The Relationship of Alcohol Consumption and Drinking Pattern to the Risk of Glomerular Hyperfiltration in Middle-aged Japanese Men: The Kansai Healthcare Study.

BACKGROUND: Glomerular hyperfiltration has been reported to be associated with adverse renal outcomes in the general population. It is not known whether drinking pattern is associated with the risk of glomerular hyperfiltration in healthy individuals. METHODS: We prospectively followed middle-aged 8,640 Japanese men with normal renal function, no proteinuria, no diabetes, and no use of antihypertensive medications at entry. Data on alcohol consumption were gathered by questionnaire. Glomerular hyperfiltration was defined as estimated glomerular filtration rate (eGFR) ≥117 mL/min/1.73 m2, which was the upper 2.5th percentile value of eGFR in the entire cohort. RESULTS: During 46,186 person-years of follow-up, 330 men developed glomerular hyperfiltration. In a multivariate model, for men who consumed alcohol on 1-3 days per week, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with the risk of glomerular hyperfiltration (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.18-4.74) compared with non-drinkers. For those who consumed alcohol on 4-7 days per week, higher alcohol consumption per drinking day was associated with a higher risk of glomerular hyperfiltration: the HRs for alcohol consumption of 46.1-69.0, and ≥69.1 g ethanol/drinking day were 1.55 (95% CI, 1.01-2.38), and 1.78 (95% CI, 1.02-3.12), respectively. CONCLUSION: For high drinking frequency per week, more alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration, while for low drinking frequency per week, only very high alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration in middle-aged Japanese men.

Differences in the Optical Response of MSU and CPP Crystals During Magnetic Orientation: Possibility of Diagnosing Gout and Pseudogout.

Pseudogout is crystalline arthritis. It has a similar clinical picture to that of gout, and it is difficult to distinguish the two diseases using conventional analysis methods. However, it is important to identify the different crystals responsible for these two cases because the treatment strategies are different. In a previous study, we reported magnetic orientation of monosodium urate (MSU) crystals, which are the causative agent of gout, at the permanent magnet level. In this study, we investigated the effect of an applied magnetic field on calcium pyrophosphate (CPP) crystals, which are the causative agent of pseudogout, and the difference in the magnetic responses of CPP and MSU crystals. We found that the CPP crystals were oriented in a magnetic field on milli-Tesla order because of the anisotropy of the diamagnetic susceptibility. In addition, the CPP crystals exhibited different anisotropic magnetic properties from those of MSU crystals, which led to a characteristic difference between the orientations of the two crystals. That is, we found that the causative agents of gout and pseudogout responded differently to a magnetic field. This report suggests that the discrimination between CPP and MSU by optical measurements is possible by application of magnetic fields appropriately. © 2023 Bioelectromagnetics Society.

Body Mass Index and the Risk of Persistent Proteinuria in Middle-Aged Men: The Kansai Healthcare Study.

INTRODUCTION: Proteinuria is a risk factor for end-stage renal failure. However, it is not known whether body mass index (BMI) is prospectively associated with the risk of future developing proteinuria, taking into account transient proteinuria. METHODS: We enrolled 9,320 nondiabetic Japanese middle-aged men who had no proteinuria, an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, no history of cancer, and no use of antihypertensive medications at baseline. "Any proteinuria" was defined as proteinuria detected for the first time during the follow-up period regardless of its frequency. "Persistent proteinuria" was defined as proteinuria that was detected at least twice consecutively at annual examinations and did not return to negative until the end of the follow-up. RESULTS: During the 11-year follow-up period, 1,972 cases of any proteinuria and 151 cases of persistent proteinuria were confirmed. Both lower and higher BMI were associated with the risk of any proteinuria. As for persistent proteinuria, in those with a BMI ≥20 kg/m2, higher BMI was associated with a higher risk of future persistent proteinuria. The association between BMI and the risk of persistent proteinuria was stronger than that between BMI and any proteinuria. In multiple-adjusted model, hazard ratios of persistent proteinuria for BMI <18.0, 18.0-19.9, 20.0-21.9, 22.0-23.9, 24.0-25.9, 26.0-27.9, and ≥28.0 kg/m2 were 1.52 (95% confidence interval 0.51-4.49), 1.07 (0.49-2.29), 1.00 (reference), 1.14 (0.64-2.01), 1.89 (1.09-3.27), 2.12 (1.15-3.93), and 3.85 (2.03-7.30), respectively. DISCUSSION/CONCLUSION: In those with a BMI ≥20 kg/m2, higher BMI was associated with a higher risk of future persistent proteinuria and any proteinuria. This relationship was stronger for persistent proteinuria than for any proteinuria.

