Measurement of the lumbrical muscle activity of the hand using electromyography supported by the ultrasound imaging technique with string navigation.

Although placing surface electrodes on small muscles by palpation is difficult, ultrasound guidance may enable electrode placement on the small muscles. This study aimed to examine whether ultrasound guidance is helpful for placement of electrodes on a small muscle, such as the hand lumbrical muscle. Twelve dominant hands of 12 healthy right-handed adults were included in this study. The first lumbrical muscle belly of the hands was identified using ultrasound guidance with a string navigation technique for placing surface electrodes. This technique was designed to identify the location of the center of the muscle belly under ultrasound imaging using a string. After the electrodes were placed on the muscle belly using this technique, the surface electromyographic signals of the first lumbrical, first dorsal interosseous, and adductor pollicis muscles were recorded. The activity of the lumbrical muscle could be separately measured of the first dorsal interosseous and adductor pollicis muscles. This technique has the potential to enable surface electromyography of small muscles for which placement of surface electrodes by palpation is challenging.

Effects of metacarpophalangeal joint position and finger joint movement speed on lumbrical muscle activity.

OBJECTIVES: The effect of metacarpophalangeal joint position and finger joint movement speed on lumbrical muscle activity remains unproven and was examined in this study. MATERIAL AND METHODS: Twenty-four healthy adults performed flexion-extension movements of the index finger in different metacarpophalangeal joint positions (extension or flexion) and movement speeds (60, 120, 240, and 360 beats per minute). The activities of the first lumbrical, first dorsal interosseous, and extensor digitorum muscles were evaluated using surface electromyography, and compared with those during finger joint extension. RESULTS: The metacarpophalangeal joint positions affected only lumbrical muscle activity, which was greater during extension. Further, finger movement speed affected the lumbrical and extensor digitorum muscle activities, which increased with increasing movement speeds. CONCLUSION: The present study suggests that position and movement speed can influence the lumbrical muscle activity during metacarpophalangeal joint extension. These findings may help expound lumbrical function and develop suitable strategies for inducing lumbrical muscle activity.

Correlation between kinesthetic motor imagery of an amputated limb and phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) is a frequent painful sensation in amputees, and motor imagery (MI) is a useful approach for the treatment of this type of pain. However, it is not clear regarding the best MI modality for PLP. OBJECTIVES: The purpose of this study was to investigate the relationship between the PLP and MI modality in upper limb amputees. STUDY DESIGN: Observational study. METHODS: Eleven patients who underwent unilateral upper limb amputation participated in this study. The MI modality (kinesthetic and visual) and PLP intensity were evaluated using the Kinesthetic and Visual Imagery Questionnaire (KVIQ)-20 and a visual analog scale. MI ability was also assessed during the hand mental rotation task. We examined the correlation between MI modalities, ability, and pain intensity. RESULTS: The total KVIQ kinesthetic score was negatively correlated with pain intensity (r = -0.71, P < 0.01): the more vivid the kinesthetic imagery, the weaker the pain. In particular, the reduction in pain intensity was associated with strong kinesthetic imagery of opposing movements of the deficient thumb (r = -0.81, P < 0.01). The KVIQ visual score and MI ability were not associated with pain intensity. CONCLUSIONS: Our data showed that the reduction of PLP could be associated with the kinesthetic modality of MI but not with visual modality or MI ability. In other words, it was suggested that the more vivid the sensation of moving muscles and joints in the defect area, the lower the PLP intensity. To reduce PLP, clinicians may prefer interventions using the kinesthetic modality.

Quantitative evaluation of abnormal finger movements in myelopathy hand during the grip and release test using gyro sensors.

