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Objective: Eosinophilic Otitis Media (EOM) is an intractable disease caused by type 2 inflammation, such as Eosinophilic Chronic Rhinosinusitis (ECRS) and bronchial asthma. Biologics have recently been used to treat ECRS and bronchial asthma. Biologics are not indicated for EOM; however, because approximately 10% of ECRS cases has concomitant EOM, concomitant EOM improvement has been observed when dupilumab is administered for ECRS. Therefore, we aimed to investigate the current status of EOM treatment and clarify the effect of dupilumab on EOM. Method: This retrospective study included 25 patients attending our hospital. The disease status of patients with EOM not treated with dupilumab (control) and those treated with dupilumab at the time of evaluation were compared. The EOM disease status was compared using the EOM severity score, temporal bone shadow on Computed Tomography (CT), and standard pure tone audiometry. Result: Twenty-four of the 25 patients with EOM had concomitant ECRS, and 12 were administered with dupilumab. The severity score of EOM, temporal bone CT score, and air conductance hearing were significantly improved after dupilumab administration in 12 patients with EOM. Comparison of EOM patients without dupilumab (control) and those treated with dupilumab at the time of evaluation revealed that the severity score of EOM, temporal bone CT score, and air conduction hearing were significantly better in patients treated with dupilumab. Conclusion: Our study demonstrated that dupilumab was administered to approximately half of the patients with EOM, suggesting that the treatment of EOM has undergone significant changes due to dupilumab administered to ECRS. Our study also suggests that dupilumab is highly effective in patients with EOMs. Level of evidence: 4.

Abstract Light-emitting electrochemical cells (LECs) are next-generation devices that are flexible, emit light and have several advantages over organic light-emitting diodes, such as a simpler structure and lower cost. However, the operation mechanism of LECs remains unknown from a microscopic viewpoint. Here, we perform an operando microscopic investigation of LECs with Super Yellow, a typical light-emitting material, by observing the spin states of electrically doped charges using electron spin resonance. The operando electron spin resonance and light emission increase as the voltage applied to the LECs increases. Through density functional theory, we determine that the origin of the electron spin resonance increases to be from electrochemically doped holes and electrons in Super Yellow. We find that the doping progress correlates with the luminance increase, suggesting that electrochemically doped charges are distributed over the light-emitting layer as the operation mechanism. Moreover, we deduce the molecular orientation of electrochemically charge-doped Super Yellow.

Abstract Integrating genomic data of multiple cancers allows de novo cancer grouping and elucidating the shared genetic basis across cancers. Here, we conduct the pan-cancer and cross-population genome-wide association study (GWAS) meta-analysis and replication studies on 13 cancers including 250,015 East Asians (Biobank Japan) and 377,441 Europeans (UK Biobank). We identify ten cancer risk variants including five pleiotropic associations (e.g., rs2076295 at DSP on 6p24 associated with lung cancer and rs2525548 at TRIM4 on 7q22 nominally associated with six cancers). Quantifying shared heritability among the cancers detects positive genetic correlations between breast and prostate cancer across populations. Common genetic components increase the statistical power, and the large-scale meta-analysis of 277,896 breast/prostate cancer cases and 901,858 controls identifies 91 newly genome-wide significant loci. Enrichment analysis of pathways and cell types reveals shared genetic backgrounds across said cancers. Focusing on genetically correlated cancers can contribute to enhancing our insights into carcinogenesis.

Currently, the Ministry of Land, Infrastructure, Transport, and Tourism (Japan) is in the process of developing an open 3D city model known as PLATEAU. Abundant measurement data related to buildings, including maps produced by private companies and mobile mapping system point clouds, have been collected to enhance the value of the 3D city model. To achieve this, it is necessary to identify the buildings for which measurement data is available. In this study, we propose and evaluate an efficient matching method for various building measurement data, primarily using geometric properties. In Numazu city, PLATEAU IDs were assigned to 88,525 Zenrin buildings as part of a private map. The results indicate that 90.6% of the polygons were matched. For aerial images, 93.6% of the extracted buildings matched the PLATEAU buildings, although only 70.9% of the PLATEAU data was extracted from the images. Using the level of detail 1 and 2 models, 46 textured building files were created from the mobile mapping system point cloud. In addition, the cover ratio for the laser profiling point cloud was mostly greater than 40%, which was higher than that of the mobile mapping system.

For accurate urban planning, three-dimensional (3D) building models with a high level of detail (LOD) must be developed. However, most large-scale 3D building models are limited to a low LOD of 1–2, as the creation of higher LOD models requires the modeling of detailed building elements such as walls, windows, doors, and roof shapes. This process is currently not automated and is performed manually. In this study, an end-to-end framework for the creation of 3D building models was proposed by integrating multi-source data such as omnidirectional images, building footprints, and aerial photographs. These different data sources were matched with the building ID considering their spatial location. The building element information related to the exterior of the building was extracted, and detailed LOD3 3D building models were created. Experiments were conducted using data from Kobe, Japan, yielding a high accuracy for the intermediate processes, such as an 86.9% accuracy in building matching, an 88.3% pixel-based accuracy in the building element extraction, and an 89.7% accuracy in the roof type classification. Eighty-one LOD3 3D building models were created in 8 h, demonstrating that our method can create 3D building models that adequately represent the exterior information of actual buildings.

