Injuries to both anterolateral ligament and Kaplan fiber of the iliotibial band do not increase preoperative pivot-shift phenomenon in ACL injury.

Background: To assess the incidence of anterolateral ligament (ALL) and Kaplan fiber of the iliotibial band (KF) injuries in patients with acute anterior cruciate ligament (ACL) injury on magnetic resonance imaging (MRI), and to investigate the association between these injuries and the magnitude of preoperative pivot-shift test. Method: One-hundred and five patients with primary ACL injury were retrospectively reviewed. ALL injury and KF injury were assessed by preoperative MRI, and subjects were allocated into four groups: Group A, neither injury; Group B, only ALL injury; Group C, only KF injury; Group D, simultaneous ALL and KF injuries. Before ACL reconstruction, tibial acceleration during the pivot-shift test was measured by an electromagnetic measurement system, and manual grading was recorded according to the International Knee Documentation Committee (IKDC) guideline. Results: In MRI, the ALL was identified in 104 patients (99.1%) and KF in 99 patients (94.3%). ALL and KF injuries were observed in 43 patients (43.9%) and 23 patients (23.5%), respectively. Patient distribution to each group was as follows; Group A: 43 patients (43.9%), Group B: 32 patients (32.7%), Group C: 12 patients (12.2%), Group D: 11 patients (11.2%). No significant differences were observed in tibial acceleration, and manual grading among the four groups. Conclusion: Simultaneous injury to both ALL and KF was uncommon, and preoperative pivot-shift phenomenon did not increase even in those patients. The finding suggests that the role of ALL and KF in controlling anterolateral rotatory knee laxity may be less evident in the clinical setting compared to a biomechanical test setting.

A 10-Year Study of the Trend of Accidental Falls in the Elderly in a Japanese Hospital.

Elderly people are prone to falls. We established the Falls Prevention Working Group (FPWG) at our hospital in 2015 to reduce the number of falls during hospitalization. This study compared the trend of in-hospital falls in the elderly in two time periods (2008/9 and 2018/9) and determined the effects of FPWG-implemented measures. Using medical records, we counted the monthly number of falls suffered by patients during hospitalization in April 2008-March 2009 and April 2018-March 2019. We also categorized the falls according to the severity of fall-related complications.A total of 3609 hospital falls were recorded during the 2008-2019 period (2008/9: n = 433, 2018/9: n = 324). Falls were more common in patients aged 70-79 in 2008/9 but were noted in those aged ≥ 80 in 2018/9. The mean number of falls/month (27.3 ± 6.4, range: 12-45) was stable throughout the year. The incidence of falls in 2018/9 (1.90/1000 per persons per day) was significantly lower than in 2008/9 (2.30/1000, p = 0.006). Level ≥ 3b accidents, reflecting serious accidents with complications, were encountered in 12 of 433 accidents in 2008/9 compared with significantly fewer accidents (2 of the same severity among 324 accidents) in 2018/9 (p = 0.030).Our results showed a decrease in in-hospital falls in 2018/9 and that the sufferers were older relative to 10 years earlier. A multidisciplinary team should recommend measures to prevent falls and an environment "resilient" to falls, and encourage patients to be aware of possible falls.

Knee Osteotomy Decreases Joint Inflammation Based on Synovial Histology and Synovial Fluid Analysis.

