessment of myocardial and LV blood pool post-contrast T1 evolution: comparison between healthy subjects and patients with hypertrophic cardiomyopathy

Published: 30 January 2013 doi:10.1186/1532-429X-15-S1-E44 Cite this article as: Kachenoura et al.: Assessment of myocardial and LV blood pool post-contrast T1 evolution: comparison between healthy subjects and patients with hypertrophic cardiomyopathy. Journal of Cardiovascular Magnetic Resonance 2013 15(Suppl 1):E44.

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Interrogating Interneurone Function using Threshold Tracking of the H Reflex in Healthy Subjects and Patients with Motor Neurone Disease

Interrogating Interneurone Function using Threshold Tracking of the H Reflex in Healthy Subjects and Patients with Motor Neurone Disease

D ISCUSSION The present study has assessed threshold tracking of the H reflex as a technique for documenting the excitability of the motoneurone pool in a conditioning-test paradigm. This method was compared in healthy subjects with the conventional constant-stimulus technique, where changes in the size of the reflex response occur when fewer or more motoneurones are recruited by the same stimulus. We have documented the advantages and limitations of the threshold-tracking technique, and these have been explored further in studies in patients with MND. We argue below that our findings in the patient group are consistent with a decrease in presynaptic inhibition in MND. We acknowledge a few reservations. MND is a heterogenous disorder, the sample sizes in this study were relatively small, and there was variability in the test outcomes in different subjects and patients. Patients were on riluzole, and some may have been taking self-prescribed agents.
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Confirmation of associations between ion channel gene SNPs and QTc interval duration in healthy subjects.

Confirmation of associations between ion channel gene SNPs and QTc interval duration in healthy subjects.

Population-based association studies have identified several polymorphic variants in genes encoding ion channel subunits associated with the electrocardiographic heart- rate corrected QT (QTc) length in healthy populations of Caucasian origin (KCNH2 rs1805123 (K897T) and rs3815459, SCN5A rs1805126 (D1819D), 1141-3 C>A, rs1805124 (H558R), and IVS24+116 G>A, KCNQ1 rs757092, KCNE1 IVS2-128 G>A and rs1805127 (G38S), and KCNE2 rs2234916 (T8A). However, few of these results have been replicated in independent populations. We tested the association of SNPs KCNQ1 rs757092, KCNH2 rs3815459, SCN5A IVS24+116 G>A, KCNE1 IVS2-128 G>A and KCNE2 rs2234916 with QTc length in two groups of 200 subjects presenting the shortest and the longest QTc from a cohort of 2008 healthy subjects. All polymorphisms were in Hardy-Weinberg equilibrium in both groups. The minor allele SCN5A IVS24+116 A was more frequent in the group of subjects with the shortest QTc, while the minor alleles KCNQ1 rs757092 G and KCNH2 rs3815459 A were more frequent in the group with the longest QTc. There was no significant difference for KCNE1 IVS2-128 G>A and KCNE2 rs2234916 between the two groups. Haplotype analysis showed a 2-fold increased risk of QTc lengthening for carriers of the haplotype combining alleles C and A of the two common KCNE1 SNPs, IVS2-129 C>T (rs2236609) and rs1805127 (G38S), respectively. In conclusion, our study confirms the reported associations between QTc length and
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The auditory P300-based single-switch brain–computer interface:Paradigm transition from healthy subjects to minimally consciouspatients

The auditory P300-based single-switch brain–computer interface:Paradigm transition from healthy subjects to minimally consciouspatients

Nevertheless, cue-directed attentional behavior could not be detected on a single-trial basis but after averaging all data seg- ments. In most patients, significant di fferences between stan- dard and deviant tones in the simple or complex paradigm could be found. Similarly to results described in [35, 36], only signif- icant di fferences exceeding a certain length were actually re- ported. In future analyses, more sophisticated statistical meth- ods (such as for example an approach described in [40]) might be required to identify significant di fferences more reliably. It is not yet clear if these significant di fferences were really P300 potentials since, sometimes, the polarity was inversed and their occurrence was very much delayed. However, Perrin et al. [20] and Schnakers et al. [41] also reported P300 potentials with latencies between 600 ms and 800 ms in MCS patients. They concluded that MCS patients might have a slower processing speed than healthy subjects, an assumption that is also in line with Kotchoubey et al. [9]. There might have been some over- lapping e ffects due to the short ISI the beep tones were pre- sented with. This might also explain why the P300 occured at later time points, an e ffect that could also be observed in some healthy subjects. Furthermore, the inversed polarity could indi- cate a (possibly delayed) mismatch negativity (MMN) instead of a P300 potential. Significant MMN e ffects could be found in most healthy subjects around 200 ms after stimulus onset fol- lowed by the P300 potential, and were also reported by Kanoh et al. [29].
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Verification of the reference intervals proposed by Abbott on Alinity ci in a population of healthy subjects from Liege, Belgium

