Normalizing hyperactivity of the Gunn rat with bilirubin-induced neurological disorders via ketanserin.

BACKGROUND: Severe neonatal hyperbilirubinemia has been known to cause the clinical syndrome of kernicterus and a milder one the syndrome of bilirubin-induced neurologic dysfunction (BIND). BIND clinically manifests itself after the neonatal period as developmental delay, cognitive impairment, and related behavioral and psychiatric disorders. The complete picture of BIND is not clear. METHODS: The Gunn rat is a mutant strain of the Wistar rat with the BIND phenotype, and it demonstrates abnormal behavior. We investigated serotonergic dysfunction in Gunn rats by pharmacological analyses and ex vivo neurochemical analyses. RESULTS: Ketanserin, the 5-HT2AR antagonist, normalizes hyperlocomotion of Gunn rats. Both serotonin and its metabolites in the frontal cortex of Gunn rats were higher in concentrations than in control Wistar rats. The 5-HT2AR mRNA expression was downregulated without alteration of the protein abundance in the Gunn rat frontal cortex. The TPH2 protein level in the Gunn rat raphe region was significantly higher than that in the Wistar rat. CONCLUSIONS: It would be of value to be able to postulate that a therapeutic strategy for BIND disorders would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after onset of BIND manifestations. IMPACT: We demonstrated serotonergic dysregulation underlying hyperlocomotion in Gunn rats. This finding suggests that a therapeutic strategy for bilirubin-induced neurologic dysfunction (BIND) would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after the onset of the BIND manifestations. Ketanserin normalizes hyperlocomotion of Gunn rats. To our knowledge, this is the first study to demonstrate a hyperlocomotion link to serotonergic dysregulation in Gunn rats.

Interactions of Cognitive and Physical Functions Associated with Toilet Independence in Stroke Patients.

OBJECTIVES: The purpose of this study was to clarify the interaction among cognitive and physical functions associated with toilet independence in stroke patients. MATERIALS AND METHODS: We retrospectively examined 125 stroke patients. We performed decision tree analysis to detect the interaction associated with toilet independent using assessment of motor function on the affected side, muscle strength on unaffected side, trunk function, neglect, motivation, and cognitive function. The interactions detected via decision tree confirmed the existence and influence using logistic regression. RESULTS: The verticality test of the Stroke Impairment Assessment Set (3 or ≤2 points) was selected at the first level, and the Revised Hasegawa's dementia scale (≥19 or ≤18 points) and age (≥70 or ≤69 y) were selected at the second level of decision tree. Interaction terms created by these factors were significantly associated with toilet independence after adjusting for the independent influence of each factor using logistic regression. CONCLUSIONS: Our results show an interaction of trunk and cognitive functions or trunk function and age associated with toilet independence. The probability of toilet independence dramatically changes if two factors of each interaction were satisfied in stroke patients.

Functions necessary for gait independence in patients with stroke: A study using decision tree.

BACKGROUND: Little is known about the existence and impact of interactions among multiple impairments to gait independence. The purpose of this study is to reveal the interaction of physical functions and its impact on gait independence in stroke patients. METHODS: This retrospective study included 108 subacute stroke patients. We conducted a decision tree analysis to examine the existence of interactions in relation to gait independence among the gross motor function of lower limb, knee extension strength, sensory function, and trunk function. Further, we confirmed the existence and impact of interaction detected via the decision tree after adjusting for the effects of confounding factors using logistic regression. RESULTS: The knee extension strength and proprioception on the affected side were selected in the first and second level of the decision tree. In addition, the knee extension strength was selected in the third level. The interaction of the knee extension strength and proprioception on the affected side was significantly associated with gait independence, both before and after adjusting for age, visuospatial perception, and cognitive functions. CONCLUSIONS: Our results suggest that the interaction of the knee extension strength and proprioception on the affected side is strongly associated with gait independence in stroke patients.

Effects of the Interaction among Motor Functions on Self-care in Individuals with Stroke.