Abstract Background Studies have demonstrated the efficacy of oxygen delivery-guided perfusion (ODGP) in preventing postoperative acute kidney injury, but the benefit of ODGP for delirium has not been confirmed. We retrospectively investigated the risk factors for postoperative delirium in patients who underwent ODGP (with oxygen delivery index [DO2i] > 300 mL/min/m2). Methods Consecutive patients who underwent on-pump cardiovascular surgery with ODGP from January 2018 to December 2020 were retrospectively analyzed. In addition to examining patients’ DO2i during cardiopulmonary bypass (CPB), we quantified the two primary DO2 components-hematocrit (Hct) and pump flow. Delirium was defined based on the Intensive Care Delirium Screening Checklist (ICDSC). Patients were divided into three groups: no delirium (ICDSC score = 0), subsyndromal delirium (ICDSC score = 1–3), and clinical delirium (ICDSC score ≥ 4). Results Multivariate analysis identified only the number of red blood cell (RBC) units transfused, intubation time, and the cumulative time below the Hct threshold of 25% as predictive factors of postoperative delirium. Although patients with higher ICDSC scores had greater hemodilution during CPB, ODGP resulted in a higher pump flow, and DO2i was maintained above 300 mL/min/m2, with no significant difference between the three groups. Conclusions A low Hct level during CPB with ODGP, the number of RBC units transfused, and intubation time were associated with postoperative delirium. Further investigations are needed to determine the ability of ODGP to prevent low Hct during CPB.

Background and objectivesPatients with benign paroxysmal positional vertigo of the posterior canal (pc-BPPV) exhibit BPPV fatigue, where the positional nystagmus diminishes with the repeated performance of the Dix–Hallpike test (DHt). BPPV fatigue is thought to be caused by the disintegration of lumps of otoconial debris into smaller parts and can eliminate positional nystagmus within a few minutes [similar to the immediate effect of the Epley maneuver (EM)]. In this study, we aimed to show the non-inferiority of the repeated DHt to the EM for eliminating positional nystagmus after 1 week.MethodsThis multicenter, randomized controlled clinical trial was designed based on the CONSORT 2010 guidelines. Patients who had pc-BPPV were recruited and randomly allocated to Group A or Group B. Patients in Group A were treated using the EM, and patients in Group B were treated using repeated DHt. For both groups, head movements were repeated until the positional nystagmus had been eliminated (a maximum of three repetitions). After 1 week, the patients were examined to determine whether the positional nystagmus was still present. The groups were compared in terms of the percentage of patients whose positional nystagmus had been eliminated, with the non-inferiority margin set at 15%.ResultsData for a total of 180 patients were analyzed (90 patients per group). Positional nystagmus had been eliminated in 50.0% of the patients in Group A compared with 47.8% in Group B. The upper limit of the 95% confidence interval for the difference was 14.5%, which was lower than the non-inferiority margin.DiscussionThis study showed the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week in patients with pc-BPPV and that even the disintegration of otoconial debris alone has a therapeutic effect for pc-BPPV. Disintegrated otoconial debris disappears from the posterior canal because it can be dissolved in the endolymph or returned to the vestibule via activities of daily living.Classification of evidenceThis study provides Class II evidence of the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week.Registration numberUMIN000016421.

Category: Ankle; Arthroscopy Introduction/Purpose: Syndesmotic instability, when subtle, can be challenging to diagnose-and often requires visualization of the syndesmosis during applied stress. Portable ultrasonography is increasingly used to evaluate ankle instability at the point of care. This study aims to evaluate 1) whether portable ultrasonography (P-US) can diagnose syndesmotic instability in the sagittal plane, and 2) how P-US measurements compare to arthroscopic evaluation. Methods: Eight fresh, above-knee cadaveric specimen were used. The syndesmosis was evaluated with P-US and arthroscopy in the intact state, and thereafter with progressive sectioning of, 1) anterior-inferior tibiofibular ligament (AITFL), 2) interosseous ligament (IOL), and 3) posterior-inferior tibiofibular ligament (PITFL). Sagittal plane translation was simulated with 100N of anterior to posterior (A to P) and posterior to anterior (P to A) directed force using a bone hook. Separately, a 50N manual force was applied to the fibular tip and measured with P-US to simulate a fibular 'shuck test' performed in the clinical setting. Results: When all three syndesmotic ligaments were transected, there was a significant increase in fibular motion in the sagittal plane when evaluated using portable ultrasonography with application of 50N of manual pressure and when applying a 100N hook test when measuring total sagittal plane motion (p=

