Proton Conduction in Chiral Molecular Assemblies of Azolium-Camphorsulfonate Salts.

Chiral molecular assemblies have attracted considerable attention because of their interesting physical properties, such as spin-selective electron transport. Cation-anion salts of three azolium cations, imidazolium (HIm+), triazolium (HTrz+), and thiazolium (HThz+), in combination with a chiral camphorsulfonate (1S-CS-) and their racemic compounds (rac-CS-) were prepared and compared in terms of phase transitions, crystal structures, dynamics of constituent molecules, dielectric responses, and proton conductivities. The cation-anion crystals containing HIm+ showed no significant difference in proton conductivity between the homochiral and racemic crystals, whereas the HTrz+-containing crystals showed higher proton conductivity and lower activation energy in the homochiral form than in the racemic form. A two-dimensional hydrogen-bonding network consisting of HTrz+ and -SO3- groups and similar in-plane rotational motion was observed in both crystals; however, the HTrz+ cation in the homochiral crystal exhibited the rotational motion modulated with translational motion, whereas the HTrz+ cation in the racemic crystal exhibited almost steady in-plane rotational motion. The different motional degrees of freedom were confirmed by crystal structure analyses and temperature- and frequency-dependent dielectric constants. In contrast, steady in-plane rotational motion with the thermally activated fluctuating motion of CS- was observed both in homochiral and racemic crystals containing HIm+, which averaged the motional space of protons resulting in similar dielectric responses and proton conductivities. The control of motional degrees of freedom in homochiral crystals affects the proton conductivity and is useful for the design of molecular proton conductors.

Knowledge distillation of neural network potential for molecular crystals.

Organic molecular crystals exhibit various functions due to their diverse molecular structures and arrangements. Computational approaches are necessary to explore novel molecular crystals from the material space, but quantum chemical calculations are costly and time-consuming. Neural network potentials (NNPs), trained on vast amounts of data, have recently gained attention for their ability to perform energy calculations with accuracy comparable to quantum chemical methods at high speed. However, NNPs trained on datasets primarily consisting of inorganic crystals, such as the Materials Project, may introduce bias when applied to organic molecular crystals. This study investigates the strategies to improve the accuracy of a pre-trained NNP for organic molecular crystals by distilling knowledge from a teacher model. The most effective knowledge transfer was achieved when fine-tuning using only soft targets, i.e., the teacher model's inference values. As the ratio of hard target loss increased, the efficiency of knowledge transfer decreased, leading to overfitting. As a proof of concept, the NNP created through knowledge distillation was used to predict elastic properties, resulting in improved accuracy compared to the pre-trained model.

Stereotactic body radiation therapy to the spine: contouring the cauda equina instead of the spinal cord is more practical as the organ at risk.

Background: Stereotactic body radiotherapy (SBRT) is recognized as a curative treatment for oligometastasis. The spinal cord becomes the cauda equina at the lumbar level, and the nerves are located dorsally. Recently, a consensus has been reached that the cauda equina should be contoured as an organ at risk (OAR). Here, we examined the separate contouring benefits for the spinal canal versus the cauda equina only as the OAR. Materials and methods: A medical physicist designed a simulation plan for 10 patients with isolated lumbar metastasis. The OAR was set with three contours: the whole spinal canal, cauda equina only, and cauda equina with bilateral nerve roots. The prescribed dose for the planning target volume (PTV) was 30 Gy/3 fx. Results: For the constrained QAR doses, D90 and D95 were statistically significant due to the different OAR contouring. The maximum dose (Dmax) was increased to the spinal canal when the cauda equina max was set to ≤ 20 Gy, but dose hotspots were observed in most cases in the medullary area. The Dmax and PTV coverage were negatively correlated for the cauda equina and the spinal canal if Dmax was set to ≤ 20 Gy for both. Conclusions: A portion of the spinal fluid is also included when the spinal canal is set as the OAR. Thus, the PTV coverage rate will be poor if the tumor is in contact with the spinal canal. However, the PTV coverage rate increases if only the cauda equina is set as the OAR.

