Low plasma 25-hydroxyvitamin D levels are not associated with a high risk of recurrent falls in community-dwelling Japanese adults: the Murakami cohort study.

Reports on the association between vitamin D levels and fall risk have been mixed, and long-term follow-up studies are lacking. This 5-year cohort study of 5,343 community-dwelling Japanese people aged 40-74 years found that low vitamin D levels are not associated with a high risk of recurrent falls. PURPOSE: Findings of cohort studies on the association between plasma 25-hydoxyvitamin D (25[OH]D) levels and fall risk have been mixed, and long-term follow-up studies are lacking. The present study investigated whether low plasma 25(OH)D levels are longitudinally associated with a high risk of recurrent falls in adults. METHODS: This 5-year cohort study included 5,343 community-dwelling Japanese people aged 40-74 years. Baseline blood collection and a questionnaire survey were conducted in 2011-2013. Plasma 25(OH)D levels were determined and divided into quintiles after stratification by season, sex, and age group. Information on recurrent falls occurring in the year before the survey 5 years later was obtained, and participants with two or more falls were considered to have experienced recurrent falls. Covariates were sex, age, marital status, education, occupation, BMI, total physical activity levels, calcium intake, vitamin K intake, smoking, drinking, and disease history. RESULTS: Mean age and 25(OH)D levels were 60.9 years and 50.9 nmol/L, respectively. In the follow-up survey, 209 recurrent falls were reported. Plasma 25(OH)D levels were not significantly associated with the occurrence of recurrent falls in men, women, or men/women-combined (adjusted P for trend = 0.1198, 0.8383, and 0.2355, respectively). In men and men/women-combined, adjusted ORs for recurrent falls in the lowest quintile were significantly lower (adjusted OR = 0.42 and 0.59, respectively) than the middle quintile (reference). CONCLUSION: Low plasma 25(OH)D levels are not associated with a high risk of recurrent falls in middle-aged and older people. Further longitudinal studies will be needed to confirm our findings in other populations.

Neck and shoulder pain in thoracic adolescent idiopathic scoliosis 10 years after posterior spinal fusion.

PURPOSE: We aimed to determine the clinical significance of neck and shoulder pain (NSP) 10 years after posterior spinal fusion (PSF) for thoracic adolescent idiopathic scoliosis (AIS) and the relationship between radiographic parameters and NSP. METHODS: Of 72 patients who underwent PSF for thoracic AIS (Lenke 1 or 2) between 2000 and 2013, we included 52 (46 females; Lenke type 1 in 34 patients and type 2 in 18; mean age, 25.6 years) who underwent NSP evaluation using visual analog scale (VAS, 10 cm) 10 years postoperatively (follow-up rate, 72.2%). Correlation analyses were performed using Spearman's rank correlation coefficient (r). RESULTS: The VAS for NSP was 2.6 cm in median and 3.4 cm in mean at 10 years. The VAS had significant negative correlations with several SRS-22 domain scores (rs = - 0.348 for pain, - 0.347 for function, - 0.308 for mental health, and - 0.372 for total) (p < 0.05). In addition, the VAS score was significantly correlated with cervical lordosis (CL) (rs = 0.296), lumbar lordosis (rs = - 0.299), and sacral slope (rs = 0.362) (p < 0.05). Furthermore, at the 10-year follow-up, CL was significantly negatively correlated with T1 slope (rs = - 0.763) and thoracic kyphosis (TK) (- 0.554 for T1-12 and - 0.344 for T5-12) (p < 0.02). CONCLUSION: NSP was associated with deterioration in SRS-22 scores, indicating that NSP is a clinically significant long-term issue in PSF for thoracic AIS. Restoring or maintaining the TK and T1 slopes, which are controllable factors during PSF, may improve cervical lordosis and alleviate NSP at 10-year follow-up.

Delayed paraparesis after posterior spinal fusion for congenital scoliosis: a case report.

