Temporal validation of a clinical prediction rule for distinguishing locomotive syndromes in community-dwelling older adults: A cross-sectional study from the DETECt-L study.

Objectives: Clinical prediction rules are used to discriminate patients with locomotive syndrome and may enable early detection. This study aimed to validate the clinical predictive rules for locomotive syndrome in community-dwelling older adults. Methods: We assessed the clinical prediction rules for locomotive syndrome in a cross-sectional setting. The age, sex, and body mass index of participants were recorded. Five physical function tests-grip strength, single-leg standing time, timed up-and-go test, and preferred and maximum walking speeds-were measured as predictive factors. Three previously developed clinical prediction models for determining the severity of locomotive syndrome were assessed using a decision tree analysis. To assess validity, the sensitivity, specificity, likelihood ratio, and post-test probability of the clinical prediction rules were calculated using receiver operating characteristic curve analysis for each model. Results: Overall, 280 older adults were included (240 women; mean age, 74.8 ± 5.2 years), and 232 (82.9%), 68 (24.3%), and 28 (10.0%) participants had locomotive syndrome stages ≥ 1, ≥ 2, and = 3, respectively. The areas under the receiver operating characteristics curves were 0.701, 0.709, and 0.603, in models 1, 2, and 3, respectively. The accuracies of models 1 and 2 were moderate. Conclusions: These findings indicate that the models are reliable for community-dwelling older adults.

Clinical impacts of severe thrombocytopenia in the first cycle of azacitidine monotherapy and cytogenetics in patients with myelodysplastic syndrome: The Kyoto Conditional Survival Scoring System.

Azacitidine (AZA) has been one of the standard treatments for transplantation-ineligible patients with myelodysplastic syndrome (MDS); however, hematological toxicities frequently cause treatment interruption in the early phase of the therapy. The present study conducted a multicenter retrospective study to investigate the prognostic impacts of various factors, including factors included in the Revised International Prognostic Scoring System (IPSS-R) and severe cytopenia in the early phase of AZA monotherapy in 212 patients with MDS. Severe cytopenia was evaluated after the initiation of therapy by absolute neutrophil counts on the 29th day after AZA (ANC29) initiation, and red cell concentrates (RCC) and platelet concentrate (PC) transfusion units required within 28 days from the start of AZA, designated in the present study as RCC28 and PC28, respectively. The survival period was determined from the 29th day of AZA treatment to death from any cause as the conditional survival period after the first cycle of AZA (CS-AZA1). Multivariate analysis demonstrated that severe thrombocytopenia defined by >30 units of PC28 and very poor risk cytogenetics according to IPSS-R were independent prognostic factors for CS-AZA1. The Kyoto Conditional Survival Scoring System was subsequently developed by incorporating severe thrombocytopenia defined by PC28 and very poor risk cytogenetics, which successfully stratified the risks of the patients in CS-AZA1. In conclusion, extreme PC transfusion dependency during the first cycle of AZA and very poor risk cytogenetics are important prognostic factors in AZA monotherapy for MDS.

Estimation of Reference Values of Gait Spatiotemporal and Kinematic Parameters in the Lower Extremities and Trunk Using a Markerless Motion Capture System for Healthy Older Japanese Adults.

