In order to explore the influence of space ultraviolet radiation on spacecraft lubricating materials, an in-situ friction experimental device simulating space ultraviolet radiation was developed in the laboratory, and the experimental verification was carried out. This paper firstly introduced the design index, structure and working principle of the space ultraviolet irradiation simulation device, and then calibrated and tested the parameters of the whole device, and also conducted a virtual operation of the device’s operation effect by simulation software, and the results showed that it met the design index. Finally, the validation tested of the ultraviolet irradiated in-situ friction experimental device were described in detail. By using the device to irradiate the samples, it was found that the in-situ ultraviolet irradiation device could achieve the expected irradiation effect, and the irradiation would lead to changes in the surface structure and properties of the PTFE material, while also achieving the need for in-situ spatial friction property testing of the material, providing favorable conditions for future testing. The solar radiation energy is very large, which can be described quantitatively by solar constant (S0). It is defined as the total radiant energy per unit area of the outer edge of the atmosphere perpendicular to the solar rays at the mean distance between the sun and the earth within a unit time, which is approximately equal to 1353 ± 21 W/m2. In the solar radiation spectrum, ultraviolet (UV) radiation with a wavelength of 100~400 nm provides about 117.7 W/m2 of energy, accounting for only 8.7% of the total solar radiation energy, but it has a very important impact on the properties of materials, especially polymer materials. According to the characteristics of photons of different wavelengths, UV radiation can be further subdivided into vacuum ultraviolet radiation with a wavelength of less than 200 nm, medium ultraviolet radiation with a wavelength of 200~320 nm, and near ultraviolet radiation with a wavelength of 320~400 nm [Space equipment is subject to intense solar irradiation during orbit . The spe2 coating and diamond-like film [UV irradiation has a very important effect on the properties of materials ,4,5. In ike film ,7,8, espike film ,10,11, t2, which was about 1 times the solar constant; Tokoroyaman [2, about three times the solar constant; The UV radiation intensity used in the study of Géraldine Theiler was only 40 W/m2 [2 [2, about 6 times the solar ultraviolet intensity. The UV intensity of the device has been improved, but the device can not be used for in-situ tribological performance test.Ground simulation tests of space ultraviolet rays were carried out very early, such as the Marshall Space Flight Center of NASA completed the design and put into use of CEETC2 and CEETC3 systems in 1990 and 1996, respectively. Sugimura  studied oroyaman ,14 was uoroyaman  designed 40 W/m2 ; the spa W/m2 [2 ,18. The 2O3 filler role in the polyimide composites, to improve the anti-irradiation and wear resistance. In reference [In this study, a new type of simulated space ultraviolet irradiation device was developed through a series of work such as the selection of light source and the design of optical path, so that it can produce ultraviolet rays that are the same as the ultraviolet spectrum of solar light. At the same time, the device can be used in conjunction with the existing MSTS-1 vacuum friction and wear tester , which reference  Skurat eeference  the effeAccording to the above design indexes, the developed space UV irradiation device should not only cover the whole UV spectrum range as much as possible, but also realize that the radiation intensity is far greater than that of the sun in the same wavelength range, so as to carry out accelerated test. It is planned to simulate vacuum UV radiation, near UV radiation and medium UV radiation respectively by using double light sources. Among them, short-wavelength vacuum UV rays cannot pass through the quartz window and are easily absorbed by the air, so the deuterium lamp is directly hung in the vacuum chamber and near the sample table for simulation. A special light source and light path transformation mechanism are used to simulate the near UV radiation device. The light emitted by the two light sources is not linear, and the middle superposition area can completely cover the middle ultraviolet spectrum. The structure of the whole set of UV irradiation simulator integrated with MSTS-1 is shown in 2. As shown in L7293-50 deuterium lamp produced by Hamamatsu company of Japan was selected as the light source for simulating vacuum UV. Its shape and luminous spectrum distribution are shown in 1) of the ellipsoid reflector, and the light from the light source converges to the optical integrating mirror group near the second focus (F2). The integrating mirror group superposes the light lines in different space regions and projects them to the collimator. The collimator converges the divergent light into parallel beams and parallel beams. It acts directly on the sample table in the vacuum chamber through the quartz window.The near UV irradiation device is mainly composed of light source, power supply and controller. The power supply and control circuit include high power steady current source, timing alarm, programmed electric shutter, high voltage mercury xenon lamp trigger circuit and protection circuit. The structure of the light source device is shown in The optical path design scheme is helpful to ensure the intensity, uniformity and collimation of ultraviolet irradiation on the sample table. The design process and principle of key components in optical path are introduced as follows:(1) Choice of light source: the energy conversion efficiency of the UV light source is usually 8~10%. To achieve the irradiation intensity of three UV constants in the range of 50 mm × 50 mm, the power of the light source is about 350 W. The GXZ500 type 500 W spherical high-pressure mercury xenon lamp produced by Shanghai Hualun Bulb Factory was selected as the near UV light source. Its appearance is shown in (2) Design of condenser: the function of the condenser is to converge the light emitted from the spherical high-pressure mercury-xenon lamp source to the vicinity of the second focal plane, so as to make full use of the luminous energy of the mercury-xenon lamp to meet the requirements of UV radiation energy and help improve the unevenness of irradiation.0 and e can be calculated by Equations (3) and (4):0 is the vertex curvature radius; e is the eccentricity; f2 is the second focal length of the ellipsoidal condenser, f2 = M0f1; f1 is the first focal length of the ellipsoidal condenser; M0 is the paraxial imaging magnification of the ellipsoidal condenser; u is the aperture angle. Because of the axial symmetry of the mercury-xenon lamp light source, the use of an ellipsoidal reflective condenser can obtain a better concentrating effect. The overall dimensions of the condenser lens can be calculated by Equations (1) and (2):In order to reduce the loss of light energy as far as possible, the ellipsoidal reflector adopts numerical control processing to ensure the accuracy of surface shape, and the surface vacuum deposition of highly reflective metal film has a surface reflectance of more than 95%.(3) Ultraviolet transmittance optical plate: in order to eliminate the non-ultraviolet components in the spectrum emitted by the mercury xenon lamp light source, the light is filtered before entering the lens group of the integrator field. The ultraviolet filter is made of quartz glass substrate and coated with high temperature dielectric film in vacuum. The transmittance of UV light from 200 to 400 nm is more than 90%, and the transmittance of visible light and infrared light is less than 10%.(4) Optical integrating mirror group: the function of the optical integrating mirror group is to project the light radiation of different space areas onto the collimator. The integrator is the most important optical element to realize the uniform distribution of irradiance in the irradiation plane. The integrator lens group is divided into two groups: the field lens group and the projection lens group. Each group is composed of multiple small element lenses and the supporting base lens. All element lenses and supporting lenses of the integrated mirror group are made of UV transparent quartz glass, and then connected by optical glue technology to ensure the stability of long-term work under high temperature conditions. According to the design index, it is necessary to ensure that the uniform irradiation area is not less than Φ50 mm. After preliminary calculations, the overall dimension of the element lens should be designed as a regular hexagon less than 10 mm for splicing, but it is very difficult to process such a size element lens into hexagon, which not only greatly increases the cost, but also can’t guarantee the processing accuracy, which affects the realization of the overall index of the equipment. For this reason, the shape of the element mirror is changed to square, and the shape of the corresponding irradiation surface is also changed to square. It is finally determined that the field lens and projection lens of the integrating lens group are arranged closely with 9 square element mirrors with a side length of 10 mm and a center thickness of 2 mm. The size of the photoresist base is Φ 60 mm × 8 mm. The structure of the optical integrating mirror group is shown in (5) The design of collimating mirrors: the function of the collimator is to gather the light from the integrator into a parallel beam. As shown in In this design, the collimator lens is installed in the flange of the rubber ring, which not only plays the role of converging the beam, but also serves as the sealed quartz window of the vacuum chamber. This design can reduce the attenuation of UV light by a quartz window. The collimator is made of quartz optical glass. In order to minimize the loss of UV light energy, the ultraviolet antireflective film is deposited on the surface of collimator in vacuum.