INTRODUCTION: Although multimodal intraoperative neuromonitoring (IONM), which has high sensitivity and specificity, is typically performed during spinal deformity surgery, neurological status may deteriorate with delay after surgical maneuvers. Here, we report a rare case of delayed postoperative neurological deficit (DPND) that was not detected by IONM during posterior spinal fusion (PSF) for congenital scoliosis. CASE PRESENTATION: A 14-year-old male presented with congenital scoliosis associated with T3 and T10 hemivertebrae. Preoperative Cobb angle of proximal thoracic (PT) and main thoracic (MT) curves were 50° and 41°, respectively. PSF (T1-L1) without hemivertebrectomy was performed, and the curves were corrected to 31° and 21° in the PT and MT curves, respectively, without any abnormal findings in IONM, blood pressure, or hemoglobin level. However, postoperative neurological examination revealed complete loss of motor function. A revision surgery, release of the curve correction by removing the rods, was immediately performed and muscle strength completely recovered on the first postoperative day. Five days postoperatively, PSF was achieved with less curve correction (36° in the PT curve and 26° in the MT curve), without postoperative neurological deficits. DISCUSSION: Possible mechanisms of DPND in our patient are spinal cord ischemia due to spinal cord traction caused by scoliosis correction and spinal cord kinking by the pedicle at the concave side. Understanding the possible mechanisms of intra- and postoperative neural injury is essential for appropriate intervention in each situation. Additionally, IONM should be continued to at least skin closure to detect DPND observed in our patient.

Quantitative assessment of muscle activity of back and lower extremities, whole body sagittal alignment, body sway, and health-related quality of life in adult spinal deformity patients before and after spinopelvic correction surgery: From the standpoint of the "cone of economy".

BACKGROUND AND AIMS: Pain and muscle fatigue in the low back and lower extremity associated with adult spinal deformity (ASD) markedly limit daily activities and affect quality of life. This study aimed to clarify if spinal correction surgery decreases the muscle activity requirements in relation to alignment and balance parameters. METHODS: Integrated electromyogram (I-EMG) studies of the low back and lower extremity in addition to whole body alignment, body sway, and health-related quality of life (HRQOL) were evaluated in 16 patients with ASD before and after surgery. Sixteen healthy volunteers were included as control subjects. Muscle activities of the bilateral lumbar paravertebral, biceps femoris, rectus femoris, gastrocnemius, and tibialis anterior were measured using surface electromyogram in both resting and working standing positions. Surgical outcomes were based on improvements in muscle fatigue using the sum of the whole muscle I-EMGs and body sway. HRQOL was evaluated by SRS-22r, which measures 4 domains (function, pain, self-image, mental health) and subtotal scores. RESULTS: In controls, the sum of the 10 whole I-EMGs (mVms; mean ± SD) was 3316 ± 1247 in the resting standing position and 5625 ± 2065 in the working standing position. The I-EMG values were higher in ASD patients than in healthy subjects; in the resting standing position, the sum of the whole 10 I-EMGs significantly decreased from baseline (9125 ± 3529) to 3 (6088 ± 1793) and 6 (6381 ± 1776) months postoperatively (p < 0.01). In the working standing position, the sum in ASD patients also significantly decreased from baseline (14,160 ± 5474) to 3 (8085 ± 2540) and 6 (8557 ± 3025) months postoperatively (p < 0.01). I-EMG values did not differ significantly between the 3- and 6-month time points in either condition. Body sway was also improved postoperatively at 3 months and maintained at 6 months along with the amelioration of whole-body sagittal alignment, and 4 domains and subtotal SRS-22r scores significantly increased postoperatively. CONCLUSION: Following spinopelvic correction surgery, whole body sagittal alignment was improved, and muscle activity based on I-EMG and body sway were significantly decreased. The SRS-22r scores after surgery also indicated significant improvement, suggesting that muscle fatigue in the standing position was ameliorated, i.e., the "cone of economy" was normalized.

Instrumentation failure following pediatric spine deformity growth-sparing surgery using traditional growing rods or vertical expandable prosthetic titanium ribs.