Relationship between QT and JT peak interval variability in prepubertal children.

BACKGROUND: The QT variability index (QTVI) is a noninvasive index of repolarization lability that has been applied to subjects with cardiovascular disease. QTVI provides a ratio of normalized QT variability to normalized heart rate variability, and therefore includes an assessment of autonomic nervous activity. However, measurement of QT time is particularly difficult in children, who exhibit physiologically high heart rates compared with adults. In this study, we developed a set of standard values of J-point to Tpeak interval (JTp) for infants by age, and assessed the correlation of QTVI with the JTp variability index (JTpVI). METHODS: Subjects included 623 infants and children (0-7 years of age) without heart disease and 57 healthy university students. All subjects were divided into three groups by age. QTVI and JTpVI were calculated based on an electrocardiogram, and age-specific standard values, a gender-specific classification, and a standard growth curve were constructed. RESULTS: JTpVI markedly decreased in infancy and slowly decreased thereafter, reaching adult values by school age. There was also a strong correlation of JTpVI with QTVI (r = .856). CONCLUSIONS: JTp can be used to evaluate the variability of the repolarization time in healthy infants, and may be useful for detection of early repolarization abnormalities.

Variability of Myocardial Repolarization in Pediatric Patients with a Ventricular Septal Defect.

In patients with a ventricular septal defect, left-to-right shunting increases the left ventricular preload. This pathological change affects myocardial depolarization and repolarization and has the potential to evoke arrhythmogenic substrates. We examined the effect of ventricular septal defects on myocardial repolarization by investigating the variability in the repolarization interval. This retrospective study included 19 patients (mean age, 1.8 ± 2.1 years) who underwent surgical closure (mean left-to-right shunt ratio, 2.60 ± 0.55) and 26 age-matched healthy controls from 2008 to 2015. Using preoperative electrocardiograms, we studied two electrocardiographic parameters (heart rate-corrected repolarization and variability of repolarization) and four repolarization intervals (QT, JT, J point to T peak [JTp], and T peak to T end [Tp-e] intervals). The variability index (VI) was calculated from the logarithm of the ratio of the repolarization parameter variance to heart rate variance. The various measures were compared between the patients and controls, and significant differences were found in the corrected QT, JTp, and Tp-e intervals (p < 0.05). The VI of the four intervals also showed significant differences (patients vs. CONTROLS: QTVI, -0.55 ± 0.61 vs. -1.10 ± 0.53; JTVI, -0.33 ± 0.60 vs. -0.86 ± 0.57; JTpVI, -0.15 ± 0.78 vs. -0.73 ± 0.56; Tp-eVI, 0.75 ± 0.70 vs. 0.11 ± 0.73, respectively; p < 0.05). No correlation was found between the QTVI and corrected QT interval using linear regression analysis. These repolarization characteristics provide not only electrophysiological indices but also a new index with which to assess the pathophysiology of congenital heart disease.

Chronological Course and Clinical Features after Denver Peritoneovenous Shunt Placement in Decompensated Liver Cirrhosis.