Verification of the reference intervals proposed by Abbott on Alinity ci in a population of healthy subjects from Liege, Belgium

Our results confirm the reference values as provided in the Abbott instructions for use for all parameters, except Cholinesterase. Indeed, 30% of healthy men were outside the range. As a consequence reference range need to established by running at least 120 samples coming from healthy subjects. Future evaluations are planned. For FSH, LH and Prolactin assays, samples from healthy women on contraception were found outside the range. The three hormonal parameter of the outsiders were consistent with each other. As women have hormonal cycle it’s difficult to develop reference values following the cycle. For estradiol, plan is to also run assays on mass spectrometry especially for children and men to hopefully achieve better accuracy in the lo range (LOQ = 23,7 pg/ml).
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Analysis of hand synergies in healthy subjects during bimanual manipulation of various objects

Analysis of hand synergies in healthy subjects during bimanual manipulation of various objects

Background The building of synergies - that are also usually called inter-joint coordination- is a fundamental aspect of human motor control to overcome the redundancy of the motor system, as pointed originally by N. Bernstein [1]: synergies are solutions to the problem of selecting one movement among the infinite possibilities of motor solu- tions to perform a specific task. Mathematically speaking, synergies can be represented as task specific covariations of elemental variables with the purpose to stabilize a per- formance variable [2]. A synergy can be expressed in several spaces: muscular activities, joint positions, joint velocities or joint torques. A recent view attributes three essential properties to the concept of synergy: the shar- ing pattern of rotations; flexibility allowing automatic compensation between elements and task dependency [2]. Several research groups have already been working on the identification of hand synergies, especially aiming at designing under-actuated hand prosthetics. Santello et al. in [3] studied postural synergies in healthy subjects grasp- ing objects. Experiments were conducted during which subjects were asked to realize hand postures mimicking the grasp of 57 objects, instead of grasping them phys- ically. Two principal components (PC) explained more than 80% of the variance observed among the 15 measured hand DoFs (Degrees of Freedom): the first PC repre- sented the coupling of flexion/extension of metacarpal- phalangeal (MCP) and abductions joints whereas the second PC represented the thumb rotation and the flex- ion/extension of the inter-phalangeal joints.
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Analytical and clinical evaluation of the new Fujirebio Lumipulse G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodia

Analytical and clinical evaluation of the new Fujirebio Lumipulse G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients

The first comparison was achieved in 100 young healthy sub- jects spanning the measuring range that had been included in a supplementation trial. The second comparison was performed with samples obtained from 30 women referred to a specialized osteopo- rosis clinic. We also compared the methods in populations who are known to present different VDBP concentrations: the first one was 3rd trimester pregnant women (n = 30; high VDBP values) and the second one was African healthy subjects from the area of Abidjan, Côte d’Ivoire (n = 30; low VDBP values). We also compared the meth- ods in a population of 30 stable hemodialyzed (HD) patients and in 30 patients from the general intensive care unit of our hospital. Indeed, these subjects can have a serum matrix which is very differ- ent from healthy individuals due to nitrogen products accumulation or proteins carbamylation or fluid shifts [5–7, 15]. Finally, we com- pared the assays in subjects presenting high C3-epimer concentra- tions and endogenous high 25(OH)D2 levels, as determined by our LC-MS/MS.
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Lean regional muscle volume estimates using explanatory bioelectrical models in healthy subjects and patients with muscle wasting