BACKGROUND: Instrumentation failure (IF) is a major complication associated with growth-sparing surgery for pediatric spinal deformities; however, studies focusing on IF following each surgical procedure are lacking. We aimed to evaluate the incidence, timing, and rates of unplanned return to the operating room (UPROR) associated with IF following each surgical procedure in growth-sparing surgeries using traditional growing rods (TGRs) and vertical expandable prosthetic titanium ribs (VEPTRs). METHODS: We reviewed 1,139 surgical procedures documented in a Japanese multicenter database from 2015 to 2017. Of these, 544 TGR and 455 VEPTR procedures were included for evaluation on a per-surgery basis. IF was defined as the occurrence of an implant-related complication requiring revision surgery. RESULTS: The surgery-based incidences of IF requiring revision surgery in the TGR and VEPTR groups were 4.3% and 4.0%, respectively, with no significant intergroup difference. Remarkably, there was a negative correlation between IF incidence per surgical procedure and the number of lengthening surgeries in both groups. In addition, rod breakage in the TGR group and anchor-related complications in the VEPTR group tended to occur relatively early in the treatment course. The surgery-based rates of UPROR due to IF in the TGR and VEPTR groups were 2.0% and 1.5%, respectively, showing no statistically significant difference. CONCLUSIONS: We found that IF, such as anchor related-complications and rod breakage, occurs more frequently earlier in the course of lengthening surgeries. This finding may help in patient counseling and highlights the importance of close postoperative follow-up to detect IF and improve outcomes.

Anatomical Pelvic Parameters Using the Anterior Pelvic Plane: Normative Values and Estimation of the Standing Sagittal Alignment in Healthy Volunteers.

Introduction: In this study, we aim to estimate the natural standing sagittal alignment in patients with adult spinal deformity (ASD), firstly by investigating the normative values of anatomical pelvic parameters based on the anterior pelvic plane (APP) in a healthy population, and to clarify the relationships between the anatomical and positional pelvic parameters in standing position. Methods: The images of biplanar slot-scanning full-body stereoradiography in 140 healthy Japanese volunteers (mean age, 39.5 years; 59.3% female) were examined. In addition to three-dimensional measurements including pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT), the APP angle (APPA; anterior tilting=positive) was measured as the angle between the APP and the vertical line using the two-dimensional lateral image. Anatomical SS and PT (aSS and aPT) were calculated as the angles of SS and PT in reference to APP. Results: The mean (range) values of APPA, aSS, and aPT were determined to be 0.7° (-16.8°/15.5°), 36.8° (18.3°/64.9°), and 13.2° (-0.6°/28.7°), respectively. Moreover, SS was found to be significantly correlated with PI and aSS, while PT was significantly correlated with PI, aSS, aPT, and body weight. Also, PT was significantly larger in females than in males. Multiple linear regression analysis deduced the following equations: SS=0.404×aSS+0.203×PI+12.463, PT=-0.391×aSS+0.774×PI+1.950×sex (male=0, female=1)-12.971, wherein aSS had the greatest effect for predicting SS among the included factors and PI had the greatest effect for predicting PT. In addition, no significant differences were noted between PT/PI and aPT/PI. Conclusions: As per the results of this study, significant correlations were noted among parameters and predicting models for positional parameters (SS and PT) using anatomical parameters (aSS and aPT) in a healthy population. This novel measurement concept based on the APP has been considered to be useful in estimating natural SS and PT in standing position using the anatomical pelvic parameters in patients with ASD.

Usefulness of the spectral shaping dual-source computed tomography imaging technique in posterior corrective fusion for adolescent idiopathic scoliosis.

PURPOSE: Since childhood exposure to radiation has been demonstrated to increase cancer risk with increase in radiation dose, reduced radiation exposure during computed tomography (CT) evaluation is desired for adolescent idiopathic scoliosis (AIS). Therefore, this retrospective study aimed to investigate the radiation dose of dual-source CT using a spectral shaping technique and the accuracy of the thoracic pedicle screw (TPS) placement for posterior spinal fusion (PSF) in patients with AIS. METHODS: Fifty-nine female patients with thoracic AIS who underwent PSF using CT-guided TPSs were included and divided into two groups comprised of 23 patients who underwent dual-source CT (DSCT) with a tin filter (DSCT group) and 36 who underwent conventional multislice CT (MSCT group). We assessed the CT radiation dose using the CT dose index (CTDIvol), effective dose (ED), and accuracy of TPS insertion according to the established Neo's classification. RESULTS: The DSCT and MSCT groups differed significantly (p < 0.001) in the mean CTDIvol (0.76 vs. 3.31 mGy, respectively) and ED (0.77 vs. 3.47 mSv, respectively). Although the correction rate of the main thoracic curve in the DSCT group was lower (65.7% vs. 71.2%) (p = 0.0126), the TPS accuracy (Grades 0-1) was similar in both groups (381 screws [88.8%] vs. 600 screws [88.4%], respectively) (p = 0.8133). No patient required replacement of malpositioned screws. CONCLUSION: Spectral shaping DSCT with a tube-based tin filter allowed a 75% radiation dose reduction while achieving TPS insertion accuracy similar to procedures based on conventional CT without spectral shaping.