Previous studies have reported qualitative characteristics of myelopathy hand, but few studies have reported quantitative kinematic parameters of this condition. Our purpose of this study was to quantitatively evaluate the abnormal finger movements in patients with cervical compressive myelopathy (CCM) (termed myelopathy hand) and to understand the characteristics of myelopathy hand during the grip and release test (GRT) using gyro sensors. Sixty patients with CCM (severe: n = 30; mild-to-moderate: n = 30) and sixty healthy adults (age-matched control: n = 30; young control: n = 30) were included in this study. All participants performed the GRT. The index and little fingers' and the wrist's movements during the GRT were recorded using three gyro sensors. The number of cycles, switching time-delay, time per cycle, and peak angular velocity were calculated and compared between groups. Patients with severe CCM had the lowest number of cycles and longest switching time-delays, followed by patients with mild-to-moderate CCM, the age-matched control group, and the young control group. The time per cycle and the peak angular velocities of fingers in participants with severe CCM were significantly lower than those in participants with mild-to-moderate CCM; however, there were no significant differences between the control groups. The peak angular velocities of fingers were significantly lower during extension motions than during flexion motions in participants with CCM. Participants with CCM have lower peak angular velocities during finger movement. Finger extension also is impaired in participants with CCM. Abnormal finger movements and the severity of myelopathy in participants with CCM can be assessed using gyro sensors.

Transcranial direct current stimulation reduces ischemia-induced sensory disturbance in the hands of healthy subjects.

INTRODUCTION/AIMS: The treatment of entrapment neuropathies, such as carpal tunnel syndrome or cubital tunnel syndrome, has significant challenges that have yet to be solved. To a large extent, the success of the treatment of peripheral nerve damage is dependent on brain plasticity during the recovery process. Recently, noninvasive brain stimulation procedures, such as transcranial direct current stimulation (tDCS), to modulate brain activity have been developed. This study aimed to determine whether tDCS can improve artificially induced ischemic sensory disturbances in the finger. METHODS: Ten right-handed, healthy volunteers, with an average age of 25.5 years, participated in this study. A rubber bandage at the base of the right index finger was used to induce a regional sensory disturbance for 30 minutes. An anodal tDCS was applied over their left M1 area 15 minutes into the session. The current perception threshold (CPT) in the index and little finger pad was evaluated using the PainVision system and used as a measure of the sensory threshold. RESULTS: In the index finger, the CPT increased significantly with time, a finding that was absent after tDCS application. DISCUSSION: It has been reported that anodal tDCS over M1 primarily modulates the functional connectivity of sensory networks, and our findings demonstrate that it improved ischemia-induced sensory disturbances. Modulating the central nervous system using tDCS represents a potential avenue for treating entrapment neuropathies.

Association between medial meniscus extrusion under weight-bearing conditions and pain in early-stage knee osteoarthritis.

PURPOSE: This study aimed to investigate the association between the severity of medial meniscus extrusion (MME) under weight bearing and pain in patients with early-stage knee osteoarthritis (OA). METHODS: Twenty-eight patients with symptomatic early-stage knee OA (Kellgren and Lawrence grade ≤ 2) who visited our outpatient clinic between 2016 and 2018 were included in this cross-sectional study (mean age: 58.0 ± 11.6 years, female: n = 10). MME was evaluated under weight-bearing conditions using ultrasonography. Patients were divided into two groups according to the severity of MME under weight bearing: those with MME ≥ 3 mm were assigned to the severe group, whereas those with MME < 3 mm were assigned to the mild group. The knee injury osteoarthritis outcome score (KOOS) system was used to evaluate knee pain. The incidence of bone marrow lesions (BMLs) was evaluated using magnetic resonance images. RESULTS: The KOOS pain score was significantly lower in the severe group than in the mild group (P < 0.05). The incidence of BMLs was significantly higher in the severe group (69%) than in the mild group (7%) (P < 0.001). CONCLUSION: Patients with early-stage knee OA who have greater MME under weight-bearing have more intense knee pain and a higher incidence of BMLs.

Brachialis Muscle Activity Can Be Measured With Surface Electromyography: A Comparative Study Using Surface and Fine-Wire Electrodes.

Muscle activities of the elbow flexors, especially the brachialis muscle (BR), have been measured with intramuscular electromyography (EMG) using the fine-wire electrodes. It remains unclear whether BR activity can be assessed using surface EMG. The purpose of this study was to compare the EMG patterns of the BR activity recorded during elbow flexion using surface and fine-wire electrodes and to determine whether surface EMG can accurately measure the BR activity. Six healthy men were asked to perform two tasks-a maximum isometric voluntary contractions (MVICs) task and an isotonic elbow-flexion task without lifting any weight. The surface and intramuscular EMG were simultaneously recorded from the BR and the long and short heads of the biceps brachii muscle (BBLH and BBSH, respectively). The locations of the muscles were identified and marked under ultrasonographic guidance. The peak cross-correlation coefficients between the EMG signals during the MVICs task were calculated. For the isotonic elbow-flexion task, the EMG patterns for activities of each muscle were compared between the surface and the fine-wire electrodes. All cross-correlation coefficients between the surface EMG signals from the muscles were lower than 0.3. Furthermore, the EMG patterns of the BR activity were not significantly different between the surface and the fine-wire electrodes. The BR has different EMG pattern from the BBLH and the BBSH. The BR activity, conventionally measured with intramuscular EMG, can be accurately accessed with surface EMG during elbow flexion performed without lifting any weight, independent from the BBLH and BBSH activities.