Characteristics, Antithrombotic Patterns, and Prognostic Outcomes in Claudication and Critical Limb-Threatening Ischemia Undergoing Endovascular Therapy.

PURPOSE: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study aimed to clarify differences in clinical features and prognostic outcomes between IC and CLTI, and prognostic factors in patients undergoing endovascular therapy (EVT). MATERIALS AND METHODS: A total of 692 patients with 808 limbs were enrolled from 20 institutions in Japan. The primary measurements were the 3-year rates of major adverse cardiovascular event (MACE) and reintervention. RESULTS: Among patients, 79.0% had IC and 21.0% had CLTI. Patients with CLTI were more frequently women and more likely to have impaired functional status, undernutrition, comorbidities, hypercoagulation, hyperinflammation, distal artery disease, short single antiplatelet and long anticoagulation therapies, and late cilostazol than patients with IC. Aortoiliac and femoropopliteal diseases were dominant in patients with IC and infrapopliteal disease was dominant in patients with CLTI. Patients with CLTI underwent less frequently aortoiliac intervention and more frequently infrapopliteal intervention than patients with IC. Longitudinal change of ankle-brachial index (ABI) exhibited different patterns between IC and CLTI (pinteraction=0.002), but ABI improved after EVT both in IC and in CLTI (p<0.001), which was sustained over time. Dorsal and plantar skin perfusion pressure in CLTI showed a similar improvement pattern (pinteraction=0.181). Distribution of Rutherford category improved both in IC and in CLTI (each p<0.001). Three-year MACE rates were 20.4% and 42.3% and 3-year reintervention rates were 22.1% and 46.8% for patients with IC and CLTI, respectively (log-rank p<0.001). Elevated D-dimer (p=0.001), age (p=0.043), impaired functional status (p=0.018), and end-stage renal disease (p=0.019) were independently associated with MACE. After considering competing risks of death and major amputation for reintervention, elevated erythrocyte sedimentation rate (p=0.003) and infrainguinal intervention (p=0.002) were independently associated with reintervention. Patients with CLTI merely showed borderline significance for MACE (adjusted hazard ratio 1.700, 95% confidence interval 0.950-3.042, p=0.074) and reintervention (adjusted hazard ratio 1.976, 95% confidence interval 0.999-3.909, p=0.05). CONCLUSIONS: The CLTI is characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared with IC. Also, CLTI has approximately twice MACE and reintervention rates than IC, and the underlying inflammatory coagulation disorder per se is associated with these outcomes. CLINICAL IMPACT: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study, JPASSION study found that CLTI was characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared to IC. Also, CLTI had approximately twice major adverse cardiovascular event (MACE) and reintervention rates than IC. Intriguingly, the underlying inflammatory coagulation disorder per se was independently associated with MACE and reintervention. Further studies to clarify the role of anticoagulation and anti-inflammatory therapies will contribute to the development of post-interventional therapeutics in the context of peripheral artery disease.

Carnitine supplements for people with chronic kidney disease requiring dialysis.

