Search

Abstract Background Low birthrates and an aging society during population decline have brought about labor shortages and increased medical care needs. Medical resources should be distributed appropriately, particularly in rural areas. High‐quality primary care can make the medical system more effective and contribute to rural residents' health. However, there are no reports on the impact of primary care on health in the rural areas of Japan. This study examined the effect of primary care quality on self‐rated health in a rural Japanese area. Methods We conducted a cross‐sectional study using a questionnaire survey of residents of a rural area in northern Shiga Prefecture in 2021. Self‐rated health (SRH) was used as the health outcome (1–5 points), and the Japanese Primary Care Assessment Tool Short Form (JPCAT‐SF) was used to measure the patients' experience of primary care (0–100 points). We conducted a multivariate analysis using logistic regression analysis and examined the association between good SRH (4 points or more) and high JPCAT‐SF scores (above average score), adjusted for sociodemographic confounding factors. Results A total of 1108 men and 1412 women responded to the survey. The mean patient age was 69.8 years. The mean JPCAT‐SF score was 51.8 points. Among the 1172 patients with chronic diseases, good SRH was associated with high JPCAT‐SF scores (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.009–1.73). Conclusions Good SRH among rural residents with chronic disease was associated with high primary care quality.

Abstract Dissipative structures often appear as an unstable counterpart of ordered structures owing to fluctuations that do not form a homogeneous phase. Even a multiphase mixture may simultaneously undergo one chemical reaction near equilibrium and another one that is far from equilibrium. Here, we observed in real time crystal seed formation and simultaneous nanocrystal aggregation proceeding from CeIV complexes to CeO2 nanoparticles in an acidic aqueous solution, and investigated the resultant hierarchical nanoarchitecture. The formed particles exhibited two very different size ranges, resulting in further pattern formation with opalescence. The hierarchically assembled structures in solutions were CeO2 colloids, viz. primary core clusters (1–3 nm) of crystalline ceria and secondary clusters (20–30 nm) assembled through surface ions. Such self-assembly is widespread in multi-component complex fluids, paradoxically moderating hierarchical reactions. Stability and instability are not only critical but also complementary for co-optimisation around the nearby free energy landscape prior to bifurcation.

In recent years, high-precision gears are expected to be used in vehicles and robots. Currently, gear hobbing is widely used as a roughing process while shaving and grinding are used as finishing processes to improve the accuracy and surface quality of the gears. The increasing demand for gears requires a gear machining method that is more efficient than the conventional machining processes. In this study, high-speed gear hobbing that achieves accuracy comparable to shaving and grinding was performed at a cutting speed 12 times that of conventional hobbing. Experiments were conducted using Cr-Mo steel as the workpiece and cemented carbide as the hob cutter in the cutting speed range of 200 - 2450 m/min. The relationship between the hardness and the depth from the gear surface was investigated with a comparison with the change in the material structure of the gear surface layer. The results showed that the hardness of the gear surface layer increased in the high-speed hobbing process compared to the conventional hobbing due to the strain and crystal grain refinement caused by the high cutting speed. In addition, experiments were performed at each cutting speed in the range of 400 - 1200 m/min to investigate the possible changes in machining characteristics when the number of machined pieces increased to 30. The results showed that despite the number of machined gears, the surface hardness increased at high cutting speeds. The effects of the number of machined gears on tool wear and surface roughness were also insignificant, indicating that high-speed hobbing is a promising efficient production method of gears with high surface quality.