Virtual reality-based action observation facilitates the acquisition of body-powered prosthetic control skills.

BACKGROUND: Regular body-powered (BP) prosthesis training facilitates the acquisition of skills through repeated practice but requires adequate time and motivation. Therefore, auxiliary tools such as indirect training may improve the training experience and speed of skill acquisition. In this study, we examined the effects of action observation (AO) using virtual reality (VR) as an auxiliary tool. We used two modalities during AO: three-dimensional (3D) VR and two-dimensional (2D) computer tablet devices (Tablet). Each modality was tested from first- and third-person perspectives. METHODS: We studied 40 healthy right-handed participants wearing a BP prosthesis simulator on their non-dominant hands. The participants were divided into five groups based on combinations of the different modalities and perspectives: first-person perspective on VR (VR1), third-person perspective on VR (VR3), first-person perspective on a tablet (Tablet1), third-person perspective on a tablet (Tablet3), and a control group (Control). The intervention groups observed and imitated the video image of prosthesis operation for 10 min in each of two sessions. We evaluated the level of immersion during AO using the visual analogue scale. Prosthetic control skills were evaluated using the Box and Block Test (BBT) and a bowknot task (BKT). RESULTS: In the BBT, there were no significant differences in the amount of change in the skills between the five groups. In contrast, the relative changes in the BKT prosthetic control skills in VR1 (p < 0.001, d = 3.09) and VR3 (p < 0.001, d = 2.16) were significantly higher than those in the control group. Additionally, the immersion scores of VR1 (p < 0.05, d = 1.45) and VR3 (p < 0.05, d = 1.18) were higher than those of Tablet3. There was a significant negative correlation between the immersion scores and the relative change in the BKT scores (Spearman's rs = - 0.47, p < 0.01). CONCLUSIONS: Using the BKT of bilateral manual dexterity, VR-based AO significantly improved short-term prosthetic control acquisition. Additionally, it appeared that the higher the immersion score was, the shorter the execution time of the BKT task. Our findings suggest that VR-based AO training may be effective in acquiring bilateral BP prosthetic control, which requires more 3D-based operation.

Transcranial direct current stimulation effects on hand sensibility as measured by an objective quantitative analysis device: a randomized single-blind sham-control crossover clinical trial.

Studies show that transcranial direct current stimulation (tDCS) can modulate somatosensory processing, but optimum parameters for tDCS effects on hand sensibility remain in question. We aimed to test the effects of anodal tDCS (atDCS) and cathodal tDCS (ctDCS) compared with sham tDCS (stDCS) of primary motor (M1) and sensory (S1) cortices on healthy subjects' hand sensibility. In this single-blind clinical trial, 30 randomized healthy volunteers received six tDCS sessions over 6 weeks: one session each of atDCS, ctDCS and stDCS over M1, and one session each of atDCS, ctDCS and stDCS over S1. Current perception threshold (CPT) was assessed using an objective quantitative analysis device (PainVision) at baseline, immediately (T0) and 30 min (T30) after each intervention. Our results showed that both atDCS and ctDCS of S1 and M1 significantly increased CPT. M1 ctDCS at T30 had the greatest effect of all M1 and S1 stimulation conditions (mean difference: 32.94%, Z: 3.12, effect size: 1.82, P < 0.001 The largest effect at S1 was for atDCS at T30 (mean difference: 29.87%, Z: 2.53, effect size: 1.72, P < 0.001. Our results are consistent with tDCS' modulatory effects on hand sensation, especially M1 ctDCS and S1 atDCS.

Correlation between spinal and pelvic movements during gait and aggravation of low back pain by gait loading in lumbar spinal stenosis patients.