OBJECTIVE: This preliminary study aimed to explore the reference values of spatiotemporal and kinematic parameters in the lower extremities and trunk during gait for the healthy older adults. METHODS: Walking speed, stride length and time, cadence, walk ratio, and step width were calculated as spatiotemporal parameters of gait. Forward tilting of the trunk (FTT), hip flexion and extension, knee flexion and extension, and their laterality were measured as peak angles during one-gait cycle. The bootstrap method was conducted to estimate the 95% confidence interval (CI). RESULTS: This study included 334 healthy older adults (255 women). The following gait parameters were estimated with 95%CI: walking speed (95%CI 1.21-1.30), cadence (95%CI 116.35-121.20), walk ratio (95%CI 0.0055-0.0060), step width (95%CI 0.15-0.17), FTT (95%CI 1.91-4.19), hip flexion (95%CI 28.54-31.01), hip extension (95%CI 19.30-22.27), knee extension (95%CI 0.09-0.14), laterality of hip flexion (95%CI 1.31-2.02), laterality of hip extension (95%CI 1.32-1.97), laterality of knee flexion (95%CI 3.41-4.77), and laterality of knee extension (95%CI 0.07-0.13) in men, and walking speed (95%CI 1.28-1.34), walk ratio (95%CI 0.0050-0.0054), FTT (95%CI 2.54-3.73), hip flexion (95%CI 32.80-34.28), laterality of hip flexion (95%CI 1.65-2.05), laterality of hip extension (95%CI 2.06-2.57), and laterality of knee flexion (95%CI 3.04-3.89) in women. CONCLUSION: This study suggested provisional reference values of spatiotemporal and kinematic parameters in the lower extremities and trunk during gait for the healthy older adults.

Genome-wide association studies in the Japanese population identified genetic loci and target gene associated with epidermal turnover.

The epidermis is an essential organ for life by retaining water and as a protective barrier. The epidermis is maintained through metabolism, in which basal cells produced from epidermal stem cells differentiate into spinous cells, granular cells and corneocytes, and are finally shed from the epidermal surface. This is epidermal turnover, and with aging, there is a decline in epidermis function. Other factors that may affect epidermal turnover include ultraviolet damage and genetic factors. These genetic factors are of particular interest as little is known. Although recent skin-focused genome-wide association studies (GWAS) have been conducted, the genetic regions associated with epidermal turnover are almost uninvestigated. Therefore, we conducted a GWAS on epidermal turnover in the Japanese population, using the corneocyte area, which correlates to the rate of epidermal turnover, as an indicator. As a result, rs2278431 (p = 1.29 × 10-7 ) in 19q13.2 was associated with corneocyte size. Furthermore, eQTL analysis suggested that rs2278431 was related to the SPINT2 gene. In addition, SPINT2 knockdown studies using epidermal keratinocytes revealed that SPINT2 is involved in keratinocyte proliferation and in corneocyte size regulation in reconstructed epidermis. These results suggest that rs2278431 is involved in the expression of SPINT2 and affects epidermal turnover.

Cervical Local Cytokine Release Syndrome Following Chimeric Antigen Receptor T-cell Therapy in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma.

The use of chimeric antigen receptor T-cell (CAR-T) therapy for hematologic malignancies is rapidly increasing, and appropriately managing adverse events (AEs) is crucial. Cytokine release syndrome (CRS) is a common AE of CAR-T therapy, characterized by systemic symptoms such as fever and respire-circulatory failure. We present two cases with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) accompanied by a rare complication of cervical local CRS as an acute inflammatory reaction at a specific site after CAR-T infusion. Case 1: A 60-year-old gentleman with diffuse large B cell lymphoma (DLBCL) developed grade 1 CRS on day one that required three doses of tocilizumab. Then he developed remarkable cervical edema as local CRS on day five. His local CRS spontaneously improved from day seven without additional therapy. Case 2: A 70-year-old gentleman with DLBCL developed grade 1 CRS on day two that required three doses of tocilizumab. Then he developed remarkable cervical edema and muffled voice as local CRS on day three. He received dexamethasone because of concerns about airway obstruction, and his local CRS improved immediately after dexamethasone administration. Before Tisa-Cel infusion, neither patients had a lymphoma lesion in their necks. To summarize, local CRS may occur at the site without lymphoma involvement after CAR-T therapy. An appropriate diagnosis and careful observation are required to determine the need for additional treatment.

Real-world practice-based prognostic model for higher-risk myelodysplastic syndromes treated with azacitidine monotherapy: The Kyoto prognostic scoring system.