PURPOSE: To examine the biological changes in the joints of patients with knee osteoarthritis (OA) before and after around-knee osteotomy (AKO), focusing on synovial fluid (SF) and synovial pathological changes. METHODS: Patients who underwent AKO for medial compartment knee OA between 2019 and 2021 were examined. SF and synovium were obtained at the time of AKO and plate removal after bone union (mean, 16.8 months [range: 11-38 months] postoperatively). SF volume and interleukin (IL)-6 concentrations in SF were assayed using enzyme-linked immunosorbent assay. Synovitis was assessed histologically using a semiquantitative scoring system. Macrophage infiltration was assessed by immunohistochemistry using a semiquantitative score for F4/80 expression. The M1/M2 ratio was calculated using percentage of cells positive for CD80 and CD163. The expression of proinflammatory cytokines was assessed by the percentage of IL-1ß- and IL-6-positive cells. The number of vascular endothelial growth factor-positive luminal structures was counted to assess angiogenesis. The change in each parameter was compared before and after AKO using the Wilcoxon matched-pairs signed-rank test. RESULTS: Twenty-four knees of 21 patients were included. SF volume and IL-6 concentration significantly decreased postoperatively (12.6 ± 2.1 mL vs 4.2 ± 0.6 mL; P < .0001 and 50.5 ± 8.6 pg/mL vs 20.7 ± 3.8 pg/mL; P = .0001, respectively). A significant reduction in synovitis score (P = .0001), macrophage infiltration (P < .0003), M1/M2 ratio (P < .0007), angiogenesis (P < .0001), and the percentage of IL-1ß- and IL-6-positive cells in the intima (P < .008 and P < .002, respectively) was found after AKO. CONCLUSIONS: SF volume and IL-6 concentrations in the SF decreased and inflammatory synovium pathology improved after AKO. In addition to biomechanical changes, the biological environment of the joint can be improved after AKO. LEVEL OF EVIDENCE: Level IV, retrospective therapeutic case series.

Multimodal treatment, including extracorporeal shock wave therapy, for refractory chronic tension-type headache: a case report.

BACKGROUND: Few reports have described multidisciplinary treatment, including extracorporeal shock wave therapy, for patients with refractory chronic tension-type headache. In this study, we conducted multidisciplinary treatment for a patient with chronic tension-type headache who suffered from chronic headache refractory to treatment. CASE PRESENTATION: The patient was a 45-year-old Japanese male suffering from 20 years of headache. As his headache had worsened recently, he visited a local clinic. With the diagnosis of suspected tension-type headache, its treatment was unsuccessful and he was referred to our hospital. The neurology department confirmed the tension-type headache and prescribed another medication, but he showed no improvement. Then, the patient was referred to the rehabilitation medicine department for consultation. At the initial visit, we identified multiple myofascial trigger points in his bilateral posterior neck and upper back regions. At the initial visit, he was prescribed 10 mL of 1% lidocaine injected into the muscles in these areas. In addition, he received 2000 extracorporeal shock wave therapy into bilateral trapezius muscles, and was instructed to take oral Kakkonto extract granules, benfotiamine, pyridoxine hydrochloride, and cyanocobalamin. Cervical muscle and shoulder girdle stretches and exercises were also recommended. At follow-up treatment visits, we used extracorporeal shock wave therapy to bilateral trapezius muscles, which led to immediate pain relief. After 11 weeks, he was not taking any medication and his headache was subjectively improved and his medical treatment ended. CONCLUSION: A patient with chronic tension-type headache refractory to regular treatment was successfully treated with a multimodal approach including extracorporeal shock wave therapy in addition to standard treatment. For patients with tension-type headache accompanied by myofascial trigger points, it may be recommended to promptly consider aggressive multimodal treatment that includes extracorporeal shock wave therapy.

Rehabilitation therapy for a severe case of coronavirus disease 2019: a case report.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) infection require a long period of time to return to work and society due to significant physical weakness even after recovery. Here we report a patient with a history of nephrectomy who developed severe COVID-19 infection associated with muscle weakness but was able to return to society after rehabilitation therapy. CASE PRESENTATION: A Japanese man in his 40s was admitted to the hospital with PCR-based COVID-19 diagnosis. The respiratory condition worsened rapidly and was treated with extracorporeal membrane-assisted ventilation in the intensive case unit. On admission to the Rehabilitation Department on day T + 30 [T: day patient became febrile (38 °C)], he was unable to stand for a long time and used a walker. Rehabilitation therapy was postponed to prevent COVID-19 spread, but the patient was encouraged to exercise during isolation to improve trunk and lower extremity muscle strength. Physical therapy commenced on day T + 49 to improve gait and trunk and lower limb muscle strength. He was able to walk independently and later returned to work following discharge on day T + 53. A computed tomography scan showed an increase in psoas muscle volume from 276 before to 316 cm3 after physical therapy, together with a decrease in whole-body extracellular water:total body weight ratio from 0.394 to 0.389. CONCLUSIONS: We have described the beneficial effects of rehabilitation therapy in a patient with severe COVID-19 infection. In addition to exercise, we believe that nutrition is even more important in increasing skeletal muscle mass. Rehabilitation therapy is recommended to enhance the return of severely ill COVID-19 patients to routine daily activity.