BACKGROUND: Lumbar alignment of posterior or anterior tilts affects the exacerbation and remission of symptoms of lumbar spinal stenosis patients. This study aimed to clarify the correlation between spinal and pelvic movements during gait and the aggravation of low back pain after gait loading in lumbar spinal stenosis patients. METHODS: A total of 29 patients with lumbar spinal stenosis completed leg and low back pain assessments and gait analysis before and after gait loading tests. Patients were divided into leg and low back pain change (n = 8), leg pain only change (n = 12), and non-change (n = 9) groups based on the differences of leg and low back pain between before and after the tests. Peak kinematic values of the anterior tilts of the trunk, thoracic spine, lumbar spine, and pelvis during the stance phase were obtained via three-dimensional gait analysis. RESULTS: In the leg and low back pain change group, the anterior lumbar and pelvic tilts were larger after than before the tests; however, in the leg pain only change and non-change groups, only the anterior lumbar tilt was larger after than before the tests. Anterior lumbar tilt before and after the tests negatively correlated with the aggravation of low back pain, and an increase in the anterior pelvic tilt positively correlated with the aggravation of low back pain. CONCLUSIONS: In lumbar spinal stenosis patients, smaller anterior lumbar tilt and larger anterior pelvic tilt during gait loading may affect the aggravation of low back pain by gait loading. Increasing in lumbar lordosis during gait might be one of the factors leading to low back pain in lumbar spinal stenosis patients.

Evaluation of electrokinetic parameters for all DNA bases with sputter deposited nanocarbon film electrode.

The electrokinetic parameters of all the DNA bases were evaluated using a sputter-deposited nanocarbon film electrode. It is very difficult to evaluate the electrokinetic parameters of DNA bases with conventional electrodes, and particularly those of pyrimidine bases, owing to their high oxidation potentials. Nanocarbon film formed by employing an electron cyclotron resonance sputtering method consists of a nanocrystalline sp(2) and sp(3) mixed bond structure that exhibits a sufficient potential window, very low adsorption of DNA molecules, and sufficient electrochemical activity to oxidize all DNA bases. A precise evaluation of rate constants (k) between all the bases and the electrodes is achieved for the first time by obtaining rotating disc electrode measurements with our nanocarbon film electrode. We found that the k value of each DNA base was dominantly dependent on the surface oxygen-containing group of the nanocarbon film electrode, which was controlled by electrochemical pretreatment. In fact, the treated electrode exhibited optimum k values for all the mononucleotides, namely, 2.0 × 10(-2), 2.5 × 10(-1), 2.6 × 10(-3), and 5.6 × 10(-3) cm s(-1) for GMP, AMP, TMP, and CMP, respectively. The k value of AMP was sufficiently enhanced by up to 33 times with electrochemical pretreatment. We also found the k values for pyrimidine bases to be much lower than those of purine bases although there was no large difference between their diffusion coefficient constants. Moreover, the theoretical oxidation potential values for all the bases coincided with those obtained in electrochemical experiments using our nanocarbon film electrode.

An sp2 and sp3 hybrid nanocrystalline carbon film electrode for anodic stripping voltammetry and its application for electrochemical immunoassay.

A hybridized nanocrystalline carbon film electrode consisting of sp(2) and sp(3) bonds was investigated to reveal the reduction properties of Cd(2+) and for application as a highly sensitive and reliable electrochemical immunoassay. Conductive nanocrystalline carbon film consisting of about 60% sp(2) and 40% sp(3) bonds was fabricated using electron cyclotron resonance (ECR) sputtering equipment, and then the Cd(2+) concentrations were measured with an ECR sputtered carbon (ECR nano-carbon) electrode by employing an anodic stripping voltammetry (ASV) technique. The preconcentrated Cd was analyzed with Kelvin probe force microscopy and energy dispersive X-ray spectroscopy while observing the morphology change with an atomic force microscope and a scanning electron microscope. The preconcentrated Cd on the ECR nano-carbon electrode was revealed to be a thin sheet structure, which was significantly different from the Cd on a conventional carbon material that grows with a coralloid structure. The background current during an ASV measurement maintains a low level equivalent to that found with boron-doped diamond because the surface of the ECR nano-carbon is robust and angstrom-level flat. The carbon-electrode performance for ASV was improved by controlling its structure at a nanometer scale without any metal doping or coating. Finally, the ECR nano-carbon was used for biomolecular determination by electrochemical immunoassay with a CdSe nanoparticle label. Electrochemical immunoassay results were successfully obtained with the ECR nano-carbon, and they correlated well with fluorescence results obtained for CdSe nanoparticles.

