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Methylglyoxal (MGO), a highly reactive dicarbonyl metabolite of glucose primarily formed during the glycolytic pathway, is a precursor of advanced glycation end-products (AGEs). Recently, numerous studies have shown that MGO accumulation can cause pain and hyperalgesia. However, the mechanism through which MGO induces pain in the spinal dorsal horn remains unclear. The present study investigated the effect of MGO on spontaneous excitatory postsynaptic currents (sEPSC) in rat spinal dorsal horn neurons using blind whole-cell patch-clamp recording. Perfusion of MGO increased the frequency and amplitude of sEPSC in spinal horn neurons in a concentration-dependent manner. Additionally, MGO administration increased the number of miniature EPSC (mEPSC) in the presence of tetrodotoxin, a sodium channel blocker. However, 6-cyano-7-nitroqiunocaline-2,3-dione (CNQX), an AMPA/kainate receptor antagonist, blocked the enhancement of sEPSC by MGO. HC-030031, a TRP ankyrin-1 (TRPA1) antagonist, and capsazepine, a TRP vanilloid-1 (TRPV1) antagonist, inhibited the action of MGO. Notably, the effects of MGO were completely inhibited by HC-030031 and capsazepine. MGO generates reactive oxygen species (ROS) via AGEs. ROS also potentially induce pain via TRPA1 and TRPV1 in the spinal dorsal horn. Furthermore, we examined the effect of MGO in the presence of N-tert-butyl-α-phenylnitrone (PBN), a non-selective ROS scavenger, and found that the effect of MGO was completely inhibited. These results suggest that MGO increases spontaneous glutamate release from the presynaptic terminal to spinal dorsal horn neurons through TRPA1, TRPV1, and ROS and could enhance excitatory synaptic transmission.
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Acetanilidas , Capsaicina/análogos & derivados , Óxido de Magnésio , Purinas , Aldeído Pirúvico , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Aldeído Pirúvico/farmacologia , Aldeído Pirúvico/metabolismo , Ratos Sprague-Dawley , Óxido de Magnésio/metabolismo , Óxido de Magnésio/farmacologia , Corno Dorsal da Medula Espinal/metabolismo , Células do Corno Posterior/metabolismo , Dor/metabolismo , Transmissão Sináptica/fisiologiaRESUMO
PURPOSE: Spinal fusion surgery is often performed with pelvic fixation to prevent distal junctional kyphosis. The inclusion of spinopelvic fixation has been reported to induce progression of hip joint arthropathy in a radiographic follow-up study. However, its biomechanical mechanism has not yet been elucidated. This study aimed to compare the changes in hip joint moment before and after spinal fusion surgery. METHODS: This study was an observational study and included nine patients (eight women and one man) who were scheduled to undergo spinopelvic fusion surgery. We calculated the three-dimensional external joint moments of the hip during gait, standing, and climbing stairs before and 1 year after surgery. RESULTS: During gait, the maximum extension moment was 0.51 ± 0.29 and 0.63 ± 0.40 before and after spinopelvic fusion surgery (p = 0.011), and maximum abduction moment was 0.60 ± 0.33 and 0.83 ± 0.34 before and after surgery (p = 0.004), respectively. During standing, maximum extension moment was 0.76 ± 0.32 and 1.04 ± 0.21 before and after spinopelvic fusion surgery (p = 0.0026), and maximum abduction moment was 0.12 ± 0.20 and 0.36 ± 0.22 before and after surgery (p = 0.0005), respectively. During climbing stairs, maximum extension moment was - 0.31 ± 0.30 and - 0.48 ± 0.15 before and after spinopelvic fusion surgery (p = 0.040), and maximum abduction moment was 0.023 ± 0.18 and - 0.02 ± 0.13 before and after surgery (p = 0.038), respectively. CONCLUSION: This study revealed that hip joint flexion-extension and abduction-adduction moments increased after spinopelvic fixation surgery in the postures of standing, walking, and climbing stairs. The mechanism was considered to be adjacent joint disease after spinopelvic fusion surgery including sacroiliac joint fixation.