Introduction: Dravet syndrome (DS) is an intractable epilepsy syndrome concomitant with neurodevelopmental disorder that begins in infancy. DS is dominantly caused by mutations in the SCN1A gene, which encodes the α subunit of a voltage-gated Na channel. Pre-synaptic inhibitory dysfunction is regarded as the pathophysiological mechanism, but an effective strategy for ameliorating seizures and behavioral problems is still under development. Here, we evaluated the effects of KRM-II-81, a newly developed positive allosteric modulator for α 2/3 subunit containing GABAA receptors (α2/3-GABAAR) in a mice model of DS both in vivo and at the neuronal level.Methods: We used knock-in mice carrying a heterozygous, clinically relevant SCN1A mutation (background strain: C57BL/6 J) as a model of the DS (Scn1aWT/A1783V mice), knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V). Seizure threshold and locomotor activity was evaluated by using the hyperthermia-induced seizure paradigm and open filed test, respectively. Anxiety-like behavior was assessed by avoidance of the center region in locomotor activity. We estimated a sedative effect by the total distance traveled in locomotor activity and grip strength. Inhibitory post synaptic currents (IPSCs) were recorded from a hippocampal CA1 pyramidal neuron in an acutely prepared brain slice.Results: KRM-II-81 significantly increased the seizure threshold of Scn1aWT/A1783V mice in a dose-dependent manner. A low dose of KRM-II-81 specifically improved anxiety-like behavior of Scn1aWT/A1783V mice. A sedative effect was induced by relatively high dose of KRM-II-81 in Scn1aWT/A1783V mice, the dose of which was not sedative for WT mice. KRM-II-81 potentiated IPSCs by increasing its decay time kinetics. This effect was more prominent in Scn1aWT/A1783V mice.Discussion: Higher activation of α2/3-GABAAR by KRM-II-81 suggests a compensatory modification of post synaptic inhibitory function against presynaptic inhibitory dysfunction in Scn1aWT/A1783V. The increased sensitivity for KRM-II-81 may be relevant to the distinct dose-dependent effect in each paradigm of Scn1aWT/A1783V mice.Conclusion: Selective activation for α2/3-GABAAR by KRM-II-81 could be potential therapeutic strategy for treating seizures and behavioral problems in DS.

Abstract Some patients with developmental and epileptic encephalopathy (DEE) respond to adrenocorticotropic hormone (ACTH) therapy but relapse soon after. While long‐term ACTH therapy (LT‐ACTH) has been attempted for these patients, no previous studies have carefully assessed adrenal function during LT‐ACTH. We evaluated the effectiveness of LT‐ACTH, as well as adverse effects (AE), including their adrenal function in three DEE patients. Patients underwent a corticotropin‐releasing hormone (CRH) stimulation test during LT‐ACTH, and those with peak serum cortisol below 15 μg/dL were considered to be at high risk of adrenal insufficiency (AI). Two of three responded, and their life‐threatening seizures with postgeneralized electroencephalogram (EEG) suppression decreased. Although no individuals had serious AE, CRH stimulation test revealed relatively weak responses, without reaching normal cortisol peak level (18 μg/dL). Hydrocortisone replacement during stress was prepared in a case with lower cortisol peak than our cutoff level. LT‐ACTH could be a promising treatment option for cases of DEE that relapse soon after effective ACTH treatment. The longer duration and larger cumulative dosage in LT‐ACTH than in conventional ACTH could increase the relative risk of AI. Careful evaluation with pediatric endocrinologists, including hormonal stimulation tests, might be useful for continuing this treatment safely.

While H2 can serve as a renewable fuel, its large scale production, storage, and transport are challenging. Here, authors show H2O2 to serve as a potential energy carrier via the photocatalytic production of H2 from stabilized H2O2 solutions and metal-free catalysts.

Knowledge of interfacial structures in liquid–liquid systems is imperative, especially for improving two-phase biological and chemical reactions. Therefore, we developed a new sample cell for neutron reflectometry (NR), which enables us to observe the layer structure around the interface, and investigated the adsorption behavior of a typical surfactant, sodium dodecyl sulfate (SDS), on the toluene-d8-D2O interface under the new experimental conditions. The new cell was characterized by placing the PTFE frame at the bottom to produce a smooth interface and downsized compared to the conventional cell. The obtained NR profiles were readily analyzable and we determined a slight difference in the SDS adsorption layer structure at the interface between the toluene-d8-D2O and air-D2O systems. This could be owing to the difference in the adsorption behavior of the SDS molecules depending on the interfacial conditions.