Efficient direct electron transfer with enzyme on a nanostructured carbon film fabricated with a maskless top-down UV/ozone process.

We have developed a new carbon film electrode material with thornlike surface nanostructures to realize efficient direct electron transfer (DET) with enzymes, which is very important for various enzyme biosensors and for anodes or cathodes used in biofuel cells. The nanostructures were fabricated using UV/ozone treatment without a mask, and the obtained nanostructures were typically 2-3.5 nm high as confirmed by atomic force microscopy measurements. X-ray photoelectron spectroscopy and transmission electron microscopy revealed that these nanostructures could be formed by employing significantly different etching rates depending on nanometer-order differences in the local sp(3) content of the nanocarbon film, which we fabricated with the electron cyclotron resonance sputtering method. These structures could not be realized using other carbon films such as boron-doped diamond, glassy carbon, pyrolyzed polymers based on spin-coated polyimide or vacuum-deposited phthalocyanine films, or diamond-like carbon films because those carbon films have relatively homogeneous structures or micrometer-order crystalline structures. With physically adsorbed bilirubin oxidase on the nanostructured carbon surface, the DET catalytic current amplification was 30 times greater than that obtained with the original carbon film with a flat surface. This efficient DET of an enzyme could not be achieved by changing the hydrophilicity of the flat carbon surface, suggesting that DET was accelerated by the formation of nanostructures with a hydrophilic surface. Efficient DET was also observed using cytochrome c.

Direct electrochemical detection of DNA methylation for retinoblastoma and CpG fragments using a nanocarbon film.

We describe the direct electrochemical detection of DNA methylation in relatively long sequences by using a nanocarbon film electrode. The film was formed by employing the electron cyclotron resonance sputtering method and had a nanocrystalline sp(2) and sp(3) mixed bond structure. Our methylation detection technique measures the differences between the oxidation currents of both 5-methylcytosine and cytosine without a bisulfite reaction or labeling. This was possible because this film electrode has a wide potential window while maintaining the high electrode activity needed to quantitatively detect both bases by direct oxidation. By optimizing the electrode surface conditions using electrochemical pretreatment, we used this film to quantitatively detect single cytosine methylation regardless of the methylation position in the sequence including retinoblastoma gene fragments (approximately 24 mers). This was probably due to the high stability of this film electrode, which we achieved by controlling the surface hydrophilicity to suppress the fouling, and by maintaining electrode activity against all the bases. The pH optimization of the oligonucleotide measurements was also useful for distinguishing both bases separately. Under the optimized conditions, this film electrode allowed us to realize the quantitative detection of DNA methylation ratios solely by measuring methylated 5'-cytosine-phosphoguanosine (CpG) repetition oligonucleotides (60 mers) with different methylation ratios.

Transcriptional effect of a calmodulin inhibitor, W-7, on the ligninolytic enzyme genes in Phanerochaete chrysosporium.

We investigated the effects of a calmodulin (CaM) inhibitor, W-7, on the expression of lignin peroxidase (LiP) and manganese peroxidase (MnP) genes in Phanerochaete chrysosporium to consider the role of cam gene, which was upregulated in parallel with the total activities of LiP and MnP in our previous transcriptomic analysis. The addition of 100 µM W-7 to the fungal cultures repressed the total activities of LiP and MnP, whereas the addition of 100 µM W-5, which is a control drug of W-7, retained approximately half of them, indicating that the effect of W-7 was attributable to CaM inhibition. Real-time reverse transcription polymerase chain reaction analysis revealed that most of lip and mnp isozyme genes predicted from whole-genome data were significantly inhibited by W-7 at the transcription level (P ≤ 0.05). These results suggest that CaM has an important role for the expression of isozyme genes of LiP and MnP at the transcription level.

Local imaging of an electrochemical active/inactive region on a conductive carbon surface by using scanning electrochemical microscopy.