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Articulação do Quadril , Cifose , Masculino , Humanos , Feminino , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Coluna Vertebral/cirurgia , Pelve/diagnóstico por imagem , Pelve/cirurgiaRESUMO
PURPOSE: This study aimed to evaluate the progression of hip pathology and risk factors after ASD surgery. METHODS: This case-control study enrolled 123 patients (246 hips); seven hips underwent hip arthroplasty were excluded. We measured the center-edge (CE) angle, joint space width (JSW), and Kellgren-Lawrence (KL) grade. We defined a CE angleË25° as developmental dysplasia of the hip (DDH). We evaluated S2 alar-iliac (AI) screw loosening at final follow-up. RESULTS: The annual decrease in the JSW was 0.31 mm up to 1 year, and 0.13 mm after 1 year (p = 0.001). KL grade progression occurred in 24 hips (10.0%; group P), while no progression occurred in 215 (90.0%; group N) hips. Nonparametric analysis between groups P and N revealed that significant differences were observed in sex, DDH, KL grade, ratio of S2AI screw fixation at baseline, and ratio of S2AI screw loosening at final follow-up. Multiple logistic regression analysis revealed that DDH (p = 0.018, odds ratio (OR) = 3.0, 95%CI = 1.2-7.3), baseline KL grade (p < 0.0001, OR = 37.7, 95%CI = 7.0-203.2), and S2AI screw fixation (p = 0.035, OR = 3.4, 95%CI = 1.1-10.4) were significant factors. We performed sub-analysis to elucidate the relationship between screw loosening and hip osteoarthritis in 131 hips that underwent S2AI screw fixation. Non-loosening of the S2AI screw was a significant factor for KL grade progression (p < 0.0001, OR = 8.9, 95%CI = 3.0-26.4). CONCLUSION: This study identified the prevalence and risk factors for the progression of hip osteoarthritis after ASD surgery. Physicians need to pay attention to the hip joint pathology after ASD surgery.
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Osteoartrite do Quadril , Fusão Vertebral , Adulto , Humanos , Osteoartrite do Quadril/cirurgia , Estudos de Casos e Controles , Ílio/cirurgia , Parafusos Ósseos/efeitos adversos , Articulação do Quadril , Sacro/cirurgiaRESUMO
The extracellular signal-regulated kinase is an important protein kinase for cortical plasticity. Long-term potentiation in the anterior cingulate cortex is believed to play important roles in chronic pain, fear, and anxiety. Previous studies of extracellular signal-regulated kinase are mainly focused on postsynaptic form of long-term potentiation (post-long-term potentiation). Little is known about the relationship between extracellular signal-regulated kinase and presynaptic long-term potentiation (pre-long-term potentiation) in cortical synapses. In this study, we examined whether pre-long-term potentiation in the anterior cingulate cortex requires the activation of presynaptic extracellular signal-regulated kinase. We found that p42/p44 mitogen-activated protein kinase inhibitors, PD98059 and U0126, suppressed the induction of pre-long-term potentiation. By contrast, these inhibitors did not affect the maintenance of pre-long-term potentiation. Using pharmacological inhibitors, we found that pre-long-term potentiation recorded for 1 h did not require transcriptional or translational processes. Our results strongly indicate that the activation of presynaptic extracellular signal-regulated kinase is required for the induction of pre-long-term potentiation, and this involvement may explain the contribution of extracellular signal-regulated kinase to mood disorders.
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MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Giro do Cíngulo/enzimologia , Giro do Cíngulo/fisiologia , Potenciação de Longa Duração , Animais , Butadienos/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Flavonoides/farmacologia , Ácido Glutâmico/metabolismo , Giro do Cíngulo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Nitrilas/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Sinapses/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacosRESUMO
Dopamine (DA) possesses potent neuromodulatory properties in the central nervous system. In the anterior cingulate cortex, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) are key ion channels in mediating nerve injury induced long-term potentiation (LTP) and chronic pain phenotype. In the present study, we reported the effects of DA on glutamate mediated excitatory post-synaptic currents (EPSCs) in pyramidal neurons of layer II/III of the ACC in adult mice. Bath application of DA (50 µM) caused a significant, rapid and reversible inhibition of evoked EPSCs (eEPSC). This inhibitory effect is dose-related and was absent in lower concentration of DA (5 µM). Furthermore, selective postsynaptic application of GDP-ß-S (1.6 mM) in the internal solution completely abolished the inhibitory effects of DA (50 µM). We also investigated modulation of spontaneous EPSCs (sEPSCs) and TTX sensitive, miniature EPSCs (mEPSCs) by DA. Our results indicated mixed effects of potentiation and inhibition of frequency and amplitude for sEPSCs and mEPSCs. Furthermore, high doses of SCH23390 (100 µM) and sulpiride (100 µM) revealed that, inhibition of eEPSCs is mediated by postsynaptic D2-receptors (D2R). Our finding posits a pre- and postsynaptic mode of pyramidal neuron EPSC modulation in mice ACC by DA.