(6) Focusing mechanism: The focusing mechanism adopts a manual mechanical 3D combined displacement adjustment platform, which is used to adjust the arc position of the spherical high-pressure mercury lamp so that it is at the first focus of the ellipsoidal reflection condenser.The PTFE sample material used was cut from the PTFE die casting plate with a thickness of 6 mm. The raw material was prepared by Beijing Plastics Factory, and the purity of raw materials was about 99.99%. A group of PTFE samples were irradiated by the UV simulation device for 10 h in vacuum environment.The developed UV irradiation simulation device was installed on the self-developed MSTS-1 vacuum friction and wear tester, and the ball-on-disc friction and wear test of PTFE samples was carried out in vacuum environment. The other group of samples were directly subjected to vacuum friction and wear test without UV irradiation. When the load was 3 N, the speed was 100 RPM, the grinding material was GCr15, the ball diameter was 9.525 mm, and the test time was 1200 s. The wear scar morphology was characterized by scanning electron microscope (SEM). The equipment model was Navo NanoSEM 450 field emission scanning electron microscope. The optical design of near-UV irradiation device was verified by virtual operation test using LightTools optical modeling software. Then, The three-dimensional surface morphology of PTFE samples before and after UV irradiation was observed by Nanoscope V atomic force microscope (AFM). The scanning area was 40 × 40 μm. The phase composition and chemical composition changes of PTFE sample surface before and after UV irradiation were analyzed by X-ray photoelectron spectroscopy (XPS). The spectrometer was ESCALab220i XLX-ray photoelectron spectrometer produced by Semerfeld. It used Mg-Kα excitation source with power of about 300 W and spot diameter of about 500 μm.A self-developed indentation device was used to test the mechanical properties of PTFE samples such as fracture toughness and plastic deformation resistance before and after UV. The device was equipped with an acoustic emission detector ,26. WhenUnder the conditions of deuterium lamp working current of 300 mA and mercury xenon lamp current of 20 A, according to the method specified in GB/T12637-90 ‘General specification of solar simulator’, the key parameters of the whole set of UV irradiation device are tested according to the above technical indicators. 2 in the range of Φ 50 mm, which is about 6 solar constants.(1) Measurement of irradiance: the ultraviolet irradiance intensity was measured by the ultraviolet irradiance meter verified by the Chinese Academy of Metrology. The results show that the average irradiance is 590 W/mmax is the maximum irradiance on the irradiation surface (or within the volume); Emin is the minimum irradiance; E is the average irradiance. The irradiance intensity at the center and four vertices of the square spot was measured by UV irradiance meter. The maximum and minimum irradiance in the irradiation plane were 630 W/m2 and 565 W/m2 respectively. According to Formula (5), the irradiance nonuniformity was ±5.44%.(2) Measurement of irradiation non-uniformity: Irradiation non-uniformity refers to the difference of irradiance in different areas in the irradiation space. Generally, it can be divided into surface irradiation nonuniformity and volume irradiation nonuniformity, which can be calculated according to Equation (5):(3) Measurement of quasi-right angle: using the pinhole imaging method, the spot size at different irradiation distances of the near-UV irradiation device was measured, and the quasi right angle θ = 4 of the near-UV irradiation device was calculated by Equation (6):max, Emin is the maximum and minimum irradiance in the measurement time T; ∆E/E|T is the irradiation instability in time T. Using constant temperature silicon photocell as detection element, the irradiance of the sample center is measured every 1 h during the continuous operation of the UV irradiation device for 15 h. The calculation shows that the irradiation instability of the developed UV irradiation device is (1%)/h.(4) Measurement of irradiation instability: irradiation instability refers to the change in irradiance over time during long-term operation of the UV irradiation device. The irradiation instability can be obtained from Formula (7):To sum up, the comparison of design index and actual index of UV irradiation device is shown in The above optical design of the near UV irradiation device was tested by LightTools optical modeling software. The simulation light path is shown in The three-dimensional surface morphology of the samples before and after UV irradiation is shown in 3, C-F2, C-O and C-C bonds, respectively. However, the bond structure of the samples changed greatly after irradiation. For the samples after UV irradiation, it can be found that the peak intensities of C-F3 and C-F2 bonds are significantly reduced, while the peak intensities of C-O and C-C bonds are significantly increased. In addition, the fifth peak at 288.83 eV corresponds to the C=O bond, which is mainly caused by the oxidation of carbon on the surface of the sample. The XPS C1s spectra of PTFE samples before and after UV irradiation are shown in (a)2, and the uniform radiation area was 50 mm × 50 mm. Therefore, the device can not only emit high-intensity space ultraviolet rays, but also meet the requirements of in-situ friction performance test.In order to study the tribological properties of lubricating materials under space UV irradiation environment, an in-situ Tribological Testing Machine for simulating space UV radiation on ground conditions was developed. The relevant indexes of the device were as follows: the spectral range was 115~404 nm, average irradiation intensity is 590 W/m(b)Through the UV irradiation test of PTFE, which is commonly used as solid lubricating material, the test machine can induce the damage and failure of PTFE material similar to space flight test. After irradiation with high-energy UV photons, some molecular chains on the surface of the sample are broken, and some bonds are recombined. The surface of the sample is carbonized, the color is deepened, and the surface roughness of the sample is reduced.(c)After UV irradiation, the tribological and mechanical properties of PTFE materials will change. The brittleness of the surface layer of PTFE increases obviously, and the fluctuation range of friction coefficient becomes larger in the process of friction and wear test. However, the action depth of UV irradiation is limited to the surface layer of the sample. After removing the “brittle layer” on the surface of the sample for a period of time, the average value of the friction coefficient during the stable period is not significantly different from that of the unirradiated sample.


Von Willebrand Factor (vWf) is a giant multimeric extracellular blood plasma involved in hemostasis. In this work we present multi-scale simulations of its three-domains fragment A1A2A3. These three domains are essential for the functional regulation of vWf. Namely the A2 domain hosts the site where the protease ADAMTS13 cleavages the multimeric vWf allowing for its length control that prevents thrombotic conditions. The exposure of the cleavage site follows the elongation/unfolding of the domain that is caused by an increased shear stress in blood. By deploying Lattice Boltzmann molecular dynamics simulations based on the OPEP coarse-grained model for proteins, we investigated at molecular level the unfolding of the A2 domain under the action of a perturbing shear flow. We described the structural steps of this unfolding that mainly concerns the  Von Willebrand Factor (vWf) is a giant extracellular blood plasma protein that plays a key role in arterial hemostasis and thrombosis. Normally, in vivo vWf is a linear multimer consisting of 40–200 covalently linked monomers . With a The three neighbouring globular domains A1, A2 and A3 attract the most attention as they provide important properties related to platelet adhesion and aggregation. A3 domain is responsible for binding to collagen and thus initiation of thrombosis. A1 domain can establish adhesive bonds with GPIb platelet membrane receptors and is crucial for platelet plug formation under high shear stress ,17. MechDuring primary hemostasis in arteries and arterioles, platelet adhesion depends on the length distribution of the vWf multimers ,19,20. TMechanical stability of A2 domain is thus one of the major points of interest with respect to vWf thrombogenic activity and regulation. Characterization of the mechanical properties of vWf at the molecular scale is important for understanding its hemostatic functions. Prior studies underline the resistive role of the central e regime . Structue regime . Howevere regime . Severale regime ,32,33,34e regime ,35,36) ae regime ,38, Optie