Sequence-based engineering of dynamic functions of micrometer-sized DNA droplets.

DNA has the potential to achieve a controllable macromolecular structure, such as hydrogels or droplets formed through liquid-liquid phase separation (LLPS), as the design of its base sequence can result in programmable interactions. Here, we constructed "DNA droplets" via LLPS of sequence-designed DNA nanostructures and controlled their dynamic functions by designing their sequences. Specifically, we were able to adjust the temperature required for the formation of DNA droplets by designing the sequences. In addition, the fusion, fission, and formation of Janus-shaped droplets were controlled by sequence design and enzymatic reactions. Furthermore, modifications of proteins with sequence-designed DNAs allowed for their capture into specific droplets. Overall, our results provide a platform for designing and controlling macromolecular droplets via the information encoded in component molecules and pave the way for various applications of sequence-designed DNA such as cell mimics, synthetic membraneless organelles, and artificial molecular systems.

Impact of major earthquakes on Parkinson's disease.

In April of 2016, major earthquakes occurred in Kumamoto, Japan. There is limited information on how major earthquakes affect patients with Parkinson's disease (PD). This study investigates the effect of major earthquakes on patients with PD. The participants were outpatients with PD from hospitals located in areas heavily damaged by the earthquakes. We performed an anonymous survey at nine medical institutions to investigate the condition of these patients during the month following the earthquakes. We collected questionnaires from 335 patients with PD. The mean age was 72.6, and the mean disease duration was 7.4 years. Regarding physical conditions, 29.3% of the patients worsened, 1.5% improved, and 68.1% had no change. The mental health of 35.2% of the patients worsened, 2.4% improved, and 57.9% had no change. The most frequently exacerbated neurologic symptoms included bradykinesia (56.1%), gait disturbance (51.0%), freezing of gait (40.8%), extension of "off" time (38.8%), and constipation (38.8%). The worsening mental conditions included fear of an aftershock (77.1%), anxiety (49.2%), insomnia (47.5%), melancholy feelings (45.8%), and fatigability (38.1%). Patients forced to evacuate reported significantly more physical and mental health symptoms (p < 0.01). The influences of major earthquakes on patients with PD were identified. After major earthquakes, we should consider the care required for patients' physical and mental health especially for those who experienced evacuation.

The effects of the Kumamoto earthquake on the clinical symptoms of patients with Parkinson's disease.

Our hospital is the designated treatment base for intractable neurological diseases in the Kumamoto Prefecture. It is located in the center of the prefecture where the major 7.3-magnitude Kumamoto earthquake was recorded in 2016. In order to examine whether this earthquake affected the clinical symptoms of patients with Parkinson's disease in this hospital, we investigated outpatients examined up to 4 weeks after the earthquake. The subjects were 26 consecutive patients without any changes in anti-Parkinson's disease treatment or their attending physician during the examination period. All of the items in Part III of the Unified Parkinson's Disease Rating Scale (UPDRS), which is a clinician-scored scale for monitoring and evaluating motor function, were confirmed with the subjects before and after the earthquakes. After the earthquakes, worsened symptoms were found in 7 patients and 7 patients felt better. On the UPDRS, worsened symptoms were most commonly found among the items examining "muscle rigidity" and "slowness of movement and decreased movement" among the 7 patients with exacerbated symptoms. After the earthquake, clinical symptoms worsened significantly in women (P = 0.0188), patients with mild symptoms (P = 0.0111), and those who suffered a high degree of personal loss, such as those whose homes were damaged, who were forced to take refuge, or who had to sleep in their car (P = 0.0184). The mental and emotional burden due to the earthquake might be particularly high in the group of patients with worsened symptoms, suggestive of a relationship between stress and the exacerbation of parkinsonian symptoms.

Intratumoral hemorrhage in a patient with malignant meningioma under anticoagulant therapy.

We report the case of an elderly woman with malignant meningioma and atrial fibrillation who started taking anticoagulants after an ischemic stroke and subsequently developed intratumoral hemorrhage. Further studies are required to confirm whether a particular anticoagulant agent is suitable for patients with brain tumor and atrial fibrillation.

Earlier and better high-resolution single breast imaging during bilateral breast dynamic scans at 3-T MRI: comparison with post dynamic high-resolution imaging.

