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Focal dystonia (FD) can develop after thalamic lesions. Abnormal somatic sensations were argued to be responsible for FD. Our patient experienced FD-like movement disorders, agraphesthesia, and a reduced sense of shear force on the skin and pressure to deep tissues of the right upper limb following a small infarction in the left posterolateral thalamus. FD-like symptoms improved while the skin was being pulled or the deep tissue was being pushed in a manner proportional to the strength of muscle contractions. Therefore, the lack of these sensations was suggested to be related to FD-like symptoms.

Introduction: Robotic assisted therapy and modified constraint-induced movement therapy are used evidence-based approach in stroke rehabilitation. However, there is no study showing a combination of robotic assisted therapy and modified constraint-induced movement therapy (combined therapy) in the subacute phase. This study investigated the effectiveness of combined therapy in stroke patients with moderate to severe upper limb paresis compared with conventional occupational therapy at subacute setting. Methods: This research used a case–control study. The intervention group ( n = 15) consisting of patients with moderate to severe upper limb paresis (Brunnstrom recovery stage upper extremity III or IV and above hand III) 4–8 weeks since stroke onset received a combined therapy for 3 weeks (total intervention time: 1440 minutes). The control group ( n = 15) extracted by propensity score matching received a conventional occupational therapy for 4 weeks (total intervention time: 1680–2240 minutes). The primary outcome was the Fugl-Meyer assessment upper limb score change before and after the intervention. Results: The intervention group exhibited significantly greater improvement on Fugl-Meyer assessment upper lim change ( p = 0.005). Conclusion: In the subacute phase, the combined therapy of robotic assisted therapy and modified constraint-induced movement therapy helped improve upper limb motor function more effectively and efficiently than conventional occupational therapy.

Numbsense is a phenomenon, wherein patients can correctly respond to somatosensory stimuli at a higher rate than expected by chance, but cannot perceive the same stimuli consciously. Previously, numbsense has been reported in tactile localization of stimuli on the patient's own body. Here, we describe a patient with numbsense that involved touched objects. The patient could not recognize the majority of somatosensory stimuli after left parietal infarction, but could correctly select shape, texture, and object stimuli more frequently than expected by chance.

No study has reported a unilateral localized cerebral lesion of the posterior insula bilaterally reducing noxious stimuli perception. A 57-year-old man with an infarct involving the right posterior insula presented with reduced somatosensory response in the upper and lower left extremities. Furthermore, there was a reduced response to noxious stimulation in the right upper and lower limbs. We noted reductions in pain, noxious heat and cold perceptions, and sensitivity to increasing temperature. Other somatic sensations, including non-noxious temperatures, remained intact in the right upper and lower extremities. These findings in our patient with a unilateral insular lesion indicated a bilaterally reduced perception of noxious stimulation.

Branch atheromatous disease (BAD) is often associated with corticospinal tract injury, and some patients develop early neurological deterioration (END) in the acute phase. This study investigated the progress of upper limb prognosis after BAD in the acute phases and examined the factors related to the prognosis of upper limb function.108 subjects diagnosed with BAD were included. Then subjects were classified into two groups: those with good recovery of upper limb function and those with poor recovery of upper limb function. Univariate and multivariate analyses were performed with the objective variable being good or poor upper limb function. The following factors were used as explanatory variables: age, the volume of infarction, initial Fugl-Meyer assessment (FMA) upper limb score, and presence of END.The univariate analysis showed significant differences in age and volume of infarction (p 0.05). Multivariate analysis showed the following finding: age;(OR 0.977,95%CI 0.917-0.997,p = 0.0061; volume of infarction;(OR 0.645,95%CI 0.461-0.902,p = 0.0104). A significant difference was found in the age and volume of the infarct.This study finding suggests that age and volume of infarction are associated with the prognosis of upper extremity paralysis in BAD.