BACKGROUND: Carnitine deficiency is common in patients with chronic kidney disease (CKD) who require dialysis. Several clinical studies have suggested that carnitine supplementation is beneficial for dialysis-related symptoms. However, the clinical effectiveness and potential adverse effects of carnitine supplementation in dialysis patients have not been determined. OBJECTIVES: This review aimed to evaluate the effectiveness and safety of carnitine supplementation for the treatment of dialysis-related complications in CKD patients requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 16 August 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth, or other predictable methods) that compared carnitine supplements with placebo or standard care in people with CKD requiring dialysis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted study data and assessed study quality. We used a random-effects model to perform a quantitative synthesis of the data.  We used the I² statistic to measure heterogeneity amongst the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with 95% confidence intervals (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. MAIN RESULTS: We included 52 studies (47 parallel RCTs and five cross-over RCTs) (3398 randomised participants). All studies compared L-carnitine with a placebo, other treatment, or no treatment. Standard care was continued as co-interventions in each group. Most studies were judged to have an unclear or high risk of bias. L-carnitine may have little or no effect on the quality of life (QoL) SF-36 physical component score (PCS) (4 studies, 134 participants: SMD 0.57, 95% CI -0.15 to 1.28; I² = 73%; low certainty of evidence), and the total QoL score (Kidney Disease Quality of Life (KDQOL), VAS (general well-being), or PedsQL) (3 studies, 230 participants: SMD -0.02, 95% CI -0.29 to 0.25; I² = 0%; low certainty of evidence). L-carnitine may improve SF-36 mental component score (MCS) (4 studies, 134 participants: SMD 0.70, 95% CI 0.22 to 1.18; I² = 42%; low certainty of evidence). L-carnitine may have little or no effect on fatigue score (2 studies, 353 participants: SMD 0.01, 95% CI -0.20 to 0.23; I² = 0%; low certainty of evidence), adverse events (12 studies, 1041 participants: RR, 1.14, 95% CI 0.86 to 1.51; I² = 0%; low certainty of evidence), muscle cramps (2 studies, 102 participants: RR, 0.44, 95% CI 0.18 to 1.09; I² = 23%; low certainty of evidence), and intradialytic hypotension (3 studies, 128 participants: RR, 0.76, 95% CI 0.34 to 1.69; I² = 0%; low certainty of evidence). L-carnitine may improve haemoglobin levels (26 studies, 1795 participants: MD 0.46 g/dL, 95% CI 0.18 to 0.74; I² = 86%; low certainty of evidence) and haematocrit values (14 studies, 950 participants: MD 1.78%, 95% CI 0.38 to 3.18; I² = 84%; low certainty of evidence). AUTHORS' CONCLUSIONS: The available evidence does not currently support the use of carnitine supplementation in the treatment of dialysis-related carnitine deficiency. Although carnitine supplementation may slightly improve anaemia-related markers, carnitine supplementation makes little or no difference to adverse events. However, these conclusions are based on limited data and, therefore, should be interpreted with caution.

Microwave Spectroscopy of the Low-Temperature Skyrmion State in Cu_{2}OSeO_{3}.

In the cubic chiral magnet Cu_{2}OSeO_{3} a low-temperature skyrmion state (LTS) and a concomitant tilted conical state are observed for magnetic fields parallel to ⟨100⟩. Here, we report on the dynamic resonances of these novel magnetic states. After promoting the nucleation of the LTS by means of field cycling, we apply broadband microwave spectroscopy in two experimental geometries that provide either predominantly in-plane or out-of-plane excitation. By comparing the results to linear spin-wave theory, we clearly identify resonant modes associated with the tilted conical state, the gyrational and breathing modes associated with the LTS, as well as the hybridization of the breathing mode with a dark octupole gyration mode mediated by the magnetocrystalline anisotropies. Most intriguingly, our findings suggest that under decreasing fields the hexagonal skyrmion lattice becomes unstable with respect to an oblique deformation, reflected in the formation of elongated skyrmions.

New Strategy to Prevent Acute Myocardial Infarction by Public Education　- A Position Statement of the Committee on Public Education About Emergency Medical Care of the Japanese Circulation Society.

Although many efforts have been made to prevent death from acute myocardial infarction (MI) by quick revascularization therapy and use of mechanical circulation support devices, and to prevent the occurrence of acute MI by optimal medical therapy, acute MI is still a leading cause of death worldwide. Because the majority of fatal MI cases occur outside hospital and death occurs so rapidly after MI onset, it is difficult to effectively prevent deaths from acute MI by improving the in-hospital treatment strategy of acute MI or by reducing the prehospital delay in the treatment. Therefore, we need a new strategy to prevent death from acute MI, mainly by preventing the occurrence of acute MI itself. In this review, we summarize the present status and propose a new strategy, the "STOP MI Campaign", to prevent acute MI by public education.

