•Cooling was maintained by an epidural device implanted for a medium-term period.•Seizure suppression in large animals was achieved using a coolant-perfused system.•A histological evaluation showed ...no adverse effects of implantation of the device.
Focal brain cooling (FBC) is under investigation in preclinical trials of intractable epilepsy (IE), including status epilepticus (SE). This method has been studied in rodents as a possible treatment for epileptic disorders, but more evidence from large animal studies is required. To provide evidence that FBC is a safe and effective therapy for IE, we investigated if FBC using a titanium cooling plate can reduce or terminate focal neocortical seizures without having a significant impact on brain tissue. Two cats and two macaque monkeys were chronically implanted with an epidural FBC device over the somatosensory and motor cortex. Penicillin G was delivered via the intracranial cannula for induction of local seizures. Repetitive FBC was performed using a cooling device implanted for a medium-term period (FBC for 30min at least twice every week; 3 months total) in three of the four animals. The animals exhibited seizures with repetitive epileptiform discharges (EDs) after administration of penicillin G, and these discharges decreased at less than 20°C cooling with no adverse histological effects. The results of this study suggest that epidural FBC is a safe and effective potential treatment for IE and SE.
Background
Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) remains an important problem with a complex pathophysiology. We used data from a single-center randomized ...trial to assess the effect of a phosphodiesterase inhibitor, cilostazol, in patients with aneurysmal SAH to explore the relationships of DCI with vasospasm, spreading depolarization (SD) and microcirculatory disturbance.
Methods
A post hoc analysis of a single-center, prospective, randomized trial of the effect of cilostazol on DCI and SD after aneurysmal SAH was performed. From all randomized cohorts, patients who underwent both SD monitoring and digital subtraction angiography (DSA) on day 9 ± 2 from onset were included. Cerebral circulation time (CCT), which was divided into proximal CCT and peripheral CCT (as a measure of microcirculatory disturbance), was obtained from DSA. Logistic regression was conducted to determine factors associated with DCI.
Results
Complete data were available for 28 of 50 patients. Of the 28 patients, 8 (28.5%) had DCI during the study period. Multivariate analysis indicated a strong association between the number of SDs on the day DSA was performed (i.e., a delayed time point after SAH onset) and DCI (odds ratio 2.064, 95% confidence interval 1.045–4.075,
P
= 0.037, area under the curve 0.836), whereas the degree of angiographic vasospasm and peripheral CCT were not significant factors for DCI.
Conclusions
There is a strong association between SD and DCI. Our results suggest that SD is an important therapeutic target and a potentially useful biomarker for DCI.
Background: Occupational dysfunction (OD) can become a major health problem for community-dwelling older adults. OD can be experienced by older adults despite the absence of an apparent medical ...diagnosis or disability. Therefore, OD may be a new health indicator in the field of preventive medicine. Objectives: This study investigated possible predictors of OD in community-dwelling older adults. Methods: Fifty-four participants (aged 63-94) in Japan completed a demographic questionnaire, the Classification and Assessment of Occupational Dysfunction Scale (CAOD), assessments of functional health (Five Times Sit-to-Stand Test, Timed Up & Go, Automatic Thoughts Questionnaire-Revised, and Japan Science and Technology Agency Index of Competence), and responded about their subjective health (self-rated health). Only seven participants were men; therefore, male data were excluded from the analysis. Independent t-test and analysis of multiple regression model was performed to identify the predictors of OD. Results: The results of the independent samples t-test shows that the OD group correlated to a significant younger age, more negative automatic thoughts, and better social engagement in older women. The results of the multiple regression analysis showed that negative automatic thoughts was a significant predictor of OD among older women. Conclusion: Negatively evaluating stressful events related to occupational engagement may be associated with OD. It may be useful to assess, maintain, and improve negative automatic thoughts to prevent OD. The results of this study can provide an assessment perspective and intervention strategy focusing on occupations to occupational therapists active in the field of preventive occupational therapy.