regime ,33) weree regime ,39,40, ae regime .Further insights emphasize the importance of the structure of globular domains and flexible linker segments for understanding biogenesis, shear-induced conformational changes, platelet recruitment abilities, and mechano-chemical regulation of von Willebrand factor ,41,42. TIn the present work we use computer simulations to study molecular details of the A2 unfolding and the exposure of the scissile bond Tyr1605-Met1606  collisional operator  with a lFor the dynamics of the A1A2A3 system we used a multiple time stepping to separate the integration of the bonded interactions involved in the flexible A2 domain, the A1/A3 elastic network domains and Lde MUPHY . Technicde MUPHY ,58,61. TAll-atom simulations of clamp-force unfolding of the A2 domain were carried out in Gromacs 2018.4 patched with PLUMED 2.5, using the Amber a99SB-disp force-field for disordered and ordered proteins together with its TIP4P-disp water model . The strk:The unfolding kinetics of a protein subjected to a pulling tensile force has been often described using a two-state irreversible Markovian model for the underlying evolution. In this model, the first passage time According to Bell’s model , when an systems . Moreoveordinate . In thatIn order to characterize the unfolding dynamics of the A2 domain under the action of an external pulling force, or fluid shear, we followed the time evolution of several independent runs and introduced a suitable order parameter to describe the time-dependent unfolding. At a given threshold of the order parameter, an unfolding event is recorded, yielding for that simulation a first unfolding time The best estimate n forces , t and To support that intuition we analyzed the number of native hydrogen bonds formed between each The number of contacts for the three pairs of This sequence of unfolding detected in our simulations is consistent with that described in previous work using SMD simulations ,36.It is worth noticing that the cleavage of vWf-A2 is a multistage process that obeys the known “key-lock” principle. The active domain of metalloproteinase ADAMTS13 has relatively low proteolytic activity against human von Willebrand factor, and they are sometimes considered as a non-optimal enzyme-substrate pair . Before recognition site. In case of force-pulling since the force is applied at the C-terminus the recognition site is exposed before the cleavage site, see In the disintegrin-like domain of ADAMTS13 a disordered region called V-loop is present. Although being variable in length and sequence, such region is also found in different ADAM-family proteins . In ADAM2 domain ,70,71. R2 domain . This hy2 domain . Given tIn the previous section we have shown that the OPEP model describes the force induced unfolding paths and kinetics of the isolated A2 domain very similarly to what obtained by an all-atom model in explicit solvent. Here, we investigate a more realistic system, with the A2 domain linked to the neighbouring domains, A1 and A3, as found in the vWf. The complete system is described in the Methods section. In order to study the effect of shear flow we first generated a set of independent initial states by equilibrating the system in the absence of shear perturbation and by extracting a configuration every 1 ns. In these initial configurations the A1 and A3 domains are not in contact with A2, but the linkers are not fully extended. Each configuration was used to start a simulation where the fluid shear flow was activated. First we considered the high shear regime that induces unfolding and exposure of the cleavage site on a timescale of tenths of nanoseconds.The exposure dynamics of The elongation dynamics in shear flow can also be followed by monitoring the chain extension of the A2 domain expressed by its end-to-end distance, see 9 s−1 and a directional mechanical force of 500–700 pN.By using the same strategy adopted for the force-induced unfolding, we quantified the unfolding kinetics by applying the diffusive model (the most adequate to fit the data), see We have then verified the simultaneous exposure of the cleavage and recognition sites, see In this section we relate more explicitly the fluid shear flow to the mechanical tensile force that triggers the unfolding of the A2 domain. We recall that, at longer length scales, and considering specifically the multimeric vWf, the analysis of the tension profile recorded along the vWf chain modelled as a polymer moving under the action of shear flow and hydrodynamics interactions, suggested a general mechanism  that leads to the transition from the collapsed to the elongated shape . By comb ∼109s−1 ,61. At timescale .We now quantify at the level of the A2 terminus, where the unfolding starts, how the action of the shear translates in a mechanical pulling force. In our model the terminal residues of the A2 domain are attached to the initial beads of the linkers LIn nal flow . The actIn 5–106 s−1).In order to better characterize the competitive effects on the three domains of the extensional and rotational components of the shear flow, we built a second model of the A1A2A3 system. In this model, all three domains are described by an elastic network so that also the A2 domain maintains its folded structure. The model allows us to span longer timescales in the simulation since we can increase the integration time-step and reduce the intramolecular degrees of freedom for A2. Therefore we can investigate the overall rotational dynamics of the molecular construct, and the inter-domains interactions, even at small shear rate values  First, we quantify the rotational dynamics of the two peripheral domains, A1 and A3, with respect to the central A2 domain. This is done by computing for each simulated system The obtained TCFs decay in time but their trend do not fit to standard decay models . Therefore, from each TCF, we have individuated the value when it reaches zero the first time. These characteristic times averaged over independent trajectories and as a function of the shear rates are plotted in panel A and B of The rotational dynamics implies that the molecular three-domain system is exposed cyclically, at least at the highest shear rates, to the tensile force and to angular acceleration. The angular velocity of the peripheral domains A1 and A3 with respect to the central A2 is computed by considering the variation of the vector connecting the centers of mass in the unit of time In the same spirit of previous work , but at  scaling ,73). How scaling , and theIn the present paper we used both full-atomistic and coarse-grained computer simulations to explore the unfolding of the A2 domain of vWf in two perturbative regimes typical of experimental setups: the AFM-like unidirectional pulling with a constant force, and the Couette flow typical for near-wall regimes of micro-fluidic flow chambers and rotational viscosimeters. We considered the isolated A2 domain and the A1A2A3 tri-domain construct of the vWf monomer. Our results show that the unfolding pathway of the A2 domain is controlled by the sequential disruption of the The unfolding kinetics under extremely large forces, according to the presented analysis, deviate from Bell’s law and are better approximated by the inverse Gaussian model. The exposure of the Tyr1605-Met1606 cleavage site may correspond to partial unfolding of the A2 domain. However, under stronger forcing, complete unfolding events leading to a fully linear unfolded protein structure have been observed in simulations over tens of nanoseconds timescale.The unfolding pathway of the A2 domain depends on the deformation mode, applied forcing, and, importantly, on whether the individual A2 domain or the tri-domain A1A2A3 structure is loaded. For the A1A2A3 assembly in Couette flow the deformation pathway consists of the stretching of the A2 domain punctuated by relatively long periods of rotation-induced refolding, at least under high shear stress. Due to the tumbling motion, A2 can not only adopt a linear, extended conformation, but also a melted globule one that hinders ADAMTS13 binding and subsequent proteolysis. This contrasts with the behaviour of the individual A2 domain under hydrodynamic shear, in which we mostly detected transient periods of partial unfolding. Moreover, the results of CG simulations suggest that, if the shear stress is strong enough, the rotational component of the flow dominates over the protein’s Brownian motion above a critical threshold. In the shear flow we observed two different scenarios of A2 extension, revealing a complex interplay between fluid dynamics and molecular structure.Several intriguing questions emerge, including the refolding pathway of the A2 domain after deformation, the reversibility of the unfolding, the structure of the compacted globule and influence of the protein’s molecular surroundings on this process. According to , refoldiFinally, by focusing on the relative inter-domain dynamics, we have individuated a shear-rate controlled dynamical configurational transition among a stable collapsed structure of the three domains (low shear) and a cyclically alternated collapsed/elongated structure (high shear). The preferential inter-domain interactions visible in the collapsed structures highlight the key role of these interactions in self-inhibition to cleavage.The present study is a step toward a better understanding of the biophysical mechanisms that govern mechanoreception and mechanotransduction in proteins at the molecular level.