The recycling of rare metals such as platinum (Pt) from secondary resources, such as waste electronic and electrical equipment and automotive catalysts, is an urgent global issue. In this study, simple secondary amides and urea, N-(2-ethylhexyl)acetamide, N-(2-ethylhexyl)octanamide, and 1-butyl-3-(2-ethylhexyl)urea, which selectively extract Pt(IV) from a simulated effluent containing numerous metal ions, such as in an actual hydrometallurgical process, were synthesized and achieved efficient Pt(IV) stripping using only water. Comparison of Pt(IV) extraction behavior with a tertiary amide without N–H moieties suggests that the secondary amides and urea extractants effectively use hydrogen bonding to the hexachloroplatinate anion by N–H moieties. Examining the conditions for the third phase formation revealed that the secondary amide extractant with the longest alkyl chain can be used in the extraction process for a long time without forming any third phase, despite its lower Pt(IV) extraction capacity. The practical trial with simple compounds developed in this study should contribute to the development of Pt separation and purification processes.

Nagilactone E, an antifungal agent derived from the root bark of Podocarpus nagi, inhibits 1,3-β glucan synthesis; however, its inhibitory activity is weak. Anethole, the principal component of anise oil, enhances the antifungal activity of nagilactone E. We aimed to determine the combinatorial effect and underlying mechanisms of action of nagilactone E and anethole against the budding yeast Saccharomyces cerevisiae. Analyses using gene-deficient strains showed that the multidrug efflux pump PDR5 is associated with nagilactone E resistance; its transcription was gradually restricted in cells treated with the drug combination for a prolonged duration but not in nagilactone-E-treated cells. Green-fluorescent-protein-tagged Pdr5p was intensively expressed and localized on the plasma membrane of nagilactone-E-treated cells but not in drug-combination-treated cells. Quick-freeze deep-etch electron microscopy revealed the smoothening of intertwined fiber structures on the cell surface of drug-combination-treated cells and spheroplasts, indicating a decline in cell wall components and loss of cell wall strength. Anethole enhanced the antifungal activity of nagilactone E by enabling its retention within cells, thereby accelerating cell wall damage. The combination of nagilactone E and anethole can be employed in clinical settings as an antifungal, as well as a food preservative to restrict food spoilage.

A thermoacoustic heat pump heater is a device having the ability to produce heat from acoustic power. The heat pump investigated was composed of an acoustic driver, a branched tube, and a looped tube. A porous component composed of many stacked steel screen meshes, called regenerator, was installed inside the looped tube. When an acoustic wave is supplied to the looped tube, filled with nitrogen gas at 0.5 MPa, heat pumping spontaneously occurs inside the regenerator. A numerical code was developed and tested. Then, the coefficient of performance was calculated for different temperatures by optimizing the regenerator flow channel radius and position inside the looped tube. It was found that the temperature affects considerably the regenerator optimum parameters.

Simulation study of a solar adsorption refrigeration system using a wing type compound parabolic concentrator (CPC) is presented. The system consists of the wing type collector set at optimum angles, adsorption bed, a condenser and a refrigerator. The wing type collector captures the solar energy efficiently in the morning and afternoon and provides the effective temperature for a longer period of time compared to that achieved by a linear collector. The objectives of the study were to evaluate the system behavior, the effect of wing length, and to compare the performance of the systems with wing type and linear CPCs. A detailed dynamic simulation model was developed based on mass and energy balance equations. The simulation results show that the system performance with wing type CPC increases by up to 6% in the summer and up to 2% in the winter, compared to the performance with a linear CPC having same collector length. The ice production also increases up to 13% in the summer with the wing type CPC. This shows that the wing type CPC is helpful to increase the performance of the system compared to the linear CPC with the same collector length and without the need for tracking.

We designed a compound parabolic concentrator (CPC) with wings angled toward the east and west. Normally, solar collectors are straight, facing south, and the effective temperature is only achieved for a short period of time at midday. In the proposed design, the collector is divided into three parts, with the ends angled and tilted at different orientations. The objective was to increase the duration of the effective temperature period by capturing the maximum solar energy in the morning and afternoon without tracking by the collector. A simulation model was developed to evaluate the performance of the proposed CPC. The tilt and bending angles of the CPC wings were optimized for year-round operation in Tokyo, Japan. A 35° tilt for the south-facing central part of the CPC and a 45° tilt for the wings with 50° angles toward the east and west were found to be optimal. Analyses were conducted at these optimum settings with temperatures of 70, 80, and 90 °C as minimum requirements. The effective duration increased by up to 2 h in the winter and up to 2.53 h in the summer using the proposed CPC. The proposed CPC will improve the efficiency of solar-driven systems by providing useful heat for longer periods of time with the same collector length and without the need for tracking.