Effect of computed tomography value error on dose calculation in adaptive radiotherapy with Elekta X-ray volume imaging cone beam computed tomography.

PURPOSE: We evaluated the effect of changing the scan mode of the Elekta X-ray volume imaging cone beam computed tomography (CBCT) on the accuracy of dose calculation, which may be affected by computed tomography (CT) value errors in three dimensions. METHODS: We used the electron density phantom and measured the CT values in three dimensions. CT values were compared with planning computed tomography (pCT) values for various materials. The evaluated scan modes were for head and neck (S-scan), chest (M-scan), and pelvis (L-scan) with various collimators and filter systems. To evaluate the effects of the CT value error of the CBCT on dose error, Monte Carlo calculations of dosimetry were performed using pCT and CBCT images. RESULTS: The L-scan had a CT value error of approximately 800 HU at the isocenter compared with the pCT. Furthermore, inhomogeneity in the longitudinal CT value profile was observed in the bone material. The dose error for ±100 HU difference in CT values for the S-scan and M-scan was within ±2%. The center of the L-scan had a CT error of approximately 800 HU and a dose error of approximately 6%. The dose error of the L-scan occurred in the beam path in the case of both single field and two parallel opposed fields, and the maximum error occurred at the center of the phantom in the case of both the 4-field box and single-arc techniques. CONCLUSIONS: We demonstrated the three-dimensional CT value characteristics of the CBCT by evaluating the CT value error obtained under various imaging conditions. It was found that the L-scan is considerably affected by not having a unique bowtie filter, and the S-scan without the bowtie filter causes CT value errors in the longitudinal direction. Moreover, the CBCT dose errors for the 4-field box and single-arc irradiation techniques converge to the isocenter.

Assessment of longitudinal beam property and contrast uniformity for 256- and 320-row area detector computed tomography scanners in the 160-mm nonhelical volume-acquisition mode.

BACKGROUND: Because the x-ray property of patient longitudinal axis in area detector computed tomography (ADCT) depends on a heel effect, radiation dose and beam quality are not uniform along the long axis of the patient. OBJECTIVE: This study aimed to measure the longitudinal beam properties and contrast uniformity of ADCT scanners in the 160-mm nonhelical volume-acquisition (NVA) mode and provide useful datasets for the radiation dose reduction in ADCT examinations. MATERIALS AND METHODS: Two different types of ADCT scanners were used in this study. To assess the heel effect in 256- and 320-row ADCT scanners, we measured dose profile, half-value layer, and iodine contrast uniformity along longitudinal beam direction. RESULTS: The maximum effective energy difference within a 160-mm x-ray beam is approximately 4 keV. Maximum radiation dose on the anode side of the x-ray tube showed approximately 40%-45% reduction compared with that on the isocenter position; the heel effect properties longitudinally differed throughout the x-ray beam, and the decrease in the radiation dose in 256- and 320-row ADCT scanners was observed on the patient table side and gantry side respectively. The CT numbers of iodinated solutions for 256-row ADCT scanner were independent of the heel effect; nevertheless, the CT numbers of 320-row ADCT scanner tended to increase on the patient table (cathode) side. CONCLUSION: This study reveals that the radiation dose on the anode side of the x-ray tube shows approximately 40%-45% reduction compared with that on the isocenter position, and the heel effect properties for 256- and 320-row ADCT scanners longitudinally differ throughout the x-ray beam. The x-ray tube for individual ADCT scanners is mounted in an opposite direction along the long axis of the patient.

Investigation of the changes in the prostate, bladder, and rectal wall sizes during external beam radiotherapy.