The prognostic impact of patient-related factors, including age, nutritional parameters, and inflammation status, in higher-risk myelodysplastic syndromes (HR-MDS) has been largely unexplored. This multicenter retrospective study aimed to establish a real-world practice-based prognostic model for HR-MDS by considering both disease- and patient-related parameters in 233 patients treated with AZA monotherapy at seven institutions. We found that anemia, presence of circulating blasts in peripheral blood, low absolute lymphocyte count, low total cholesterol (T-cho) and albumin serum levels, complex karyotype, and del(7q) or - 7 were poor prognostic factors. Therefore, we developed a new prognostic model called the Kyoto Prognostic Scoring System (KPSS) by incorporating the two variables with the highest C-indexes (complex karyotype and serum T-cho level). The KPSS classified patients into the following three groups: good (0 risk factors), intermediate (1), and poor (2). Median overall survival for these groups was 24.4, 11.3, and 6.9, respectively (p < 0.001). The discriminatory power of the KPSS was higher than that of the traditional International Prognostic Scoring System. In conclusion, we identified several nutritional parameters with prognostic relevance in patients with HR-MDS and generated a prognostic model consisting of complex karyotype and serum T-cho level that enabled excellent risk stratification.

Derivation of a clinical prediction rule for chronic post-surgical pain after total knee arthroplasty considering biopsychosocial factors: A prospective cohort study.

BACKGROUND: Biopsychosocial factors are involved in the occurrence of chronic post-surgical pain (CPSP) after total knee arthroplasty (TKA). The purpose of this study was to develop a clinical prediction rule (CPR) that considers biopsychosocial factors to predict which patients are more likely to develop CPSP after TKA. METHODS: CPSP after TKA was dichotomized into CPSP and non-CPSP groups using the Likert scale and Minimal clinically important difference, and binomial logistic regression analysis was performed. Cut-off values were then calculated using the extracted factors and dichotomized variables. The cut-off values and dichotomized variables were then used to derive a CPR that discriminates between groups with and without CPSP. RESULTS: Seventy-one TKA patients were included in the study. Binomial logistic regression analysis revealed that Central Sensitization Inventory (CSI) and Pittsburgh Sleep Quality Index (PSQI) were associated with CPSP. The cut-off values for CSI and PSQI were 26 and 7, respectively. The CPSP scale was created using the cut-off values of CSI and PSQI, with a score of 0 for being below the cut-off values of both CSI and PSQI, 1 for being above the cut-off values of either CSI or PSQI, and 2 for being above the cut-off values of both CSI and PSQI. Furthermore, the area under the curve (AUC) for CPR created by the presence of CPSP and using the CPSP scale was significant (AUC = 0.766; P = 0.001). CONCLUSION: The combination of the two tests, CSI and PSQI, suggested the possibility of predicting CPSP after TKA.

Drug cytotoxicity screening using human intestinal organoids propagated with extensive cost-reduction strategies.

Organoids are regarded as physiologically relevant cell models and useful for compound screening for drug development; however, their applications are currently limited because of the high cost of their culture. We previously succeeded in reducing the cost of human intestinal organoid culture using conditioned medium (CM) of L cells co-expressing Wnt3a, R-spondin1, and Noggin. Here, we further reduced the cost by replacing recombinant hepatocyte growth factor with CM. Moreover, we showed that embedding organoids in collagen gel, a more inexpensive matrix than Matrigel, maintains organoid proliferation and marker gene expression similarly when using Matrigel. The combination of these replacements also enabled the organoid-oriented monolayer cell culture. Furthermore, screening thousands of compounds using organoids expanded with the refined method identified several compounds with more selective cytotoxicity against organoid-derived cells than Caco-2 cells. The mechanism of action of one of these compounds, YC-1, was further elucidated. We showed that YC-1 induces apoptosis through the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway, the mechanism of which was distinct from cell death caused by other hit compounds. Our cost-cutting methodology enables large-scale intestinal organoid culture and subsequent compound screening, which could expand the application of intestinal organoids in various research fields.