Lean regional muscle volume estimates using explanatory bioelectrical models in healthy subjects and patients with muscle wasting

data available in women. Stahn et al. 17 reported higher accu- racy of estimates of lower limb SMV when using higher fre- quencies (i.e. 500 kHz). However, the potential advantage of multifrequency acquisitions within such models remains to be scrutinized. The value of the muscle conductivity con- stant is the most critical aspect of these models. In previous works, 15–17 the authors used published muscle conductivity constants 18–21 so that uncertainties regarding true in vivo values of skeletal muscle conductivity remain. Whether these models may be applicable in patients with severe muscle wasting associated with degenerative changes, in particular, intramuscular fat in filtration, has never been investigated. Although using a relatively small number of measurements over the whole lower limb has been reported to provide rea- sonable estimates, 16 it remains unclear whether these models could be applied within shorter segments such as the thigh in both healthy subjects and patients with muscle impairments. Another aspect that has never been investigated is the between ‐day reproducibility of S BIA
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Awakening efficacy of a vibrotactile device in patients on home nocturnal ventilatory assistance and healthy subjects as family caregiver proxies

Awakening efficacy of a vibrotactile device in patients on home nocturnal ventilatory assistance and healthy subjects as family caregiver proxies

among the limitations of the study, and that, therefore, additional data need to be obtained in caregivers. It seems however reasonable to speculate that sleep iner- tia would be less marked in caregivers actually respon- sible for life-saving interventions in response to a ventilator alarm, especially when the expected inter- ventions are clearly defined in a protocol and when the caregivers have been trained in these interventions. Of note, two of our healthy subjects were older than 60; one subject woke up with cognitive arousal in response to the five alarms and the other subject failed to wake up with cognitive arousal only once. We acknowledge that this is not sufficient to rule out the risk that an age-related decrease in sleep quality could negatively influence the awakening performances of the vibrotac- tile device. Complementary data will need to be obtained in a population of actual caregivers of older age.
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Ankle dorsi- and plantar-flexion torques measured by dynamometry in healthy subjects from 5 to 80 years.

Ankle dorsi- and plantar-flexion torques measured by dynamometry in healthy subjects from 5 to 80 years.

Reliability assessment The significant positive differences between retest and test sessions suggest that there might be a minor learning effect in performing maximal voluntary contractions for ankle movements. This phenomenon may also be explained by the apprehension of the subject to hurt himself during the first trial as was previously mentioned or by the fact that this function is not performed isometrically in everyday life and can therefore be difficult to perform at first. This in- crease in strength during the retest session on plantar- flexion strength measurements has been observed by several authors [14,15]. Standard error of measurements and ICCs found in our study are similar or higher to those found in other studies assessing reliability in dorsi-flexion or plantar-flexion strength [14,25,34]. Due to the possible learning effect in assessing ankle strength, a training session should be recommended in clinical trials where there is a follow up of patient strength over time. A training session would also be useful in evaluating the smallest detectable differences that is relevant to the patient population stud- ied. Indeed the smallest detectable difference found in our study was established in healthy subjects and may not be a good criterion for detecting changes in subjects with much lower strength values as it can be noticed in our results (see Figure 3) that the difference between test and retest session is higher for higher strength values. Moreover, the variations in subsequent measurements depend on motiv- ation, skill, learning effect and several individual variables that are complex to analyse. This can affect estimates of reliability.
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Effects of Ingested Fructose and Infused Glucagon on Endogenous Glucose Production in Obese Niddm Patients, Obese Non-Diabetic Subjects, and Healthy Subjects

Effects of Ingested Fructose and Infused Glucagon on Endogenous Glucose Production in Obese Niddm Patients, Obese Non-Diabetic Subjects, and Healthy Subjects

Glucagon plays a central role in the regulation of EGP. However, the autoregulation of EGP does not involve suppression of glucagon secretion because it is also present when glucagon concentrations are maintained constant by means of infusions of somatostatin and exogenous glucagon [2, 5]. Hyperglucagonaemia is nonetheless, frequently found in NIDDM patients, and many stimulate gluconeogenesis and EGP from an increased supply of endogenous gluconeogenic precursors. In order to further delineate the effects of hyperglucagonaemia on substrate-induced EGP, healthy subjects were further studied during ingestion of fructose with hyperglucagonaemia or during hyperglucagonaemia alone. In lean subjects, ingestion of 13 C
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Analysis of hand synergies in healthy subjects during bimanual manipulation of various objects.