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Dopamina/farmacologia , Giro do Cíngulo/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Benzazepinas/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Giro do Cíngulo/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Inibição Neural/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Ácido Caínico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulpirida/farmacologia , Tetrodotoxina/toxicidade , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/metabolismoRESUMO
BACKGROUND: Glia-neuron interactions play an important role in the development of neuropathic pain. Expression of the pro-inflammatory cytokne âcytokine Interferon-gamma (IFNγ) is upregulated in the dorsal horn after peripheral nerve injury, and intrathecal IFNγ administration induces mechanical allodynia in rats. A growing body of evidence suggests that IFNγ might be involved in the mechanisms of neuropathic pain, but its effects on the spinal dorsal horn are unclear. We performed blind whole-cell patch-clamp recording to investigate the effect of IFNγ on postsynaptic glutamate-induced currents in the substantia gelatinosa neurons of spinal cord slices from adult male rats. RESULTS: IFNγ perfusion significantly enhanced the amplitude of NMDA-induced inward currents in substantia gelatinosa neurons, but did not affect AMPA-induced currents. The facilitation of NMDA-induced current by IFNγ was inhibited by bath application of an IFNγ receptor-selective antagonist. Adding the Janus activated kinase inhibitor tofacitinib to the pipette solution did not affect the IFNγ-induced facilitation of NMDA-induced currents. However, the facilitatory effect of IFNγ on NMDA-induced currents was inhibited by perfusion of the microglial inhibitor minocycline. These results suggest that IFNγ binds the microglial IFNγ receptor and enhances NMDA receptor activity in substantia gelatinosa neurons. Next, to identify the effector of signal transmission from microglia to dorsal horn neurons, we added an inhibitor of G proteins, GDP-ß-S, to the pipette solution. In a GDP-ß-S-containing pipette solution, IFNγ-induced potentiation of the NMDA current was significantly suppressed after 30 min. In addition, IFNγ-induced potentiation of NMDA currents was blocked by application of a selective antagonist of CCR2, and its ligand CCL2 increased NMDA-induced currents. CONCLUSION: Our findings suggest that IFNγ enhance the amplitude of NMDA-induced inward currents in substantia gelatinosa neurons via microglial IFNγ receptors and CCL2/CCR2 signaling. This mechanism might be partially responsible for the development of persistent neuropathic pain.
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Comunicação Celular/efeitos dos fármacos , Interferon gama/farmacologia , Microglia/citologia , Microglia/metabolismo , Células do Corno Posterior/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Quimiocina CCL2/metabolismo , Ativação do Canal Iônico/efeitos dos fármacos , Masculino , Microglia/efeitos dos fármacos , Modelos Biológicos , N-Metilaspartato/farmacologia , Células do Corno Posterior/citologia , Células do Corno Posterior/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores CCR2/metabolismo , Receptores de Interferon/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia , Receptor de Interferon gamaRESUMO
BACKGROUND: Transient receptor potential (TRP) channels are nonselective cation channels expressed in a variety of sensory structures, and are important molecular mediators of thermal, mechanical, cellular and chemical signals. We investigated the function of one key member of the TRP superfamily, TRPA1, in the spinal dorsal horn using in vivo patch-clamp recordings. RESULTS: The application of allyl isothiocyanate (AITC), a TRPA1 agonist, significantly increased the frequency and amplitude of inhibitory postsynaptic currents (IPSCs; holding potential (VH) = 0 mV) as well as excitatory postsynaptic currents (EPSCs; VH = -70 mV) in substantia gelatinosa (SG) neurons. The AITC-induced increases in EPSC frequency and amplitude were resistant to the Na(+) channel blocker tetrodotoxin (TTX). In the presence of the glutamate receptor antagonists CNQX and AP5, AITC did not generate any synaptic activity. The AITC-induced increases in IPSC frequency and amplitude were abolished by TTX or glutamate receptor antagonists. Moreover, the duration of IPSCs enhanced by TRPA1 activation were significantly longer than those of EPSCs enhanced by activation of this channel in the spinal dorsal horn. AITC induced hyperpolarization of the membrane potential of SG neurons in the spinal cord but depolarized the membrane potential in the presence of TTX. Furthermore, we examined the effects of mechanical stimuli to the skin during TRPA1 activation in the spinal dorsal horn in normal rats in both voltage-clamp and current-clamp modes. In the peripheral tissue stimuli test, AITC significantly suppressed EPSCs evoked by pinch or air puff stimulation of the skin. In current-clamp mode, AITC significantly suppressed excitatory postsynaptic potentials (EPSPs) evoked by pinch stimuli. CONCLUSIONS: TRPA1 appears to be localized not only at presynaptic terminals on SG neurons, enhancing glutamate release, but also in the terminals of primary afferents innervating spinal inhibitory interneurons, which have synaptic interactions with SG neurons. This study offers further insight into the mechanisms underlying the possible antinociceptive actions of TRPA1 activation in the spinal dorsal horn. Our findings suggest that pharmacological activation of spinal TRPA1 channels may have therapeutic potential for the treatment of pain.