The design of a four-bed three-stage adsorption cycle has been proposed to reduce the volume of the six-bed three-stage adsorption cycle. A simulation model for the proposed innovative cycle was developed to analyse the influence of cycle time on the system performance identifying the specific cooling power (SCP) and coefficient of performance (COP). A particle swarm optimization (PSO) technique was used to optimize the cycle time enabling us to maximize the SCP. PSO results showed that the optimal cycle time was decreased with heat source temperature and SCP value was proportional to heat source temperature. It was found that the proposed cycle could be driven by waste heat as low as 40 °C, along with coolant at 30 °C. Comparative study of optimized result indicated that the proposed cycle increased the performance significantly over a whole range of temperatures from 40 to 70 °C and reduced two adsorbent beds, compared to the six-bed three-stage cycle.

The objective of this study is to optimize the design of thermoacoustic engines driven by LNG in order to exploit its unused energy at low temperature. LNG at 111K provides low temperature heat source while the environment has a role of high temperature heat source. The design variables such as regenerator channel radius, regenerator length, regenerator position, frequency and loop tube length were optimized based on Particle Swarm Optimization method in two cases of maximizing the acoustic power and the efficiency of energy conversion. In the optimization process the calculation of the acoustic field inside the regenerator and the buffer tube was simplified so that the temperature would have a given distribution. The comparison with the calculation assuming adiabatic condition verified that the proposed method was effective to derive optimal solution. It is also suggested that objective function needs to be estimated with the theoretical method to obtain precise value of the power generation. The optimization results indicate the strategies to design the thermoacoustic engine utilizing LNG. There is a clear trade-off relationship between the power generation and the efficiency. Consequently, it was found that the maximal power intensity of 1.9 MW/m2 with 4 m loop tube or the maximal efficiency of 52% with 2 m loop tube would be attainable. Based on the power intensity, the scale of the loop tube was estimated to generate 1 or 10 kW of acoustic power.

This study presents experimental results on Photovoltaic-thermal (PVT) solar systems, the commercial photovoltaic (PV) panels used as solar absorbers in PVT collectors, which are amorphous and multi-crystalline silicon. Testing was done with outdoor experiments in the climate of Bangkok corresponding to energy consumption behavior of medium size Thai families. The experimental results show that the thermal recovery of amorphous silicon PVT collector is almost the same as that of multi-crystalline silicon PVT collectors while electricity generation of multi crystalline silicon PVT is 1.2 times as much as that of amorphous silicon PVT. The maximum of heat gain from the PVT systems were obtained in March in summer. It was found that PVT collectors of unit area annually produced 1.1 × 103 kWh/m2 .year of heat and 55–83 kWh/m2.year of electricity, respectively. The results show that annual average solar factor of hot water supply is 0.45 for unit collector area. Economical evaluation based on energy costs in Thailand was conducted, which estimated the payback time would be 7 and 14 years for a-Si PVT and mc-Si PV, respectively.

A standing-wave thermoacoustic engine is essentially composed of a stack, two heat exchangers, and tubes; the stack has many narrow flow channels and is located inside one of the tubes. One end and the other end of the stack are thermally connected to hot and cold heat sources via the heat exchangers, respectively. When the ratio of temperatures of the heat sources exceeds a critical value, the gas inside the tubes spontaneously oscillates and the stack generates acoustical energy using heat from the hot heat source. In this study, the critical temperature ratio needed for exciting the spontaneous gas oscillation was numerically calculated by changing the stack's length, flow channel radius, and position. Further, the thermal efficiency with the critical temperature ratio was calculated. These calculations allowed us to design and construct the engine in accordance with the heat source temperatures. The constructed engine worked with the heat sources having the temperature ratio 1.7 and achieved 8% of the Carnot efficiency. These obtained values quantitatively agreed with the design ones.