Background Mechanical Thrombectomy (MT) is a recommended approach for post-cerebral ischemia in acute settings. Although a large amount of evidence suggests the use of MT, existing evidence has primarily focused on assessing lower limb performance or gait performance as an outcome measure. Methods This study was to investigate whether MT would be an effective approach for improving upper limb performance in post-stroke patients.This case control was divided into two groups: 154 patients as a control group only given conventional rehabilitation; and 25 patients as an intervention group given MT and conventional rehabilitation. Outcome variables were measured by calculating the change of Fugl-Meyer Assessment score at the last intervention compared with the beginning of the intervention. Result By comparing the FMA scores after, the propensity matching compared between before receiving therapy intervention and after, the intervention group showed as follows: 30.4 ± 26.4–44.3 ± 25.4, p = 0.0019, r = 0.59. The control group showed as follows: 39.9 ± 24.1–49.1 ± 21.3, p = 0.002, r = 0.69. Lastly, a comparison of the intervention group with the control group about their FMA score change indicates as follows: intervention group: 13.9 ± 19.4, control group 9.2 ± 10.0, p = 0.2967, r = 0.15. Conclusion This study indicated that there was no significant difference between MT and a conventional approach for improving UE function. However, this is the first study to investigate the course of recovery of UE function in the acute phase after MT, and this finding supports the need for further research.

A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC50 EP2 = 1.1 nM, EP3 = 1.0 nM) with acceptable selectivity over the EP1 and EP4 subtypes (>2000-fold). Further fine-tuning of compound 10 led to identification of ONO-8055 as a clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg, po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly promising drug for UAB.

Background and Purpose Spasticity, an aspect of upper motor neuron syndrome, is a widespread problem in patients with stroke. To date, no study has reported the long-term (up to 1 year) outcomes of botulinum toxin (BTX) injection in combination with constraint-induced movement therapy in patients with chronic stroke. In this case report, the long-term (1 year) effects of the combination of BTX type A injection and constraint-induced movement therapy on spasticity and arm function in a patient with chronic stroke and arm paresis are described. Case Description The patient was a 66-year-old man who had had an infarction in the right posterior limb of the internal capsule 4 years before the intervention. At screening, the patient was not able to voluntarily extend his interphalangeal or metacarpophalangeal joints beyond the 10 degrees required for constraint-induced movement therapy. From 12 days after BTX type A injection, the patient received 5 hours of constraint-induced movement therapy for 10 weekdays. Outcomes All outcome measures (Modified Ashworth Scale, Fugl-Meyer Assessment, Action Research Arm Test, and amount of use scale of the Motor Activity Log) improved substantially over the 1-year period (before intervention to 1 year after intervention). Repeat BTX type A injections were not necessary because muscle tone and arm function did not worsen during the observation period. Discussion The improved arm function may have reflected improvements in volitional movements and coordination or speed of movements in the paretic arm as a result of a reduction in spasticity, a reduction of learned nonuse behaviors, or use-dependent plasticity after the combination of BTX type A injection and constraint-induced movement therapy. In addition, the possibility of an influence of the passage of time or the Hawthorne effect cannot be ruled out. If this approach proves useful in future controlled studies, it may reduce the rising medical costs of the treatment of stroke.

Despite the confirmed short-term effects of constraint-induced movement therapy, the long-term effects have not been sufficiently verified in terms of functional improvement of the affected arm.To evaluate the long-term effects and relationship between arm use in activities of daily living and arm improvement with modified constraint-induced movement therapy in chronic stroke patients.At 1 year after completing modified constraint-induced movement therapy, arm function (Fugl-Meyer Assessment) and amount of daily arm use (motor activity log) were assessed.Fourteen post-stroke patients with mild to moderate impairment of arm function were analyzed. One year after completing modified constraint-induced movement therapy, participants consistently showed improvements in arm function and amount of daily arm use (analysis of variance: Fugl-Meyer Assessment, P 0.001; Motor Activity Log, P 0.001). For the Fugl-Meyer Assessment, post-hoc tests detected significant improvements (pre versus post, P = 0.009; pre versus 1 year, P 0.0001; post versus 1 year, P 0.036). For the Motor Activity Log, post-hoc tests also detected significant improvements (pre versus post, P = 0.0001; pre versus 1 year, P 0.0001; post versus 1 year, P = 0.0014). The magnitude of the change in Fugl-Meyer Assessment score correlated significantly with the change in Motor Activity Log score (R = 0.778, P = 0.001).Among post-stroke patients with mild to moderate impairments of arm function, modified constraint-induced movement therapy without any other rehabilitation after intervention may improve arm function and increase arm use for 1 year. In addition, increasing arm use may represent an important factor in improving arm function, and vice versa.