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Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Corno Dorsal da Medula Espinal/metabolismo , Canais de Cátion TRPC/metabolismo , Analgésicos/farmacologia , Animais , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Neurônios/metabolismo , Técnicas de Patch-Clamp/métodos , Ratos Sprague-Dawley , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Substância Gelatinosa/citologia , Substância Gelatinosa/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Canal de Cátion TRPA1RESUMO
BACKGROUND: Falls among the elderly are a major societal problem. While observations of medium-distance walking using inertial sensors identified potential fall predictors, classifying individuals at risk based on single gait cycles remains elusive. This challenge stems from individual variability and step-to-step fluctuations, making accurate classification difficult. METHODS: We recruited 44 participants, equally divided into high and low fall-risk groups. A smartphone secured on their second sacral spinous process recorded data during indoor walking. Features were extracted at each gait cycle from a 6-dimensional time series (tri-axial angular velocity and tri-axial acceleration) and classified using the gradient boosting decision tree algorithm. FINDINGS: Mean accuracy across five-fold cross-validation was 0.936. "Age" was the most influential individual feature, while features related to acceleration in the gait direction held the highest total relative importance when aggregated by axis (0.5365). INTERPRETATION: Combining acceleration, angular velocity data, and the gradient boosting decision tree algorithm enabled accurate fall risk classification in the elderly, previously challenging due to lack of discernible features. We reveal the first-ever identification of three-dimensional pelvic motion characteristics during single gait cycles in the high-risk group. This novel method, requiring only one gait cycle, is valuable for individuals with physical limitations hindering repetitive or long-distance walking or for use in spaces with limited walking areas. Additionally, utilizing readily available smartphones instead of dedicated equipment has potential to improve gait analysis accessibility.
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Acidentes por Quedas , Marcha , Aprendizado de Máquina , Humanos , Acidentes por Quedas/prevenção & controle , Idoso , Marcha/fisiologia , Feminino , Masculino , Algoritmos , Caminhada/fisiologia , Aceleração , Medição de Risco/métodos , Acelerometria/métodos , Smartphone , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Árvores de Decisões , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The medial meniscus extrusion (MME) is associated with increased stress on the knee joint, which leads to cartilage degeneration. To evaluate the etiology of knee osteoarthritis, it is extremely important to create animal models of the disease that more closely resemble actual clinical conditions in terms of symptomatology, molecular biology, and histology. This study aimed to create a clinically relevant model of MME in rats. DESIGN: Behavioral, molecular biological, and histological changes in the newly developed rat MME model were compared with those in sham and medial meniscus transection and medial collateral ligament transection (MMT) models to examine the characteristics of this model. RESULTS: In the MME rat model, behavioral evaluation shows abnormalities in gait compared with the other 2 groups, and molecular biological evaluation of the infrapatellar synovia of rats shows that gene expression of inflammatory cytokines, matrix-degrading enzymes, and pain-related nerve growth factor was increased compared with the sham group. Furthermore, histological evaluation reveals that cartilage degeneration was the most severe in the MME group. CONCLUSIONS: The newly developed MME model reproduced the characteristic pathology of MME in clinical practice, such as severe pain, inflammation, and rapid progression of osteoarthritis. The MME model, which might more closely mimic human knee osteoarthritis (OA), could be a useful model for elucidating the pathophysiology and considering therapeutic management for knee OA.