Analysis of hand synergies in healthy subjects during bimanual manipulation of various objects.

Background The building of synergies - that are also usually called inter-joint coordination- is a fundamental aspect of human motor control to overcome the redundancy of the motor system, as pointed originally by N. Bernstein [1]: synergies are solutions to the problem of selecting one movement among the infinite possibilities of motor solu- tions to perform a specific task. Mathematically speaking, synergies can be represented as task specific covariations of elemental variables with the purpose to stabilize a per- formance variable [2]. A synergy can be expressed in several spaces: muscular activities, joint positions, joint velocities or joint torques. A recent view attributes three essential properties to the concept of synergy: the shar- ing pattern of rotations; flexibility allowing automatic compensation between elements and task dependency [2]. Several research groups have already been working on the identification of hand synergies, especially aiming at designing under-actuated hand prosthetics. Santello et al. in [3] studied postural synergies in healthy subjects grasp- ing objects. Experiments were conducted during which subjects were asked to realize hand postures mimicking the grasp of 57 objects, instead of grasping them phys- ically. Two principal components (PC) explained more than 80% of the variance observed among the 15 measured hand DoFs (Degrees of Freedom): the first PC repre- sented the coupling of flexion/extension of metacarpal- phalangeal (MCP) and abductions joints whereas the second PC represented the thumb rotation and the flex- ion/extension of the inter-phalangeal joints.
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Implementation and validation of a stride length estimation algorithm, using a single basic inertial sensor on 
healthy subjects and patients suffering from Parkinson’s disease

Implementation and validation of a stride length estimation algorithm, using a single basic inertial sensor on healthy subjects and patients suffering from Parkinson’s disease

= tend hor corrected d StrideLength ³ v  t t (8) 2.2. Experimental Protocol 10 healthy subjects, (5 male, 5 female; Age range: 23 to 61 years; Height range: 1.55 to 1.89 m) and 12 patients suffering from Parkinson’s disease (9 male, 3 female; Age range: 63 to 82 years) participated to the study. The protocol has been approved by the local ethical committee (international identification number NCT02317289). Patients were recruited at the Neurology (Chauliac Hospital) and Gerontology (Balmes Center) departments of Montpellier hospital (CHU Montpellier). The participants provided their written informed consent. Subjects walked continuously for approximately 7 m along the GAITRite © electronic walkway (spatial accuracy ±0.0127 m, CIR Systems, Inc., Havertown, PA, USA) with two HikoB Fox © (HikoB © Villeurbanne, France) inertial measurement units respectively strapped to the foot and the shank of each leg, as illustrated in Figure 3 . The distance D between the IMU and the ankle joint was systematically measured once the subject equipped. Each subject from the healthy group performed two iterations of the walk at self-selected walking speeds (‘normal’ and “fast”). Subjects from PD group only walked at their comfort speed. The IMU were remotely controlled and synchronized each other via a radio beacon. The GAITRite device provided a +5V trigger output for synchro- nizing data acquisition with the HikoB inertial sensors, enabling to include all the strides of each gait sequence. Based on each single IMU, individual stride lengths were estimated from the previously explained algorithm and compared one by one to the stride lengths provided by the GAITRite software. For each of the two sensors lo- cated on each leg, we observed the influence of the IMU location (shank or foot mounted), the walking speed, the sampling rate and the filtering on the mean and maximum stride length calculation error.
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Influence of Genetic Variations on Levels of Inflammatory Markers of Healthy Subjects at Baseline and One Week after Clopidogrel Therapy; Results of a Preliminary Study

Influence of Genetic Variations on Levels of Inflammatory Markers of Healthy Subjects at Baseline and One Week after Clopidogrel Therapy; Results of a Preliminary Study