Abnormal Gait Pattern Examination Screening for Physical Activity Level after One Year in Patients with Knee Osteoarthritis.

This study examined the relationship between abnormal gait pattern and physical activity level one year later in patients with knee osteoarthritis (KOA) and determined the clinical utility of the abnormal gait pattern examination. Initially, the patients' abnormal gait pattern was assessed using seven items, based on the scoring system reported in a previous study. The grading was based on a three-criteria system with 0: no abnormality, 1: moderately abnormal, and 2: severely abnormal. The patients were then classified into three groups according to physical activity level one year after gait pattern examination: low, intermediate, and high physical activity groups, respectively. Cut-off values for physical activity levels were calculated based on abnormal gait pattern examinations results. On follow-ups with 24 of the 46 subjects, age, abnormal gait pattern, and gait speed showed significant differences among the three groups according to the amount of physical activity. Effect size of abnormal gait pattern was higher than age and gait speed. Patients with KOA with physical activity < 2700 steps/day and <4400 steps/day at one year had abnormal gait pattern examination scores of ≥8 and ≥5, respectively. Abnormal gait pattern is associated with future physical activity. The results suggested that abnormal gait pattern examinations in patients with KOA could be used to screen for the possibility of physical activity being <4400 steps one year later.

The effects of walking training with poles on walking ability: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to consolidate the level of evidence for the effects of walking training with poles (pole walking; PW) on walking ability using a systematic review and meta-analysis. TYPE: Systematic review and meta-analysis. LITERATURE SURVEY: Databases including PubMed, Cochrane Library, Physiotherapy Evidence Database (PEDro), Cumulative Index to Nursing and Allied Health Literature databases, and Igaku Chuo Zasshi were searched on June 20, 2021. METHODOLOGY: Data from randomized controlled trials (RCTs) comparing the effects of PW with walking without poles and/or other exercise interventions in disease-specific and aging populations were collected. Data on walking speed, functional mobility, and walking endurance were collected for the meta-analyses. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated from postintervention means and standard deviations. The PEDro scale was used for assessing the risk of bias, and the Grading of Recommendations Assessment, Development, and Evaluation system was used to determine the quality of evidence. SYNTHESIS: This study included 13 RCTs comprising 750 participants; of these, six RCTs were included in the meta-analysis. The results showed that moderate-quality evidence supports the positive effects of PW on walking speed in patients with Parkinson disease (walking speed: SMD = 0.42, 95% CI = 0.04-0.80). In contrast, PW did not significantly improve functional mobility in patients with Parkinson disease and walking speed in older adults. CONCLUSIONS: There was moderate-quality evidence that PW improved walking speed in patients with Parkinson disease.

Clinical prediction rule for locomotive syndrome in older adults: A decision tree model.

BACKGROUND: No previous studies have proposed a clinical prediction rule that analyzes the factors related to the severity of locomotive syndrome. This study developed and assessed a clinical prediction rule for the severity of locomotive syndrome in older adults. METHODS: A total of 186 patients were assessed using the locomotive syndrome risk test. Classification and regression tree methodologies were used to develop the clinical prediction rule. This study developed three prediction models based on the severity of the locomotive syndrome, of which Model 3 assessed the most severe condition. The following potential predictive factors were measured and entered into each model; single-leg standing time, grip strength, preferred and maximum walking time, and timed up and go test. RESULTS: The single-leg standing test (≤59.4 or >59.4 s) was the best single discriminator for Model 1. Among those with a single-leg standing time >59.4 s, the next best predictor was grip strength (≤37.8 or >37.8 kg). In Model 2, the single-leg standing test was also the best single discriminator (≤12.6 or >12.6 s). Among those with a single-leg standing time ≤12.6, the next best predictor was TUG (≤7.9 or >7.9 s). Additionally, among those with a single-leg standing time >12.6, the next best predictor was single-leg standing time (≤55.3 or >55.3 s). In Model 3, predictive value in Model 2 was the best single discriminator (0 or 1). Among those with 1, the next best predictor was maximum walking time (≤3.75 or >3.75 s). The area under the receiver operating characteristic curves of Models 1, 2, and 3 were 0.737, 0.763, and 0.704, respectively. CONCLUSIONS: A clinical prediction rule was developed to assess the accuracy of the models. These results can be used to screen older adults for suspected locomotive syndrome.