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Transient receptor potential families play important roles in the pathology of osteoarthritis (OA) of the knee. While transient receptor potential ankyrin 1 (TRPA1) is also an essential component of the pathogenesis of various arthritic conditions, its association with pain is controversial. Thus, we researched whether TRPA1 is involved in knee OA pain by in vivo patch-clamp recordings and evaluated the behavioral responses using CatWalk gait analysis and pressure application measurement (PAM). Injection of the Trpa1 agonist, allyl isothiocyanate (AITC), into the knee joint significantly increased spontaneous excitatory synaptic current (sEPSC) frequency in the substantia gelatinosa of rats with knee OA, while injection of the Trpa1 antagonist, HC-030031, significantly decreased the sEPSC. Meanwhile, AITC did not affect the sEPSC in sham rats. In the CatWalk and PAM behavioral tests, AITC significantly decreased pain thresholds, but no difference between HC-030031 and saline injections was observed. Our results indicate that Trpa1 mediates knee OA-induced pain. We demonstrated that Trpa1 is activated in the knee joints of rats with OA, and Trpa1 activity enhanced the pain caused by knee OA.
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In general, it is known that extreme climatic conditions such as El Niño and positive Indian Ocean Dipole (IOD+) cause prolonged drought in Indonesia's tropical peatlands so that groundwater levels (GWL) drop and peat is prone to fire. However, 27 years of GWL measurements in Central Kalimantan peat forests show the opposite condition, where the lowest GWL occurs several weeks before El Niño and after IOD+ reaches its peaks. We show that the dropped sea surface temperature anomaly induced by anomalously easterly winds along the southern Java-Sumatra occurs several weeks before the GWL drop to the lowest value. Local rainfall decreased, and GWL dropped sharply by 1.0 to 1.5 m, during the super El Niño events in 1997/98 and 2015, as well as remarkable events of IOD+ in 2019. It is suggested that the tropical peatland ecohydrological system (represented by the GWL), El Niño Southern Oscillation (ENSO), and IOD+ are teleconnected. Hence, monitoring GWL variability of peatland over the IMC is a possibility an alert for extreme climate events associated with El Niño and/or moderate IOD+.
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El Niño Oscilação Sul , Água Subterrânea , Indonésia , Estações do Ano , Oceano Índico , SoloRESUMO
[This corrects the article DOI: 10.22603/ssrr.2021-0231.].
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PURPOSE: Although it has been recognized that the medial meniscus extrusion (MME) leads to progressive cartilage loss and osteoarthritis (OA), about 20% of cases with MME had minor symptoms and poor progression of knee OA. However, it is still unclear which patients will have minimal symptoms or will not progress to degeneration. The purpose of this study is to compare the effect of the relationship between the MME and Joint line convergence angle (JLCA) on knee stress with the finite element (FE) analysis method. METHODS: The 65 year-old female was taken computer tomography (CT) from thigh to ankle. A 3-dimentional nonlinear FE model was constructed from the patient's DICOM data. We made the six models, which was different from JLCA and MME. Contact stresses on the surfaces between femoral and tibial cartilages and both side of meniscus are analyzed. RESULTS: As the JLCA or MME increased, the stress load on the medial compartment increased. The effect of MME was stronger on the femoral side, while the effect of JLCA was stronger for the tibia and meniscus. If the JLCA was tilted valgus, the stress in the medial compartment did not increase even in the presence of MME. CONCLUSIONS: This study revealed that the MME is associated with increased a stress loading on medial compartment structures. Furthermore, this change was enhanced by the varus tilt of the JLCA. In the case of valgus alignment, the contact pressure of the medial compartment did not increase so much even if with the MME. LEVEL OF EVIDENCE: Level V.
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Wound healing is an important process in various diseases, and elucidating the underlying mechanism is essential for developing therapeutic strategies. We investigated whether the loss of transient receptor potential ankyrin 1 (TRPA1) affects the cutaneous wound healing process in mice. We assessed the formation of granulation tissue by myofibroblasts and macrophages, re-epithelialization, and related gene expression. TRPA1-null (KO) and wild-type (WT) C57BL/6 mice were used for establishing the wound model. Two round full-thickness excision wounds (diameter, 5.0 mm) were produced in the dorsal skin of mice under general anesthesia. After specific intervals, healing was evaluated using macroscopic observation, histology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction (RT-PCR). TRPA1 KO retarded the formation of granulation tissue and re-epithelialization in the healing of cutaneous wound. Furthermore, TRPA1 KO suppressed the appearance of myofibroblasts, macrophage infiltration, and mRNA expression of αSMA, F4/80, and Col-1α2. These findings indicate that TRPA1 is required for cutaneous wound healing in mice. The lack of TRPA1 retards macrophage infiltration and the subsequent fibrotic tissue formation, which might further impair the fibrogenic behavior of fibroblasts.
