Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double-blind (BLESS) study.

AIMS: Inadequate antidepressant response interrupts effective treatment of major depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate antidepressant therapy (ADT) response. METHODS: This placebo-controlled, randomized, multicenter, parallel-group phase 2/3 study randomized Japanese MDD patients (Hamilton Rating Scale for Depression 17-item total score ≥ 14; historical inadequate response to 1-3 ADTs) with inadequate response to 8-week single-blind, prospective SSRI/SNRI treatment to 6-week adjunctive treatment with brexpiprazole 1 mg, 2 mg, or placebo. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline. Secondary endpoints included MADRS response, remission rate, and Clinical Global Impression-Improvement score. Safety was comprehensively evaluated, especially regarding antipsychotic adverse events (AEs). RESULTS: Of 1194 screened patients, 740 were randomized and 736 (1 mg, n = 248; 2 mg, n = 245; placebo, n = 243) had ≥1 baseline/post-baseline MADRS total score. The LSM (SE) change from baseline in MADRS total score at Week 6 by MMRM analysis was -8.5 (0.47) with brexpiprazole 1 mg, -8.2 (0.47) with brexpiprazole 2 mg, and -6.7 (0.47) with placebo (placebo-adjusted LSM difference [95% CI]: 1 mg, -1.7 [-3.0, -0.4]; P = 0.0089; 2 mg, -1.4 [-2.7, -0.1]; P = 0.0312). Secondary efficacy results supported the primary endpoint. Brexpiprazole was generally well tolerated. CONCLUSION: Brexpiprazole 1 mg daily was an appropriate starting dose and both 1 mg and 2 mg daily were effective and well tolerated as adjunctive therapy for Japanese MDD patients not adequately responsive to ADT.

Predictive factors for walking in acute stroke patients: a multicenter study using classification and regression tree analysis.

[Purpose] Walking ability should be predicted as early as possible in acute stroke patients. The purpose is to construct a prediction model for independent walking from bedside assessments using classification and regression tree analysis. [Participants and Methods] We conducted a multicenter case-control study with 240 stroke patients. Survey items included age, gender, injured hemisphere, the National Institute of Health Stroke Scale, the Brunnstrom Recovery Stage for lower extremities, and "turn over from a supine position" from the Ability for Basic Movement Scale. The National Institute of Health Stroke Scale items, such as language, extinction, and inattention, were grouped under higher brain dysfunction. We used the Functional Ambulation Categories to classify patients into independent (four or more the Functional Ambulation Categories; n=120) and dependent (three or fewer the Functional Ambulation Categories; n=120) walking groups. A classification and regression tree analysis was used to create a model to predict independent walking. [Results] The Brunnstrom Recovery Stage for lower extremities, "turn over from a supine position" from the Ability for Basic Movement Scale, and higher brain dysfunction were the splitting criteria for classifying patients into four categories: Category 1 (0%), severe motor paresis; Category 2 (10.0%), mild motor paresis and could not turn over; Category 3 (52.5%), with mild motor paresis, could turn over, and had higher brain dysfunction; and Category 4 (82.5%), with mild motor paresis, could turn over, and no higher brain dysfunction. [Conclusion] We constructed a useful prediction model for independent walking based on the three criteria.

An exploratory database study of factors influencing the continuation of brexpiprazole treatment (prescription) in patients with schizophrenia using information from psychiatric electronic medical records processed with natural language processing.