Hallux valgus (angle > 20°) of the big toe at the latest follow-up recurred in 10 (32%), 9 (60%), and 16 (100%) patients in the PP, PR, and RR groups, respectively. A revision surgery was performed in one patient each in the PP and PR groups. Conclusions: Joint-preserving surgery is superior to resection arthroplasty in preventing function loss and the recurrence of hallux valgus.Background: Joint-preserving surgery for the forefoot has been increasingly performed for rheumatoid arthritis (RA). We compared joint-preserving surgeries with resection arthroplasty for RA in the forefoot. Methods: Forefoot surgeries were performed on 62 toes in 42 patients with RA  between 2002 and 2018. Three groups were compared: PP—31 toes treated with joint-preserving surgery involving the modified Mann method for the big toe and offset osteotomy for lesser toes, PR—15 toes treated with joint-preserving surgery for the big toe and resection arthroplasty for lesser toes, and RR—16 toes treated with resection arthroplasty for all the toes. Results: The PP group had significantly higher mean scores on a scale for RA in the foot and ankle at the latest follow-up than the RR group (86 vs. 75 points;  Forefoot deformities have been reported to occur in approximately 90% of the patients with rheumatoid arthritis (RA) ,2. ForefVarious surgical procedures have been reported for forefoot deformity ,5,6,7. RResection arthroplasty and arthrodesis of the MTP joint have been the standard interventions for foot deformity due to RA ,4,5. BioThus, in this study, we aimed to compare the mid- to long-term results of MTP joint-preserving surgeries involving the modified Mann method for the big toe and offset osteotomy for lesser toes with those of resection arthroplasty.All the patients with RA included in this study satisfied the criteria for RA established in 1987 by the American College of Rheumatology  or in 20A total of 42 patients (40 women and 2 men) were treated by five surgeons . The surgeons performed resection arthroplasty if severe subluxation and dislocation of the MTP joint with contractures and stiffness were observed upon manipulation or stress radiographs.The mean age of the patients at the time of surgery was 61 years . The mean duration of RA was 13.3 years . According to the Steinbrocker functional classification, RA was stage III in 24 patients, stage IV in 18, class 2 in 27, and class 3 in 15. The mean level of C-reactive protein (CRP) at the time of surgery was 1.6 mg/dL , and the mean Disease Activity Score in 28 Joints (DAS28) calculated with CRP (DAS28-CRP) was 3.7 . Of the 42 patients, 10 (24%) received biologics , 23 (55%) received methotrexate (mean dosage: 6.2 mg/week), and 12 (29%) received prednisolone . All the procedures were performed in accordance with the relevant guidelines and regulations. This study was conducted in accordance with the Declaration of Helsinki.We rated the clinical outcomes according to the Japanese Society for Surgery of the Foot (JSSF) RA foot and ankle scale . Radiogrp-values < 0.05 as significant.To perform one-factor analysis of variance, the Mann–Whitney U test of the null hypothesis, and the Tukey–Kramer tests, we used the PASW 25 software . We considered For the PP group, the modified Mann method was used in combination with (a) elevation of the abductor hallucis tendon, which was dislocated to the plantar side of the big toe toward the tibial side of the metatarsal bone; (b) cutting of the MTP joint capsule of the big toe on the tibial side in a Y-shape, which was plicated and shortened for the closing of the joint capsule after the modified Mann osteotomy; (c) partial resection of the distal end of the adductor hallucis tendon and transverse metatarsal ligament from the lateral aspect of the fibular sesamoid and base of the proximal phalanx; (d) removal of the connective tissue that was inflamed as a result of bunions; (e) proximal osteotomy of the metatarsal bone for the shortening and correction of the varus deformity and its internal rotational deformity with the use of a fixed 1.6-mm Kirschner wire; and (f) offset osteotomy of the metatarsal bone with the MTP joints of the lesser toes [For the PR group, the modified Mann method was used for the big toe following the same procedure as that used for the PP group. Resection arthroplasty of the MTP joint was performed for the lesser toes affected by severe subluxation, dislocation of these joints, contracture, and stiffness. The resection included 10–15 mm of the end of the metatarsal head, followed by fixation using a Kirschner wire from the tip of the toe to the tarsometatarsal joint through the MTP joint for 3 weeks. An example is shown in Resection arthroplasty for the big and lesser toes was performed in the same way as that described for the PR group, and soft tissue repair was performed as that described for the PP group. An example is shown in The patients were able to walk 1 or 2 days after surgery with a non-weight-bearing orthosis of the forefoot . After 3p < 0.05; The mean JSSF scores were 38.7  before surgery and 78.6  at the latest follow-up. The mean JSSF score at the latest follow-up was significantly higher in the PP group than in the RR group  before surgery and 23.8°  at the latest follow-up. The mean HVAs at the latest follow-up did not differ significantly between the three groups . Hallux Two revision surgeries were performed—one in the PP group 3 years after the first surgery and the other in the PR group 8 years in the PR group after the first surgery—because of the recurrence of painful plantar callosities in lesser toes. Delayed healing of the surgical wound was observed in one, one, and three patients in the PP, PR, and RR groups, respectively. Nonunion was not observed in this study.Joint-preserving surgery has been increasingly performed for forefoot deformities in patients with RA . RecentlIn this study, joint-preserving forefoot surgery involving the modified Mann method for the big toe and offset osteotomy for the lesser toes (PP group) produced results superior, according to the JSSF scale scores and radiographic measurements, to those observed in the PR and RR groups. However, the recurrence rate of the hallux valgus deformity of the big toe in this study was higher (26%) than that reported in other studies regarding MTP joint-preserving surgery ,14,24. OFukushi et al.  also repIn our study, the mean DAS28-CRP for the PP group was 3.8 , and the indication for joint-preserving surgery was Larsen’s grade 4 severity. Our cohort included patients with challenging cases involving high disease activity and severe joint destruction, particularly those who underwent joint-preserving surgery in or before 2003. In Japan, biologics have been approved for the treatment of RA since 2003 and the methotrexate dosage had been restricted to < 8 mg/week until 2011 ,15, or aIn our study, the outcomes in the PR group were superior to those in the RR group but inferior to those in the PP group. Hulse et al. reported that a subsequent resection of the first metatarsal head was necessary at the second surgery because of a high rate of pain recurrence in the patients receiving MTP joint arthroplasty with metatarsal head resections of lesser toes and without that of the big toe at the initial surgery . In thisTwo patients in this study underwent revision surgery for the recurrence of painful plantar callosities of lesser toes. The recurrences resulted from the undercorrection of the deformity and insufficient dissection of adhesions around the metatarsal head of lesser toes ,26.Yano et al.  reportedPerioperative rehabilitation is important for achieving better outcomes after surgery. Early partial weight bearing prevents the disuse-related atrophy of muscles and bones . Hirao eThis study has several limitations. Firstly, the patient-reported outcome measure was not evaluated. A self-administered foot evaluation questionnaire (SAFE-Q) was developed in 2013 for Japanese patients for foot evaluation . Ebina eJoint-preserving forefoot surgery involving the modified Mann method for the big toe and offset osteotomy for lesser toes may prevent function loss after the restoration of forefoot deformities compared with resection arthroplasty for the big and lesser toes in combination with biologic therapy for RA.


The degradation effects of ordinary TiO2 and modified TiO2 on automobile exhaust were compared by test system in the laboratory. The results show that the modified TiO2 can effectively improve the performance of vehicle exhaust degradation. Moreover, the molecular dynamics method was used to establish the channel model of TiO2, and the dynamic process of automobile exhaust diffusion and absorption was simulated. The diffusion law and adsorption process of different types of automobile exhaust gas such as NO, CO, and CO2 in the TiO2 channel were analyzed from the molecular scale through the radial concentration distribution and adsorption energy.With the growth of the economy, the number of automobiles on the road is fast growing, resulting in substantial environmental pollution from exhaust gas emissions. In the automobile factory, some improvements have been achieved by constructing devices to degrade automobile exhaust. However, although most of the vehicle exhaust emissions have met the national standards, the exhaust gas is superimposed at the same time period due to the increasing traffic volume, making the exhaust emissions seriously reduce the air quality. Therefore, the scholars in the road field began to study new road materials to degrade vehicle exhaust, which has gradually become one of the effective ways to reduce automobile exhaust. Photocatalyst materials have been widely concerned because of their ability to oxidize harmful gases by solar photocatalysis. Yet, the effect has been not satisfactory because of the small light response range of photocatalyst material, which restricts the catalytic effect. In this study, this paper attempts to use Fe In many air quality monitoring centers in big cities, automobile exhaust has become the primary air pollutant.With the improvement of the economic level and the rapid development of automobile manufacturing industry, the number of automobiles has increased rapidly, resulting in substantial environmental pollution from automobile emissions . Also, t2, SnO2, ZrO2) and semiconductor sulfides . Among them, TiO2 is widely used because it has many advantages, such as fast degradation rate, mild reaction conditions, low price, non-toxic , an, an27], 2 powder has some degradation effect on CO, NO, NO2 and CxHy in automobile exhaust. After 60 min, the degradation efficiency of these gas reached 7.89%, 40.74%, 10.87% and 9.93%, respectively. It can be seen that TiO2 powder had good degradation effect on NO. At the same time, a part of NO2, CxHy and CO was also degraded. After TiO2 modified by Fe3+ions, the degradation effect of NO was significantly improved (increase by 51.57%). Due to its extrinsic bandgap with low energy, Fe3+ incorporated into the crystal structure of TiO2 promotes electron-hole separation, and deposits active sites on the surface of TiO2, thus improving the adsorption of small molecular weight of NO with fast diffusion velocity .