Influence of Injury to the Kaplan Fibers of the Iliotibial Band on Anterolateral Rotatory Knee Laxity in Anterior Cruciate Ligament Injury: A Retrospective Cohort Study.

BACKGROUND: Biomechanical cadaveric studies have shown that Kaplan fibers (KFs) of the iliotibial band play a role in controlling anterolateral rotatory knee laxity in anterior cruciate ligament (ACL) injury. However, in the clinical setting, the contribution of injury to KFs on anterolateral rotatory laxity remains unclear. PURPOSE: To use magnetic resonance imaging (MRI) scans to detect concomitant KF injury in ACL-injured knees and to then examine the effect of KF injury on anterolateral rotatory laxity as measured by the pivot-shift test in a clinical setting. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: The study enrolled 91 patients with primary ACL tears (mean age 25 ± 11 years; 46 male and 45 female) whose MRI was conducted within 90 days after injury. KF injury was assessed by MRI according to previously reported criteria, and the patients were allocated to a KF injury group and a no-KF injury group. At the time of ACL reconstruction, the pivot-shift test was performed with the patient under anesthesia and quantitatively evaluated by tibial acceleration using an electromagnetic measurement system. Manual grading of the pivot-shift test was assessed according to guidelines of the International Knee Documentation Committee. The data were statistically compared between the 2 groups using Mann-Whitney U test and Fisher exact test (P < .05). RESULTS: KFs were identified in 85 patients (93.4%), and KF injury was detected in 20 of the 85 patients (23.5%). No significant differences were observed between the KF injury group (n = 20) and the no-KF injury group (n = 65) in demographic characteristics, the period from injury to MRI (8.0 ± 14.0 days vs 8.9 ± 12.1 days, respectively), the rate of meniscal injury (50.0% vs 53.8%), or the rate of anterolateral ligament injury (45.0% vs 44.6%). Regarding the pivot-shift test, no significant differences were observed in tibial acceleration (1.2 m/s2 [interquartile range, 0.5-2.1 m/s2] vs 1.0 m/s2 [interquartile range, 0.6-1.7 m/s2], respectively) or manual grading between the 2 groups. CONCLUSION: Concomitant KF injury did not significantly affect the pivot-shift phenomenon in acute ACL-injured knees. The findings suggest that the contribution of KF injury to anterolateral rotatory knee laxity may be limited in the clinical setting.

Facilitatory Effect of Extending the Course Duration on Dissemination of Educational Content.

The physiological practice course at Saitama Medical University provides students with the opportunity to learn physiological principles through wet labs and discussions. To develop a more effective method for maximizing learning outcomes, we extended the course's schedule from one day (1d) to two days (2d) per theme, evaluated self-administered questionnaires between two different years (pre and post-change), and examined whether the increased course length affected learning outcomes. Within the 2018 curriculum year, every theme of the course was completed in a day, including experiments in the wet lab and discussions. In 2019, each theme was assessed for two days. The second-year undergraduate medical students anonymously submitted the self-assessment questionnaire that addressed several aspects, such as understanding of the theme, through a 5-point Likert scale. The average Likert scores varied from 4 to 4.5 point for all questions, and significant differences were not found between the 1d and 2d courses. However, the ratio of students with the highest points increased for one question of the 2d course: 43.6% (1d) to 53.4% (2d) for understanding. Further, the standard deviation (SD) values decreased in the 2d course for every question: 0.29 (1d) to 0.15 (2d) for interest, 0.33 (1d) to 0.19 (2d) for understanding, 0.30 (d) to 0.17 (d) for communication, 0.34 (1d) to 0.19 (2d) for general evaluation. This reduction in the SD values indicated that the educational content was imparted more efficiently to students in the 2d course. Thus, we concluded that extending the course time facilitated dissemination of educational content for every theme. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01563-4.