Using natural language processing (NLP) technology to analyze and organize textual information in psychiatric electronic medical records can identify undiscovered factors associated with treatment discontinuation. This study aimed to evaluate brexpiprazole treatment continuation rate and factors affecting brexpiprazole discontinuation using a database that employs the MENTAT® system with NLP technology. This retrospective observational study evaluated patients with schizophrenia who were newly initiated on brexpiprazole (April 18, 2018-May 15, 2020). The first prescriptions of brexpiprazole were followed up for 180 days. Factors associated with brexpiprazole discontinuation were assessed using structured and unstructured patient data (April 18, 2017-December 31, 2020). The analysis population comprised 515 patients; mean (standard deviation) age of patients was 48.0 (15.3) years, and 47.8 % were male. Using Kaplan-Meier analysis, the cumulative brexpiprazole continuation rate at 180 days was 29 % (estimate: 0.29; 95 % confidence interval, 0.25-0.33). Univariate Cox proportional hazards analysis identified 16 variables independently associated with brexpiprazole discontinuation. Multivariate analysis identified eight variables associated with treatment discontinuation: variables with hazard ratio <1 were the presence of physical complications, longer hospitalization duration, and maximum chlorpromazine-equivalent dose of antipsychotics of >200 to ≤400 mg/day vs ≤200 mg/day in the past year; variables with hazard ratio >1 were previous electroconvulsive therapy, availability of key contact person information, a history of crime committed/reported, increase in brexpiprazole dose to 2 mg in >28 days, and appearance/worsening of symptoms other than positive symptoms. In conclusion, we identified potential new factors that may be associated with brexpiprazole discontinuation, which may improve the treatment strategy and continuation rate in patients with schizophrenia.

Analyses of weight-bearing asymmetry pattern for standing in the early phase after stroke: a cross-sectional study.

BACKGROUND: How the weight-bearing asymmetry pattern and related maximum lateral weight-bearing capacity, physical functions, balance, and mobility involved in weight-bearing asymmetry and lesions are related to weight-bearing asymmetry in patients with early-onset stroke remains unclear. OBJECTIVE: To investigate the difference between weight-bearing in the early phase after stroke categorized as symmetrical or nonsymmetrical regarding impairments, balance, walking, and independence, and any lesion location difference. METHODS: This cross-sectional study included 46 persons with hemiparetic stroke within 3 weeks from onset undergoing inpatient rehabilitation and classified into symmetrical, paretic, and non-paretic groups. We performed posturographic, functional, mobility, and lesion location assessments on participants once the evaluation was possible. RESULTS: The symmetrical, paretic, and non-paretic groups included 14, 11, and 21 patients, respectively. The non-paretic group had lesser mean % body weight in maximum lateral weight-bearing to the paretic direction (79% versus 55%, p < .001), motor function of the hip lower limb (64 versus 58, p = .003) per the Stroke Impairment Assessment Set, Trunk Impairment Scale (18 versus 15, p = .020), and Berg Balance Scale (42 versus 32, p = .047) than the paretic group with more lesions in the insula (55% versus 0%, p < .001) and parietal cortex (36% versus 0%, p = .009) than the non-paretic group. CONCLUSION: The non-paretic group had low dynamic balance, severe motor paresis, and trunk dysfunction. The paretic group had lesions in the insula or parietal cortex.

Immediate effect of standing and sit-to-stand training on postural vertical for backward disequilibrium following stroke: a case report.

BACKGROUND: Effects of therapeutic interventions backward disequilibrium following stroke are scarcely reported. OBJECTIVE: To clarify the effects of standing and sit-to-stand/stand-to-sit training aimed at postural deviation in the anterior direction for backward disequilibrium and posterior deviation of subjective postural vertical. CASE DESCRIPTION: The participant presented with backward disequilibrium and pontine hemorrhage-associated sensory impairment of the extremities. Physical therapy included standing and sit-to-stand/stand-to-sit training, expected to bias the center of gravity in the anterior direction. We measured subjective postural vertical on the sagittal plane to assess vertical perception. Backward disequilibrium was evaluated using the Backward Disequilibrium Scale. Walking ability was assessed using the functional ambulation category. These outcomes were assessed before and at 3 days post-intervention. OUTCOMES: Neurological findings were unchanged between pre- and post-intervention. Post-intervention, in subjective postural vertical, tilt direction modulated from -6.1° to 1.3°, variability changed from 5.9° to 3.3°, and Backward Disequilibrium Scale score improved from 7 to 1 point. Functional ambulation category changed from 2 to 3. CONCLUSION: Standing and sit-to-stand/stand-to-sit training aimed at shifting center of gravity and subjective postural vertical in the anterior direction appeared to improve backward disequilibrium and correct tilt to the anterior direction for this participant. Long-term effects of the training for this participant were not determined.