Category: Ankle; Sports; Trauma Introduction/Purpose: Despite the success of surgical intervention, about 13-35% of patients continue to have ankle symptoms after surgery for lateral ankle instability which could be due to presence of undetected and thus untreated injury to other ankle ligaments.Concomitant lateral ankle ligament and syndesmotic ligamentous injuries are common. It is unknown, however, whether syndesmotic ligaments directly contribute to lateral ankle stability. Therefore, the aim of this study was to fluoroscopically evaluate whether the syndesmotic ligaments contributes to lateral ankle stability. Methods: Twenty-four above-knee cadaveric specimens were divided into three groups that underwent fluoroscopic evaluation for lateral ankle stability. In all the groups, the assessment was first done with all syndesmotic and ankle ligaments intact. Thereafter, Group 1 underwent sequential transection of the lateral ankle ligaments: (1) anterior talofibular ligament (ATFL), (2)calcaneofibular ligament(CFL), and (3)posterior talofibular ligament (PTFL). Group 2 underwent sequential transection of the lateral ankle ligaments followed by the syndesmotic ligaments: (1) ATFL, (2) CFL, (3) PTFL, (4) anterior inferior tibiofibular ligament(AITFL), (5)interosseous ligament(IOL), and (6)posterior inferior tibiofibular ligament (PITFL). Group 3 alternating and sequential transection of the syndesmotic and lateral ankle ligaments: (1) AITFL, (2) ATFL, (3) CFL, (4) IOL, (5) PTFL, and (6) PITFL. In all scenarios, three loading conditions were considered:(1)An anterior drawer test at 50N and 80N of direct force, (2) talar tilt under 1.7Nm torque, and (2) lateral clear space (LCS) under 1.7Nm torque. Wilcoxon rank-sum test was used to compare the findings of each ligamentous transection state to the intact state. Results: The lateral ankle remained stable after transection of all syndesmotic ligaments (AITFL, IOL, PITFL). However, after additional transection of the ATFL, the lateral ankle became unstable in varus and anterior drawer testing conditions (p-values ranging from 0.036-0.012). Lateral ankle instability was also observed after transection of the ATFL and AITFL (p-values ranging from 0.036-0.012). Subsequent transection of the CFL worsened the lateral ankle instability. Conclusion: Our findings suggest that syndesmotic injuries can destabilize otherwise stable lateral ankle sprains. When treating lateral ankle instability, clinician should maintain a lower threshold for operative intervention for syndesmotic stabilization if there are any residual symptoms over the AITFL.

Category: Ankle Introduction/Purpose: Portable ultrasonography (P-US) is increasingly used to diagnose syndesmotic instability. The aim of this study was to evaluate syndesmotic instability by measuring the distal tibiofibular clear space (TFCS) in a cadaveric model using P- US with progressive stages of syndesmotic ligamentous transection. Methods: Ten fresh lower leg cadaveric specimens amputated above the proximal tibiofibular joint were used. Using P-US, the TFCS was evaluated in the intact stage and after progressive sectioning of the 1) anterior-inferior tibiofibular ligament (AITFL), 2) interosseous ligament (IOL), and 3) posterior-inferior tibiofibular ligament (PITFL). The TFCS was measured in both the unstressed (0 Nm) state and with 4.5 Nm, 6.0 Nm, 7.5 Nm, and 9.0 Nm of external rotation stress at each stage of ligamentous transection stage using both P-US and fluoroscopy. Results: When assessed with P-US, partial syndesmotic injury encompassing the AITFL and IOL resulted in significant TFCS widening at 4.5 Nm of external rotation torque when compared to intact state with a TFCS-opening of 2.6 +- 2 mm, p = 0.01. In contrast, no significant differences in TFCS were detected using fluoroscopy. Only a moderate correlation was found between P- US and fluoroscopy. Conclusion: P-US is much more sensitive than fluoroscopy in diagnosing syndesmotic instability during external rotation stress examination. Extrapolated to the clinical setting, 4.5 Nm of force can be used when comparing to the stressed, uninjured side, and may be better tolerated by patients than higher torque values. When using P-US, a TFCS-opening of 2.6 mm is likely to correlate with syndesmotic instability. While absolute threshold values may vary between individuals, the ready availability of the contralateral, uninjured side overcomes this constraint.

Category: Ankle; Trauma Introduction/Purpose: Despite the fact that stress fluoroscopy is the most common method of quantifying lateral ankle instability, ultrasound evaluation has grown in popularity as a way to assess ankle stability at the point of care due to its simplicity, accuracy, low cost, and lack of exposure. The aim of this study is to introduce a new method for evaluating lateral ankle instability using ultrasound. Methods: A 37-year-old man with history of lateral ankle ligament injury underwent ultrasound and fluoroscopic evaluation. The anterior drawer distance (ADD) was quantified under anterior drawer stress. During ADD measurement, the patient sat with the knee extended and the heel on the examination table or chair, and the examiner performed the anterior drawer test (Image 1a). The amount of talar movement was measured as an ADD using an ultrasound probe placed on the posteromedial side of the ankle (Image 1b). A lateral clear space (LCS) was also measured under varus stress using ultrasound from the tip of the lateral malleolar to the lateral process of the talus. The aforementioned measurements were repeated under stress fluoroscopy and compared with ultrasound findings. Results: On ultrasound evaluation, the ADD was 7.1 mm and the LCS was 17.1 mm. Furthermore, the stress fluoroscopic evaluation yielded a similar result, with an ADD of 8.7 mm and an LCS of 17.5 mm. Conclusion: Our findings suggest that this new method of evaluation of lateral ankle instability under dynamic ultrasound appears to be a highly accurate and useful alternative for assessing lateral ankle stability at the point of care in a radiation-free, non- invasive, and low-cost manner.

Abstract Shallow landslides occur frequently on the Aso volcanic mountains. The soil materials on the Aso volcanic mountains consist of tephra layers formed by volcanic activities. This study is aimed to specify the physical properties of soil that correlate with the sliding layer of a shallow landslide on the volcanic mountain area. Tephra layers consist of kuroboku and scoria layers and the differences between these layers were specified using the physical properties of soil methods. Results showed that the plasticity index and the fine fraction content can be used for estimating the sliding layer in the Aso volcanic area.