Melanin accumulation in dermal stem cells deteriorates their exosome-mediated skin basement membrane construction in solar lentigo.

Solar lentigo (SL) is a hyperpigmented macule that occurs in sun-exposed areas and is characterized by the accumulation of melanin pigment in the epidermis. On the contrary, melanin-incorporated macrophages have also been identified in the dermis, which is thought to be caused by melanin transfer due to disruption of the basement membrane, but the detailed mechanism remains unclear. In this study, we analysed SL lesions by pathological methods and examined the mechanism of melanin accumulation in the dermis using cultured skin models in vitro. First, we observed a significant decrease in type IV collagen (COL4), a major component of the basement membrane, in SL lesions. The basement membrane is known to be formed by the interaction of keratinocytes and dermal cells. Therefore, we constructed skin models containing fibroblasts or dermal stem cells and examined their effects on basement membrane formation. The results showed a markedly enhanced production of COL4 mediated by dermal stem cell-derived exosomes. The analysis of melanin localization in the SL dermis revealed that CD163-positive macrophages and CD271-positive dermal stem cells both took up melanin pigment. Exosomes of dermal stem cells incorporating melanosomes were less effective in promoting COL4 expression. These findings suggest that while the promotion of COL4 production in keratinocytes by dermal stem cell-derived exosomes is important for maintaining basement membrane homeostasis, this mechanism is disrupted in SL lesions, leading to chronic melanin accumulation in the dermis.

Identification of mitochondrial genetic variants associated with human corneocyte size in Japanese women.

Mitochondria have their own DNA (mtDNA). Genetic variants are likely to accumulate in mtDNA, and its base substitution rate is known to be very fast, 10-20 times faster than that of nuclear DNA. For this reason, mtSNPs (mitochondrial genome single nucleotide polymorphisms) are frequently detected in mtDNA. Several thousands of copies of mtDNA are considered to be present in a cell, and variants that have occurred in mtDNA are expected to markedly affect the intracellular energy production system and ROS (reactive oxygen species) kinetics. Therefore, recently, mtSNPs have come to be considered very important as a determinant of the individual constitution such as the life-span and disease susceptibility. In this study, we searched for mtSNPs that affect the individual corneocyte size using samples from 358 Japanese women. As a result, mtSNPs 10609C and 12406A were found to be significantly related to the corneocyte size in the outermost layer of the epidermis. There have been a large number of reports concerning the association between mtSNPs and individual constitution, but little evaluation of their relationships with epidermal properties has been made. The results of the present study first suggested that mtSNPs may affect the epidermal properties in Japanese women.

Analysis of the effect of daily stress on the skin and search for genetic loci involved in the perceived stress of an individual.

Background: Stress may have various effects on our bodies. In particular, the skin may be readily influenced by stress. In addition, there are individual differences in the way we feel stress, suggesting the involvement of genetic factors in such individual differences. Objectives: In this study, we analysed the influence of stress on skin condition and ageing involving Japanese females, and investigated single nucleotide polymorphisms (SNPs) that influence perceived stress of an individual. Methods: We collected genotype data from 1200 Japanese females. At the same time, a questionnaire was conducted on the degree of stress that each subject feels on a daily basis and the current skin condition. We analysed the effects of stress on skin condition and searched for SNPs related to individual stress susceptibility by genome-wide association studies. Results: Our data suggested that stress influences skin condition and ageing, as previously reported. And, we found rs74548608 as a SNP that affects perceived stress of an individual. This SNP is located on the upstream of Patched-1, which is a gene that functions as a sonic hedgehog receptor. Conclusions: Our study has identified new genetic factors for perceived stress of an individual in the Japanese female. The SNP found in this study may be a candidate factor important for understanding the perceived stress of an individual of Japanese.

