Effects of docosahexaenoic acid or arachidonic acid supplementation on the behavior of cardiomyocytes derived from human pluripotent stem cells

Background:Human heart changes its energetic substrates from lactate and glucose to fatty acids during the neonatal period.Noticing the lack of fatty acids in media for the culture of cardiomyocytes derived from human pluripotent stem cells(hiPS-CM),researchers have supplemented mixtures of fatty acids to hiPS-CM and reported the enhancement in the maturation of hiPS-CM.In our previous studies,we separately supplemented two polyunsaturated fatty acids(PUFAs),docosahexaenoic acid(DHA)or arachidonic acid(AA),to rat fetal cardiomyocytes and found that the supplementations upregulated the expressions of mRNAs for cardiomyocyte differentiation,fatty acid metabolism,and cellular adhesion.The enhancement in cellular contractility was attributed to the improvement in intercellular connection rather than a direct enhancement of the contractile force.Methods:This study reports the successive results of the effects of DHA or AA supplementation on hiPS-CM.In addition to the contractile force and mRNA measurements used in the previous study,we further investigated the effect of different cellular aggregations on the contractile force output by means of finite element analysis,measured glucose and fatty acids metabolites,and assessed cTNT and MLC2v expressions through immunofluorecsence evaluation.Results:It showed that the sole supplementation of albumin-conjugated DHA or AA can be taken up by hiPS-CM without other uptake-enhancing factors,and the supplementations may activate the CD36_ERRγmetabolic pathway.DHA or AA supplementation increased the cellular contractile ratio on collagen gels and AA supplementation stimulated hiPS-CM aggregation to form cellular clusters.The enhancement effect on the hiPS-CM contractile force was modest since the increase in contractile force was not significant.AA supplementation was more effective than DHA supplementation because it significantly upregulated mRNA expressions of P300 and CD36.However,finite element analysis showed that the formation of clusters on a collagen gel attenuated the contractile force exerted by the gel on its surroundings.Conclusion:DHA and AA,as having been supplemented in infant formulas,have no direct and significant enhancement effect on the performance of the hiPS-CM when they were supplemented individually,although they were able to enter the cellular metabolic system.The AA supplementation showed some auxiliary effect on the maturation of hiPS-CM,which is worthy of further investigation under the consideration of membrane composition alteration and remodeling of membrane molecules.

Role of PV-Powered Vehicles in Low-Carbon Society and Some Approaches of High-Efficiency Solar Cell Modules for Cars

Development of highly-efficient photovoltaic (PV) modules and expanding its application fields are significant for the further development of PV technologies and realization of innovative green energy infrastructure based on PV. Especially, development of solar-powered vehicles as a new application is highly desired and very important for this end. This paper presents the impact of PV cell/module conversion efficiency on reduction in CO2 emission and increase in driving range of the electric based vehicles. Our studies show that the utilization of a highly-efficient (higher than 30%) PV module enables the solar-powered vehicle to drive 30 km/day without charging in the case of light weight cars with electric mileage of 17 km/kWh under solar irradiation of 3.7 kWh/m2/day, which means that the majority of the family cars in Japan can run only by the sunlight without supplying fossil fuels. Thus, it is essential to develop high-efficiency as well as low-cost solar cells and modules for automotive applications. The analytical results developed by the authors for conversion efficiency potential of various solar cells for choosing candidates of the PV modules for automotive applications are shown. Then we overview the conversion efficiency potential and recent progress of various Si tandem solar cells, such as III-V/Si, II-VI/Si, chalcopyrite/Si, and perovskite/Si tandem solar cells. The III-V/Si tandem solar cells are expected to have a high potential for various applications because of its high conversion efficiency of larger than 36% for dual-junction and 42% for triple-junction solar cells under 1-sun AM1.5 G illumination, lightweight and low-cost potentials. The analysis shows that III-V based multi-junction and Si based tandem solar cells are considered to be promising candidates for the automotive application. Finally, we report recent results for our 28.2% efficiency and Sharp’s 33% mechanically stacked InGaP/GaAs/Si triple-junction solar cell. In addition, new approaches which are suitable for automotive applications by using III-V triple-junction, and static low concentrator PV modules are also presented.