AIM AND BACKGROUND: The change in the prostate size for radiotherapy has not yet been elucidated. The coverage of radiation dose is affected by changes in the prostate size. We evaluated the changes in the prostate, rectum, and bladder wall sizes during IMRT of fraction 2 Gy/day using MRI. MATERIALS AND METHODS: Twenty-four patients with prostate cancer were enrolled in this study. MRI was performed at three time points. While the initial MRI was performed before the start of radiotherapy (RT), the second MRI was performed at 38 Gy (range: 36-40 Gy), which represented the halfway point of the RT course. The last MRI was performed on the day of completion of the RT course (76 Gy; range: 74-78 Gy). We estimated the prostate, rectum, and bladder wall sizes at three time points. RESULTS: We observed no significant difference between the estimated sizes of the prostate during RT in all three phases. In addition, the volume of the rectal wall remained unchanged in all phases. However, the volume of the bladder wall significantly decreased from the initial to the last time points. Furthermore, the standard deviation (SD) obtained by subtracting the final size from the initial one was large (mean, 30.1; SD, 10.1). CONCLUSIONS: The volume of the bladder wall decreased during IMRT. The range of subtraction of the volume of the bladder wall was extensive. Thus, the estimation of the bladder wall may be useful to reduce the inter-fraction variation.

Brachial-Ankle Pulse Waves Reflect the Hemodynamics of Valvular Heart Disease.

BACKGROUND: Brachial-ankle pulse wave (ba-PW) analysis is an established technique for assessing arterial stiffness and cardiovascular risk. The peripheral arterial pulse wave configuration may be useful for valvular heart disease (VHD) detection because it is closely related to the physical signs of VHD; however, few reports have been made assessing the efficacy of ba-PW analysis for VHD screening. METHODS: Consecutive VHD patients scheduled for valve surgery were enrolled in the study. These included 58 patients with aortic stenosis (AS) (mean age 74 ± 1.1 years), 67 with aortic regurgitation (AR) (mean age 59 ± 1.9 years), and 65 with mitral regurgitation (MR) (mean age 62 ± 1.6 years). Ba-PW analysis was conducted using the VaSera VS-1500 screening system before and after surgery. Upstroke time (UT), ejection time (ET), pre-ejection period (PEP), PEP/ET ratio, mean arterial pressure (%MAP), and cardio-ankle vascular index (CAVI) were compared with a control group (n = 65; mean age 69 ± 1.5 years) without VHD. RESULTS: The UT was significantly shorter in the AR group (132.9 ± 4.0 ms) and MR group (134.5 ± 2.5 ms), but significantly longer in the AS group (178.2 ± 2.8 ms) compared to controls (149.6 ± 3.6 ms; all p <0.01). The ET was significantly longer in the AS group (318.5 ± 7.4 ms) and AR group (320.0 ± 4.6 ms), but significantly shorter in the MR group (289.0 ± 3.8 ms) compared to controls (305.3 ± 3.4 ms; all p <0.05). In ROC analyses of each group compared to controls, areas under the curve of UT, corrected (c)UT, ET and cET in the AS group, UT/ET ratio in the AR group, and PEP/UT ratio in the MR group were all >0.7. CONCLUSIONS: Multiple pulse wave parameters reflect VHD hemodynamics and may be useful for screening for the condition.

Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC-/-) mice subjected to periaortic application of CaCl2 developed AAAs. Six weeks after CaCl2 treatment, internal and external aortic diameters were significantly increased in MURC-/- AAAs compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica media of MURC-/- AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC-/- AAAs compared with WT AAAs at 5 days after CaCl2 treatment. At 6 weeks after CaCl2 treatment, MURC-/- AAAs exhibited attenuated JNK activity compared with WT AAAs. There was no difference in the activity of MMP-2 or -9 between saline and CaCl2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFα-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC-/-, apolipoprotein E-/- (ApoE-/-), and MURC/Cavin-4 and ApoE double-knockout (MURC-/-ApoE-/-) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE-/- and MURC-/-ApoE-/- mice infused for 4 weeks with Ang II, AAAs were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC-/-ApoE-/- mice compared with Ang II-infused ApoE-/- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates AAA progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA progression.