–35.32–352 channels are shown in Figs 2, and the diffusion rates of these two gases were very close. The third was C12H12, which had the largest molecular weight because the heavy molecule slowed down the diffusion velocity due to its large volume and weight. The molecule of the gas with the slowest diffusion speed was SO2, and this law was consistent in the modified and unmodified TiO2 channels. It shows that the adsorption powder of TiO2 for SO2 molecules was weaker than other exhaust molecules. From the energy point of view, the diffusion process is caused by energy gradient, and it is also the process of system transition from the unsteady state (high energy) to steady-state (low energy). It also reflects the change of various forces when the system tends to be stable.The diffusion velocity of different types of automobile exhaust molecules in the modified and unmodified TiO2 and C12H12 molecules in the modified TiO2 channel was faster than that in the unmodified TiO2 channel, while the adsorption of SO2 molecules had almost no change. The results show that the modification of TiO2 improved its attraction to most automobile exhaust molecules and promoted the directional diffusion of these molecules to the surface of TiO2. This is due to the incorporation with Fe3+, there are more active sites on the surface of titanium dioxide, which accelerates the adsorption of exhaust gas molecules, thus promoting the diffusion of exhaust gas molecules on the crystal surface .g.g2 lay2 powder under three conditions . It can be seen that after modification, the radial concentration of automobile exhaust absorption at the same position in the TiO2 channel has been significantly increased, and the order of concentration is 100% Fe3 + modified TiO2 > 50% Fe3 + modified TiO2 > unmodified TiO2. Especially, the difference was more obvious in the near end of TiO2. This may be attributed to the fact that the titanium dioxide fully modified by iron ions with low bandgap promotes the separation of electron/hole and further improves the catalytic efficiency [3 + can effectively improve the adsorption of TiO2 powder to automobile exhaust, and the more complete the modification, the better the effect.ficiency . This ph2 on automobile exhaust gas adsorption was analyzed from the perspective of radial relative concentration, and the adsorption strength was determined from the perspective of distance and concentration. This section will quantitatively analyze the absorption effect of modified TiO2 on automobile exhaust from the perspective of energy.In the previous section, the improvement effect of modified TiO2 channel, the two independent systems of vehicle exhaust and TiO2 gradually become a whole system, and refer to other systems, the reduction of system energy is considered as the adhesion work [2) and the sum of the surface energy of vehicle exhaust and TiO2 respectively before adsorption. The larger the adhesion work value between automobile exhaust and TiO2, the more difficult the automobile exhaust to separate from the surface of TiO2, which means that the adsorption is more difficult to be destroyed [Wadhension represents the work of adhesion at the interface (mJ m-2). Etotal represents the interfacial potential energy of TiO2 and automobile exhaust after molecular dynamic adsorption equilibrium . Egas is the potential values of the automobile exhaust after MD simulation . ETiO2 are the potential values of the TiO2 after MD simulation . A represents the Connolly area of the interface (Å2). △E represents the Variation value of automobile exhaust gas during the adsorption process .K = 695 [When the automobile exhaust gas is adsorbed in the TiOion work . In otheestroyed ,42. The .K = 695  is the c2 (solid), the model of TiO2 adsorption on automobile exhaust was built. And it is shown in 2 model and automobile exhaust model. The energy function of force module in Materials Studio software was used to calculate the energy of interface model (a), the disassembled TiO2 model (b) and automobile exhaust model (c) respectively, so as to calculate the adhesion work between TiO2 and automobile exhaust gas using the above formula. The calculation results are shown in 2 was obviously improved. The 50% Fe3+ and 100% Fe3+modified TiO2 increased about 40% and 73%, respectively. The incorporation of Fe3+ into the structure of TiO2, causing the reduction of the bandgap, the prevention of recombination of electron/hole and extension of the life of charge separation, increases the number of active points and absorbs more exhaust molecules, which results in the increase of adhesion work [3+ modification is beneficial to enhance the adsorption capacity of TiO2 on automobile exhaust, thus improving the degradation effect.After the MD equilibrium calculation of the two-phase interface model of automobile exhaust (gas) and TiOion work . Therefo3+ was used to modify the photocatalyst material TiO2. Through the absorption test of automobile exhaust and the diffusion and absorption of automobile exhaust gas in the TiO2 channel simulated by molecular dynamics method, it is proved that the modification can effectively improve the degradation effect of TiO2 on automobile exhaust. The conclusions are as follows:In this study, Fe2 can obviously improve the degradation effect of NO in automobile exhaust, but it is not obvious to improve the degradation effect of other exhaust gases such as CO and NO2.Test results show that the modification of TiO2 channels is faster than that in the unmodified TiO2 channels, which indicates that the modification of TiO2 improves the attraction of most automobile exhaust molecules and promotes the directional diffusion of automobile exhaust molecules to the surface of TiO2.MD simulation shows that the diffusion velocity of most automobile exhaust molecules in the modified TiO2 channel, it is concluded that Fe3 + modification of TiO2 powder is beneficial to improve the adsorption of automobile exhaust molecules, and the more the modification, the better the effect.Through MD simulation and analysis of the radial concentration and the adsorption energy of exhaust molecules in the TiOS1 File(XLSX)Click here for additional data file.


The number of intratympanic gentamicin (ITG) injections needed to achieve vertigo control in patients with intractable Ménière's disease (MD) may vary from a single dose to several instillations. Changes in different vestibular test results have been used to define an endpoint of treatment, including the decrease of the vestibulo-ocular reflex (VOR) gain elicited by the head-impulse test.To assess the accuracy of the VOR gain reduction after horizontal canal stimulation, as measured with the video head-impulse test (vHIT) 1 month after the first intratympanic injection, in predicting the need for one or more instillations to control vertigo spells in the long term.The VOR gain reduction was calculated in 47 patients submitted to (ITG) therapy 1 month after the first instillation.Single intratympanic treatment with gentamicin has a 59.6% efficacy in vertigo control in the long term. Hearing change in the immediate period after treatment (1 month) is not significant to pre-treatment result and is similar for patients who needed multiple doses due to recurrence. Chronic disequilibrium and the need for vestibular rehabilitation were less frequent in patients with a good control of vertigo with just one single injection of gentamicin. A fair accuracy was obtained for the VOR gain reduction of the horizontal canal  in predicting the need for one or more ITG.Single intratympanic treatment with gentamicin is an effective treatment for patients with MD. That modality of treatment has very limited damaging effect in hearing. The degree of vestibular deficit induced by the treatment is significant as measured by the reduction in the gain of the VOR but not useful for prognostic purposes. Ménière's disease (MD) is an idiopathic inner ear disorder characterized by episodic vertigo spells lasting from 20 min to 12 h, fluctuating low-frequency hearing loss during the initial spells with associated aural fullness, and tinnitus  is an effective treatment  because patients –8. It isIn this modality of treatment, gentamicin gets into the inner ear mainly through the round window membrane and the oval window. It has been shown in the experimental situation that the distribution of gentamicin either in the scala tympani or in the scala vestibuli will be the result of different interactions . In expeSeveral methods have been used to define a safety endpoint in this modality of treatment, including modification of bedside testing  or vestibular laboratory test results . However, there is yet no consensus on the optimal dose and concentration of gentamicin to be delivered to obtain a significant clinical result. In a previous report, Marques et al. proposed an endpoint of treatment, such that a horizontal canal VOR reduction of at least 17.8% [area under the curve (AUC) of Receiver Operating Characteristic (ROC) curve = 0.843] and a posttreatment asymmetry of at least 7% in the horizontal semicircular canal (AUC = 0.861) was associated with a good vertigo control, which meant that there was no need of further injections during a mean period of 21 months of follow-up . HoweverThe first follow-up after ITG is 1 month in different studies based on the short-term dynamics of the vestibulo-toxic effect of ITG. Previous researchers have shown that throughout the first month, there is a significant reduction in the gain of the VOR which stabilizes 1 month after treatment .Our study aimed to assess the following aspects pertinent to the result of the treatment: (1) The effectiveness of one-single dose of gentamicin for long-term vertigo control, (2) How accurately immediate VOR gain reduction (as measured 1 month after the first injection) differentiates patients that need a further injection to achieve long-term vertigo control, i.e., does that change in VOR predict clinical course during the