Phosphatidylserine (PS) is a relatively minor constituent of biological membranes. Despite its low abundance, PS in the plasma membrane (PM) plays key roles in various phenomena such as the ...coagulation cascade, clearance of apoptotic cells, and recruitment of signaling molecules. PS also localizes in endocytic organelles, but how this relates to its cellular functions remains unknown. Here we report that PS is essential for retrograde membrane traffic at recycling endosomes (REs). PS was most concentrated in REs among intracellular organelles, and evectin-2 (evt-2), a protein of previously unknown function, was targeted to REs by the binding of its pleckstrin homology (PH) domain to PS. X-ray analysis supported the specificity of the binding of PS to the PH domain. Depletion of evt-2 or masking of intracellular PS suppressed membrane traffic from REs to the Golgi. These findings uncover the molecular basis that controls the RE-to-Golgi transport and identify a unique PH domain that specifically recognizes PS but not polyphosphoinositides.
Under the state of emergency, it has been reported that the amount of physical activity among community-dwelling older adults has decreased significantly due to refraining from going out, and there ...are strong concerns about the Geriatric Locomotive Function Scale and deterioration of mental health. Therefore, this study aimed to investigate whether the depressive state before the coronavirus disease 2019 (COVID-19) pandemic affected the 25-Geriatric Locomotive (GLFS) score during the COVID-19 pandemic among community-dwelling older adults.
The participants were 194 community-dwelling older adults (45 men, 149 women) with an average age of 75.5 ± 5.5 years who responded to a self-administered survey conducted three times (preliminary, second, and third) from before the 2018 COVID-19 pandemic to March 2021. Individuals with a score of ≥ 10 on the Geriatric Depression Scale 15 (GDS 15) were excluded. The survey items included the 25-question Geriatric Locomotive Function Scale (GLFS25), GDS 15, and other basic attributes. Those with scores of 5 to 9 on the GDS 15 and those with scores of 0 to 4 were assigned to the depressive symptoms (DS) group and the non-DS group, respectively. Statistical analysis was performed using two-way analysis of variance. The Mann-Whitney U test was used for comparisons between the groups.
In total, 187 patients were included in the analysis, excluding 7 patients. GLFS 25 showed a significant increase in scores at the second and third time points compared with baseline, and a main effect was confirmed in both groups, with no interaction effect. The second time, the score was 10.0 ± 8.5 and 13.7 ± 10.5 in the non-DS and DS groups, respectively. The third time, the non-DS and DS groups scored 10.8 ± 10.5 and 14.9 ± 10.1 points, respectively, indicating a significant difference.
Our results revealed that the increase in the GLFS 25 score in community-dwelling older adults during the COVID-19 pandemic was related to their DS during normal times before the pandemic. Evaluating such individuals and providing social support may effectively reduce the deterioration of the GLFS 25 score.
Local brain cooling of an epileptic focus at 15°C reduces the number of spikes on an electrocorticogram (ECoG), terminates seizures, and maintains neurological functions. In this study, we attempted ...to suppress generalized motor seizures (GMSs) by cooling a unilateral sensorimotor area. GMSs were induced in rats by intraperitoneal injection of bicuculline methiodide, an antagonist of gamma-aminobutyric acid. While monitoring the ECoG and behavior, the right sensorimotor cortex was cooled for 10 min using an implanted device. The number of spikes recorded from the cooled cortex significantly decreased to 71.2% and 62.5% compared with the control group at temperatures of 15 and 5°C (both P <0.01), respectively. The number of spikes recorded from the contralateral mirror cortex reduced to 61.7% and 62.7% (both P <0.05), respectively. The ECoG power also declined to 85% and 50% in the cooled cortex, and to 94% and 49% in the mirror cortex by the cooling at 15 and 5°C, respectively. The spikes regained in the middle of the cooling period at 15°C and in the late period at 5°C. Seizure-free durations during the 10-min periods of cooling at 15 and 5°C lasted for 4.1 ± 2.2 and 5.9 ± 1.1 min, respectively. Although temperature-dependent seizure alleviation was observed, the effect of local cortical cooling on GMSs was limited compared with the effect of local cooling of the epileptic focus on GSMs.