Received: 7 June 2013; in revised form: 29 July 2013 / Accepted: 30 July 2013 / Published: 8 August 2013 Abstract: We aimed to assess the association between the most common polymorphisms of cytochrome P450 (CYP) epoxygenases on the plasma levels of inflammatory markers in a population of healthy subjects. We also sought to determine whether CYP2C19*2 polymorphism is associated with the anti-inflammatory response to clopidogrel. In a population of 49 healthy young males, the baseline plasma levels of inflammatory markers including C-reactive protein, haptoglobin, orosomucoid acid, CD-40 were compared in carriers vs. non-carriers of the most frequent CYP epoxygenase polymorphisms: CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C8*2 and CYP2J2*7. Also, the variation of inflammatory markers from baseline to 7 days after administration of 75 mg per day of clopidogrel were compared in carriers vs. non-carriers of CYP2C19* allele and also in
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Immediate effect of bilateral talocrural joint manipulation on postural balance in healthy subjects

Immediate effect of bilateral talocrural joint manipulation on postural balance in healthy subjects

Abstract The aim of this study was to assess the immediate effect of bilateral talocrural joint manipulation on the postural balance of healthy subjects. Ninety healthy subjects (21 males and 69 females) were included in this study. The mean age, height and body weight of the subjects were 22.21 years, 165.1 cm and 62.58 Kg, respectively. Following collection of anthropometric data, the subjects were allocated randomly into an experimental group (receiving real talocrural joint manipulation), a placebo group and a control group. Before and after manipulation, the subjects performed two postural balance tasks, inquiet standing position (eyes open and eyes closed) on a force platform. The stabilometric data were recorded for 60 seconds in each condition. Sway area, medio-lateral (ML) and antero- posterior (AP) velocities and median frequency were calculated from the center of pressure (COP) displacements. The results showed that in the experimental group the COP sway velocity decreased in both directions of movement (AP and ML) and in both visual tasks (eyes open and eyes closed). In general, the placebo and control groups had similar postural balance across balance parameterss. Significant effect of the bilateral talocrural joint manipulation was found on main balance parameter like COP velocity in the anteroposterior and mediolateral directions. These results have some much implications for manual therapy rehabilitation of individuals with ankle instability.
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Sympathetic Effect of Auricular Transcutaneous Vagus Nerve Stimulation on Healthy Subjects: A Crossover Controlled Clinical Trial Comparing Vagally Mediated and Active Control Stimulation Using Microneurography.

Sympathetic Effect of Auricular Transcutaneous Vagus Nerve Stimulation on Healthy Subjects: A Crossover Controlled Clinical Trial Comparing Vagally Mediated and Active Control Stimulation Using Microneurography.

21. Matsukawa T, Sugiyama Y, Watanabe T, Kobayashi F, Mano T. Gender difference in age-related changes in muscle sympathetic nerve activity in healthy subjects. The American journal of physiology 1998;275:R1600-4. 22. Kraus T, Hosl K, Kiess O, Schanze A, Kornhuber J, Forster C. BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation. Journal of neural transmission (Vienna, Austria : 1996) 2007;114:1485-93. 23. Kraus T, Kiess O, Hosl K, Terekhin P, Kornhuber J, Forster C. CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study. Brain stimulation 2013;6:798-804.
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Self-defining memories and self-concept clarity: A comparative study of depressed patients, bipolar patients and healthy subjects

Self-defining memories and self-concept clarity: A comparative study of depressed patients, bipolar patients and healthy subjects

Self-defining memories and self-concept clarity: A comparative study of depressed patients, bipolar patients and healthy subjects Self-defining memories (SDMs) are… (Blagov & Singer, 2004) • Vivid, emotionally intense and well-rehearsed autobiographical memories; • Reflections of the central goals, values and conflicts of an individual’s life;

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Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

4.1. Behavioral pain ratings On average, over the 10 consecutive trials, there was no signif- icant decrease in laser pain ratings during the conditioning cold stimulation. Facilitatory CPM (i.e. hyperalgesia) was observed in other studies, though overall in a smaller proportion of subjects. In pre-operative pain-free patients, facilitatory CPM predicts sub- sequent post-surgery chronic pain [40] and higher analgesic con- sumption [41] . The likelihood to have facilitatory CPM of a heat test stimulus by tourniquet ischemic noxious conditioning was higher in subjects with low 5-HTT expression [42] . In our study, only 29% of subjects had pain reduction, while 29% had no change and 42% increased laser pain, clearly demonstrating inter-individual differ- ences. This contrasts with other CPM studies [15,16] and could have several non-mutually exclusive explanations.
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