Category: Ankle; Arthroscopy; Basic Sciences/Biologics Introduction/Purpose: The lateral hook test is considered the gold standard for the diagnosis of coronal plane syndesmotic instability during arthroscopy. The amount of distal tibiofibular space is directly related to the amount of lateral directed applied force. This study aims to determine the optimal amount of forced needed during a lateral hook test to evaluate syndesmotic instability in the coronal plane. The secondary aim was to determine the amount of displacement variation that occurs when the lateral force is angled anteriorly or posteriorly. Methods: Ten fresh-frozen above-knee amputated cadaveric specimens underwent arthroscopic evaluation of the distal tibiofibular joint. The assessment was done first with all syndesmotic and ankle ligaments intact and subsequently with transection of the anterior inferior tibiofibular ligament (AITFL) and the interosseous ligament (IOL). In all scenarios, a lateral hook test was performed under increasing force from 0N to 120N of direct force, with increments of 20N. The lateral hook test was performed in: 1) the neutral position (no angulation), 2) anterior inclination of 15 degrees, and 3) posterior inclination of 15 degrees under the aforementioned force. Anterior and posterior coronal plane distal tibiofibular space were arthroscopically measured. Descriptive statistics were employed to determine the force and the most sensitive method to pull during arthroscopic evaluation to detect syndesmotic instability. Results: Among the specimens, after transection of AITFL and IOL, the anterior and posterior coronal plane space increased with increment in force until 60N and then displayed no change in these measurements despite the increase in force. In the intact state, there was an increase in syndesmosis coronal space with increase in force. Of the three methods of force application, the posteriorly directed force has the largest absolute value for the anterior and posterior coronal space, suggesting it is the most sensitive in distinguishing between stable and unstable syndesmotic injury. Conclusion: Arthroscopic coronal plane evaluation under 60N of direct force is best suited to distinguish stable from an unstable syndesmosis. Syndesmosis anterior and posterior coronal plane space measurement demonstrate the largest absolute difference when subjected to posteriorly directed force, suggesting that this new method of assessment has the highest potential for diagnosing even subtle syndesmotic instability, along with a lower propensity for error.

Category: Ankle; Trauma Introduction/Purpose: Destabilizing injuries to the deltoid ligament have historically relied on radiographic stress examination for diagnosis, with a focus on medial clear space (MCS) widening. Increasingly, Portable ultrasound (P-US) has increasingly been used in the clinical setting, allowing dynamic and non-invasive evaluation at the point of care. This study aims to determine whether the P-US assisted MCS evaluation during the gravity stress (GST), weight-bearing, and external rotation stress test can detect medial side instability in supination-external rotation (SER) type ankle injuries with sequential disruption of the anterior inferior tibiofibular ligament (AITFL) (stage I), the fibula (Weber B fracture) (stage II), the posterior inferior tibiofibular ligament (PITFL) (stage III), the superficial deltoid ligament (stage IVa) and the deep deltoid ligament (stage IVb). Methods: Ten fresh-frozen cadaveric specimens were used. Medial ankle instability was assessed by the P-US. The assessment was performed with all structures intact and later with sequential transection of the AITFL, Weber-B fibular fracture, the PITFL, the superficial and deep deltoid ligament. In all scenarios, three loading conditions were considered, including the GST, the external rotation stress test (45N), and the simulated weight-bearing (750N). The P-US measurement of the MCS was assessed at the anteromedial aspect and inferomedial aspect of the ankle joint. Three different MCS distances were measured, as demonstrated in Figure 1. To investigate the correlation between the P-US measurements and the staging of SER ankle injuries, a Spearman rank correlation was used. To detect a difference in MCS distances between each injured stage and the intact stage for each stress test, a Wilcoxon signed-rank test was used. P-values were adjusted for multiple comparisons using the Holm- Bonferroni method. Results: MCS values measured with the P-US increased as the SER ankle injury stage progressed. The Spearman's rank correlation coefficient ranged from 0.43 to 0.90 (p-values

Category: Ankle; Trauma Introduction/Purpose: Diagnosis of destabilizing deltoid ligament injuries remains challenging and is best identified with dynamic imaging techniques. This study aims to assess and compare medial clear space (MCS) distances in various stages of sequentially created supination external rotation (SER) ankle injury model using portable ultrasound (P-US) and fluoroscopy. We hypothesize that there is a strong correlation between the P-US and fluoroscopic measurements for the assessment of medial ankle instability in SER type ankle injury during the gravity stress test (GST), weight-bearing, or external rotation stress test. Methods: Ten cadaveric specimens were used for assessing medial ankle instability. The assessment was performed with all structures intact, and later with sequential transection of the anterior inferior tibiofibular ligament (Stage I), fibular (Weber-B fracture) (Stage II), posterior inferior tibiofibular ligament (Stage III), superficial deltoid ligament (Stage IVa), and deep deltoid ligament (Stage IVb). In all scenarios, the GST, external rotation stress test(45N), and Simulated weight-bearing condition(750N) were performed. The P-US measurement of the MCS was assessed at the anteromedial and inferomedial aspect of the ankle joint. Three different MCS distances were measured, as demonstrated in Figure 1. The fluoroscopic MCS measurements were assessed on a true mortise ankle view achieved during each loading condition. Spearman rank correlation was used to investigate the relationship between the P-US and fluoroscopic measurements. The inter- and intra-observer agreement was assessed using the intraclass correlation coefficient (ICC) through a two-way mixed-effects model with absolute agreement. Results: The P-US and fluoroscopic assessed medial ankle instability values during the GST, weight-bearing, and the external rotation stress test increased as the SER ankle injury stage progressed. The P-US values measured during all stress tests demonstrated a moderate to strong positive correlation with those measured with the fluoroscopy (Spearman's rank correlation ranged from 0.61-0.93, p-values