A highly potent and well-balanced dual agonist for the EP

Botulinum toxin type A (BtxA) injection, constraint-induced movement therapy (CIMT), and robotic therapy (RT) each represent promising approaches to enhance arm motor recovery after stroke. To provide more effective treatment for a 50-year-old man with severe left spastic hemiparesis, we attempted to facilitate CIMT with adaptive approaches to extend the wrist and fingers using RT for 10 consecutive weeks after BtxA injection. This combined treatment resulted in substantial improvements in arm function and the amount of arm use in activities of daily living, and may be effective for stroke patients with severe arm paresis. However, we were unable to sufficiently prove the efficacy of combined treatment based only on a single case. To fully elucidate the efficacy of the combined approach for patients with severe hemiparesis after stroke, future studies of a larger number of patients are needed.

Background We sought to examine the effects of constraint-induced movement therapy on spasticity in patients with hemiparesis after stroke in 10 patients with chronic hemiparesis in their upper extremities. Methods Patients underwent a modified version of constraint-induced movement therapy (5 hours daily for 10 weekdays over 2 consecutive weeks). Motor function was assessed by the Fugl-Meyer Assessment, Wolf Motor Function Test, and the Motor Activity Log. Spasticity was assessed by the modified Ashworth scale and electromyography (F frequency, mean F/M ratio). These assessments were obtained immediately before and after the 2-week intervention. Wilcoxon rank sum tests were performed on these data ( P Results Constraint-induced movement therapy significantly improved hand and arm function as indicated by the Fugl-Meyer Assessment, Wolf Motor Function Test, and the Motor Activity Log scores. Constraint-induced movement therapy also reduced spasticity as assessed by the modified Ashworth scale, F frequency, and mean F/M ratio. Conclusions Comparable to motor function, constraint-induced movement therapy effectively reduces spasticity as confirmed by electromyography.

Objective: To investigate the long-term effects of the ‘transfer package’ in constraint-induced movement therapy, which is an optional protocol to facilitate actual use of the trained affected arm in activities of daily living. Design: A pilot quasi-randomized controlled trial with a blinded single assessor with six-month follow-up. Setting: Hospitalized care at university hospital. Subjects: Twenty-one post-stroke patients were quasi-randomized to either a group with transfer package during constraint-induced movement therapy or a control group (without transfer package). Interventions: The transfer package group received 4.5 hours of intensive task training and 0.5 hours of transfer package whereas the control group received 5.0 hours of intensive task training per day during 10 consecutive weekdays. Main measures: Arm function was measured with Fugl-Meyer Assessment and Amount of Use score of Motor Activity Log. Results: Twenty-three patients were quasi-randomized, but data from two patients were missing from the long-term follow-up. Both groups showed increase in arm function postintervention. However, at six months’ follow-up only the transfer package group showed consistent increase in arm function (with transfer package group versus control group; Fugl-Meyer Assessment, mean (± SD) from 48.6 ± 7.8 (preintervention) to 55.7 ± 4.5 (postintervention) and 59.0 ± 3.6 (six months postintervention) versus from 49.1 ± 5.5 to 52.8 ± 6.0 and 53.3 ± 4.9, P= 0.003; Amount of Use scale of Motor Activity Log, mean from 1.3 ± 0.55 (preintervention) to 2.12 ± 0.55 (postintervention) and 2.79 ± 0.98 (six months postintervention) versus from 1.18 ± 0.70 to 1.61 ± 0.54 and 1.65 ± 0.68, P= 0.002). Conclusions: Our results confirmed the long-term effects of the transfer package in constraint-induced movement therapy.

Upon electrochemical oxidation of configurationally stable biphenyl-based electron donors (Rax)-1a and -1b to butane-1,4-diyl dications (M)-2a2+ and -2b2+, drastic changes were induced not only in ...