BACKGROUND: No study to date has focused on what combinations of motor functions are strongly associated with self-care independence in individuals with stroke. The purpose of this study is to clarify the impact of motor function interactions on self-care independence in individuals with stroke. METHODS: This retrospective observational study included 132 individuals with first stroke. We conducted a decision tree analysis to examine the impact on daily living skills of numerous key functions - the upper and lower limbs on the affected side, bilateral grip strength and lower limb muscle strength on the unaffected side, bilateral upper limb and trunk function, and balance. Further, we confirmed the interaction effects detected via the decision tree approach using logistic regression. RESULTS: As per the decision tree analysis, the interaction between balance and upper limb function of the affected side showed an association with self-care independence. The interaction terms of balance and upper limb function we analyzed were significantly associated with the ability to achieve self-care independence, after some adjustments to eliminate the influence of confounding factors. CONCLUSIONS: These results suggest that the combination of functional status of balance and upper limb function of the affected side are strongly associated with the independence of self-care. The decision tree created in this study could serve as an effective guide when implementing a remedial approach for individuals with stroke aiming to achieve self-care independence.

Use of a multilayer perceptron to create a prediction model for dressing independence in a small sample at a single facility.

[Purpose] This study aimed to assess the accuracy of a prediction model for dressing independence created with a multilayer perceptron in a small sample at a single facility. [Participants and Methods] This retrospective observational study included 82 first-stroke patients. The prediction models for dressing independence at hospital discharge were created using a multilayer perceptron, logistic regression, and a decision tree, and compared for predictive accuracy. Age, dressing performance, trunk function, visuospatial perception, balance, and cognitive function at admission were used as variables. [Results] The area under the receiver operating characteristic curve, classification accuracy, sensitivity, specificity, positive-predictive value, and negative-predictive value for training data were highest with the multilayer perceptron model. Cochran's Q and multiple comparison tests revealed a significant difference between logistic regression and multilayer perceptron models. Testing of data in 10-fold cross-validation yielded the same results, except for sensitivity. [Conclusion] The present study suggested that higher accuracy could be expected with a multilayer perceptron than with logistic regression and a decision tree when creating a prediction model for independence of activities of daily living in a small sample of stroke patients.

Relationship between Grooming Performance and Motor and Cognitive Functions in Stroke Patients with Receiver Operating Characteristic Analysis.

BACKGROUND: This study aimed to elucidate the relationship between grooming performance of stroke patients and various motor and cognitive functions and to examine the cognitive and physical functional standards required for grooming independence. METHODS: We retrospectively analyzed the data of 96 hospitalized patients with first stroke in a rehabilitation hospital ward. Logistic regression analysis and receiver operating characteristic curves were used to investigate the related cognitive and motor functions with grooming performance and to calculate the cutoff values for independence and supervision levels in grooming. RESULTS: For analysis between the independent and supervision-dependent groups, the only item with an area under the curve (AUC) of .9 or higher was the Berg Balance Scale, and the calculated cutoff value was 41/40 (sensitivity, 83.6%; specificity, 87.8%). For analysis between the independent-supervision and dependent groups, the items with an AUC of .9 or higher were the Simple Test for Evaluating Hand Function (STEF) on the nonaffected side, Vitality Index (VI), and FIM® cognition. The cutoff values were 68/67 for the STEF (sensitivity, 100%; specificity, 72.2%), 9/8 points for the VI (sensitivity, 92.3%; specificity, 88.9%), and 23/22 points for FIM® cognition (sensitivity, 91.0%; specificity, 88.9%). CONCLUSIONS: Our results suggest that upper-extremity functions on the nonaffected side, motivation, and cognitive functions are particularly important to achieve the supervision level and that balance is important to reach the independence level. The effective improvement of grooming performance is possible by performing therapeutic or compensatory intervention on functions that have not achieved these cutoff values.

Simple Indicator to Judge the Independence Level Required in Dressing in a Hospital Ward for Patients with Stroke.