Category: Ankle; Basic Sciences/Biologics; Sports; Trauma Introduction/Purpose: There is a high prevalence of coexisting lateral ankle ligament injuries and syndesmotic ligamentous injuries. However, it is unclear whether syndesmotic ligaments directly contribute toward the stability of the lateral ankle. Dynamic ultrasonography (US) is an imaging modality increasingly used for the care of orthopaedic foot and ankle patients because it allows dynamic evaluation of structures at the point of care with little risk to the patient and at low-cost. The aim of this study is to assess the effect of syndesmotic injury as well as combined syndesmotic and lateral ankle injury on the stability of the lateral ankle. Methods: Sixteen fresh frozen above-knee amputated cadaveric specimens, divided into two groups, underwent ultrasound evaluation for lateral ankle stability. In both the groups, the assessment was first done with all ligaments intact and later with sequential transection of anterior inferior tibiofibular ligament (AITFL), interosseous ligament (IOL), posterior inferior tibiofibular ligament (PITFL), anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL) and posterior talofibular ligament (PTFL). In all scenarios, two loading conditions were considered: (1) Anterior drawer test: 50N and 80N and (2) Lateral clear space (LCS): 1.7Nm torque. The talar translation and LCS to the fixed tibial plafond were measured using Image J. Wilcoxon rank-sum test was used to compare the findings of each ligamentous transection state to the intact state. A p-value

Category: Ankle; Trauma Introduction/Purpose: Syndesmotic instability, when subtle, is challenging to diagnose and often requires visualization of the syndesmosis during applied stress. The purpose of this study was to determine the association between tibiofibular clear space (TFCS) values measured with 1) a portable ultrasound (US) device and 2) fluoroscopy during applied external roation stress for the evaluation of syndesmotic instability. Methods: Eight fresh lower leg cadaveric specimen amputated above the proximal tibiofibular joint were used in this study. Portable US device (Butterfly iQ, Butterfly Network Inc) images and fluoroscopic images taken by a mini C-arm were used to evaluate the ankle syndesmosis in the intact stage, and after sequentially sectioning of the anterior-inferior tibiofibular ligament (AITFL), interosseous ligament (IOL), and posterior-inferior tibiofibular ligament (PITFL) at 7.5Nm torque. A Pearson’s correlation was performed to investigate the correlation between the TFCS among the two modalities. A paired t-test was used to compare TFCS values measured with US or fluoroscopy. Three cadavers were measured by two independent observers to assess reliability of the measurements for each diagnostic modality and analyzed using intraclass correlation coefficients (ICC). P-values of < 0.05 were considered significant. Results: The mean TFCS (+- SD mm) values measured with the US and fluoroscopy are presented in Table 1. TFCS values obtained with the US and fluoroscopy correlated (rho 0.60). Between the imaging modalities similar TFCS values were found in the intact state (difference 0.81+-1.0, p-value 0.061). Compared with fluoroscopy, the TFCS values measured using US increased significantly after sequential transection of the AITFL (0.039), IOL (p=0.004) and PITFL (p

Category: Ankle Introduction/Purpose: To evaluate whether sagittal translation could be detected with ultrasound and arthroscopy and to compare the increasing tibiofibular sagittal translation seen with ultrasound (US) and Arthroscopy. Methods: Eight fresh lower leg cadaveric specimen amputated above the proximal tibiofibular joint were used in this study. The ankle syndesmosis was evaluated using a handheld US device (Butterfly iQ, Butterfly Network Inc, Guilford) and arthroscopy with intact-, and after sequent sectioning of anterior-inferior tibiofibular ligament (AITFL), interosseous ligament (IOL), and posterior- inferior tibiofibular ligament (PITFL). Sagittal plane translation was simulated with 100N of anterior to posterior (A-to-P) and posterior to anterior (P-to-A) hook force which was applied 5cm above of the ankle joint (Figure 1). Pearson’s correlation, one- way repeated measures ANOVA, and Wilcoxon signed-rank test were used for comparison. Three cadavers were measured by two independent observers to assess reliability and analyzed using intraclass correlation coefficients (ICC). Results: A-to-P translation values obtained with US and Arthroscopy had a correlation of -0.14, and P-to-A translation correlation of 0.44. Using US, intact translation was 0.94+-0.62 with A-to-P hook and 0.87+-0.5 with P-to-A hook. Subsequent A- to-P and P-to-A translation increased with 0.07+-0.96mm and 0.04+-0.76 after AITFL cut, with 0.53+-0.9 and 0.15+-0.5 after IOL cut, and with 0.81+-1.3mm and 0.45+-0.8 after PITFL cut (p-values between 0.122 and 0.270) . Using arthroscopy, intact translation was 0.40 +-0.3 with A-to-P hook and 0.99+-0.5 with P-to-A hook. Subsequent A-to-P and P-to-A translation increased from intact with; 0.001+-0.3 and 0.30+-0.4 after AITFL cut, 0.19+-0.4 and 0.74+-0.7 after IOL cut, and 0.40+-0.5 and 1.1+-0.9 after PITFL cut (p-values between 0.005 and 0.037). No statistical differences between US and Arthroscopy were found. Conclusion: US was unable to differentiate between the different stages of injury, even though a similar increase in translation was seen as compared to arthroscopy. Probably this is due to the high variability seen in the US translation values. As US does have several advantages over arthroscopy; availability, non-invasiveness, low costs, and allowance of using the contralateral side as a direct comparison, this technique should be further explored as a potential diagnostic assessment technique of diagnosing occult syndesmotic instability in the sagittal plane.