Development of a genome-wide marker design workflow for onions and its application in target amplicon sequencing-based genotyping.

Onions are one of the most widely cultivated vegetables worldwide; however, the development and utilization of molecular markers have been limited because of the large genome of this plant. We present a genome-wide marker design workflow for onions and its application in a high-throughput genotyping method based on target amplicon sequencing. The efficiency of the method was evaluated by genotyping of F2 populations. In the marker design workflow, unigene and genomic sequence data sets were constructed, and polymorphisms between parental lines were detected through transcriptome sequence analysis. The positions of polymorphisms detected in the unigenes were mapped onto the genome sequence, and primer sets were designed. In total, 480 markers covering the whole genome were selected. By genotyping an F2 population, 329 polymorphic sites were obtained from the estimated positions or the flanking sequences. However, missing or sparse marker regions were observed in the resulting genetic linkage map. We modified the markers to cover these regions by genotyping the other F2 populations. The grouping and order of markers on the linkages were similar across the genetic maps. Our marker design workflow and target amplicon sequencing are useful for genome-wide genotyping of onions owing to their reliability, cost effectiveness, and flexibility.

Treatment Discontinuation Among Patients with Schizophrenia Treated with Brexpiprazole and Other Oral Atypical Antipsychotics in Japan: A Retrospective Observational Study.

INTRODUCTION: Treatment continuation is essential for relapse prevention in patients with schizophrenia. The aim of this exploratory study was to compare the time to treatment discontinuation between patients with schizophrenia prescribed brexpiprazole (BRX group) and those prescribed other atypical antipsychotics (OAA group) in clinical settings in Japan using health insurance claims data. METHODS: De-identified data of working individuals with schizophrenia aged < 75 years and their dependents were assessed from April 2017 to May 2020 using a nationwide claims database. Cox proportional hazards models, adjusted for baseline patient variables, were used to compare the time to treatment discontinuation (primary outcome) for 180 days between BRX and OAA groups and to estimate the hazard ratio (HR) with 95% confidence interval (CI). The cumulative treatment continuation rates at 180 days were also estimated. Sensitivity and subgroup analyses were conducted for the primary outcome. RESULTS: The analysis included 978 and 4898 patients in the BRX and OAA groups, respectively. Patients in the BRX group were significantly less likely to discontinue treatment than those in the OAA group (HR 0.86, 95% CI 0.78-0.95; p = 0.0024). The cumulative treatment continuation rates were higher in the BRX group (45.9%, 95% CI 42.5-49.2]) than in the OAA group (39.5%, 95% CI 38.1-41.0; log-rank test, p < 0.0001). Based on patients matched by propensity score, the BRX group was significantly less likely to discontinue treatment than the OAA group (log-rank test, p = 0.0466). Similar results were obtained in sensitivity and subgroup analyses. CONCLUSION: This real-world study showed that patients in the BRX group were less likely to discontinue treatments than those in the OAA group. These findings suggest that BRX may contribute to treatment continuation among patients with schizophrenia. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000044682.

Effects of Dynamic Sitting Exercise with Delayed Visual Feedback in the Early Post-Stroke Phase: A Pilot Double-Blinded Randomized Controlled Trial.