Diagnostic Accuracy of Physical Examination Tests for Suspected Acute Anterior Cruciate Ligament Injury: A Systematic Review and Meta-Analysis.

Background: Many tests are used to examine the knee when anterior cruciate ligament (ACL) injury is suspected. However, evidence of diagnostic accuracy in the Lachman, anterior drawer, pivot shift, and lever sign tests is limited. Purpose: The purpose of this study was to perform a systematic review and meta-analysis of original research studies that assessed the diagnostic accuracy of four physical examination tests for ACL injury acutely after an injury. Study design: Systematic review and meta-analysis. Methods: A literature search was conducted in the PubMed, MEDLINE, CINAHL, Web of Science, and Ichushi databases. Original articles with prospective cohort and cross-sectional studies in English and Japanese were included. The searched words were "anterior cruciate ligament", "injury"," rupture"," tear", "lachman test", "pivot shift test", "anterior drawer test", "lever sign test". The methodological quality of the diagnostic studies was evaluated using QUADAS-2. Summary sensitivity, specificity, likelihood ratio (LR)+, and LR- with 95% confidence intervals were calculated. Results: Eight studies were included in this review. The methodological quality of the included studies was mostly favorable. For the domain of flow and timing in the QUADAS-2, three studies did not assess the timing between the reference and index tests. The pooled sensitivities were 0.79, 0.78, 0.55, and 0.82 in the Lachman, anterior drawer, pivot shift, and lever sign tests, respectively, and the pooled specificities were 0.91, 0.91, 0.96, and 0.88, respectively. The lever sign test had the lowest LR- (0.21) and the pivot shift test had the highest LR+ (11.60). The area under the curve for the four physical examinations was > 0.70. Conclusion: The lever sign and pivot shift tests are useful for diagnosing ACL injuries in an acute setting. Level of Evidence: Level 2.

Organoid-derived intestinal epithelial cells are a suitable model for preclinical toxicology and pharmacokinetic studies.

Intestinal organoids are physiologically relevant tools used for cellular models. However, the suitability of organoids to examine biological functions over existing established cell lines lacks sufficient evidence. Cytochrome P450 3A4 (CYP3A4) induction by pregnane X receptor ligands, glucose uptake via sodium/glucose cotransporter 1, and microsomal triglyceride transfer protein-dependent ApoB-48 secretion, which are critical for human intestinal metabolism, were observed in organoid-derived two-dimensional cells but little in Caco-2 cells. CYP3A4 induction evaluation involved a simplified method of establishing organoids that constitutively expressed a reporter gene. Compound screening identified several anticancer drugs with selective activities toward Caco-2 cells, highlighting their characteristics as cancer cells. Another compound screening revealed a decline in N-(4-hydroxyphenyl)retinamide cytotoxicity upon rifampicin treatment in organoid-derived cells, under CYP3A4-induced conditions. This study shows that organoid-derived intestinal epithelial cells (IECs) possess similar physiological properties as intestinal epithelium and can serve as tools for enhancing the prediction of biological activity in humans.

Increase in inhibin beta A/Activin-A expression in the human epidermis and the suppression of epidermal stem/progenitor cell proliferation with aging.