Category: Ankle; Sports; Trauma Introduction/Purpose: There is a high incidence of concomitance between lateral ankle ligament injuries and syndesmotic ligamentous injuries. However, it is unclear whether syndesmotic ligaments directly contribute toward the stability of the lateral ankle. Stress radiographs are an accepted technique to assess the degree of lateral ankle instability by providing a static view of the ankle when subjected to the anterior drawer (AD) and talar tilt (TT) tests. The aim of this study is to assess the effect of syndesmotic injury as well as combined syndesmotic and lateral ankle injury on the stability of the lateral ankle. Methods: Sixteen fresh frozen above-knee amputated cadaveric specimens, divided into two groups, underwent fluoroscopic evaluation for lateral ankle stability. In both the groups, the assessment was first done with all ligaments intact and later with sequential transection of anterior inferior tibiofibular ligament (AITFL), interosseous ligament (IOL), posterior inferior tibiofibular ligament (PITFL), anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL) and posterior talofibular ligament (PTFL). In all scenarios, two loading conditions were considered: (1) Anterior drawer test: 50N and 80N and (2) Talar tilt and Lateral clear space (LCS): 1.7Nm torque. The talar translation, talar tilt, and LCS were measured using Image J. Wilcoxon rank-sum test was used to compare the findings of each ligamentous transection state to the intact state. A p-value

Category: Ankle; Arthroscopy; Sports; Trauma Introduction/Purpose: Numerous studies have shown a high incidence of associated lateral ankle and syndesmotic ligamentous injuries. It is unclear, however, if there is a direct contribution of the lateral ligaments towards stabilizing the syndesmosis. Using arthroscopy, we assessed to what extent lateral ankle ligaments contribute to syndesmotic stability in the coronal and sagittal plane. Our hypothesis was that lateral ankle ligament injury has effect on syndesmosis instability. Methods: Sixteen fresh frozen above-knee amputated cadaveric specimens were divided into two groups that underwent arthroscopic evaluation for syndesmotic stability. In both the groups, the assessment was done with all syndesmotic and ankle ligaments intact and later with sequential transection of the anterior talofibular ligament (ATFL), the calcaneofibular ligament (CFL), the posterior talofibular ligament (PTFL), anterior inferior tibiofibular ligament (AITFL), the interosseous ligament (IOL) and the posterior inferior tibiofibular ligament (PITFL). In all scenarios, coronal and sagittal loading conditions were considered under 100N of direct force to fibula. The measurements of the distal tibiofibular coronal plane space at the anterior and posterior third of syndesmosis were performed using arthroscopic probes with increment of 0.2mm diameter. Further the sagittal translation were measured by arthroscopic scaled probe. Dunnett test was used to compare the findings of each ligamentous transection state to the intact state. A p-value < 0.05 was considered significantly defferent. Results: Compared with the intact ligamentous state, there was no difference in coronal and sagittal stability when the lateral ankle ligaments (ATFL, CFL, PTFL) and AITFL were transected (Table1 and 2, Group1). However, after subsequent transection of the IOL, or after transection of the lateral ankle ligaments (ATFL, CFL or and PTFL) alongside the AITFL and IOL, both coronal space and sagittal translation increased as compared with the intact state (p-values p