follow-up?, (3) Are there significant short-term changes in hearing after the first ITG treatment?, and (4) Is vestibular rehabilitation more frequently indicated after one or multiple doses of ITG?.We retrospectively analyzed 47 patients admitted to our clinic who were diagnosed with unilateral definite MD according to diagnostic criteria  from AugAll patients underwent a complete clinical assessment and bedside testing which consisted of microscopic examination of the eardrum, routine otolaryngological examination, search for spontaneous nystagmus and head-shaking nystagmus under Frenzel's glasses, clinical head impulse test, and positional nystagmus. The Dizziness Handicap Inventory (DHI) was used to evaluate the self-perceived handicapping effects of dizziness; the version used was taken from the original  and valiAudiometric findings were reported in terms of the mean pure-tone average (PTA), calculated on air conduction thresholds at 0.5, 1, 2, and 3 kHz of the symptomatic or affected ear and the asymptomatic ear or non-affected ear. Patients were classified into four stages according to the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS)  for the six semicircular canals, with 20 impulses in each direction according to the canal plane. The parameter evaluated was the VOR mean gain and the presence of refixation saccades, namely, overt and covert saccades. Gain is obtained from the gain value after each of the impulses is performed and is automatically provided for all paired semicircular canals assessed. Data were evaluated from the symptomatic (Gs) and asymptomatic (Gas) ears. Due to modifications in the hardware, horizontal canals were examined in 53 patients, and data from the vertical canals were obtained from 43 patients (38 in the treatment group and 5 in the untreated group).The medication used was gentamicin sulfate (40 mg/ml) buffered with sodium bicarbonate to pH 6.4 and a final concentration of 26.7 mg/ml, and 0.5–1.5 mL (1.06 ± 0.31) of the gentamicin solution was injected slowly in the affected ear through the posterior-inferior quadrant of the tympanic membrane. Care was taken to observe the progressive filling of the middle ear and of the round window niche when possible. The patients were asked to lie in a supine position with the affected ear for up to 30 min and were encouraged not to swallow.The study was performed according to the following protocol, as previously approved by the Ethics and Medical Deontology Commission at our hospital. All patients that fulfilled the inclusion criteria and signed the corresponding informed consent received the first injection of gentamicin. Patients were then instructed to inform us of any symptoms that developed during the first month after the ITG injection. When necessary, vestibular suppressants were prescribed to treat vestibular symptoms. At the time of the first follow-up visit 1 month after the ITG injection, the clinical status of the patient was reviewed, and bedside vestibular examination, vHIT, and audiometric assessment were performed. After the first follow-up visit, all the patients were instructed to record any vertigo spell resembling those experienced before the treatment in case of chronic disequilibrium impacting daily activities. When new attacks developed, a decision was then made to treat the patient with another injection of gentamicin or with vestibular suppressants. In case of no more vertigo crises but chronic disequilibrium with a high-level handicap as defined by a DHI score >54, then the patient was treated with vestibular rehabilitation. Telephonic contact was maintained with every patient  to assess any vertigo recurrence. For patients without vertigo recurrences, follow up at the end of the study (2 years) was made mostly by telephonic and/or e-mail contact.t-test or the one-way ANOVA test. For non-normally distributed data, the Wilcoxon test or the Kruskal-Wallis test was performed. Median and interquartile range (25th and 75th percentiles) are shown for not normally distributed data. Otherwise, mean and standard deviation are shown. Differences between percentages were determined by using Fisher's exact test.For demographic analysis, differences between normally distributed data were assessed with Student's According to the number of injections needed to achieve vertigo control, patients were classified into two treatment groups: one group treated with one single dose of ITG (group 1) and another group who needed during follow-up a subsequent or more ITG injections (group 2). The untreated group was designated as group 0.*100.The results of the vestibular evaluation were analyzed in terms of VOR gain reduction according to the formula: [(pre-treatment gain – post-treatment gain)/(pre-treatment gain)]Both data were combined such that patients were classified as “unexpected” when, in group 1, gain reduction was lower than 17.8% or, in group 2, >17.8%, Data were classified as “expected” when, in group 1, gain reduction was >17.8% or, in group 2, lower than 17.8%. A chi-square test was performed to compare the number of expected and unexpected results between treatment groups.D was calculated for assessing the size effect if considered clinically relevant.A description of the time course of recurrent vertigo was performed with the Kaplan-Meier survival analysis which allows quantification of the percentage of patients who had adequate control of their vertigo using the need for a second injection as a definition of “failure.” ROC curve analysis was performed for vestibular function (VOR gain) reduction regarding treatment outcome. A two-way factorial mixed ANOVA design was performed for VOR gain reduction as dependent variable, treatment groups as between-subjects factors, and ear and time as within-subjects factors. Differences between factors have been tested using contrasts. Cohen's p < 0.05 was considered statistically significant. For interactions terms, a value of p < 0.1 has been considered statistically significant.All analyses were performed using the STATA 15.0 statistical software . A value of The study included 47 subjects (28 women and 19 men) with definite MD that belong to the group of patients treated with ITG and 6 patients in the untreated group. There were 11 additional patients (4 in group 1 and 7 in group 2) not included because the first follow-up was not in the expected period of time (1 month) after treatment. There were 6 patients (2 in group 1 and 4 in group 2) who attended the post-treatment visit at the expected time but then lost to follow-up.Of all those included, 11 were lost to follow-up (4 in group 1 and 7 in group 2) Demographic characteristics by groups are outlined in p = 0.015). The mean VOR gain after head impulses in the plane of each of the six semicircular canals showed no differences between the three groups of patients when analyzed at baseline in group 0 and before treatment in groups 1 and 2 , 5 months  between the second and the third injection, 10 months  between the third and the fourth injection, and 1 month between the fourth and the fifth ITG injection (1 subject). Among the patients receiving 4 injections, in 2 of them, an exploratory tympanotomy was further performed for direct application of gentamicin to the round window. In both patients, no fibrosis was found in the round window niche which was otherwise normal and access to the membrane was uneventful, and, in both patients, vertigo symptoms resolved after the procedure.A survival curve represents a follow-up of treated (groups 1 and 2) patients . Twenty-After ITG, 5 patients had to follow a vestibular rehabilitation treatment: 2 (7.1%) in group 1 and 3 (15.7%) in group 2. They mentioned chronic disequilibrium severe enough to limit their activities although there were no more vertigo crises. Those in group 1 had a very intense reduction in the gain of the VOR that affected the three semicircular canals: superior semicircular canal by 44 and 40%, horizontal canal by 82 and 78%, and posterior canal by 50 and 54%, respectively, for each patient. They were each treated 2 and 3 months, respectively, after the first follow-up visit. Those in group 2 were patients that each needed 2 injections (for 2 patients) and 3 injections (for 1 patient). The treatment took place 4 months after the last injection in all three cases.We found that after 1 month and in a stable clinical status (no new vertigo spell), the gain of the VOR showed very small modification as what occurred in the non-affected ear. It is, however, of interest to note an increase of the mean gain of the VOR close to 20% in the case of the anterior canal in the affected ear. The change in mean PTA both in the affected and unaffected ear was not significant and, in all of them, the difference from baseline to 1 month after the initial visit was <10dB. Particularly, it was worse in group 2 and better in group 4.p = 0.133; Cohen's D = 0,41).The change in the gain of the VOR in the first follow-up visit (1 month after ITG treatment), with respect to the pre-treatment value, is shown in D = 1,64) (In the asymptomatic (non-treated) ear, we found a small fluctuation in the value of the VOR gain in the case of head-impulses in the plane of the posterior semicircular canal such that the difference to pre-treatment values was significantly higher in patients in group 1 with respect to patients in the group 2. In addition, there was a trend toward significance with respect to group 0 but with a great size effect  .The ROC analysis for the reduction of the gain of the VOR of the horizontal semicircular canal of both treatment groups showed an AUC of.729 with a VOR reduction cutpoint of 11.6% .p = 0.582), not even with group 0 (p = 0.347). Also, no differences were found regarding the number of expected and unexpected results in each treatment group .A more detailed analysis of the VOR gain reduction of the horizontal canal in each treatment group and follow-up is shown in No differences were found between the subgroups of subjects with expected and unexpected results in both treatment groups or with the control group regarding age, sex, affected ear, number of crises before treatment, time since the last vertigo spell, duration of the disease, Tumarkin crises, migraine, or time of follow-up.Further analysis showed that 2 subjects in group 2 showed no changes in the VOR gain, and 6 subjects (1 subject in group 1 and 5 subjects in group 2) showed an increase in the VOR gain in the horizontal canal of the symptomatic ear after the first ITG injection.p = 0.075; Cohen's D = 0,33). Interestingly, there were no significant differences between those