BACKGROUND: Age-related thinning and reduced cell proliferation in the human epidermis are associated with the accumulation of senescent cells and decreases in the number and function of epidermal stem cells. OBJECTIVE: This study examined the expression of INHBA/Activin-A in human epidermis and expression differences with age, and the effect of Activin-A on epidermal stem/progenitor cells. METHODS: Immunohistochemical staining was used to analyze age-related changes in the expression of INHBA/Activin-A in the epidermal tissue of young and old subjects. Epidermal INHBA/Activin-A expression levels, epidermal morphology, and the number of epidermal stem/progenitor cells or proliferating cells were investigated using older abdominal skin samples. The effects of Activin-A on the development of a three-dimensional (3D) reconstructed epidermis and cell proliferation were also assessed. RESULTS: INHBA/Activin-A expression levels in the human epidermis increased with age, although they varied among individuals. In the epidermis of older abdominal skin samples, INHBA/Activin-A expression levels negatively correlated with epidermal thickness, the rete ridge depth and the interdigitation index. The proportion of epidermal stem/progenitor cells and proliferating cells decreased with increases in INHBA/Activin-A expression levels. Activin-A had no effect on the differentiation of keratinocytes in the 3D-reconstructed epidermis; however, thinning of the 3D epidermis was noted. Moreover, the addition of Activin-A inhibited the proliferation of epidermal stem/progenitor cells in a concentration-dependent manner. CONCLUSIONS: Age-related increased in INHBA/Activin-A expression levels were observed in the human epidermis, and may contribute to epidermal thinning and decreases in the number of epidermal stem/progenitor cells and proliferative activity.

Genome-wide association studies in Japanese women identified genetic loci associated with wrinkles and sagging.

Wrinkles and sagging are caused by various factors, such as ultraviolet rays; however, recent findings demonstrated that some individuals are genetically predisposed to these phenotypes of skin aging. The contribution of single nucleotide polymorphisms (SNPs) to the development of wrinkles and sagging has been demonstrated in genome-wide association studies (GWAS). However, these findings were mainly obtained from European and Chinese populations. Limited information is currently available on the involvement of SNPs in the development of wrinkles and sagging in a Japanese population. Therefore, we herein performed GWAS on wrinkles at the outer corners of the eyes and nasolabial folds in 1041 Japanese women. The results obtained revealed that 5 SNPs (19p13.2: rs2303098 (p = 3.39 × 10-8 ), rs56391955 (p = 3.39 × 10-8 ), rs67560822 (p = 3.50 × 10-8 ), rs889126 (p = 3.78 × 10-8 ), rs57490083 (p = 3.99 × 10-8 )) located within the COL5A3 gene associated with wrinkles at the outer corners of the eyes. Regarding nasolabial folds, 8q24.11 (rs4876369; p = 1.05 × 10-7 , rs6980503; p = 1.25 × 10-7 , rs61027543; p = 1.25 × 10-7 , rs16889363; p = 1.38 × 10-7 ) was suggested to be associated with RAD21 gene expression. These SNPs have not been reported in other populations, and were first found in Japanese women population. These SNPs may be used as markers to examine the genetic predisposition of individuals to wrinkles and sagging.

Developing a Clinical Prediction Rule for Gait Independence at Discharge in Patients with Stroke: A Decision-Tree Algorithm Analysis.

OBJECTIVES: To develop a clinical prediction rule (CPR) for gait independence at discharge in patients with stroke, using the decision-tree algorithm and to investigate the usefulness of CPR at admission to the rehabilitation ward. MATERIALS AND METHODS: We included 181 subjects with stroke during the postacute phase. The Chi-squared automatic interaction detection analysis method with 10-fold cross-validation was used to develop two CPRs; CPR 1 using easily obtainable data available at admission; CPR 2 using easily obtainable data available 1 month after admission, for prediction of gait independence at discharge. RESULTS: The degree of independence of toileting was extracted as a first node in the development of two CPRs to predict gait independence at discharge. CPR 1 included the presence of delirium. CPR 2 included problem-solving abilities. The accuracy and area under the curve of CPR 1 were 84.5% and 0.911, respectively; those of CPR 2 were 89.0% and 0.958, respectively. CONCLUSIONS: Toileting independence is a key factor in predicting the gait independence for the discharge of patients with stroke during the postacute phase. Early intervention, during the acute phase, for delirium and cognitive decline, as well as for toileting, increases the possibility of gait independence at discharge.