Category: Sports; Ankle Introduction/Purpose: Destabilizing injuries to the lateral ligament have relied on physical examination and radiographic stress test for diagnosis, with a focus on anterior translation and tilting of the talus relative to the tibial bone. Portable ultrasonography (PUS) has increasingly been used in the clinical setting, allowing dynamic and non-invasive evaluation. The primary aim of this study was to assess the anterior translation and tilting of the talus with PUS in various stages of lateral ankle ligamentous injury. Secondary, we compared the instability values measured with PUS with those measured on fluoroscopy. Third, we aimed to determine the optimal cutoff values of the PUS that distinguish stable from unstable state. Methods: 8 fresh-frozen cadaveric specimens underwent PUS and fluoroscopic evaluation for lateral ankle stability. The assessment was done with all ligaments intact and later with sequential transection of the anterior-talofibular ligament (ATFL), the calcaneofibular ligament (CFL), and the posterior-talofibular ligament (PTFL). In all scenarios, 2 loading conditions were considered; 1) Performing the anterior drawer test under 50N and 80N of force, anterior translation was measured with PUS and fluoroscopy; 2) Performing the talar tilt test under 1.7Nm of torque, the lateral clear space (the distance between the fibular tip and lateral process of the talus) was measured with PUS, and the talar tilt angle was measured with fluoroscopy (Figure1). Pearson’s and Spearman’s rank correlation was used to determine the correlation. Youden’s J statistic was used to determine the optimal cutoff values for the PUS to distinguish intact or ATFL injury versus ATFL-CFL or ATFL-CFL-PTFL injuries under various loading conditions. Results: Strong positive correlations were found between PUS and fluoroscopic measurements (Pearson correlation:r=0.78- 0.85). PUS and fluoroscopic measurements during anterior translation and talar tilt test increased as additional ligaments were transected (Spearman’s rank correlation: anterior translation; r=0.74, p < 0.001: talar tilt; r=0.81, p=0.8). The optimal PUS cutoff values for distinguishing intact or ATFL injury from ATFL-CFL or ATFL-CFL-PTFL injuries were >=3.40mm (sensitivity 87.5%, specificity 81.25%) and >=4.78mm (sensitivity 87.5%, specificity 81.25%) of anterior talar translation under 50N and 80N of force respectively, as well as >=3.09mm (sensitivity 75%, specificity 93.75%) of the lateral clear space under 1.7Nm of torque. Conclusion: Portable ultrasonography for the diagnosis of lateral ankle instability was strongly correlated with fluoroscopic findings, and thus, can be a valuable diagnostic tool at the point of care. We recommend future in vivo research to investigate the accuracy of this new ultrasound application in a clinical setting.

Category: Ankle; Sports; Trauma Introduction/Purpose: About one-fifth of all patients diagnosed with an ankle sprain also suffer a ligamentous injury of the ankle syndesmosis. Despite the common concomitant injuries, it is still unclear whether there is a direct contribution of the lateral ligaments towards stabilizing the syndesmosis. Portable ultrasonography (PUS) has increasingly been used in the clinical setting, allowing dynamic and non-invasive evaluation at the point of care. The primary aim of this study was to assess to what extent lateral ankle ligaments contribute to syndesmotic stability in the sagittal and rotational plane using PUS. Secondary, we determine if PUS is a reliable tool for the assessment of syndesmotic instability. Our primary hypothesis was that lateral ankle ligaments contribute significantly to the stability of the ankle syndesmosis. Methods: 16 fresh-frozen cadaveric specimens were equally divided into 2 groups that underwent PUS evaluation for syndesmotic stability. The assessment was done at the intact state and later with sequential ligament transection. In group 1, the anterior talofibular ligament (ATFL) was transected, followed by the calcaneofibular ligament (CFL), the posterior talofibular ligament (PTFL), the anteroinferior tibiofibular ligament (AITFL), the interosseous ligament (IOL), and the posteroinferior tibiofibular ligament (PITFL). In group 2, the transection started with the AITFL then followed by the ATFL, the CFL, the IOL, the PTFL, and the PITFL. PUS measurements were performed during anterior to posterior (AP), posterior to anterior (PA), and external rotated loading condition (Figure 1). One-way ANOVA and post hoc Dunnett test were used to compare the findings of each state to the intact. Besides, we assessed the inter-rater and intra-rater reliability using the intraclass correlation coefficient (ICC) through a two-way mixed-effects model. Results: In group 1, showed that compared to the intact stage, fibular translation in the sagittal plane and the anterior tibiofibular clear space (TFCS) distance did not increase after transection of all three lateral ankle ligaments. However, the syndesmotic PUS measurements did increase after subsequent transection of the AITFL and IOL (p-values ranging from 0.047 to

Background: Vestibular compensation (VC) after unilateral labyrinthectomy (UL) consists of the initial and late processes. These processes can be evaluated based on the decline in the frequency of spontaneous nystagmus (SN) and the number of MK801-induced Fos-positive neurons in the contralateral medial vestibular nucleus (contra-MVe) in rats. Histamine H3 receptors (H3R) are reported to be involved in the development of VC. Objective: We examined the effects of betahistine, an H3R antagonist, on the initial and late processes of VC in UL rats. Methods: Betahistine dihydrochloride was continuously administered to the UL rats at doses of 100 and 200 mg/kg/day using an osmotic minipump. MK801 (1.0 mg/kg) was intraperitoneally administered on days 7, 10, 12, and 14 after UL, while Fos-positive neurons were immunohistochemically stained in the contra-MVe. Results: The SN disappeared after 42 h, and continuous infusion of betahistine did not change the decline in the frequency of SN. The number of MK801-induced Fos-positive neurons in contra-MVe significantly decreased on days 7, 10, and 12 after UL in a dose-dependent manner in the betahistine-treated rats, more so than in the saline-treated rats. Conclusion: These findings suggest that betahistine facilitated the late, but not the initial, process of VC in UL rats.

While the activation of the transcription factor interferon regulatory factor 5 (IRF5) is critical for the induction of innate immune responses, it also contributes to the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). IRF5 phosphorylation is a hallmark of its activation in the Toll-like receptor (TLR) pathway, where active IRF5 induces type I interferon and proinflammatory cytokine genes. By using the phosphate-binding molecule Phos-tag, without either radioisotopes or phospho-specific antibodies, the protocol described here enables detection of the phosphorylation of both human and murine IRF5, as well as that of other proteins.