Analysis of bone union after medial closing wedge distal femoral osteotomy using a new radiographic scoring system.

INTRODUCTION: To compare bone union after medial closing wedge distal femoral osteotomy (MCWDFO) with that after lateral closing wedge distal femoral osteotomy (LCWDFO) using a novel scoring system. MATERIALS AND METHODS: The data of 30 patients who received biplanar MCWDFO for valgus knees (MCWDFO group) were retrospectively examined and compared to that of 22 patients (25 knees) who underwent biplanar LCWDFO via a double-level osteotomy (DLO) for varus knees (LCWDFO group). The progression of bone union of the transverse osteotomy plane in the femur was assessed using a newly developed scoring system using radiographs taken immediately after surgery and 3 and 6 months postoperatively. The scoring system is based on a scale of zero to six points with higher scores indicating better bone union. The incidence of hinge fractures was assessed using CT images, and the rates of reoperation were evaluated using medical record data. RESULTS: The mean bone union score was significantly lower in the MCWDFO group than in the LCWDFO group 3 months (2.1 ± 1.9 vs. 3.7 ± 1.7, P < 0.01) and 6 months (3.8 ± 2.1 vs 4.9 ± 1.5, P < 0.05) postoperatively. The incidence ratio of hinge fractures was significantly higher in the MCWDFO group than in the LCWDFO group (70.0% vs. 32.0%, P < 0.01). Two patients in the MCWDFO group underwent reoperation for delayed bone union or non-union. CONCLUSION: Bone union progression was slower and hinge fractures were more frequently observed after MCWDFO than after LCWDFO via DLO. MCWDFO is technically challenging, and patients must be monitored closely during and after surgery.

The coronal lateral collateral ligament sign in the anterior cruciate ligament-injured knees was observed regardless of the knee laxity based on the quantitative measurements.

PURPOSE: The coronal lateral collateral ligament (LCL) sign has been reported to be associated with deviated position of the tibia on MRI due to anterior cruciate ligament (ACL) injuries. However, the relationships between LCL sign and clinical knee laxity evaluations are still unclear. The purpose of the study was to investigate the relationship between the coronal LCL sign and knee laxity measurements. METHODS: A retrospective review of unilateral ACL injured patients who underwent ACL reconstruction was performed. The coronal LCL sign was determined using magnetic resonance imaging (MRI). Clinical grading of the pivot-shift test, KT-1000 measurements, and quantitative measurements of the Lachman test and the pivot-shift test using an electromagnetic system, were compared between patients with positive and negative coronal LCL sign. A subgroup analysis of different age groups was then performed, dividing patients to adolescent (age ≤ 18 years) and adult (age > 18 years) groups. RESULTS: A total of 85 patients were enrolled, of which 45 patients had coronal LCL signs. The coronal LCL sign was not associated with the pivot-shift test clinical grading (n.s), KT-1000 measurement (n.s), the tibial translation during the Lachman test (n.s), or with tibia acceleration (n.s) and translation (n.s) during the pivot-shift test. The subgroup analysis also showed that the aforementioned parameters were not associated with the coronal LCL sign in either adolescent or adult subgroups. CONCLUSION: The occurrence of coronal LCL sign in MRI did not imply greater clinical knee laxity evaluations in patients with ACL tears. The knee laxity should routinely be evaluated regardless the coronal LCL sign. LEVEL OF EVIDENCE: Level III.

Patellofemoral Osteoarthritis Progresses After Medial Open-Wedge High Tibial Osteotomy: A Systematic Review.