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Introduction: Adult spinal fusion surgery improves lumbar alignment and patient satisfaction. Adult spinal deformity surgery improves saggital balance not only lumbar lesion, but also at hip joint coverage. It was expected that hip joint coverage rate was improved and joint stress decreased. However, it was reported that adjacent joint disease at hip joint was induced by adult spinal fusion surgery including sacroiliac joint fixation on an X-ray study. The mechanism is still unclear. We aimed to investigate the association between lumbosacral fusion including sacroiliac joint fixation and contact stress of the hip joint. Methods: A 40-year-old woman with intact lumbar vertebrae underwent computed tomography. A three-dimensional nonlinear finite element model was constructed from the L4 vertebra to the femoral bone with triangular shell elements (thickness, 2 mm; size, 3 mm) for the cortical bone's outer surface and 2-mm (lumbar spine) or 3-mm (femoral bone) tetrahedral solid elements for the remaining bone. We constructed the following four models: a non-fusion model (NF), a L4-5 fusion model (L5F), a L4-S1 fusion model (S1F), and a L4-S2 alar iliac screw fixation model (S2F). A compressive load of 400 N was applied vertically to the L4 vertebra and a 10-Nm bending moment was additionally applied to the L4 vertebra to stimulate flexion, extension, left lateral bending, and axial rotation. Each model's hip joint's von Mises stress and angular motion were analyzed. Results: The hip joint's angular motion in NF, L5F, S1F, and S2F gradually increased; the S2F model presented the greatest angular motion. Conclusions: The average and maximum contact stress of the hip joint was the highest in the S2F model. Thus, lumbosacral fusion surgery with sacroiliac joint fixation placed added stress on the hip joint. We propose that this was a consequence of adjacent joint spinopelvic fixation. Lumbar-to-pelvic fixation increases the angular motion and stress at the hip joint.
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Riluzole (2-amino-6-(trifluoromethoxy)benzothiazole) is a drug known for its inhibitory effect on glutamatergic transmission and its anti-nociceptive and anti-allodynic effects in neuropathic pain rat models. Riluzole also has an enhancing effect on GABAergic synaptic transmission. However, the effect on the spinal dorsal horn, which plays an important role in modulating nociceptive transmission, remains unknown. We investigated the ameliorating effect of riluzole on mechanical allodynia using the von Frey test in a rat model of neuropathic pain and analyzed the synaptic action of riluzole on inhibitory synaptic transmission in substantia gelatinosa (SG) neurons using whole-cell patch clamp recordings. We found that single-dose intraperitoneal riluzole (4 mg/kg) administration effectively attenuated mechanical allodynia in the short term in a rat model of neuropathic pain. Moreover, 300 µM riluzole induced an outward current in rat SG neurons. The outward current induced by riluzole was not suppressed in the presence of tetrodotoxin. Furthermore, we found that the outward current was suppressed by simultaneous bicuculline and strychnine application, but not by strychnine alone. Altogether, these results suggest that riluzole enhances inhibitory synaptic transmission monosynaptically by potentiating GABAergic synaptic transmission in the rat spinal dorsal horn.
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BACKGROUND AND OBJECTIVES: Gait can be severely affected by pain, muscle weakness, and aging resulting in lameness. Despite the high incidence of lameness, there are no studies on the features that are useful for classifying lameness patterns. Therefore, we aimed to identify features of high importance for classifying population differences in lameness patterns using an inertial measurement unit mounted above the sacral region. METHODS: Features computed exhaustively for multidimensional time series consisting of three-axis angular velocities and three-axis acceleration were carefully selected using the Benjamini-Yekutieli procedure, and multiclass classification was performed using LightGBM (Microsoft Corp., Redmond, WA, USA). We calculated the relative importance of the features that contributed to the classification task in machine learning. RESULTS: The most important feature was found to be the absolute value of the Fourier coefficients of the second frequency calculated by the one-dimensional discrete Fourier transform for real input. This was determined by the fast Fourier transformation algorithm using data of a single gait cycle of the yaw angular velocity of the pelvic region. CONCLUSIONS: Using an inertial measurement unit worn over the sacral region, we determined a set of features of high importance for classifying differences in lameness patterns based on different factors. This completely new set of indicators can be used to advance the understanding of lameness.