Sitting ability in the early post-stroke phase affects functional balance ability and other prognoses. We investigated whether dynamic sitting exercise with delayed visual feedback in the mediolateral and anteroposterior directions affected postural control in the early post-stroke phase. In this pilot randomized controlled trial, 27 hemiparetic stroke patients were randomized to experimental (n = 13) and control (n = 14) groups. Dynamic sitting exercise (30 times/day, 5 days/week) in the mediolateral and anteroposterior directions, with 500-ms-delayed (experimental group) or real-time (control group) visual feedback on a computer, was added to usual physical therapy. We evaluated the postural assessment scale for stroke (PASS), static and dynamic sitting balance tasks, the five-times sit-to-stand test, trunk impairment scale, functional ambulation category, and functional independence measure−motor items. In intention-to-treat analysis, the experimental group demonstrated a significant intervention effect on the PASS score (p < 0.05). The mean percentage of body weight on the moving side in the lateral sitting task and the number of successes in the five-times sit-to-stand test were significantly higher in the experimental group than those in the control group (p < 0.05). Thus, the proposed exercise improves postural control, dynamic sitting balance, and sit-to-stand ability in early post-stroke patients.

Improving Quantitative Traits in Self-Pollinated Crops Using Simulation-Based Selection With Minimal Crossing.

Genomic selection and marker-assisted recurrent selection have been applied to improve quantitative traits in many cross-pollinated crops. However, such selection is not feasible in self-pollinated crops owing to laborious crossing procedures. In this study, we developed a simulation-based selection strategy that makes use of a trait prediction model based on genomic information to predict the phenotype of the progeny for all possible crossing combinations. These predictions are then used to select the best cross combinations for the selection of the given trait. In our simulated experiment, using a biparental initial population with a heritability set to 0.3, 0.6, or 1.0 and the number of quantitative trait loci set to 30 or 100, the genetic gain of the proposed strategy was higher or equal to that of conventional recurrent selection method in the early selection cycles, although the number of cross combinations of the proposed strategy was considerably reduced in each cycle. Moreover, this strategy was demonstrated to increase or decrease seed protein content in soybean recombinant inbred lines using SNP markers. Information on 29 genomic regions associated with seed protein content was used to construct the prediction model and conduct simulation. After two selection cycles, the selected progeny had significantly higher or lower seed protein contents than those from the initial population. These results suggest that our strategy is effective in obtaining superior progeny over a short period with minimal crossing and has the potential to efficiently improve the target quantitative traits in self-pollinated crops.

Effect of Exercise Involving Standing Weight Shifting to the Nonparetic Side on an Inclined Surface in the Early Phase After a Stroke: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to clarify whether an exercise involving weight shifting to the nonparetic side while standing on an inclined surface improves standing balance in the early phase after stroke. METHODS: This assessor-blinded, randomized controlled trial included people undergoing inpatient rehabilitation at a university hospital. Participants (N = 52) with hemiparesis caused by a stroke were randomly assigned to an experimental group (n = 26) or control group (n = 26). Participants performed a weight-shifting exercise to the nonparetic side using a goal-directed reaching strategy while standing on an inclined surface that was elevated 5 degrees to the nonparetic side in the experimental group or a flat surface in the control group. The reaching exercise was conducted 30 times per day for 5 days. Primary outcome was the Berg Balance Scale. Secondary outcomes were the posturographic examination (static standing and lateral weight shifting to the nonparetic and paretic sides), Trunk Control Test, Trunk Impairment Scale, Functional Ambulation Category, and Functional Independent Measure motor item scores. RESULTS: Through intention-to-treat analysis, no significant intervention effects were observed between groups on the Berg Balance Scale. A significant intervention effect was observed, however, with the experimental group on the lateral weight shifting to the nonparetic side in the mean percentage bodyweight values and center-of-pressure moving distance and to the paretic side in center-of-pressure moving distance and Functional Ambulation Category. There were no significant interaction effects concerning other outcomes. CONCLUSION: These results suggest that standing reaching exercises to the nonparetic side while standing on an inclined surface could improve lateral weight-shifting capacity and gait ability in participants in the early poststroke phase. IMPACT: This intervention should be incorporated into standard treatment programs focusing on the paretic side during early stroke rehabilitation.