PURPOSE: To investigate the progression of patellofemoral (PF) osteoarthritis (OA) after medial open-wedge high tibial osteotomy (OWHTO) and whether PF OA progression has an influence on clinical outcomes. METHODS: According to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA), EMBASE, PubMed, and Cochrane Library were searched in June 2020 for English-language studies that presented data on PF OA or cartilage degeneration before and after OWHTO. Descriptive statistics are presented. RESULTS: Twenty studies comprising 1,173 patients were included. The mean age was 57.1 years (range 18-84) with 826 (70.4%) female. The mean follow-up was 27.1 months (range 7-144). Ten studies reported the trochlear International Cartilage Research Society (ICRS) scores, with each of these studies reporting a greater proportion of patients with grades 2-4 OA postoperatively compared with preoperatively (relative risk = 1.19-2.76, I2 = 1.9%). Similarly, 7 studies reported patellar ICRS scores and found a greater proportion with grades 2-4 OA postoperatively (relative risk = 1.08-2.44, I2 = 0%). Four studies assessed PF Kellgren-Lawrence grade, each of which reported a greater proportion of patients with grades 2-4 OA postoperatively (relative risk = 1.25-21.0, I2 = 31%). The PF OA assessments were heterogenous, and studies using classifications except the ICRS score or Kellgren-Lawrence grade were not included in statistical analysis. Fifteen studies assessed patellar height; 10 studies reported significant decrease in patellar height after OWHTO. Only 3 studies reported clinical outcomes for patients with and without PF OA progression. Outcome reporting was variable across these studies, and a relationship between PF OA progression and clinical outcome could not be definitively determined. CONCLUSIONS: Patients appear to have progression of PF OA after medial OWHTO. However, there are currently insufficient studies with inconsistent measurements of outcomes to make meaningful conclusions regarding the impact of PF OA on clinical outcomes. LEVEL OF EVIDENCE: Level IV, systematic review of Level III-IV studies.

Differences in preoperative planning for high-tibial osteotomy between the standing and supine positions.

INTRODUCTION: Previous studies have reported that alignment changes depend on the patient's position in orthopedic surgery. However, it has not yet been well examined how the patient's position affects the preoperative planning in high-tibial osteotomy (HTO). Therefore, the aim of this study was to investigate the effects of the patient's position on preoperative planning in HTO. MATERIALS AND METHODS: A total of 60 knees in 55 patients who underwent HTO were retrospectively examined. Virtual preoperative planning for medial open-wedge HTO (OWHTO), lateral closed-wedge HTO (CWHTO), and hybrid CWHTO were performed by setting the percentage of the weight-bearing line (%WBL) at 62% as an optimal alignment. The correction angle differences between the supine and standing radiographs were measured. The virtual %WBL (v%WBL) was determined by applying the correction angle obtained from the standing radiograph to the supine radiograph. The %WBL discrepancy (%WBLd) was calculated as v%WBL - 62 (%) to predict the possible correction errors during surgeries. A single regression analysis was performed to examine the correlation between the correction angle difference and %WBLd. RESULTS: The mean correction angle was significantly higher when the preoperative planning was based on standing radiographs than when based on supine radiographs (P < 0.001), and the mean difference was 2.2 ± 1.5°. The difference between the two conditions in the medial opening gaps for OWHTO, lateral wedge sizes (mm) for CWHTO, and hybrid CWHTO were 2.6 ± 2.0, 2.3 ± 1.6, and 1.9 ± 1.4, respectively. The mean v%WBL was 71.2% ± 7.3%, and the mean %WBLd was 10.1% ± 7.4%. A single regression analysis revealed a linear correlation between the correction angle difference and %WBLd (%WBLd = 4.72 × correction angle difference + 0.08). No statistically significant difference in the parameters was found between the supine and standing radiographs postoperatively. CONCLUSIONS: We found significant differences in the estimated correction angles between the supine and standing radiographs in the planning for HTO. Therefore, surgeons should carefully consider the difference between supine and standing radiographs and estimate the possible correction error during surgery when planning a HTO.