Chronic Pain in the Lower Extremities and Low Back is Associated With Recurrent Falls in Community-Dwelling Japanese People Aged 40-74 Years.

OBJECTIVE: To determine the longitudinal association between chronic pain in the lower extremities and low back and the odds of recurrent falls in middle-aged and older people. DESIGN: A cohort study. SETTING: Communities in Japan. PARTICIPANTS: Participants were 7540 community-dwelling volunteers aged 40-74 years (N=7540). The baseline survey was a self-administered questionnaire conducted between 2011-2013. Predictors were presence of chronic pain in the knee, foot or ankle, and low back, with the degree of pain categorized as none, very mild/mild, moderate, or severe/very severe. Covariates in the multivariate model of chronic pain in a site were demographics, body mass index, physical activity level, disease history, and chronic pain in the other 2 sites. Logistic regression analysis was used to calculate odds ratios (ORs). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Recurrent falls in the year before the 5-year follow-up survey. RESULTS: Mean participant age was 60.2 years. Higher degrees of chronic pain were associated with higher odds of recurrent falls for the knee (P=.0002) with a higher OR of 1.48 (95% CI: 1.11-1.97), for the foot or ankle (P=.0001) with a higher OR of 1.97 (95% CI: 1.36-2.86), and for the low back (P=.0470) with a higher OR of 1.45 (95% CI: 1.09-1.91) in those with any degree of pain relative to those without pain. Higher degrees of chronic knee pain were associated with higher odds of recurrent falls in women (P=.0005), but not in men (P=.0813). Meanwhile, higher degrees of chronic low back pain were associated with the odds of recurrent falls in men (P=.0065), but not in women (P=.8735). CONCLUSIONS: Chronic pain in the knee, foot or ankle, and lower back was independently and dose-dependently associated with a higher risk of recurrent falls. A marked sex-dependent difference was also noted in the association.

An easy-to-implement, non-invasive head restraint method for monkey fMRI.

Functional magnetic resonance imaging (fMRI) in behaving monkeys has a strong potential to bridge the gap between human neuroimaging and primate neurophysiology. In monkey fMRI, to restrain head movements, researchers usually surgically implant a plastic head-post on the skull. Although time-proven to be effective, this technique could create burdens for animals, including a risk of infection and discomfort. Furthermore, the presence of extraneous objects on the skull, such as bone screws and dental cement, adversely affects signals near the cortical surface. These side effects are undesirable in terms of both the practical aspect of efficient data collection and the spirit of "refinement" from the 3R's. Here, we demonstrate that a completely non-invasive fMRI scan in awake monkeys is possible by using a plastic head mask made to fit the skull of individual animals. In all of the three monkeys tested, longitudinal, quantitative assessment of head movements showed that the plastic mask has effectively suppressed head movements, and we were able to obtain reliable retinotopic BOLD signals in a standard retinotopic mapping task. The present, easy-to-make plastic mask has a strong potential to simplify fMRI experiments in awake monkeys, while giving data that is as good as or even better quality than that obtained with the conventional head-post method.

Generation of canine induced pluripotent stem cells under feeder-free conditions using Sendai virus vector encoding six canine reprogramming factors.

Although it is in its early stages, canine induced pluripotent stem cells (ciPSCs) hold great potential for innovative translational research in regenerative medicine, developmental biology, drug screening, and disease modeling. However, almost all ciPSCs were generated from fibroblasts, and available canine cell sources for reprogramming are still limited. Furthermore, no report is available to generate ciPSCs under feeder-free conditions because of their low reprogramming efficiency. Here, we reanalyzed canine pluripotency-associated genes and designed canine LIN28A, NANOG, OCT3/4, SOX2, KLF4, and C-MYC encoding Sendai virus vector, called 159cf. and 162cf. We demonstrated that not only canine fibroblasts but also canine urine-derived cells, which can be isolated using a noninvasive and straightforward method, were successfully reprogrammed with or without feeder cells. ciPSCs existed in undifferentiated states, differentiating into the three germ layers in vitro and in vivo. We successfully generated ciPSCs under feeder-free conditions, which can promote studies in veterinary and consequently human regenerative medicines.