Effects of diagonally aligned sitting training with a tilted surface on sitting balance for low sitting performance in the early phase after stroke: a randomised controlled trial.

PURPOSE: To clarify the effects of diagonally aligned sitting training using a tilted surface on sitting balance for patients with low sitting performance in the early phase after stroke. MATERIALS AND METHODS: This was an assessor-blinded randomised controlled trial. The experimental group used a surface tilted 10° backward and down toward the most affected side; the control group trained on a horizontal surface. Both groups were asked to move their trunk diagonally forward toward the least affected side. Participants performed the activity 40 times/session for seven sessions over 8 days. Sitting performances were assessed using the function in sitting test (FIST), subjective postural vertical (SPV) on the diagonal plane, and trunk impairment scale (TIS). RESULTS: Thirty-three stroke patients were randomly allocated into two groups. Treatment effects differed significantly: mean differences between groups for FIST (total score, static, dynamic, scooting, and reactive) were 8.96, 2.35, 3.01, 1.27, and 1.72 points, for the mean SPV value was 1.82°, and for the TIS (total score and static) were 1.87 and 1.58 points, respectively. These results were more favourable in the experimental group. CONCLUSIONS: Diagonally aligned sitting training on a tilted surface improves sitting balance and modulates the SPV compared with a horizontal surface.

A Method for Identifying Environmental Stimuli and Genes Responsible for Genotype-by-Environment Interactions From a Large-Scale Multi-Environment Data Set.

It has not been fully understood in real fields what environment stimuli cause the genotype-by-environment (G × E) interactions, when they occur, and what genes react to them. Large-scale multi-environment data sets are attractive data sources for these purposes because they potentially experienced various environmental conditions. Here we developed a data-driven approach termed Environmental Covariate Search Affecting Genetic Correlations (ECGC) to identify environmental stimuli and genes responsible for the G × E interactions from large-scale multi-environment data sets. ECGC was applied to a soybean (Glycine max) data set that consisted of 25,158 records collected at 52 environments. ECGC illustrated what meteorological factors shaped the G × E interactions in six traits including yield, flowering time, and protein content and when these factors were involved in the interactions. For example, it illustrated the relevance of precipitation around sowing dates and hours of sunshine just before maturity to the interactions observed for yield. Moreover, genome-wide association mapping on the sensitivities to the identified stimuli discovered candidate and known genes responsible for the G × E interactions. Our results demonstrate the capability of data-driven approaches to bring novel insights on the G × E interactions observed in fields.

Factors Influencing Sitting Ability During the Acute Post-Stroke Phase: A Multicenter Prospective Cohort Study in Japan.

OBJECTIVES: Sitting ability during the acute phase after stroke is a useful indicator of functional outcomes; however, factors that affect this ability have not been evaluated. Therefore, this study aimed to identify and evaluate factors that affect sitting ability in the acute phase after stroke. MATERIALS AND METHODS: This multicenter prospective cohort study included hemispheric stroke patients who underwent an inpatient rehabilitation program after acute stroke from five acute care hospitals. The effect of age, sex, lesion side, etiology, consciousness disorder, stroke and dementia history, stroke-related complications, National Institutes of Health Stroke Scale score, hemiparalysis, turn-over movement from the supine position and sit-up movement, and Scale for Contraversive Pushing on the "remain sitting" item in the revised version of the Ability of Basic Movement Scale at the time of acute hospital discharge were investigated. Factors affecting sitting ability were identified using binomial logistic regression analysis. RESULTS: We included 293 stroke patients. Age (odds ratio: 0.943, 95% confidence interval: 0.910-0.977, p=0.001), National Institutes of Health Stroke Scale score (odds ratio: 0.862, 95% confidence interval: 0.811-0.916, p<0.001), and Scale for Contraversive Pushing score (odds ratio: 0.543, 95% confidence interval: 0.419-0.705, p<0.001) were identified as independent predictors of sitting ability at the time of hospital discharge (median; 23.0 days). CONCLUSIONS: Older patients and those with high Scale for Contraversive Pushing and National Institutes of Health Stroke Scale scores experienced difficulties in regaining sitting ability. These results may guide physical therapy for patients with impaired sitting ability due to hemispheric stroke.