GABAergic and glycinergic systems regulate ON-OFF electroretinogram by cooperatively modulating cone pathways in the amphibian retina.

The network mechanisms underlying how inhibitory circuits regulate ON- and OFF-responses (the b- and d-waves) in the electroretinogram (ERG) remain unclear. The purpose of this study was to investigate the contribution of inhibitory circuits to the emergence of the b- and d-waves in the full-field ERG in the newt retina. To this end, we investigated the effects of several synaptic transmission blockers on the amplitudes of the b- and d-waves in the ERG obtained from newt eyecup preparations. Our results demonstrated that (a) L-APB blocked the b-wave, indicating that the b-wave arises from the activity of ON-bipolar cells (BCs) expressing type six metabotropic glutamate receptors; (b) the combined administration of UBP310/GYKI 53655 blocked the d-wave, indicating that the d-wave arises from the activity of OFF-BCs expressing kainate-/AMPA-receptors; (c) SR 95531 augmented both the b- and the d-wave, indicating that GABAergic lateral inhibitory circuits inhibit both ON- and OFF-BC pathways; (d) the administration of strychnine in the presence of SR 95531 attenuated the d-wave, and this attenuation was prevented by blocking ON-pathways with L-APB, which indicated that the glycinergic inhibition of OFF-BC pathway is downstream of the GABAergic inhibition of the ON-system; and (e) the glycinergic inhibition from the ON- to the OFF-system widens the response range of OFF-BC pathways, specifically in the absence of GABAergic lateral inhibition. Based on these results, we proposed a circuitry mechanism for the regulation of the d-wave and offered a tentative explanation of the circuitry mechanisms underlying ERG formation.

Dose-response of rPMS for upper Limb hemiparesis after stroke.

INTRODUCTION: Repetitive peripheral magnetic stimulation (rPMS) therapy is an innovative and minimally invasive neurorehabilitative technique and has been shown to facilitate neural plasticity. However, there is at present no research that clarifies the dose-response of rPMS therapy on the recovery of upper limb hemiparesis after stroke. This trial aims to clarify the dose-response of rPMS therapy combined with intensive occupational therapy (OT) for chronic stroke patients with moderate to severe upper limb hemiparesis. METHODS AND ANALYSIS: This multicenter, prospective, assessor-blinded, randomized controlled study with 3 parallel groups will be conducted from January 20, 2020 to September 30, 2022. Fifty patients will be randomly assigned in a ratio of 1:2:2 to the control group, the group receiving daily 2400 pulses of rPMS, or the group receiving daily 4800 pulses of rPMS, respectively. From the day after admission (Day 1), rPMS therapy and intensive OT will be initiated. The primary outcome is the change in the motor function of the affected upper extremity (Fugl-Meyer Assessment) between the time of admission (Day 0) and the day after 2 weeks of treatment (Day 14). Secondary outcomes will include the changes in spasticity, active range of motion, motor evoked potential, and activity of daily living. ETHICS AND DISSEMINATION: The study was approved by the Jikei University Certified Review Board for all institutions (reference number: JKI19-020). Results of the primary and secondary outcomes will be published in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients. TRIAL REGISTRATION NUMBER: jRCTs032190191.

Assessment for resumed driving in stroke patients via Functional Independence Measure1.

BACKGROUND: Some stroke survivors hope to resume driving after hospital discharge. For those who had driven frequently before their stroke, a normal daily life depends on being able to drive. OBJECTIVE: Our objective was to determine whether Functional Independence Measure (FIM) scores predict patient driving ability, which would make them a suitable index for determining if a stroke patient can resume driving. METHODS: This was a retrospective study of 71 patients who suffered from stroke. We divided them into three groups based on their driving status after discharge: (1) resumed driving (Driver), (2) wish to resume driving (Wisher), and (3) no wish to resume driving (Non-wisher). We compared total FIM scores and subcategories of FIM scores across groups. RESULTS: Scores on the Motor-FIM and Cognitive-FIM were highest in the Driver group, followed by the Wisher and Non-wisher groups. Moreover, scores on the 'problem solving' and 'memory' subcategories of the Cognitive-FIM were significantly higher in the Driver group than in the Wisher group. CONCLUSIONS: The FIM could be a useful assessment tool for determining whether or not stroke patients can resume driving. Moreover, among the Cognitive-FIM sub-categories, problem solving and memory ability might be the scores most relevant for this decision.