Body mass index, height, and osteoporotic fracture risk in community-dwelling Japanese people aged 40-74 years.

INTRODUCTION: The association between body size and fracture risk is complex and varies by sex and ethnicity. This study aimed to examine associations of body mass index (BMI) and height with osteoporotic fracture risk in middle-aged and older people. MATERIALS AND METHODS: This 10-year cohort study included 13,151 community-dwelling Japanese people aged 40-74 years. A self-administered questionnaire survey was conducted at baseline to obtain information on demographic characteristics, body size, lifestyle, and disease history. BMI (kg/m2) was categorized as underweight (< 18.5), low-normal (18.5-21.7), high-normal (21.8-24.9), overweight (25.0-29.9), and obese (≥ 30.0). Height was categorized into quartiles. All incident cases of major osteoporotic fractures, including fractures of the distal radius, neck of the humerus, neck or trochanter of the femur, and vertebrae, were obtained from medical records during follow-up. RESULTS: Mean participant age was 58.8 years. In men, the underweight group had a significantly higher hazard ratio (HR) for total fracture (adjusted HR = 2.46), and the obese group had significantly higher HRs for total (adjusted HR = 3.01) and vertebral (HR = 3.77) fractures relative to the reference (overweight) group. No significant associations were observed between BMI and risk of any fracture in women. Higher quartiles of height were associated with higher vertebral fracture risk (adjusted P for trend = 0.023) only in women. CONCLUSION: BMI and osteoporotic fracture risk showed a U-shaped association in men, whereas higher height was associated with higher vertebral fracture risk in women, suggesting sex-dependent differences in these associations.

Characteristics of back pain in patients with adolescent idiopathic scoliosis: Considerations in candidates for corrective surgery.

BACKGROUND: Previous studies have demonstrated that the point prevalence of back pain ranges from 12 % to 33 % and that the lifetime prevalence of back pain ranges from 28 % to 51 % in adolescents. However, few studies on back pain in patients with Adolescent idiopathic scoliosis (AIS) have been conducted, and these studies had significant limitations, including a lack of comparative controls and detailed information about scoliotic deformity or pain location. This study aimed to determine whether adolescents with AIS experience back pain in specific regions. METHODS: This retrospective case-control study included 189 female adolescents with AIS who underwent corrective fusion from 2008 to 2020. Questionnaires on back pain and health-related quality of life (HRQOL) using the Scoliosis Research Society Outcomes Instrument-22 (SRS-22) were conducted preoperatively. The control group included 2909 general female adolescents. RESULTS: The mean Cobb angles in the main thoracic and thoracolumbar/lumbar curves were 51.4 ± 15.3° and 40.4 ± 12.9°. Back pain characteristics included higher point prevalence (25.9 %) and lifetime prevalence (64.6 %) compared to healthy controls. Adolescents with back pain showed lower scores in the pain and mental health domains of the SRS-22. Adolescents with major thoracic AIS showed more back pain in the upper and middle right back compared to adolescents with major thoracolumbar/lumbar AIS. CONCLUSION: The point and lifetime prevalence of back pain were definitely higher in patients with AIS, which affected their HRQOL. There was a relationship between pain around the right scapula and the right major thoracic curve with a rib hump deformity.

Gait Analysis by the Severity of Gait Disturbance in Patients with Compressive Cervical Myelopathy.