Starting position effects in the measurement of the postural vertical for pusher behavior.

Pusher behavior (PB) is a severe lateral postural disorder that involves a disturbed subjective postural vertical (SPV) in the frontal plane. SPV is measured by determining the mean value and standard deviation of several trials beginning on both the contralesional- and ipsilesional-tilted positions. However, the postural representation, when passively tilted to the contralesional versus ipsilesional position, is different between patients with and without PB. Therefore, we hypothesized that SPV dependence on the starting position will be influenced by PB. For 53 patients with hemispheric stroke enrolled, SPV was measured using a non-motorized vertical board with eyes closed. The mean value (tilt direction) and standard deviation (variability) were calculated in four trials, each from two positions, with the patient tilted to the contralesional position (SPV-CL condition) and then to the ipsilesional position (SPV-IL condition). Patients were categorized into the non-pusher (n = 29) and pusher (n = 24) groups. In the SPV-CL trials, the tilt direction was significantly tilted contralesionally for the pusher group (- 6.3° ± 1.6°) compared with that for the non-pusher group (- 2.2° ± 1.8°; p < 0.001), with no significant difference in variability between the groups. In the SPV-IL trials, the tilt direction was not significantly different between the groups, but the variability was significantly higher in the pusher group (4.8° ± 2.0°) than in the non-pusher group (2.2° ± 1.3°; p < 0.001). The dependence of tilt direction and variability of SPV on the starting position in patients with PB differed from those noted in patients without PB. These results may help explain this abnormal posture and optimize neurological rehabilitation strategies for PB.

Simulation-based optimization of genomic selection scheme for accelerating genetic gain while preventing inbreeding depression in onion breeding.

Genomic selection (GS) is being increasingly employed in plant breeding programs to accelerate genetic gain of economically important traits. However, its efficiency differs greatly across species, due to differences in reproduction and breeding strategies. Onion (Allium cepa L.) is an out-crossing crop but can be easily self-pollinated. High inbreeding depression occurs, and contamination of self-pollinated seeds is unavoidable in onion breeding. Taking this into consideration, 10-year breeding programs with and without GS were simulated. In addition to general GS, we proposed GS schemes to prevent inbreeding depression by avoiding co-selection of close relatives and combining the shortening of generation time and updating of the prediction model. The results showed that general GS with shortening of generation time yielded the highest genetic gain among the selection schemes in early years. However, inbreeding increased rapidly, reaching very high levels in later years. The proposed GS combining shortening of generation time with updating of the prediction model was superior to the others in later years, as it yielded relatively high genetic gain while maintaining significantly low levels of inbreeding. These results suggested that GS can be beneficial in onion breeding, and an optimal scheme should be selected depending on the selection period.

Influence of unilateral spatial neglect on vertical perception in post-stroke pusher behavior.

Pusher behavior (PB) impairs verticality in the frontal plane and is often associated with unilateral spatial neglect (USN). However, it is unclear whether USN affects verticality among patients with PB. We aimed to clarify the characteristics of verticality among PB, with and without USN. The study included 43 patients with right hemisphere stroke, including 12 without PB or USN, 10 with only USN, 10 with PB only, and 11 with PB and USN, and 15 age-matched healthy individuals. The subjective visual vertical (SVV), subjective postural vertical with eyes closed (SPV), and subjective postural vertical with eyes open were assessed. Under each condition, the mean (tilt direction) and standard deviation (variability) across trials were calculated. The variability of SVV was significantly greater among patients with only USN (6.9°±5.9°) or those with PB and USN (7.6 ± 4.3°). On SPV, the contralesional tilt was significantly greater, with higher variability, in patients with only PB (-2.2°±1.1° and 6.3°±1.4°, respectively) and those with PB and USN (-2.1°±2.0° and 6.6°±2.0°, respectively) than in the other groups. In patients with PB, SVV differed depending on the presence of USN, but it was suggested that SPV might not be affected by USN. These findings are important to plan PB treatment.