A practical route for the synthesis of both enantiomers of a functionalized bicyclo[3.2.1]octenone, which is potentially useful as a versatile chiral building block, has been developed from 1,4-cyclohexanedione monoethylene acetal by employing proline-catalyzed diastereoselective intramolecular aldolization and lipase-mediated kinetic resolution as the key steps. The synthetic utility of the bicyclo[3.2.1]octenone has been demonstrated by the conversion into a chiral bicyclo[5.3.0]decane, which should serve as the key intermediate for the synthesis of the pseudoguaianolide class of antitumor sesquiterpenes.

Background/Aims: Existing cognitive measures for moderate-to-severe dementia have shown floor effects and an inability to assess the remaining cognitive function, especially for profound dementia. Methods: We constructed the Cognitive Test for Severe Dementia (CTSD), which consists of 13 items covering 7 cognitive domains, and examined its reliability and validity. Results: Cronbach's α in severe dementia participants was 0.896. Interrater and test-retest reliability were 0.961 and 0.969, respectively. The CTSD showed a significant correlation with 3 other measures of cognitive function (Mini-Mental State Examination, Severe Cognitive Impairment Rating Scale, and Hasegawa Dementia Scale-Revised: r values = 0.870-0.922, p values Conclusion: The CTSD was able to sensitively capture the remaining cognitive function in severe dementia patients when compared with other cognitive tests.

1,3-Bis[4-(dimethylamino)phenyl]isobenzofuran (1a) and a derivative were efficiently prepared through a sequence of reactions in a single batch reactor (time integration). The o-quinodimethane-type...

Starting from enantiopure 4-cumyloxy-2-cyclopenten-1-one, a route to 5- and 6-substituted hyropyran-2-ones has been developed. The method has achieved the synthesis of 4,5- cis - and 4,5- trans -5-ethyl-4-hydroxytetrahydropyran-2-ones assigned to marine natural products simplactones A and B to disprove the former and revise the latter of the proposed structures.

Purpose To test whether diffusion tensor imaging could evaluate potential motor capability of patients with chronic cerebral infarction. Methods We used constraint-induced movement therapy (CIMT) as a rehabilitation, which reveals potential motor capability. We also investigated the relationship between the outcome of CIMT and the ratio between fractional anisotropy values (rFA) in affected and unaffected sites of the corticospinal tract before CIMT. Imaging was performed in cerebral infarction patients (n = 14) and the rFA of the posterior limb of internal capsule (PLIC) was measured before CIMT. Patients were evaluated before and after CIMT using the Fugl-Meyer (F-M) assessment, Wolf Motor Function Test, Action Research Arm Test, and Motor Activity Log and association between PLIC- rFA and these scores was determined. Results All patients showed an improvement in mobility following the 10-day CIMT session. Strong positive correlation was found only between F-M after CIMT and PLIC-rFA (r = 0.8098, p = 0.0004). A strong linear relationship was observed after CIMT. Conclusion These data support PLIC-rFA as a new marker of the CIMT-induced improvement in motor function (F-M).

A concise route to a steroid C/D-ring system leading to 25-hydroxy-Grundmann's ketone has been developed along with a new chemical resolution of the chiral starting material containing a bicyclo[3.2.1]octane framework.

Starting from enantiopure 4-cumyloxy-2-cyclopenten-1-one, a route to 5- and 6-substituted hyropyran-2-ones has been developed. The method has achieved the synthesis of 4,5- cis - and 4,5- trans -5-ethyl-4-hydroxytetrahydropyran-2-ones assigned to marine natural products simplactones A and B to disprove the former and revise the latter of the proposed structures.

A new route to (+)-estrone has been developed starting from the chiral building block having a bicyclo[3.2.1]octane framework based on the inherent stereochemical chemical nature of the chiral building block.

A concise route to the A-ring precursor of calcitriol (1α,25-dihydroxyvitamin D 3 ) has been developed starting from the chiral building block having a bicydo[3.2.1]octane framework. Since we have already developed a diastereocontrolled synthesis of the C/D-ring precursor starting with the enantiomeric chiral building block, the present synthesis implies the total synthesis of calcitriol from a single precursor in a formal sense.