BACKGROUND: This study aimed to create a simple and objective indicator for use by inexperienced nurses and family members of patients to judge the assistance level required for dressing in a hospital, while encouraging independence in activities of daily living among inpatients with stroke using the Berg balance scale. METHODS: We retrospectively analyzed the data of 108 hospitalized patients with first stroke in a rehabilitation hospital ward. Receiver operating characteristic curves were used to identify the Berg balance scale item with the highest discriminatory power against independence level in dressing. RESULTS: For comparisons between the independence and supervision or less level groups, the area under the curve of the sum score of "Retrieving object from floor" and "Standing with one foot in front" was .954, and the calculated cutoff value was 6/5 (sensitivity, 86%; specificity, 94%). For comparisons between the supervision or higher level and dependence groups, the area under the curve of the score of "Retrieving object from floor" was .930, and the calculated cutoff value was 2/1 (sensitivity, 93%; specificity, 81%). CONCLUSIONS: Our results suggested that Berg balance scale items are individually and in combination simple and useful indicators to judge independence level in dressing in a hospital ward for patients with stroke. These indices appear to be appropriate for individuals who are unfamiliar with Berg balance scale, such as inexperienced nurses and family members of patients.

Propensity-matched analysis of the gap between capacity and actual performance of dressing in patients with stroke.

[Purpose] Dressing is an activity of daily living for which stroke patients often show discrepancies between capacity and actual performance. The aim of this study was to elucidate the physical function and unilateral spatial neglect in stroke patients that reduce their level of actual performance despite having the capacity for dressing independently. [Subjects and Methods] This retrospective study included 60 first-time stroke patients judged by occupational therapists as able to dress independently. The patients were divided into two groups according to their FIM(®) instrument scores for dressing the upper and lower body: an independent group with both scores ≥6 and an assistance group with one or both scores ≤5. After adjusting for confounding factors through propensity score matching, the groups were compared by using Stroke Impairment Assessment Set items, the Simple Test for Evaluating Hand Function of both upper limbs, and the Berg balance scale. [Results] The assistance group had a significantly lower score for the Berg balance scale than the independent dressing group (31.0 ± 12.3 vs. 47.8 ± 7.4). [Conclusion] The results of the present study suggested that the balance function has an effect on the discrepancy between dressing capacity and performance.

Identification of the affected lower limb and unaffected side motor functions as determinants of activities of daily living performance in stroke patients using partial correlation analysis.

[Purpose] This study aimed to clarify the independent impact of the affected upper and lower limb, trunk, and unaffected side motor functions on activities of daily living in stroke patients using partial correlation analysis. [Subjects and Methods] This retrospective study included 77 stroke patients. Motor functions were assessed using the Stroke Impairment Assessment Set, and the activities of daily living performance was assessed using the Barthel index or Functional Independence Measure. Further, simple and partial correlation analyses were conducted between each motor function and activities of daily living parameter. [Results] Simple correlation analysis identified significant positive correlations for each pair. In contrast, partial correlation analysis only identified significant positive correlations between the affected lower limb or unaffected side functions and the Barthel index or Functional Independence Measure. This discrepancy between the two tests was explained by the significant interaction between the affected upper and lower limb functions and between the trunk and unaffected side functions. [Conclusion] The present study identified the affected lower limb and unaffected side motor functions as the major determinants of activities of daily living performance in stroke patients. These findings suggest that rehabilitation programs can be improved by targeting these areas.

Relationship between dressing and motor function in stroke patients: a study with partial correlation analysis.

[Purpose] The aim of the present study was to elucidate which motor functions are most or more important for dressing performance before and after rehabilitation. [Subjects] Seventy-nine first episode stroke patients in a hospital convalescent rehabilitation ward. [Methods] The relationships between motor function of the affected upper and lower limbs, unaffected side function, trunk function, balance, cognitive function, and independence level in dressing were examined at admission and discharge using partial correlation analysis. [Results] Independence level of dressing correlated with motor function of the affected upper limb and balance at admission, but correlated only with balance at discharge. [Conclusion] Balance function was strongly associated with level of dressing independence. The effect of gross motor function of the affected upper and lower limbs on the level of independence in dressing may thus be smaller than originally expected. Enhanced balance ability can be important for learning single-handed actions of self-dressing during rehabilitation.

Impaired hippocampal spinogenesis and neurogenesis and altered affective behavior in mice lacking heat shock factor 1.