Case Report: Reversible Cerebral Vasoconstriction Syndrome in Cerebral Malaria.

Cerebral malaria is a severe complication of falciparum malaria that occurs infrequently in adults. Here, we describe the case of a 21-year-old man who presented with fever and headache 13 days after returning from a 12-day trip to Kenya and was subsequently diagnosed with falciparum malaria. Complications of cerebral malaria developed within 1 day after the initiation of therapy with intravenous quinine, and the patient entered a deep coma. Magnetic resonance angiography (MRA) revealed multiple vasoconstrictions in his brain. The resulting neurocognitive disorders that persisted after parasite clearance improved gradually, as confirmed by MRA, enabling the patient to perform activities of daily living upon discharge. In this case of cerebral malaria, the MRA findings indicated the involvement of reversible cerebral vasoconstriction syndrome.

Effects of neuroactive agents on axonal growth and pathfinding of retinal ganglion cells generated from human stem cells.

We recently established a novel method for generating functional human retinal ganglion cells (RGCs) from human induced pluripotent cells (hiPSCs). Here, we confirmed that RGCs can also be generated from human embryonic stem cells (hESCs). We investigated the usefulness of human RGCs with long axons for assessing the effects of chemical agents, such as the neurotrophic factor, nerve growth factor (NGF), and the chemorepellent factors, semaphorin 3 A (SEMA3A) and SLIT1. The effects of direct and local administration of each agent on axonal projection were evaluated by immunohistochemistry, real-time polymerase chain reaction (PCR), and real-time imaging, in which the filopodia of the growth cone served as an excellent marker. A locally sustained agent system showed that the axons elongate towards NGF, but were repelled by SEMA3A and SLIT1. Focally transplanted beads that released SLIT1 bent the pathfinding of axons, imitating normal retinal development. Our innovative system for assessing the effects of chemical compounds using human RGCs may facilitate development of novel drugs for the examination, prophylaxis, and treatment of diseases. It may also be useful for observing the physiology of the optic nerve in vitro, which might lead to significant progress in the science of human RGCs.

The TRPM1 Channel Is Required for Development of the Rod ON Bipolar Cell-AII Amacrine Cell Pathway in the Retinal Circuit.

Neurotransmission plays an essential role in neural circuit formation in the central nervous system (CNS). Although neurotransmission has been recently clarified as a key modulator of retinal circuit development, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we investigated the role of neurotransmission from photoreceptor cells to ON bipolar cells in development using mutant mouse lines of both sexes in which this transmission is abrogated. We found that deletion of the ON bipolar cation channel TRPM1 results in the abnormal contraction of rod bipolar terminals and a decreased number of their synaptic connections with amacrine cells. In contrast, these histological alterations were not caused by a disruption of total glutamate transmission due to loss of the ON bipolar glutamate receptor mGluR6 or the photoreceptor glutamate transporter VGluT1. In addition, TRPM1 deficiency led to the reduction of total dendritic length, branch numbers, and cell body size in AII amacrine cells. Activated Goα, known to close the TRPM1 channel, interacted with TRPM1 and induced the contraction of rod bipolar terminals. Furthermore, overexpression of Channelrhodopsin-2 partially rescued rod bipolar cell development in the TRPM1-/- retina, whereas the rescue effect by a constitutively closed form of TRPM1 was lower than that by the native form. Our results suggest that TRPM1 channel opening is essential for rod bipolar pathway establishment in development.SIGNIFICANCE STATEMENT Neurotransmission has been recognized recently as a key modulator of retinal circuit development in the CNS. However, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we focused on neurotransmission between rod photoreceptor cells and rod bipolar cells in the retina. We used genetically modified mouse models which abrogate each step of neurotransmission: presynaptic glutamate release, postsynaptic glutamate reception, or transduction channel function. We found that the TRPM1 transduction channel is required for the development of rod bipolar cells and their synaptic formation with subsequent neurons, independently of glutamate transmission. This study advances our understanding of neurotransmission-mediated retinal circuit refinement.