Effectiveness of a Telenursing System to Prevent the Exacerbation of Symptoms in Patients with Cancer Undergoing Outpatient Chemotherapy

During outpatient chemotherapy, adverse events occurring at home must be carefully monitored. We have developed a tele-nursing system that can store physical information such as blood pressure and pulse measured by cancer patients in the cloud by using Bluetooth, which is wireless communication technology, and collect information from remote locations. The tele-nursing system name is T-SCOT. The purpose of this study is to conduct a randomized controlled trial to investigate the efficacy of T-SCOT intervention. Participants are those who receive T-SCOT intervention plus Care as usual as the intervention group, and those who receive only Care as usual as the control group. T-SCOT includes the following five steps: 1) Answer questions related to side effects of chemotherapy [10 items];2) Measure blood pressure, pulse, body temperature, and SPO2. The measured data is automatically saved in the cloud via Bluetooth;3) Watch a video of coping behavior for side effects;4) The data entered by the patient is visualized as a line graph;5) Utilize the videophone function with researchers if you have any problems or troubles. Utilization of ICT in telenursing makes it possible to visualize patient’s physical information and contributes to the reduction of medical expenses.

Effectiveness of a Telenursing System on Side Effects of Chemotherapy by a Crossover Trial

Background: This crossover trial aimed to examine the efficacy of the Tele-nursing Symptom Management System for Chemotherapy in Outpatient Treatment (T-SCOT) in reducing the side effects in patients undergoing out-patient chemotherapy. Methods: Using a tablet computer, participants were asked to provide information on various items, including fever, nausea, hair loss, fatigue, and vital signs. Both the participants and researchers automati-cally monitored time-dependent changes in symptoms, and the researchers proposed concrete measures to reduce patients’ complications. The primary endpoint was the M. D. Anderson Symptom Inventory (MDASI-J) score. The secondary endpoint, Quality of Life (QOL) was evaluated using the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL- ACD). Results: This study included 20 patients who met all the inclusion cri-teria, 14 of whom agreed to participate in the study. There was no significant difference between the MDASI-J and QOL-ACD pre- and post-comparison of the primary and secondary evaluations in the intervention group. The control group had significantly higher scores 3 months after the intervention for symptom intensity (p = 0.04) and symptom-induced disruption to life (p = 0.03), and the symptoms worsened. The QOL-ACD had significantly lower scores for activity (p = 0.03), overall QOL (p = 0.04), and total QOL score (p = 0.02), resulting in a lower quality of life. Conclusions: Participants used the Internet to obtain information on treatments and side effects and changed their behavior in daily life. It is speculated that the Information and Commu-nications Technology (ICT) literacy in older adults has improved, and they are benefiting from digital utilization.

Evaluation of the Long-Term Changes in Fatigue of Cancer Survivors Who Received Outpatient Chemotherapy in the Area Affected by the Great East Japan Earthquake

Objective: The aim of the study is to evaluate the long-term changes in fatigue of cancer patients receiving outpatient chemotherapy after a disaster such as the Great Earthquake. Methods: From 2012 to 2014, we measured subjective fatigue, autonomic function, and physical activity with reference to the criteria for chronic fatigue syndrome. Results: The participants were 13, 9 males (69.2%) and 4 females (30.8%). The most common cancer among the participants was lung cancer 4 patients (30.8%). In 2012, eight patients (61.6%) received anti-cancer drugs and three (23.0%) received the drug by intravenous drip and oral administration. Physical fatigue (p = 0.004), mental fatigue (p = 0.002), comprehensive fatigue (p = 0.012), and comprehensive evaluations (p = 0.032) were significantly different. Significant differences in the autonomic nervous function were observed during the three years from 2012 to 2014 (log LF [p = 0.017], log HF [p = 0.023] and log LF/HF [p = 0.039]). Similar to Subjective fatigue, Significant differences in physical activity were observed during the three years from 2012 to 2014 (DA [p = 0.042], TST [p = 0.037], SE [p = 0.018], AW [p = 0.023] and Naps [p = 0.014]). Conclusions: The participants fatigue worsened at one time, but showed improvement over time. In the event of an emergency such as a disaster, it is necessary to evaluate the physical and mental condition based on objective indicators of cancer patients receiving anti-cancer drug treatment and provide nursing support.