There is a worldwide attempt to develop prevention strategies against SARS-CoV-2 transmission. Here we examined the effectiveness of tungsten trioxide (WO3)-based visible light-responsive ...photocatalyst on the inactivation of SARS-CoV-2 under different temperatures and exposure durations. The viral titer on the photocatalyst-coated glass slides decreased from 5.93 ± 0.38 logTCID50 /mL to 3.05 ±. 25 logTCID50/mL after exposure to 3,000 lux of the visible light irradiation for 6h at 20℃. On the other hand, lighting without the photocatalyst, or the photocatalyst-coat without lighting retained viral stability. Immunoblotting and electron microscopic analyses showed the reduced amounts of spike protein on the viral surface after the photocatalyst treatment. Our data suggest a possible implication of the photocatalyst on the decontamination of SARS-CoV-2 in indoor environments, thereby preventing indirect viral spread.
To improve the thermal stability of lithium-ion batteries (LIBs) at elevated temperatures, the roles of positive or negative electrode materials in thermal runaway should be clarified. In this paper, ...we performed accelerating rare calorimetry analyses on two types of LIBs by using an all-inclusive microcell (AIM) method, where the AIM consists of all LIB components. We found that the thermal runaway in LiNi0.8Co0.15Al0.05O2 (NCA)|LiPF6 dissolved in ethylene carbonate (EC)/diethyl carbonate solution (DEC) (EC/DEC=1/1 by volume); LiPF6(EC/DEC)|artificial graphite (AG) and LiNi1/3Co1/3Mn1/3O2 (NCM)|LiPF6(EC/DEC)|AG cells is brought about by different electrodes, i.e., NCA for the former, and AG for the latter. The above difference is attributed to the different oxidation temperature of the EC/DEC solvents, indicating that we first pay attention which electrodes govern the thermal runaway. Trials for improving the thermal stability of NCA are also reported.
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•Roles of positive or negative electrodes in thermal runaway were investigated.•The oxidation temperature of solvents is important for thermal runaway.•The thermal stability of the NCA electrode was improved by electrode additives.
The world-first success of lipid nanoparticle (LNP)-based siRNA therapeutics (ONPATTRO
) promises to accelerate developments in siRNA therapeutics/gene therapy using LNP-type drug delivery systems ...(DDS). In this study, we explore the optimal composition of an LNP containing a self-degradable material (ssPalmO-Phe) for the delivery of oligonucleotides. siRNA or antisense oligonucleotides (ASO) were encapsulated in LNP with different lipid compositions. The hepatic knockdown efficiency of the target genes and liver toxicity were evaluated. The optimal compositions for the siRNA were different from those for ASO, and different from those for mRNA that were reported in a previous study. Extracellular stability, endosomal escape and cellular uptake appear to be the key processes for the successful delivery of mRNA, siRNA and ASO, respectively. Moreover, the compositions of the LNPs likely contribute to their toxicity. The lipid composition of the LNP needs to be optimized depending on the type of nucleic acids under consideration if the applications of LNPs are to be further expanded.
Stroke-prone spontaneously hypertensive rats (SHRSP) show significantly lower body weight than normotensive Wistar-Kyoto rats (WKY). Our hypotheses are as follows: weight loss of the skeletal muscle ...is related to hypertension-related diseases, and muscle hypotrophy is useful as a therapeutic target for hypertension and hypertension-related diseases. In this study, we aimed to investigate the pathophysiological characteristics of muscle hypotrophy in SHRSP to determine the therapeutic target molecule(s).
The difference in skeletal muscles in the lower leg between WKY and SHRSP was evaluated mainly through weight/tibial length, histological, gene expression, and protein expression analyses.
SHRSP had a significantly lower weight/tibial length in soleus and gastrocnemius, but not in plantaris and tibialis anterior, indicating that muscles consisting of a relatively high amount of slow muscle fiber were affected. This result was confirmed by the histological analysis of soleus, showing that type I fiber mainly decreased the fiber size. Microarray and protein expression analyses showed that the muscle-specific ubiquitin ligase, muscle RING finger 1 (MuRF1), but not atrogin-1, was highly expressed in soleus, but not in plantaris, in SHRSP. TNF-like weak inducer of apoptosis receptor (TWEAKR) was predicted as a MuRF1 up-regulator by Ingenuity Pathway Analysis and immunostained only in type II fiber in WKY but in both type I and II fibers in SHRSP.
TWEAKR is a type II-specific receptor in the skeletal muscle. Ectopic TWEAKR expression in type I fiber of SHRSP is most likely involved in slow muscle-specific hypotrophy through MuRF1 overexpression.
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