BACKGROUND: Breast MRI protocols have been improved by using a combination of dynamic scans for bilateral breasts and high-resolution imaging for a single breast which can be obtained during dynamic scans by recent technological advances. The purpose of this study was to compare high-resolution imaging during dynamic scans (HR-intra) with high-resolution imaging obtained post dynamic scans (HR-post). METHODS: Fifty-five women with pathologically proven breast cancer who underwent breast dynamic scans at 3-T MRI from February to September 2009 were enrolled in this study. Tumoral contrasts to the background breast tissue were compared by three radiologists independently in a blinded fashion. Results of visual assessment were categorized into three groups as follows: HR-intra being better (IB), equal (E), and HR-post being better (PB). The contrast to noise ratio (CNR) of the tumor and the signal to noise ratio of the normal breast gland (SNR) were compared between HR-intra and HR-post. RESULTS: Two patients were excluded because of poor MR imaging quality. Three radiologists separately categorized 64.2, 79.2, and 77.4 % of lesions as IB. The CNR of the tumor of HR-intra (mean ± SD = 6.9 ± 4.0) was significantly higher than that of HR-post (6.0 ± 3.7, p < 0.0001). The SNR of the normal breast gland of HR-intra (9.5 ± 1.7) was significantly lower than that of HR-post (10.0 ± 1.9, p < 0.0001). CONCLUSION: HR-intra during dynamic MRI provided earlier and better tumor to normal breast gland contrast than HR-post.

Decision making of amyotrophic lateral sclerosis patients on noninvasive ventilation to receive tracheostomy positive pressure ventilation.

OBJECTIVES: We retrospectively evaluated the decision-making process of amyotrophic lateral sclerosis (ALS) patients on noninvasive positive pressure ventilation (NPPV) concerning respiratory management with tracheostomy positive pressure ventilation (TPPV) in the future. PATIENTS AND METHODS: We investigated the clinical characteristics of 29 consecutive ALS patients who had been introduced to NPPV during a 7-year period from September 2001 to August 2008 at our institution. We evaluated whether they had decided or not to undergo respiratory management with TPPV when NPPV was introduced and compared the clinical characteristics of the patients in these 2 groups. RESULTS: At the point of introduction of NPPV, 16 patients had made a definite decision on whether to receive TPPV for life, whereas 13 patients made their decision after its introduction. Finally, 12 patients (75.0%) of the former group and only 3 patients (23.1%) of the latter group refused to live with TPPV. Thus, among the patients who hesitated to decide whether to receive TPPV after the initiation of NPPV, a significantly higher number (P=0.002) ultimately transferred to TPPV. CONCLUSION: In Japan, NPPV is an important factor promoting the decision to receive TPPV for patients who worried about the transition to TPPV. Further study is needed to realize what kind of an education actually influences on decision-making for TPPV and results in the happiness of ALS patients.

Associations of outdoor air pollution with hemorrhagic stroke mortality.

OBJECTIVE: Evidence linking short-term exposure to outdoor air pollution with hemorrhagic stroke is inconsistent. METHODS: We evaluated the associations between outdoor air pollution and specific types of stroke in Tokyo, Japan, from April 2003 to December 2008. We obtained daily counts of stroke mortality (n = 41,440) and concentrations of nitrogen dioxide as well as particles less than 2.5 µm in diameter. Time-series analysis was employed. RESULTS: Although same-day air pollutants were positively associated with ischemic stroke and intracerebral hemorrhage mortality, both air pollutants were more strongly associated with subarachnoid hemorrhage mortality: rate ratio was 1.041 (95% confidence interval: 1.011-1.072) for each 10 µg/m3 increase in the previous-day particles less than 2.5 µm. CONCLUSIONS: This study suggests that short-term exposure to outdoor air pollution increases the risks of hemorrhagic stroke mortality as well as ischemic stroke mortality.

Proposed dose equivalence between clonazepam and pramipexole in patients with restless legs syndrome.