Synthesis of All Stereoisomers of Monomeric Spectomycin A1/A2 and Evaluation of Their Protein SUMOylation-Inhibitory Activity.

A synthetic methodology to access all possible stereoisomers of spectomycin A1 (SMA1) and A2 (SMA2) has been established through late-stage diversification. The key reaction for the construction of all four diastereomers is an intramolecular cyclization based on the umpolung of π-allyl palladium species with bis(pinacolato)diborane (B2 (pin)2 ). Silyl group assisted direct benzylic oxidation of each isomer enabled construction of the fragile ß-hydroxytetralone skeleton to provide the SMAs. The relative and absolute stereochemistry of SMA2 was also determined, and the absolute stereochemistry of SMA1 was extrapolated based on the optical rotation of SMA2. The axial chirality of SMAs is discussed based on circular dichroism spectra and DFT calculations, and it is concluded that the M isomer is predominant in solution. Biochemical assessment of all isomers in vitro revealed that the C9 hydroxyl group and dimeric structure were both important for protein SUMOylation-inhibitory activity.

Test-retest reliability of and age-related changes in the subjective postural vertical on the diagonal plane in healthy subjects.

The subjective postural vertical (SPV) reflects gravity perception when the eyes are closed. Changes in the SPV on both the frontal and sagittal planes occur in response to neurological disorders and aging; however, these changes on the diagonal plane are unclear. Here we examined test-retest reliability (n=16) of and age-related changes (n=38) in the SPV on the diagonal plane. Subjects sat on an electrical vertical board (EVB), which was used to measure the SPV on the diagonal plane. An experimenter controlled and moved the EVB seat at a constant speed on the diagonal plane and measured the seat's tilt using a digital inclinometer when subjects verbally reported that they had reached a true vertical position. Measurement was performed for eight trials, and the mean (tilt direction) and standard deviation (variability) were calculated. To determine test-retest reliability, the same experimenter repeatedly measured the SPV 1 week later. To assess age-related changes, tilt direction and variability were compared between the young (n=20) and elderly (n=18) groups. Test-retest reliability on the right and left diagonal planes was 0.61 or more. Moreover, tilt direction on the right diagonal plane - but not on the left diagonal plane - indicated a significant diagonally backward deviation in the elderly group compared with that in the young group. Variability was significantly higher in the elderly group on both planes. SPV measurement on the diagonal plane was indicated, and age-related changes were identified. Thus, future studies should assess the potential clinical applications of SPV in neurological disorders.

Metal-free alkene oxy- and amino-perfluoroalkylations via carbocation formation by using perfluoro acid anhydrides: unique reactivity between styrenes and perfluoro diacyl peroxides.

We present a strategy for metal-free, alkene difunctionalization-type, oxy- and amino-perfluoroalkylations, using perfluoro acid anhydrides as practical and user-friendly perfluoroalkyl sources. This method provides efficient access to oxy-perfluoroalkylation products via carbocation formation due to the unique reactivity between styrenes and bis(perfluoroacyl) peroxides generated in situ from perfluoro acid anhydrides. This reaction is also applicable to metal-free intramolecular amino-perfluoroalkylation of styrenes bearing a pendant amino group. Synthetic utility of the oxy-trifluoromethylation products was confirmed by demonstrating derivatization via hydrolysis, elimination, and acid-catalyzed substitution with carbon nucleophiles. The mechanism of the carbocation formation was investigated experimentally and theoretically.