This study was aimed to evaluate and compare the pathogenicity of rabies virus isolated from bats and dogs, and to verify the efficacy of a commercial rabies vaccine against these isolates. For evaluation of pathogenicity, mice were inoculated by the intramuscular route (IM) with 500MICLD50/0.03mL of the viruses. The cross-protection test was performed by vaccinating groups of mice by the subcutaneous route and challenged through the intracerebral (IC) route. Isolates were fully pathogenic when inoculated by the IC route. When inoculated intramuscularly, the pathogenicity observed showed different death rates: 60.0% for the Desmodus rotundus isolate; 50.0% for dog and Nyctinomops laticaudatus isolates; 40.0% for Artibeus lituratus isolate; 9.5% Molossus molossus isolate; and 5.2% for the Eptesicus furinalis isolate. Mice receiving two doses of the vaccine and challenged by the IC route with the isolates were fully protected. Mice receiving only one dose of vaccine were partially protected against the dog isolate. The isolates from bats were pathogenic by the IC route in mice. However, when inoculated through the intramuscular route, the same isolates were found with different degrees of pathogenicity. The results of this work suggest that a commercial vaccine protects mice from infection with bat rabies virus isolates, in addition to a canine rabies virus isolate.O estudo avaliou e comparou as propriedades patogênicas de cinco isolados do vírus da raiva de morcegos e um isolado do vírus da raiva de cão e analisou a eficácia de vacina comercial contra estes isolados, em camundongos. Para o estudo de patogenicidade camundongos foram inoculados pela via IM com 0,1 mL contendo 500MICLD50/0,03mL das amostras de vírus. Quando inoculados pela via IC, os isolados do vírus da raiva provocaram a morte de 100% dos camundongos. No entanto, 500MICLD50/0,03mL das mesmas amostras, inoculadas pela via IM, ocasionaram mortalidade de: 60,0% quando a amostra era de Desmodus rotundus; 50,0% de cão e de Nyctinomops laticaudatus; 40,0% de Artibeus lituratus; 9,5% de Molossus molossus; e 5,2% de Eptesicus furinalis. Camundongos que receberam duas doses de vacina foram protegidos quando desafiados pela via IC, com todas as amostras testadas. Quando os camundongos receberam uma dose da mesma vacina, houve proteção parcial daqueles desafiados com a amostra de cão. Todos os isolados do vírus da raiva testados foram patogênicos para camundongos, inoculados pela IC. No entanto, pela via IM, os mesmos isolados mostraram diferentes graus de patogenicidade. Concluiu-se também que a vacina comercial contra raiva protegeu os camundongos desafiados com amostras de vírus isolados de morcegos e de cão.

O presente trabalho visou estudar dez isolados de vírus da raiva de morcegos hematófagos e não-hematófagos do Estado do Rio de Janeiro em suas características genéticas quanto aos genes N e G. Além disso, estudou-se a resposta de camundongos vacinados com a vacina antirrábica produzida pela replicação da amostra Pitman-Moore em cultivo celular, frente ao desafio com estes isolados virais, utilizando-se um ensaio imunológico baseado no teste de potência NIH. A vacina antirrábica utilizada na imunização dos camundongos ofereceu proteção em mais de 80% dos camundongos vacinados com a diluição 1:5 da vacina, frente à maioria dos isolados. A análise filogenética do gene da proteína N apresentou um padrão de agregação dividido em variante de morcego hematófago e variante de morcego insetívoro, com todos os isolados de morcegos frugívoros Artibeus sp. tendo sido segregados com a variante característica de morcegos Desmodus rotundus. Foram observadas diferenças filogenéticas entre as variantes do vírus da raiva de morcego hematófago isoladas na Região Noroeste do Estado do Rio de Janeiro e aquelas isoladas nas Regiões Metropolitana e Sul do Estado. A substituição do resíduo ácido aspártico por ácido glutâmico na posição 118, encontradas na caracterização genética da proteína G dos isolados 704/97BR-DR e 151/98BR-DR, permite inferir que esta posição esteja relacionada à antigenicidade viral. Não foram observadas diferenças genéticas temporais entre os isolados estudados. A vacina antirrábica utilizada ofereceu proteção satisfatória contra a maioria dos isolados estudados.

Background: Surgical treatment is recommended for patients with severe allergic rhinitis (AR) refractory to medical treatment. Endoscopic posterior nasal neurectomy (PNN) is primarily performed to improve rhinorrhea in severe perennial AR, however studies on its long-term prognosis are lacking. Aims / Objectives: This study aimed to investigate the long-term prognosis of PNN. Materials and Methods: A questionnaire survey was administered to 17 patients (12 men and 5 women) at least 1 year after PNN. Nasal symptoms and medications, as well as patient satisfaction with surgery at the time of survey, were scored. Furthermore, scores were compared between patients with postoperative periods of > 5 years and < 5 years. Results: Nasal symptoms and medication scores significantly improved after surgery. There was no significant difference between patients with a postoperative period of > 5 years and < 5 years in both preoperative and postoperative nasal symptoms and medication scores. No correlation was found between patient satisfaction with surgery and postoperative period. Conclusions and Significance: PNN improved nasal symptoms and medication scores in patients with severe perennial AR. Furthermore, the study results suggest that the long-term effect of PNN for perennial AR lasts for > 5 years. [ABSTRACT FROM AUTHOR]