A numerical investigation of the double-effect adsorption refrigeration cycle is examined in this manuscript. The proposed cycle is based on the cascading adsorption cycle, where condensation heat that is produced in the top cycle is utilized as the driving heat source for the bottom cycle. The results show that the double-effect cycle produces a higher coefficient of performance (COP) as compared to that of the conventional single-stage cycle for driving temperatures between 100 °C and 150 °C in which the average cycle chilled water temperature is fixed at 9 °C. Moreover, the COP of the double-effect cycle is more than twice that of the single-stage cycle when the temperature reaches 130 °C. It is also observed that the adsorbent mass ratio of the high temperature cycle (HTC) to the low temperature cycle (LTC) affects the performance of the double-effect adsorption refrigeration cycle.

This paper presents the performance of an advanced cascading adsorption cycle that utilizes a driven heat source temperature between 90–130 ºC. The cycle consists of four beds that contain silica gel as an adsorber fill. Two of the beds work in a single stage cycle that is driven by an external heat source, while the other two beds work in a mass recovery cycle that is driven by waste heat of sensible and adsorption heat of the high temperature cycle. The performances, in terms of the coefficient of performance (COP) and the specific cooling power (SCP), are compared with conventional cascading-without-mass-recovery and single-stage cycles. The paper also presents the effect of the adsorbent mass on performance. The results show that the proposed cycle with mass recovery produces as high of a COP as the COP that is produced by the conventional cascading cycle. However, it produces a lower SCP than that of the single-stage cycle.

The performance of an advanced three-bed adsorption chiller with a mass recovery cycle has been experimentally investigated in the present study. The temperature and pressure of various components of the chiller were monitored to observe the dynamic behaviour of the chiller. The performances in terms of the coefficient of performance (COP) and specific cooling power (SCP) were compared with a conventional single stage. The results show that the proposed cycle produces COP and SCP values superior to those of the conventional single stage cycle for heat source temperature below 75 °C.

Our understanding of the mechanism of cancer dormancy is emerging, but the underlying mechanisms are not fully understood. Here we analyzed mouse xenograft tumors derived from human breast cancer tissue and the human breast cancer cell line MDA-MB-231 to identify the molecules associated with cancer dormancy. In immunohistological examination using the proliferation marker Ki-67, the tumors included both proliferating and dormant cancer cells, but the number of dormant cells was remarkably increased when they metastasized to the lung. In the gene expression analysis of the orthotopic cancer cells by a single-cell multiplex real-time quantitative reverse transcription PCR followed by flow cytometric analysis, restrained cellular proliferation was associated with downregulation of the chemokine receptor CXCR4. In the immunohistological and flow cytometric analyses, the expression level of CXCR4 in the metastasized cancer cells was decreased compared with that in the cancer cells in orthotopic tumors, although the expression level of the CXCR4 ligand CXCL12 was not reduced in the lung. In addition, the proliferation of the metastasized cancer cells was further decreased by the CXCR4 antagonist administration. In the ex vivo culture of the metastasized cancer cells, the expression level of CXCR4 was increased, and in the xenotransplantation of ex vivo cultured cancer cells, the expression level of CXCR4 was again decreased in the metastasized cancer cells in the lung. These findings indicate that CXCR4 is downregulated in metastasized breast cancer cells and implicated in their dormancy.

The performance of a thermoacoustic system that is composed of a looped tube, an engine stack, a cooler stack, and four heat exchangers, is numerically investigated. Each stack has narrow flow channels, is sandwiched by two heat exchangers, and is located in the looped tube. In order to provide a design guide, the performance of the system is numerically calculated by changing the following three parameters: the radius of the flow channels in the engine stack, the radius of the flow channels in the cooler stack, and the relative position of the cooler stack. It was found that when the three parameters are optimized, the efficiency of the engine stack reaches 75% of Carnot’s efficiency and the coefficient of the performance (COP) of the cooler stack is 53% of Carnot’s COP, whereas 33% of the acoustic power generated by the engine stack is utilized in the cooler stack.