We demonstrated the imaging of local electron transfer-rate differences on a flat conductive carbon substrate, attributed to only surface functional groups, by using a scanning electrochemical microscopy (SECM) technique. These differences were clearly imaged by using a redox mediator with surface state sensitive electron transfer rates, even if the conductivity of each imaging area were almost identical. The carbon electrode surface was masked with a patterned photoresist, and selectively introduced oxygen functional groups using an oxygen plasma treatment. This patterned surface exhibited hardly any topographical features when observed by scanning electron microscopy (SEM), and a height difference of only 1.0 nm was observed with atomic force microscopy (AFM). However, the SECM feedback mode and substrate generation-tip collection (SG-TC) mode are able to distinguish these interfaces with an almost micrometer order resolution by utilizing the difference in the electron transfer rate for the Fe(2+/3+) mediator, and the current ratios for regions rich and poor in oxygen containing groups were 1.5 and 2.0, respectively. This technique could be employed for imaging and monitoring the electron transfer rates on various electrode surfaces, including fluorine and nitrogen terminated surfaces and a monolayer film patterned with micro or nano contact printing techniques.

Writing and reading methodology for biochips with sub-100-nm chemical patterns based on near-field scanning optical microscopy.

This paper demonstrates a writing and reading methodology, which allows both to create and to detect sub-100-nm carboxyl-terminated patterns on light-transmissive quartz substrates by the same instrumental system. Such a technique, capable of creating carboxyl-terminated nanopatterns, offers several benefits for the miniaturization of biochips, since the carboxyl-terminated nanopatterns allow the easy immobilization of biomolecules by amide bond formation. As a consequence, increasingly miniaturized biochips require suitable analytical methods for the detection of nanopatterns. In our approach, carboxyl-terminated nanopatterns of down to 80 nm width were created using a photolabile silane coupling agent and a UV laser coupled to a near-field scanning optical microscope (NSOM). The same NSOM system was then used in a next step to detect the fabricated carboxyl-terminated nanopatterns after modification with a fluorescent label. Furthermore, as a first step towards biochip applications, the successful immobilization of several biomolecules, such as streptavidin, IgG and DNA on carboxyl-terminated nanopatterns was demonstrated. We have shown that our approach has the potential to lead to a new bioanalytical method, which enables one to write and to read biochips on a sub-100-nm scale by the same system.

A nanocarbon film electrode as a platform for exploring DNA methylation.

We describe the quantitative nonlabel electrochemical detection of both cytosine (C) and methylcytosine (mC) in oligonucleotides using newly developed nanocarbon film electrodes. The film consists of nanocrystalline sp2 and sp3 mixed bonds formed by employing the electron cyclotron resonance (ECR) sputtering method. We successfully used this film to develop a simple electrochemical DNA methylation analysis technique based on the measurement of the differences between the oxidation currents of C and mC since our ECR nanocarbon film electrode can directly measure all DNA bases more quantitatively than conventional glassy carbon or boron-doped diamond electrodes. The excellent properties of ECR nanocarbon film electrodes result from the fact that they have a wide potential window while maintaining the high electrode activity needed to oxidize oligonucleotides electrochemically. Proof-of-concept experiments were performed with synthetic oligonucleotides including different numbers of C and mC. This film allowed us to perform both C- and mC-positive assays solely by using the electrochemical oxidation of oligonucleotides without bisulfite or labeling processes.

Newly developed chemical probes and nano-devices for cellular analysis.

A cellular analyzing system including a "real-time cellular imaging system" and a "comprehensive analyzing system for cellular responses" was developed. A "real-time cellular imaging system" is a system used to measure real-time imaging of multiple phenomena of a single cell with high special and temporal resolutions for the purpose to understand the pathology and physiology in a single cell and realize to single cell level diagnosis. A "real-time cellular imaging system" includes multi-probe imaging with AFM (atomic force microscopy), optical and SECM (scanning electrochemical microscopy) modes, which provides us with topological information and biochemical reactions at the local area of the interior and exterior of a cell. Scanning electrochemical/optical microscopy was applied to image PC12 cells. On the other hand, cells respond to their specific substances via their ligands. Therefore, the comprehensive analysis of protein-protein interaction is the important issue to determine the functions of cells. For this purpose, a "comprehensive analysis system for cellular responses" was developed. This system is based on SPR (surface plasmon resonance) and MS (mass spectrometry) using a nano-fabricated substrate. The interaction between IL-1 beta and anti-IL-1 beta antibodies was detected.