in groups 1 and 2.Regarding hearing as shown in After the first ITG injection, the PTA of groups 1 and 2 was significantly higher than that of group 0 or not treated . HoweverThe questions addressed here are all of interest when counseling patients with unilateral MD to whom we plan a treatment with gentamicin given intratympanically. A low-dose protocol has proved to be an effective method for controlling vertigo attacks with a low rate of hearing loss or persistent imbalance , 16–18.Our study first shows that 59.6% of the patients achieved complete vertigo control after one single dose of ITG after a prolonged follow-up period of up to 6 years, which is an important contribution of this report. This finding is in accordance with previously observed results .The main problems when trying to predict an individual outcome in terms of the need for one or several injections in ITG treatments are the unpredictable effect of the drug and the unpredictable recurrence of vertigo after any nonsurgical and sub-ablative treatment. The rationale of this approach is to avoid side effects of unneeded treatments and maximize class A results  but also to provide sufficient information to clinicians and patients about the possible clinical course after a given number of injections. In this way, patients could better understand their own disease and expected prognosis after the treatment. All of which contributes to better functioning and well-being during follow-up .There are a limited number of studies assessing the changes of the VOR measured by the quantitative head-impulse test in patients with MD after ITG treatment. Carey et al. observed a correlation between the reduction of the VOR gain as measured with the scleral search coil after fast head impulses and the reduction in the number of vertigo spells . Later, Given the previously mentioned evidence, the corollary question is whether the amount of change in the gain of the VOR has any significance in clinical follow-up. Despite this, our results do not fully support that purpose, and we shall cover this topic in the next paragraphs.According to our previous work, we can take into account as the endpoint of treatment at least a 17.8% of VOR gain reduction in the horizontal semicircular canal. In doing that, we found that 75% of patients in group 1 showed a gain reduction above this cut point. On the contrary, group 2 results are more heterogeneous with only 53% of subjects showing a reduction under this value. These discrepancies between the results and the observed clinical course in the present study explain the fair accuracy of the VOR gain reduction (AUC = 0.729) to correctly identify subjects who will have vertigo control with one-single dose of gentamicin and to predict the need for more treatment. Nguyen et al. observed an association between a horizontal canal VOR reduction >60% (clearly higher than our data) and a lower vertigo rate after the first round of treatment with ITG injections. However, they did not find any association between vertigo rate and VOR gain when those values were treated as continuous variables . Lin et non-responder subjects showed vertigo recurrence in the early stages of the treatment, and this can also be observed in our study according to the steepness of the survival curve to the left. The prolonged period of follow-up tries to overcome one of the main drawbacks of studies as it has been shown that vertigo recurrence rates may vary according to the duration of follow-up and that it can recur even after a symptom-free period lasting more than 2 years as said before  were performed . InteresD = 1,64). For this reason, these results should be considered with caution.This study has some limitations. First, as a retrospective study, there is a risk of selection bias. The prolonged follow-up period in many patients increases the risk of recall bias for the outcome of vertigo recurrence as it is sometimes difficult to remember whether there was a true vertigo episode. Thus, a misclassification of subjects into the wrong group could occur. Nevertheless, if this situation was true, more patients in the subgroup of expected results in group 1 would belong to a subgroup of unexpected results of group 2, supporting the fact that the VOR gain reduction cannot predict the clinical outcome. Second, we have used a measure for cutoff analysis obtained in a previous study. In the actual one, some of those patients are included, and this represents a bias in the analysis that should be taken into account. Third, the lack of information on the vertical canals in 10 subjects has precluded a detailed analysis of the horizontal canal. Very recently, it has been shown that there is a differential effect according to the semicircular canal evaluated such that the reduction in the gain of the VOR was more intense for the posterior and horizontal canal than for the superior semicircular canal . Fourth,Our results show that one single dose of intratympanic gentamicin allows for a good vertigo control in the long term with similar effectiveness to that reported by others. Compared to the untreated group, the mean VOR gain reduction of the horizontal and superior canals, as measured with the vHIT 1 month after the first injection, was significantly higher in the treatment groups. A similar finding was obtained when comparing the single-treatment group and the multiple-treatment group, where the reduction in the former was significantly higher. However, the detailed analysis of the horizontal canal VOR reduction shows that, during the follow-up, many patients do not display the expected clinical course according to our previous endpoint of treatment. This explains the only fair accuracy obtained for the horizontal canal VOR reduction, as measured 1 month after the first injection, in predicting the need for no further instillations in the long term. In other words, a significant reduction of the VOR gain after the first ITG injection is less accurate in predicting the need for only one single dose for complete vertigo control than previously reported. A prospective study with a larger number of subjects and serial VOR assessment following ITG therapy might contribute to better characterizing the effect of gentamicin on canal function in time and help understanding the discrepancy between VOR reduction and vertigo control in the long term.According to our observations, the protocol of low dosage intratympanic gentamicin as needed has proved to be a safe way to control vertigo attacks with a low risk of hearing loss.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Comite de Etica de la Investigación (CEI). The patients/participants provided their written informed consent to participate in this study.NP-F, RW-V, and EM-S contributed to conception and design of the study. RW-V and DC-G organized the database. DC-G performed the statistical analysis. RW-V wrote the first draft of the manuscript. RW-V, NP-F, RM-H, EM-S, and PM wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The duration of the TpTe (p < 0.001), QTcB (p < 0.001) and QTcF (p < 0.001) intervals were significantly longer in the group of children with ventricular arrhythmias and with abnormal T-wave compared to the values of the TpTe, QTcB, and QTcF intervals of the control group with normal morphology of the repolarization period. Only the duration of the TpTe interval was significantly (p = 0.020) longer in the group of children with ventricular arrhythmia without clinical symptoms. Conclusions: Children with benign ventricular arrhythmias recorded on a standard ECG with prolonged TpTe and QT intervals and abnormal T-wave morphology require systematic and frequent cardiac check up with long term ECG recordings due to the possibility of future more severe ventricular arrhythmias. Further follow-up studies in even larger groups of patients are necessary to confirm the values of these repolarization parameters in clinical practice.Background: The changes in the period of ventricular repolarization, i.e., QT interval, QTp (Q-Tpeak) and TpTe interval (Tpeak–Tend), make it possible to assess the electrical instability of the heart muscle, which may lead to the development of life-threatening ventricular arrhythmia. The aim of the study was to determine and evaluate the use of differences in T-wave morphology and durations of repolarization period parameters  in resting ECGs for children with ventricular arrhythmias. Methods: The retrospective analysis was made of the disease histories of 80 examined children with resting ECGs, which were admitted to the Children’s Cardiology Department. The study group consisted of 46 children aged 4 to 18 with ventricular arrhythmias and the control group consisted of 34 healthy children between 4 and 18 years of age, with no arrhythmias. Results: The duration of the TpTe interval was significantly ( Arrhythmias are an important clinical problem in the developmental population and a common cause of hospitalization. Their clinical course is most often asymptomatic, with no tangible cardiovascular abnormalities. Among the healthy population, premature ventricular beats in the standard ECG may be recorded in 0.3–2.2% of newborns, infants, and children with normal circulatory system . About 5The retrospective analysis was carried out on the histories of examined children with electrocardiographic records (12-lead ECG), which were performed after each of the children was admitted to the Children’s Cardiology Department. The information included in the medical records of younger children  was obtained from their parents or legal guardians.A group of 80 children were included in the study. The study group consisted of 46 children (21 girls and 25 boys) aged 4 to 18 years (average age 13 ± 6 years) with ventricular arrhythmias of unknown etiology which were recorded in standard ECG in 12 children (26%) or in 24 h Holter ECG monitoring in 34 children (74%).The control group consisted of 34 healthy children (volunteers) (22 girls and 12 boys) aged 4 to 18 years (average age 13 ± 3 years) without confirmed arrhythmias. All the children from the study group and the control group were hospitalized in the Children’s Cardiology Department of the Independent Public Clinical Hospital No. 6 of the Silesian Medical University in Katowice—Ligota . None of the 80 children had a positive sudden cardiac death or structural heart disease in physical examination and in echocardiography using the Doppler method as well as no arrhythmias during exercise stress (Bruce protocol). Inclusion criteria in the group of examined children: ventricular arrhythmias in standard