Aberrant transcriptional regulation in the brain is thought to be one of the key components of the pathogenesis and pathophysiology of neuropsychiatric disorders. Heat shock factors (HSFs) modulate cellular homeostasis through the control of gene expression. However, the roles of HSFs in brain function have yet to be elucidated fully. In the present study, we attempted to clarify the role of HSF1-mediated gene regulation in neuronal and behavioral development using HSF1-deficient (HSF1(-/-)) mice. We found granule neurons of aberrant morphology and impaired neurogenesis in the dentate gyrus of HSF1(-/-) mice. In addition, HSF1(-/-) mice showed aberrant affective behavior, including reduced anxiety and sociability but increased depression-like behavior and aggression. Furthermore, HSF1 deficiency enhanced behavioral vulnerability to repeated exposure to restraint stress. Importantly, rescuing the HSF1 deficiency in the neonatal but not the adult hippocampus reversed the aberrant anxiety and depression-like behaviors. These results indicate a crucial role for hippocampal HSF1 in neuronal and behavioral development. Analysis of the molecular mechanisms revealed that HSF1 directly modulates the expression of polysialyltransferase genes, which then modulate polysialic acid-neural cell adhesion molecule (PSA-NCAM) levels in the hippocampus. Enzymatic removal of PSA from the neonatal hippocampus resulted in aberrant behavior during adulthood, similar to that observed in HSF1(-/-) mice. Thus, these results suggest that one role of HSF1 is to control hippocampal PSA-NCAM levels through the transcriptional regulation of polysialyltransferases, a process that might be involved in neuronal and behavioral development in mice.

Prediction of Walking Independence in Older Women with Vertebral Compression Fracture Using Phase Angle: A Preliminary Study Using Propensity Score.

Objectives: This study aimed to clarify whether phase angle can be a predictor of walking independence in older women with vertebral compression fractures (VCFs) and to determine a clinically usable cutoff value. Methods: We retrospectively assessed data of older women (n=59; median age, 83.0 years) with VCFs. Propensity score-matching and logistic regression were performed to examine the association between phase angle at admission and walking independence at discharge. The cutoff value for the phase angle at admission for predicting walking independence was calculated based on the receiver operating characteristic curve. Results: Thirty-one patients (52.5%) could walk independently at discharge. Thirty patients were extracted from the independent and non-independent groups according to the propensity score. After propensity score matching, there was no significant difference between the groups for age, medical history, knee extension strength, skeletal muscle mass index, mini nutritional assessment-short form score, or revised Hasegawa's dementia scale score. However, the phase angle of the independent group was significantly higher than that of the non-independent group (P<0.05). Logistic regression revealed that phase angle at admission was significantly associated with walking independence at discharge (odds ratio, 12.2; 95% confidence interval, 2.1-72.0; P<0.01). The area under the receiver operating characteristic curve was 0.868, and the calculated phase angle cutoff value was 3.55°. Conclusions: This study revealed that the phase angle can predict walking independence in older women with VCFs. The cutoff values for women calculated in this study can be used as a simple and objective predictive index of walking independence.

Age-stroke related dysfunction interaction associated with home discharge of stroke inpatients in the rehabilitation ward.

The purpose of this study was to investigate whether interactions exist among cognitive and physical functions and activities of daily living (ADL) associated with home discharge of stroke patients in the rehabilitation ward. The subjects were 231 patients with a first stroke. Age, gender, affected side, the stroke impairment assessment set, ADL and discharge destination were collected from the medical record. Using a decision tree, a combination of variables that might have an interaction effect associated with home discharge was extracted. The existence of an interaction between the extracted variables was confirmed by logistic regression analysis. A combination of total score of the stroke impairment assessment set (≤27 points) and age (>76.5 years) at admission was extracted from the decision tree. As a result of the logistic regression analysis, this interaction term was significantly associated with home discharge. The findings of the present study suggest that there is an interaction between age and stroke-related dysfunction related to home discharge. Stroke patients aged over 76.5 years with the stroke impairment assessment set score of 27 or less at admission to the rehabilitation ward may need rehabilitation program considering the difficulty of home discharge.

Balance Function Required for Bathing Independence in Patients with Stroke and Hip Fracture.