Introduction: Gait disturbance due to compressive cervical myelopathy has been previously described. However, data on how gait disturbance varies with the degree of lower extremity motor impairment are limited. Therefore, we investigated the characteristics of gait analysis based on severity and determined how gait disturbance progresses in compressive cervical myelopathy. Methods: We enrolled 44 patients (32 men and 12 women; mean age, 65.0 years) out of 108 consecutive patients with compressive cervical myelopathy who underwent spinal cord decompression surgery in our hospital. The exclusion criteria were inability to gait and complications affecting gait. Twenty-two patients with Japanese Orthopaedic Association scores 1 or 2 for lower extremity motor functions were assigned to the severe group, and 22 patients who scored 3 or 4 were assigned to the moderate group. Gait analysis was performed preoperatively using a long thin-type sensor sheet, and 25 healthy volunteers were assigned to the control group. Results: Stride length, swing phase, and gait speed decreased whereas step angle, stance phase, and double support duration increased as myelopathy progressed. Step width was significantly larger in the severe group than in the moderate and control groups. The cutoff values based on severe myelopathy with the inability to ascend or descend stairs without support were 60% for the stride length percentage of body height and 100 cm/s for gait speed. Conclusions: Decreases in stride length, swing phase, and gait speed and increases in step angle, stance phase, and double support duration are compensatory changes as cervical myelopathy progresses. Step width is a compensatory change that is not significantly altered in moderate myelopathy but increases when gait becomes affected, such that the patient cannot ascend or descend stairs without support.

A nationwide multicenter study of the cost effectiveness of five leading drugs for pharmacological management of cervicobrachial symptoms.

BACKGROUND: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms. METHODS: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness. RESULTS: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL. CONCLUSIONS: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly. LEVEL OF EVIDENCE: II, prospective cohort study.

Optimal information loading into working memory explains dynamic coding in the prefrontal cortex.

Working memory involves the short-term maintenance of information and is critical in many tasks. The neural circuit dynamics underlying working memory remain poorly understood, with different aspects of prefrontal cortical (PFC) responses explained by different putative mechanisms. By mathematical analysis, numerical simulations, and using recordings from monkey PFC, we investigate a critical but hitherto ignored aspect of working memory dynamics: information loading. We find that, contrary to common assumptions, optimal loading of information into working memory involves inputs that are largely orthogonal, rather than similar, to the late delay activities observed during memory maintenance, naturally leading to the widely observed phenomenon of dynamic coding in PFC. Using a theoretically principled metric, we show that PFC exhibits the hallmarks of optimal information loading. We also find that optimal information loading emerges as a general dynamical strategy in task-optimized recurrent neural networks. Our theory unifies previous, seemingly conflicting theories of memory maintenance based on attractor or purely sequential dynamics and reveals a normative principle underlying dynamic coding.

Pet Animals Were Infected with SARS-CoV-2 from Their Owners Who Developed COVID-19: Case Series Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pets owned by coronavirus disease 2019 (COVID-19) patients has been reported around the world. However, how often the animals are exposed to SARS-CoV-2 by their owners is still unclear. We have collected swab samples from COVID-19 patients' pets and performed real-time RT-PCR to detect the viral genome. In total, 8 of 53 dogs (15.1%) and 5 of 34 cats (14.7%) tested positive for the SARS-CoV-2 N gene. The result of a virus neutralization (VN) test also showed VN antibodies in four cats and six dogs. Our results indicate that the virus often passed from infected owners to their pets, which then excreted the virus despite having no or mild clinical signs.

[Case of hereditary Y69H (p.Y89H) transthyretin variant leptomeningeal amyloidosis presenting with drop attacks and recurrent transient language disorder].

We report a 73-year-old woman who started developing recurrent transient aphasia at the age of 66 years. During the attacks, she was aware she could not understand what was being said and both her spoken and written speech were meaningless. The attacks usually lasted for a few days, following which she could explain what had happened. Anti-epileptics did not improve her symptoms. She also noticed tremor of her right hand and gait disturbance at the age of 71 years. The recurrent transient aphasia was followed by drop attacks. At the time of her admission to our hospital, she showed paraplegia, phonological paraphasia, and difficulty in understanding complex sentences. Her language disturbance resembled a logopenic variant of primary progressive aphasia. However, the symptoms fluctuated for a few days and subsequently improved. Electroencephalography showed no abnormalities. Gadolinium-enhanced brain and spinal MRI showed diffuse leptomeningeal enhancement over the surface of the spinal cord, brain stem, and cerebrum on T1-weighed imaging. Surgical biopsy of a varicose vein in the subarachnoid space at the level of the Th11 spinal cord was performed. Pathological evaluation of the biopsied specimens revealed TTR-immunolabeled amyloid deposits in the subarachnoid vessel walls and on the arachnoid membrane. Gene analysis revealed c.265T>C, p.Y89H (Y69H) TTR mutation, which is known as one of the causative mutations of familial leptomeningeal amyloidosis. Leptomeningeal forms of transthyretin amyloidosis might present transient focal neurological episodes.

iPSC-derived type IV collagen α5-expressing kidney organoids model Alport syndrome.