High tibial osteotomy combined with cancellous bone graft and osteochondral autograft transplantation in a patient with massive osteochondral defects in the medial femoral condyle.

Treatment of massive osteochondral defects of the medial femoral condyle is challenging. A 46-year-old man who had a medial femoral condyle fracture on his left knee underwent osteosynthesis in a hospital, but the pain remained and the patient was referred to our hospital 8 months after the surgery. Radiographs showed a varus alignment of the leg, and magnetic resonance image showed a massive necrotic area in the medial femoral condyle. The patient received high tibial osteotomy (HTO) combined with iliac cancellous bone graft and an osteochondral autograft transplantation. Pain and the knee function markedly improved 2 years after the surgery. A second look arthroscopy showed a well-covered bone graft site with cartilaginous tissue and a well-integrated osteochondral plug. HTO combined with cancellous bone autograft and osteochondral autograft transplantation could be an effective treatment for patients presenting with a varus knee deformity associated with massive osteochondral defects in the medial femoral condyle.

Factors influencing mother-child communication about fathers with neurobehavioural sequelae after brain injury.

OBJECTIVE: The present study clarified factors related to mother-child communication openness when fathers suffer neurobehavioural sequelae after stroke or traumatic brain injury. RESEARCH DESIGN: A cross-sectional study using self-report anonymous questionnaires was conducted. METHODS AND PROCEDURES: Forty-one mothers with 6-22-year-old children participated. The questionnaire examined personal factors (mother's psychological distress), social/family factors (family support functioning), illness-related factors (father's time at home and neurobehavioural sequelae severity) and mother's perceived level of open communication. Multiple regression was used to analyse factors related to mother-child communication openness. RESULTS: Mother-child open communication was explained by family support functioning (ß = 0.449), father's time at home (ß = -0.325) and mother's psychological distress (ß = -0.303). Neurobehavioural sequelae severity was not associated with mother-child open communication. CONCLUSIONS: Personal, social/family and illness-related factors were related to mother-child communication about paternal illness. Professionals should promote optimal family support functioning, connect families with external resources and assess families' interaction processes.

Generation of Retinal Ganglion Cells With Functional Axons From Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells.

PURPOSE: We previously generated self-induced retinal ganglion cells (RGCs) with functional axons from human induced pluripotent stem cells (hiPSCs). We investigated whether self-induced RGCs from mouse embryonic stem cells (mESCs) and induced pluripotent stem cells (miPSCs) are realized by the similar induction protocol. METHODS: Retinal ganglion cells were induced using a protocol in which floating embryoid bodies (EBs) were differentiated into a retinal cell lineage in three-dimensional culture and subsequently attached to two-dimensional culture dishes with brain-derived neurotrophic factor (BDNF) supplementation. RESULTS: Retinal ganglion cells developed in an attached clump of cells originating from the optic vesicle, and most axons grew from RGC cell bodies at the margins of the clump. The differentiation of RGCs was confirmed by the expression of specific markers, including Brn3a and Math5. The axons contained neurofilament subtypes and tau, and manifested axonal transport and sodium-dependent action potentials. The RGCs derived from mESCs and miPSCs generally showed similar profiles, including RNA and protein expression levels and function. CONCLUSIONS: Retinal ganglion cells generated from mESCs and miPSCs, especially the latter, may contribute to research associated with RGCs and to in vitro analyses of genetically modified mice.