Objectives: Little attention has been paid to the relationship between balance function and bathing independence. This research aimed to determine the degree of balance function needed by patients with stroke and patients with hip fracture (hereinafter referred to as patients with stroke and hip fracture) to bathe independently. Methods: Retrospective data analysis was performed on 59 patients with hip fracture and 201 patients with stroke. Logistic regression was performed to determine whether bathing independence was associated with the Berg Balance Scale (BBS) in patients with stroke and hip fracture. A receiver operating characteristic curve was generated to calculate cutoff values. Results: The BBS was significantly associated with bathing independence in patients with stroke and hip fracture. The calculated BBS cutoff value was 48 points for those with stroke (sensitivity, 84.7%; specificity, 79.1%) and 43 points for those with hip fracture (sensitivity, 81.3%; specificity, 77.8%). Conclusions: Balance function was independently associated with bathing independence. The level of balance function required for bathing independence may be lower for patients with hip fracture than for those with stroke. This could be a simple and useful indicator for rehabilitation professionals to interpret BBS results when conducting bathing interventions.

[Epigenetic regulation in depression].

Recent research has raised the notion that epigenetic mechanisms (e.g., DNA methylation and histone modifications), which exert lasting control over gene expression without altering the genetic code, could mediate stable changes in brain function. However, the role of environmental factors along with genetic factors in the epigenetic regulation of the pathogenesis of depression is largely unknown. Two genetically distinct mice strains, BALB/c (BALB) and C57BL/6 (B6), exhibit different behavioral responses to chronic stress. With chronic stress, BALB mice showed depressive-like behaviors, but not B6 mice, and glial cell-derived neurotrophic factor (GDNF) expression level was decreased in the ventral striatum of BALB mice but increased in B6 mice. In BALB mice, depressive-like behaviors and decreased GDNF expression were recovered by chronic antidepressant treatment. Therefore, we used these two mice strains to investigate how the epigenetic status of the GDNF gene in the ventral striatum modulates stress vulnerability. Both mice strains showed increased DNA methylation levels and MeCP2 recruitment in the GDNF promoter region. However, histone H3 acetylation level was decreased in BALB mice, but increased in B6 mice. Furthermore, BALB mice showed increased histone deacetylase2 (HDAC2) expression level and Re-ChIP assay revealed HDAC2-MeCP2 complex in BALB mice. Our results indicate the crucial role of histone modification by HDAC2 and MeCP2 complex for the control of GDNF expression and subsequent behavioral responses to chronic stress, in other words, the susceptibility to stress. In addition, we investigated the effect of antidepressants on the epigenetic regulation of GDNF expression. We found a reduced level of HDAC4 recruitment at the GDNF promoter region with antidepressants. Thus, our data suggest that antidepressants increase transcriptional activity of the GDNF gene through the modulation of histone acetylation by HDAC4. Finally, we examined the expressions of GDNF and epigenetic-related molecules mRNAs with major depressive and bipolar disorder patients by using quantitative real-time PCR. We found the aberrant expression of GDNF and epigenetic-related genes including HDAC2 and HDAC4 in mood disorder patients. Thus, our data provide novel insights suggesting that epigenetic mechanisms of GDNF expression are involved in the pathogenesis or pathophysiology of depression.

Cutoff Value for a Nutritional Indicator Related to Gait Independence in Elderly Fracture Patients: A Preliminary Study.

OBJECTIVE: Previous studies have reported the relationship between nutritional status and gait independence in elderly fracture patients. However, the degree to which nutritional indicators are related to gait independence is unclear. The purpose of this study is to calculate a cutoff value for a nutritional indicator related to gait independence in patients with hip and vertebral compression fractures. METHOD: This study included 69 patients (33 hip fracture, 36 vertebral compression fracture) who underwent rehabilitation at a convalescent rehabilitation ward. The relationships between nutritional indexes (Mini-Nutritional Assessment-Short Form [MNAⓇ-SF] and skeletal muscle mass index [SMI] ) at admission and gait independence at discharge were analyzed using logistic regression. In addition, receiver operating characteristic analysis was performed to calculate a cutoff value that predicts gait independence. RESULTS: Among the nutritional indicators used in this study, only MNAⓇ-SF was significantly able to predict gait independence at discharge, and this association was maintained, even after adjustment for confounders. The calculated MNAⓇ-SF cutoff values were 5.5 (sensitivity 100%, specificity 46.3%) and 7.5 points (sensitivity 67.9%, specificity 78.0%). CONCLUSION: This study suggests that MNAⓇ-SF may be an index for predicting gait independence in patients with hip or vertebral compression fractures in the convalescent rehabilitation ward. The cutoff values calculated in this study were simple and useful index for physical therapists to interpret the results of MNAⓇ-SF.