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors.

The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic responses, and sustained activation of the sympathetic nervous system results in disrupted circulatory homeostasis. In cardiomyocytes, α1-ARs localize to flask-shaped membrane microdomains known as "caveolae." Caveolae require both caveolin and cavin proteins for their biogenesis and function. However, the functional roles and molecular interactions of caveolar components in cardiomyocytes are poorly understood. Here, we showed that muscle-restricted coiled-coil protein (MURC)/Cavin-4 regulated α1-AR-induced cardiomyocyte hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4 was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4 overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced by α1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4 bound to α1A- and α1B-ARs as well as ERK1/2 in caveolae, and spatiotemporally modulated MEK/ERK signaling in response to α1-AR stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and efficient α1-AR signaling mediated by caveolae in cardiomyocytes, which provides a unique insight into the molecular mechanisms underlying caveola-mediated signaling in cardiac hypertrophy.

Influence of Acquisition Mode of Cone-beam Computed Tomography on Accuracy of Image Registration for Image-guided Radiotherapy.

Half scan can acquire images at the 200° rotation in image-guided radiation treatment using cone-beam CT and is useful to evaluate the influence of the half-scan-imaging start angle and imaging direction on image registration accuracy. The half-scan-imaging start angle is changed from 180° to 340° in the clockwise direction and from 180° to 20° in the counter clockwise direction to calculate the registration error. As a result, registration errors between -0.37 mm and 0.27 mm in the left and right directions occur because of the difference in the imaging start angle and approximately 0.3° in the gantry rotation direction because of the difference in the imaging direction. Because half scan does not have data for 360° rotation, depending on the subject structure, inconsistency of opposing data can lower reconstruction accuracy and cause a verification error. In addition, in image acquisition during rotation, the slower the shutter speed is, the more the actual gantry angle and angle information of the image are apart, which is considered the cause of rotation errors. Although these errors are very minute, it is thought that there is no influence on the treatment effect, but these errors are considered an evaluation item indispensable for ensuring the accuracy of high-precision radiation treatment. In addition, these errors need to be considered for ensuring the quality of high-precision radiation treatment.

Mechanical Motion of Chiral Azobenzene Crystals with Twisting upon Photoirradiation.

The photomechanical motion of chiral crystals of trans-azobenzene derivatives with an (S)- and (R)-phenylethylamide group was investigated and compared with a racemic crystal. Changes in the UV/Vis absorption spectra of the powdered crystals before and after UV irradiation were measured by using an optical waveguide spectrometer, showing that the lifetime of the cis-to-trans thermal back-isomerization of the chiral crystals was faster than that of the racemic crystals. Upon UV irradiation, a long plate-like chiral microcrystal bent away from the light source with a twisting motion. A square-like chiral microcrystal curled toward the light with some twisting. Reversible bending of a rod-like chiral microcrystal was repeatable over twenty-five cycles. In contrast, bending of a plate-like racemic microcrystal was small. A possible mechanism for the bending and twisting motion was discussed based on the optimized cis conformer determined by using calculations, showing that the bending motion with twisting is caused by elongation along the b axis and shrinkage along the a axis.

The coiled-coil domain of MURC/cavin-4 is involved in membrane trafficking of caveolin-3 in cardiomyocytes.