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Análise da Marcha/métodos , Transtornos Neurológicos da Marcha/diagnóstico , Marcha/fisiologia , Transtornos dos Movimentos/diagnóstico , Doenças Musculares/diagnóstico , Fenômenos Biomecânicos/fisiologia , Feminino , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Masculino , Transtornos dos Movimentos/fisiopatologia , Doenças Musculares/fisiopatologia , SmartphoneRESUMO
Accurate gluteus medius (GMd) volume evaluation may aid in the analysis of muscular atrophy states and help gain an improved understanding of patient recovery via rehabilitation. However, the segmentation of muscle regions in GMd images for cubic muscle volume assessment is time-consuming and labor-intensive. This study automated GMd-region segmentation from the computed tomography (CT) images of patients diagnosed with hip osteoarthritis using deep learning and evaluated the segmentation accuracy. To this end, 5250 augmented pairs of training data were obtained from five participants, and a conditional generative adversarial network was used to identify the relationships between the image pairs. Using the preserved test datasets, the results of automatic segmentation with the trained deep learning model were compared to those of manual segmentation in terms of the dice similarity coefficient (DSC), volume similarity (VS), and shape similarity (MS). As observed, the average DSC values for automatic and manual segmentations were 0.748 and 0.812, respectively, with a significant difference (p < 0.0001); the average VS values were 0.247 and 0.203, respectively, with no significant difference (p = 0.069); and the average MS values were 1.394 and 1.156, respectively, with no significant difference (p = 0.308). The GMd volumes obtained by automatic and manual segmentation were 246.2 cm3 and 282.9 cm3, respectively. The noninferiority of the DSC obtained by automatic segmentation was verified against that obtained by manual segmentation. Accordingly, the proposed GAN-based automatic GMd-segmentation technique is confirmed to be noninferior to manual segmentation. Therefore, the findings of this research confirm that the proposed method not only reduces time and effort but also facilitates accurate assessment of the cubic muscle volume.
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Processamento de Imagem Assistida por Computador/métodos , Músculo Esquelético/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Aprendizado Profundo , Feminino , Humanos , Masculino , Músculo Esquelético/patologia , Redes Neurais de Computação , Reconhecimento Automatizado de Padrão , Interpretação de Imagem Radiográfica Assistida por Computador , Reprodutibilidade dos TestesRESUMO
During the dry period of August-October 2015, a C-band Doppler weather radar of the BMKG station in a fire-prone peatland area, Palangka Raya, detected echoes with reflectivity values between - 19 and + 34 dBZ at a height below 2-3 km and a slant range of 100 km. The MERRA-2/NASA atmospheric reanalysis database is used to obtain the vertical profiles of refractive index and equivalent potential temperature of the air. The temporal variation of the radar image is due to the tropical diurnal cycle of planetary boundary layer formation, which is consistent with the results of the database analysis. The echo images are discussed in terms of Bragg scattering of microwaves at the top of the planetary boundary layer. Weather radar monitoring of the fire smoke layer-top images has a potential feasibility to support real-time management of peatland fires.
RESUMO
Long-term potentiation (LTP) of synaptic transmission in the central nervous system is a key form of cortical plasticity. The insular cortex (IC) is known to play important roles in pain perception, aversive memory and mood disorders. LTP has been recently reported in the IC, however, the signaling pathway for IC LTP remains unknown. Here, we investigated the synaptic mechanism of IC LTP. We found that IC LTP induced by the pairing protocol was N-methyl-D-aspartate receptors (NMDARs) dependent, and expressed postsynaptically, since paired-pulse ratio (PPR) was not affected. Postsynaptic calcium is important for the induction of post-LTP, since the postsynaptic application of BAPTA completely blocked the induction of LTP. Calcium-activated adenylyl cyclase subtype 1 (AC1) is required for potentiation. By contrast, AC8 is not required. Inhibition of Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) or protein kinase M zeta (PKMζ) reduced the expression of LTP. Our results suggest that calcium-stimulated AC1, but not AC8, can be a trigger of the induction and maintenance of LTP in the IC.