We previously identified an anti-inflammatory compound, zonarol, a hydroquinone isolated from the brown algae Dictyopteris undulata as a marine natural product. To ascertain the in vivo functions of zonarol, we examined the pharmacological effects of zonarol administration on dextran sulfate sodium (DSS)-induced inflammation in a mouse model of ulcerative colitis (UC). Our goal is to establish a safe and effective cure for inflammatory bowel disease (IBD) using zonarol.We subjected Slc:ICR mice to the administration of 2% DSS in drinking water for 14 days. At the same time, 5-aminosalicylic acid (5-ASA) at a dose of 50 mg/kg (positive control) and zonarol at doses of 10 and 20 mg/kg, were given orally once a day. DSS-treated animals developed symptoms similar to those of human UC, such as severe bloody diarrhea, which were evaluated by the disease activity index (DAI). Treatment with 20 mg/kg of zonarol, as well as 5-ASA, significantly suppressed the DAI score, and also led to a reduced colonic ulcer length and/or mucosal inflammatory infiltration by various immune cells, especially macrophages. Zonarol treatment significantly reduced the expression of pro-inflammatory signaling molecules, and prevented the apoptosis of intestinal epithelial cells. Finally, zonarol protected against in vitro lipopolysaccharide (LPS)-induced activation in the RAW264.7 mouse macrophage cell line.This is the first report that a marine bioproduct protects against experimental UC via the inhibition of both inflammation and apoptosis, very similar to the standard-of-care sulfasalazine, a well-known prodrug that releases 5-ASA. We believe that the oral administration of zonarol might offer a better treatment for human IBDs than 5-ASA, or may be useful as an alternative/additive therapeutic strategy against UC, without any evidence of side effects.

Introduction: Dravet syndrome (DS) is an intractable epilepsy syndrome concomitant with neurodevelopmental disorder that begins in infancy. DS is dominantly caused by mutations in the SCN1A gene, which encodes the α subunit of a voltage-gated Na channel. Pre-synaptic inhibitory dysfunction is regarded as the pathophysiological mechanism, but an effective strategy for ameliorating seizures and behavioral problems is still under development. Here, we evaluated the effects of KRM-II-81, a newly developed positive allosteric modulator for α 2/3 subunit containing GABAA receptors (α2/3-GABAAR) in a mice model of DS both in vivo and at the neuronal level. Methods: We used knock-in mice carrying a heterozygous, clinically relevant SCN1A mutation (background strain: C57BL/6 J) as a model of the DS (Scn1aWT/A1783V mice), knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V). Seizure threshold and locomotor activity was evaluated by using the hyperthermia-induced seizure paradigm and open filed test, respectively. Anxiety-like behavior was assessed by avoidance of the center region in locomotor activity. We estimated a sedative effect by the total distance traveled in locomotor activity and grip strength. Inhibitory post synaptic currents (IPSCs) were recorded from a hippocampal CA1 pyramidal neuron in an acutely prepared brain slice. Results: KRM-II-81 significantly increased the seizure threshold of Scn1aWT/A1783V mice in a dose-dependent manner. A low dose of KRM-II-81 specifically improved anxiety-like behavior of Scn1aWT/A1783V mice. A sedative effect was induced by relatively high dose of KRM-II-81 in Scn1aWT/A1783V mice, the dose of which was not sedative for WT mice. KRM-II-81 potentiated IPSCs by increasing its decay time kinetics. This effect was more prominent in Scn1aWT/A1783V mice. Discussion: Higher activation of α2/3-GABAAR by KRM-II-81 suggests a compensatory modification of post synaptic inhibitory function against presynaptic inhibitory dysfunction in Scn1aWT/A1783V. The increased sensitivity for KRM-II-81 may be relevant to the distinct dose-dependent effect in each paradigm of Scn1aWT/A1783V mice. Conclusion: Selective activation for α2/3-GABAAR by KRM-II-81 could be potential therapeutic strategy for treating seizures and behavioral problems in DS. [ABSTRACT FROM AUTHOR]