BACKGROUND: Dopamine agonists are accepted as the first-line medications for restless legs syndrome (RLS). In some Asian countries, clonazepam is one of the prevalent medications for RLS because of its effect on sleep disturbances. To date, there have not been any studies that examined equivalent doses of pramipexole and clonazepam. To evaluate equivalent doses of pramipexole and clonazepam in RLS, we investigated the efficacy and tolerability after conversion from clonazepam to pramipexole, and examined dose equivalence between the two prescriptions. METHODS: In a prospective, open-label, multicenter study, 26 RLS patients treated with clonazepam (mean age: 69.2+/-11.0years old) were enrolled and then rapidly switched to pramipexole using a conversion calculation of 4:1 for daily doses. Then the daily dose of pramipexole was up titrated or tapered by 0.125mg/day at each subsequent examination. RLS symptoms and daytime somnolence were evaluated using the International RLS Study Group rating scale (IRLS), Clinical Global Impressions - Severity of illness (CGI-S) and the Epworth Sleepiness Scale (ESS), respectively. RESULTS: Conversion from clonazepam to pramipexole resulted in significant reductions of IRLS (16.3+/-8.7 to 9.1+/-6.3) and ESS (6.5+/-4.2 to 4.4+/-3.2). CGI scores demonstrated improvement after conversion. In 4 patients (15%), adverse events such as somnolence, sensation of oppression in the lower limbs, diarrhea, or nausea were present. Correlation analysis demonstrated a significant relationship between these daily doses. Spearman's correlation coefficient was 0.662. Our study, however, has some limitations since it is an open-label trial and includes only 26 patients. Further studies using a double-blind design or a crossover design are recommended. CONCLUSIONS: Statistical analysis demonstrated a 4:1 conversion for clonazepam to pramipexole. When switchover from clonazepam to pramipexole is done, this conversion ratio may be helpful to determine the initial dose of pramipexole for treating RLS.

Whole-body MRI using a sliding table and repositioning surface coil approach.

OBJECTIVE: To introduce and assess a new way of performing whole-body magnetic resonance imaging (MRI) using a non-integrated surface coil approach as available on most clinical MRI systems worldwide. METHODS: Ten consecutive asymptomatic subjects prospectively underwent whole-body MRI for health screening. Whole-body MRI included T1-, T2- and diffusion-weighted sequences, and was performed using a non-integrated surface coil to image four different stations without patient repositioning. The four separately acquired stations were merged, creating seamless coronal whole-body T1-, T2- and diffusion-weighted images. Anatomical alignment, image quality at the boundaries of adjacent stations, and overall image quality of all stations were qualitatively assessed. RESULTS: The average time (+/-SD) taken to change the surface coil from one station to the next station was 53.8 (+/-7.1) s. The average total extra examination time +/- SD was 2 min 41.4 s (+/-15.3 s). Anatomical alignment, image quality at the boundaries of adjacent stations, and overall image quality of all stations of T1-, T2- and diffusion-weighted whole-body MRI were overall graded as "good" to "excellent". CONCLUSION: This study shows that a time-efficient and high-quality whole-body MRI examination can easily be performed by using a non-integrated sliding surface coil approach.

Neuroprotective effects of ethyl pyruvate on brain energy metabolism after ischemia-reperfusion injury: a 31P-nuclear magnetic resonance study.

The neuroprotective effects of ethyl pyruvate (EP), a stable derivative of pyruvate, on energy metabolism of rat brain exposed to ischemia-reperfusion stress were investigated by (31)P-nuclear magnetic resonance ((31)P-NMR) spectroscopy. Recovery level of phosphocreatine after ischemia was significantly greater when superfused with artificial cerebrospinal fluid (ACSF) with 2 mM EP than when superfused with ACSF without EP. EP was neuroprotective against ischemia only when administered before the ischemic exposure. Intracellular pH during ischemia was less acidic when superfused ahead of time with EP. EP did not show neuroprotective effects in neuron-rich slices pretreated with 100 microM fluorocitrate, a selective glial poison. It was suggested that both the administration of EP before ischemic exposure and the presence of astrocytes are required for EP to exert neuroprotective effects. We suggest the potential involvement of multiple mechanisms of action, such as less acidic intracellular pH, glial production of lactate, and radical scavenging ability.

Regions downstream from the WW domain of dystrophin are important for binding to postsynaptic densities in the brain.

In order to investigate the mechanism of dystrophin localization in the central nervous system (CNS), we generated adenovirus vectors that contained minidystrophin or truncated minidystrophin cDNA. We infected a primary neuronal culture derived from mdx mouse hippocampus with these viruses. Minidystrophin was observed along the plasma membrane as punctate dots or very short segments. In double immunofluorescence staining with anti-dystrophin and anti-postsynaptic density-95 antibodies, we observed that these proteins entirely colocalized. On the other hand, the truncated minidystrophin, which has deleted WW, cysteine-rich and C-terminal domains, was homogenously expressed in cytoplasm, neurites and axons. These findings suggest that a binding site to postsynaptic densities exists in the region extending from the WW domain to the C-terminal domain of dystrophin and that this site is necessary for binding to membrane.