Muscle-restricted coiled-coil protein (MURC), also referred to as cavin-4, is a member of the cavin family that works cooperatively with caveolins in caveola formation and function. Cavins are cytoplasmic proteins with coiled-coil domains and form heteromeric complexes, which are recruited to caveolae in cells expressing caveolins. Among caveolins, caveolin-3 (Cav3) is exclusively expressed in muscle cells, similar to MURC/cavin-4. In the heart, Cav3 overexpression contributes to cardiac protection, and its deficiency leads to progressive cardiomyopathy. Mutations in the MURC/cavin-4 gene have been identified in patients with dilated cardiomyopathy. In the present study, we show the role of MURC/cavin-4 as a caveolar component in the heart. In H9c2 cells, MURC/cavin-4 was localized at the plasma membrane, whereas a MURC/cavin-4 mutant lacking the coiled-coil domain (ΔCC) was primarily localized to the cytoplasm. ΔCC bound to Cav3 and impaired membrane localization of Cav3 in cardiomyocytes. Additionally, although ΔCC did not alter Cav3 mRNA expression, ΔCC decreased the Cav3 protein level. MURC/cavin-4 and ΔCC similarly induced cardiomyocyte hypertrophy; however, ΔCC showed higher hypertrophy-related fetal gene expression than MURC/cavin-4. ΔCC induced ERK activation in cardiomyocytes. Transgenic mice expressing ΔCC in the heart (ΔCC-Tg mice) showed impaired cardiac function accompanied by cardiomyocyte hypertrophy and marked interstitial fibrosis. Hearts from ΔCC-Tg mice showed a reduction of the Cav3 protein level and activation of ERK. These results suggest that MURC/cavin-4 requires its coiled-coil domain to target the plasma membrane and to stabilize Cav3 at the plasma membrane of cardiomyocytes and that MURC/cavin-4 functions as a crucial caveolar component to regulate cardiac function.

[Assessing the influence of reconstruction kernel in plaque imaging in computed tomography].

Plaque imaging using computed tomography (CT) is an important diagnostic method for predicting the risk of vascular events. However, the CT value variability of plaques, which depends on the scan parameters, remains a key challenge. The aim of this study was to evaluate the effect of reconstruction properties on the CT value, area, and shape reproducibility of plaques. In general, the types of reconstruction kernels in a CT system are limited, thus impeding the acquisition of the necessary resolution properties (modulation transfer functions: MTFs). We therefore obtained images with eight types (smoothed to edge-enhanced) of resolution property by applying frequency processing to the original CT images. We made phantoms of simulated 6-mm-diameter vessels with plaque and scanned them at different doses. The CT values, areas, and shape reproducibility of plaques were measured from each processed image. Enhanced-type resolution with no edge enhancement (not exceeding 1.0) effectively raised the CT value and shape reproducibility accuracies. However, edge-enhancement type resolution caused errors in the CT value, area and shape reproducibility.

Aversion to a High Salt Taste is Disturbed in Patients With CKD.

Introduction: A reduced salt intake is a vital lifestyle modification in the management of hypertension. Initiatives aimed at decreasing the intake of salt are based on the preference by humans for a salt taste. Salt intake behavior appears to be affected by the balance between attraction to a low salt taste and aversion to a high salt taste. However, aversion to a high salt taste has not yet been quantitively investigated in both healthy individuals and patients with chronic kidney disease (CKD). Methods: Assessments of gustatory and aversion thresholds for salt, bitter, sour, and sweet tastes were performed using a stimulant-impregnated test strip in healthy subjects and patients with CKD. Results: In a pilot taste test of 125 healthy subjects, the number of participants with an aversive reaction increased at higher salt concentrations. The threshold for normal taste perception was arbitrarily defined as 10% NaCl, with 47.2% of healthy subjects displaying an aversive reaction. In taste tests performed by 70 patients with CKD, 10% were unable to recognize a salt taste, even at the highest concentration (20% NaCl), suggesting a significant impairment in taste perception in patients with CKD. Only 15.7% of patients with CKD exhibited a normal aversion to NaCl, whereas 78.6% showed the complete loss of aversion to salt. Conclusion: The present results confirmed the anticipated aversive response to a high salt taste in humans and demonstrated its impairment in patients with CKD, implying that patients with CKD have reduced resistance to a high salt intake.