Alport syndrome (AS) is a hereditary glomerulonephritis caused by COL4A3, COL4A4 or COL4A5 gene mutations and characterized by abnormalities of glomerular basement membranes (GBMs). Due to a lack of curative treatments, the condition proceeds to end-stage renal disease even in adolescents. Hampering drug discovery is the absence of effective in vitro methods for testing the restoration of normal GBMs. Here, we aimed to develop kidney organoid models from AS patient iPSCs for this purpose. We established iPSC-derived collagen α5(IV)-expressing kidney organoids and confirmed that kidney organoids from COL4A5 mutation-corrected iPSCs restore collagen α5(IV) protein expression. Importantly, our model recapitulates the differences in collagen composition between iPSC-derived kidney organoids from mild and severe AS cases. Furthermore, we demonstrate that a chemical chaperone, 4-phenyl butyric acid, has the potential to correct GBM abnormalities in kidney organoids showing mild AS phenotypes. This iPSC-derived kidney organoid model will contribute to drug discovery for AS.

Preoperative factors affecting the two-year postoperative patient-reported outcome in single-level lumbar grade I degenerative spondylolisthesis.

Background: The choice of operative method for lumbar spinal stenosis with Meyerding grade I degenerative spondylolisthesis remains controversial. The purpose of this study was to identify the preoperative factors affecting the 2-year postoperative patient-reported outcome in Meyerding grade I degenerative spondylolisthesis. Methods: Seventy-two consecutive patients who had minimally invasive decompression alone (D group; 28) or with fusion (DF group; 44) were enrolled. The parameters investigated were the Japanese Orthopaedic Association back pain evaluation questionnaire as patient-reported assessment, and L4 slippage (L4S), lumbar lordosis (LL), and lumbar axis sacral distance (LASD) as an index of sagittal alignment for radiological evaluation. Data collected prospectively at 2 years postoperatively were examined by statistical analysis. Results: Sixty-two cases (D group; 25, DF group; 37) were finally evaluated. In multiple logistic regression analysis, preoperative L4S and LASD were extracted as significant preoperative factors affecting the 2-year postoperative outcome. Patients with preoperative L4S of 6 mm or more have a lower rate of improvement in lumbar spine dysfunction due to low back pain (risk ratio=0.188, p=.043). Patients with a preoperative LASD of 30 mm or more have a higher rate of improvement in lumbar dysfunction due to low back pain (risk ratio=11.48, p=.021). The results of multiple logistic analysis by operative method showed that there was a higher rate of improvement in lumbar spine dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more in DF group (risk ratio=172.028, p=.01). Conclusions: Preoperative L4S and LASD were extracted as significant preoperative factors affecting patient-reported outcomes at 2 years postoperatively. Multiple logistic analyses by the operative method suggested that DF may be advantageous in improving lumbar dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more.

Cycles of goal silencing and reactivation underlie complex problem-solving in primate frontal and parietal cortex.

While classic views proposed that working memory (WM) is mediated by sustained firing, recent evidence suggests a contribution of activity-silent states. Within WM, human neuroimaging studies suggest a switch between attentional foreground and background, with only the foregrounded item represented in active neural firing. To address this process at the cellular level, we recorded prefrontal (PFC) and posterior parietal (PPC) neurons in a complex problem-solving task, with monkeys searching for one or two target locations in a first cycle of trials, and retaining them for memory-guided revisits on subsequent cycles. When target locations were discovered, neither frontal nor parietal neurons showed sustained goal-location codes continuing into subsequent trials and cycles. Instead there were sequences of timely goal silencing and reactivation, and following reactivation, sustained states until behavioral response. With two target locations, goal representations in both regions showed evidence of transitions between foreground and background, but the PFC representation was more complete, extending beyond the current trial to include both past and future selections. In the absence of unbroken sustained codes, different neuronal states interact to support maintenance and retrieval of WM representations across successive trials.