ECG and in the 24 h ECG Holter method, the history of arrhythmia diagnosed, normal physical examination result apart from periodically irregular heart rhythm, without signs of infection or structural features of the heart defect, negative family history regarding structural and electrophysiological abnormalities of the heart, episodes of sudden cardiac death in the child’s relatives before 30 years of age , normal echocardiographic result, correct laboratory results excluding the presence of inflammation and ionic disorders .Criteria for inclusion in the control group: no history of complaints suggesting cardiac arrhythmias with no cardiac arrhythmias on the ECG and the 24 h ECG Holter method, negative family history regarding structural and electrophysiological abnormalities of the heart, no episodes of sudden cardiac death in relatives of a child before 30 years of age, correct physical examination result, with particular emphasis on the state of the circulatory system, without signs of inflammation or structural features of the heart defect with normal echocardiographic result, correct laboratory results excluding the presence of inflammation and ionic disorders .Exclusion criteria for testing: extra-sinus rhythm on the standard ECG and 24 h Holter ECG, features of sick sinus syndrome, atrioventricular and intraventricular conduction disorders in the right and left branches of the bundle in standard ECG and the 24 h Holter ECG recording, diagnosis of structural heart defect (including cardiomyopathies), inflammation of the heart muscle, abnormal electrolyte levels in blood laboratory tests , the use of drugs that change the repolarization period, the presence of diseases that change the repolarization period , lack of consent of the patient or their legal guardian.Standard ECG recordings were performed in the supine position using the recorder model AT2 plus Schiller AG. Baar, Switzerland. Measurements were made manually in the fifth pre-cardiac lead (V5) in 12-lead ECGs. The analysed measurements were the average of three consecutive QRS-T evolutions at a paper travel of 50 mm/s and a standard feature amplitude of 1 mV = 1 cm. The analysis of the repolarization period evaluated the duration of individual repolarization parameters as well as the amplitude and shape of the T-wave . From three consecutive QRS-T evolutions, RR intervals, total repolarization duration—QT interval, and TpTe interval (TpeakTend) were determined and recorded enlarged with a magnifying glass using a distance stepper. The total QT repolarization period was determined from the beginning of the Q wave to the end of the T-wave, defined as the place of return of the descending arm of the T-wave to the isoelectric line excluding U wave. The period of late repolarization TpTe (TpeakTend) was calculated from the top of the T-wave to the end of the T-wave ,16. The p-value (“p” for short) for a statistical test. If the p-value is greater than or equal to 0.05, then there is no reason to reject the null hypothesis at a significance level of 0.05, which usually says that there are no statistically significant differences. When the p-value is less than 0.05, we reject the null hypothesis at the significance level of 0.05 and conclude that there are statistically significant differences.The statistical analysis is based on statistical inference as a consequence of hypothesis verification. In the analysis the significant level was assumed to be 0.05. We verify the hypotheses according to the obtained Both parametric and non-parametric hypotheses were considered in the analysis. Most often, non-parametric hypotheses are applied when the assumption that the distribution of the examined feature is normal is not met. For each considered feature in all studied populations, the normality of the distribution was checked using the Shapiro–Wilk test. Depending on the obtained results, a parametric or non-parametric test was used. In the case of comparing two independent samples, the parametric Student’s t-test or the non-parametric Mann–Whitney U test was used. p-value. In the case of non-parametric tests, the following were given: the sum of ranks and the mean of the ranks obtained for the considered samples (groups of children), as well as the sample size (row N) and the name of the test used together with the p-value.The results of the statistical tests are presented in the tables. In the case of parametric tests, the following were given: arithmetic mean and standard deviation calculated for the considered samples (groups of children), as well as the number of samples (row N) and the name of the test used together with the The boxplots were also used in the presentation of the results. From such charts one can read the basic measures of descriptive statistics. And more specifically: the median—the horizontal line in the middle of the box, the first quartile—the lower base of the box, the third quartile—the top of the box, the minimum–the level of the lower whisker, the maximum—the level of the upper whisker.The calculations and the graphs used in the article were made in the Statistica software .The research project was approved by the Bioethical Committee of the Medical University of Silesia in Katowice in 2015, No. KNW/0022/KB/238/15.n = 8, 36.4%), stabbing chest pain , chest twinge  and fainting . There were no complaints in the control group of healthy children  morphology).Due to the number of registered extrasystoles in 24 h Holter ECG monitoring, 4 subgroups were distinguished in the entire study group: (1) less than 1000 a day, (2) 1000–10,000 per day, (3) over 10,000 a day, (4) recorded tachycardia.n = 39, 85%) that children recorded extrasystoles was in the number of 1000 to more than 10,000 per day  longer in the group of children with ventricular arrhythmia with an abnormal T-wave  relative to the TpTe interval in children with ventricular arrhythmia with the normal repolarization period , QTcB (p < 0.001) and QTcF (p < 0.001) intervals were significantly longer in the group of children with ventricular arrhythmias and with T-wave abnormal  compared to the values of the TpTe, QTcB, and QTcF intervals of the control group with normal morphology of the repolarization period (The duration of the TpTe (n period .p = 0.020) longer in the group of children with ventricular arrhythmia without clinical symptoms  interval was significantly longer in the group of 26% children with ventricular extrasystoles recorded on standard ECG compared to the value of the TpTe interval in the rest of children with ventricular arrhythmias on 24 h Holter ECG monitoring. Similarly, the number of ventricular extrasystoles also in bigemini and trigemini form was significantly higher in the children with ventricular arrhythmias recorded on standard ECG then in the rest of study group with ventricular arrhythmias , stinging pain in the chest 22.7%), chest twinge (22.7%), fainting (18.2%), and palpitations in 9.1% of children. Similarly, in the studies by West et al. in 219 children with ventricular arrhythmia without clinically concomitant overt heart disease, chest pain (9%), palpitations (7%), and syncope (3%) were the most commonly reported, and at other authors’ in a group of 59 children the feeling of irregular heartbeat prevailed (13.6%) .7%, ches. The impIn our own research 22% of the children with ventricular arrhythmia observed in precordial ECG leads (V4–V6) abnormal T-waves (bactrian/bifid or humid/biphasic) with a significantly prolonged duration of the TpTe interval compared to the TpTe value in children with ventricular arrhythmia and normal period repolarization and with a prolonged duration in relation to the TpTe, QTcB, and QTcF values in children in the control group. The presence of abnormal T-waves with prolonged TpTe interval, a diagnostic indicator of arrhythmogenesis , burdensThe increased duration of the QT repolarization period, especially its final phase, from the top to the end of the 262 T-wave TpTe interval is associated with an increased risk of symptomatic ventricular arrhythmias ,36,37,38In the study of Wolk et al., in 6 out of 13 adult patients with induced ventricular arrhythmia the duration of the TpTe interval was longer compared to the TpTe interval of 7 patients without provoked arrhythmia . SimilarThe evaluation of repolarization period parameters, especially the TpTe interval, is useful in identifying patients at high risk of serious cardiac arrhythmias also in other clinical conditions such as short QT syndrome , long QTThe above studies of the parameters of the repolarization period were experimental or carried out in adult patients, there are few studies in children.In our study the duration of the TpTe, QTcF and QTcB interval was significantly longer in children with ventricular arrhythmia compared to the values of these parameters in the healthy children from the control group.Additionaly, in 22% of the study group with ventricular arrhythmia, abnormal T-waves with prolonged duration of the TpTe interval compared to the TpTe value in children with ventricular arrhythmia and normal T-wave were observed. Moreover, recording of benign ventricular arrhythmias in the standard ECG in 26% of examined children with an increased number of extrasystoles also in form of bigemini and trigemini on Holter ECG, and above all with a significant prolongation of TpTe interval with a potential pro-arrhytmic effect, may be a useful prognostic tool in assessing the risk of serious and even life-threatening arrhythmias in the future.These are novel findings in children with ventricular arrhythmias of unknown etiology with the analysis of parameters of the repolarization period and no similar data have been found in available literature to date.On the basis of our work, we wanted to show how important it is in everyday clinical practice to determine the parameters of the repolarization period in the ECG standard, especially in children with diagnosed ventricular arrhythmia because detected prolongation of the TpTe and QT intervals with the abnormal T-wave morphology on a standard ECG may be useful for identifying children more predisposed to severe ventricular arrhythmias in the future.Children with benign ventricular arrhythmias recorded on a standard ECG with prolonged TpTe and QT intervals and abnormal T wave morphology require systematic and frequent cardiac check up with long term ECG recordings due to the possibility of future more severe ventricular arrhythmias. Further follow-up studies in even larger groups of patients are necessary to confirm the values of these repolarization parameters in clinical practice.