Measuring luminal esophageal temperature during pulmonary vein isolation of atrial fibrillation

AIM:To investigate the luminal esophageal temperature(LET) at the time of delivery of energy for pulmonary vein isolation(PVI).METHODS:This study included a total of 110 patients with atrial fibrillation who underwent their first PVI procedure in our laboratory between March 2010 and February 2011.The LET was monitored in all patients.We measured the number of times that LET reached the cut-off temperature,the time when LET reached the cut-off temperature,the maximum temperature(T max) of the LET,and the time to return to the original preenergy delivery temperature once the delivery of energy was stopped.RESULTS:Seventy-eight patients reached the cut-off temperature.It took 6 s at the shortest time for the LET to reach the cut-off temperature,and 216.5 ± 102.9 s for the temperature to return to the level before the de-livery of energy.Some patients experienced a transient drop in the LET(TDLET) just before energy delivery.Ablation at these sites always produced a rise to the LET cut-off temperature.TDLET was not observed at sites where the LET did not rise.Thus,the TDLET before the energy delivery was useful to distinguish a high risk of esophageal injury before delivery of energy.CONCLUSION:Sites with a TDLET before energy delivery should be ablated with great caution or,perhaps,not at all.

Effects of docosahexaenoic acid or arachidonic acid supplementation on gene expression and contractile force of rat cardiomyocytes in primary culture

While fatty acids play essential roles in the physiology of the myocardium,conventional culture media contain little lipid.We previously revealed that rat neonatal myocardium mainly contains docosahexaenoic(DHA),linoleic(LA),and arachidonic(AA)acids as polyunsaturated fatty acids(PUFAs),and these contents in cultured cardiomyocytes derived from fetal rats were markedly lower than those in the neonatal myocardium.In this study,we first assessed the effects of supplementation of DHA,LA,or AA on the fatty acid contents and the percentage change of contractile area in primarily cultured rat cardiomyocytes.Based on this assessment,we then evaluated the effects of DHA or AA supplementation on mRNA expression and further directly measured the contractile force of cardiomyocytes with the supplementations.This study revealed that percentage change of contractile area was maximized under 20μM DHA or 50μM AA supplementation while LA supplementation did not affect this contraction index,and that a widespread upregulation tendency of the mRNA expression related to differentiation,maturity,fatty acid metabolism,and cell adhesion was seen in the cultured cardiomyocytes with supplementation of DHA or AA.In particular,upregulation of the gene expression of cellular adhesion molecules connexin43 and N-cadherin were remarkable,whereas the effects on differentiation and maturation were less pronounced.Correspondingly,the increase of the percentage change of the contractile area of cardiomyocyte clusters in culture dishes with the supplementations was significant,whereas the enhancement of the contractile force was modest.These results suggest that supplementation of DHA or AA to the fetal cardiomyocyte culture may play effective roles in preventing the de-differentiation of the cardiomyocytes in culture and that the enhancement of the contractile performance may be mainly attributed to the improvement of intercellular connection.

Lipoprotein lipase and obesity

Obesity is one of the fast-growing major diseases in developed and developing countries. As has been persuasively argued, long-term imbalance between intake and expenditure of fat is a central factor in the etiology of obesity. Obesity aggravates insulin resistance and promotes cardiovascular diseases and atherosclerosis. We hypothesized that elevating lipoprOtein lipase (LPL) activity in skeletal muscle would cause an improvement of obesity. To test this hypothesis, we studied the effects of the LPL activator NO-1886 inobese animals. NO-1886 elevated LPL activity in skeletal muscle, and improved obesity as well as insulin resistance in obese rats. Furthermore, NO-1886 mitigated body weight gain induced by pioglitazone without suppressive effect on the adiponectin-increasing action of pioglitazone. LPL activators hold a lot of promise of curing several diseases shown above in clinical scene.

Effects of Fasting on Plasma Lipoprotein(a) in Cynomolgus Monkeys: Preliminary Experiments Results

Plasma lipoprotein(a) (Lp(a)) is known to be a strong independent risk factor for ischemic heart disease. However, it is not easily modulated by drugs that are presently available. Lp(a) is not present in many experimental animals except for Old World monkeys. In this study, we examined whether cynomolgus monkeys are useful model for research of human plasma Lp(a), and observed that plasma Lp(a) in cynomolgus monkeys varied as much as humans. As a result of 4 day-fasting in cynomolgus monkeys, the plasma Lp(a) level decreased in a monkey with originally high Lp(a) level. The Lp(a) level continued to decrease even 3 days after banana feeding, but returned to the original level 3 days after monkey chow feeding. On the other hand, in a monkey with low Lp(a) level, fasting had no effect on the Lp(a) level. However, in the third monkey having originally high Lp(a) level, the Lp(a) was not affected by decreasing the amount of monkey chow feeding by 50%. In summary, we found that cynomolgus monkeys may be an useful model for studying the effects of food on plasma Lp(a) in place of humans, and that high Lp(a) level may be controllable by strict diet regulation.