BACKGROUND: Refractory ascites affects the prognosis and quality of life in patients with liver cirrhosis. Peritoneovenous shunt (PVS) is a treatment procedure of palliative interventional radiology for refractory ascites. Although it is reportedly associated with serious complications (e.g., heart failure, thrombotic disease), the clinical course of PVS has not been thoroughly evaluated. OBJECTIVES: To evaluate the relationship between chronological course and complications after PVS for refractory ascites in liver cirrhosis patients. MATERIALS AND METHODS: This was a retrospective study of 14 patients with refractory ascites associated with decompensated cirrhosis who underwent PVS placement between June 2011 and June 2023. The clinical characteristics, changes in cardiothoracic ratio (CTR), and laboratory data (i.e., brain natriuretic peptide (BNP), D-dimer, platelet) were evaluated. Follow-up CT images in eight patients were also evaluated for ascites and complications. RESULTS: No serious complication associated with the procedure occurred in any case. Transient increases in BNP and D-dimer levels, decreased platelet counts, and the worsening of CTR were observed in the 2 days after PVS; however, they were improved in 7 days in all cases except one. In the follow-up CT, the amount of ascites decreased in all patients, but one patient with a continuous increase in D-dimer 2 and 7 days after PVS had thrombotic disease (renal and splenic infarction). The mean PVS patency was 345.4 days, and the median survival after PVS placement was 474.4 days. CONCLUSIONS: PVS placement for refractory ascites is a technically feasible palliative therapy. The combined evaluation of chronological changes in BNP, D-dimer, platelet count and CTR, and follow-up CT images may be useful for the early prediction of the efficacy and complications of PVS.

Evaluation of four computed tomography reconstruction algorithms using a coronary artery phantom.

Background: Despite advancements in coronary computed tomography angiography (CTA), challenges in positive predictive value and specificity remain due to limited spatial resolution. The purpose of this experimental study was to investigate the effect of 2nd generation deep learning-based reconstruction (DLR) on the quantitative and qualitative image quality in coronary CTA. Methods: A vessel model with stepwise non-calcified plaque was scanned using 320-detector CT. Image reconstruction was performed using four techniques: hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), DLR, and 2nd generation DLR. The luminal peak CT number, contrast-to-noise ratio (CNR), and edge rise slope (ERS) were quantitatively evaluated via profile curve analysis. Two observers qualitatively graded the graininess, lumen sharpness, and overall lumen visibility on the basis of the degree of confidence for the stenosis severity using a five-point scale. Results: The image noise with HIR, MBIR, DLR, and 2nd generation DLR was 23.0, 21.0, 16.9, and 9.5 HU, respectively. The corresponding CNR (25% stenosis) was 15.5, 15.9, 22.1, and 38.3, respectively. The corresponding ERS (25% stenosis) was 203.2, 198.6, 228.9, and 262.4 HU/mm, respectively. Among the four reconstruction methods, the 2nd generation DLR achieved the significantly highest CNR and ERS values. The score of 2nd generation DLR in all evaluation points (graininess, sharpness, and overall lumen visibility) was higher than those of the other methods (overall vessel visibility score, 2.6±0.5, 3.8±0.6, 3.7±0.5, and 4.6±0.5 with HIR, MBIR, DLR, and 2nd generation DLR, respectively). Conclusions: 2nd generation DLR provided better CNR and ERS in coronary CTA than HIR, MBIR, and previous-generation DLR, leading to the highest subjective image quality in the assessment of vessel stenosis.

Inhibition of MLCK­mediated migration and invasion in human endometriosis stromal cells by NF­κB inhibitor DHMEQ.

Endometriosis is initiated by the movement of endometrial cells in the uterus to the fallopian tubes, the ovaries and the peritoneal cavity after the shedding of the uterus lining. To cause endometriosis, it is often necessary for these endometrial cells to migrate, invade and grow at the secondary site. In the present study, immortalized human endometriosis stromal cells (HESC) were employed to look for the inhibitors of migration and invasion. Using a chemical library of bioactive metabolites, it was found that an NF­κB inhibitor, DHMEQ, inhibited the migration and invasion of HESC. Both whole­genome array and metastasis PCR array analyses suggested the involvement of myosin light chain kinase (MLCK) in the mechanism of inhibition. DHMEQ was confirmed to inhibit the expression of MLCK and small inhibitory RNA knockdown of MLCK reduced cellular migration and invasion. The addition of DHMEQ to the knockdown cells did not further inhibit migration and invasion. DHMEQ is particularly effective in suppressing disease models by intraperitoneal (IP) administration and this therapy is being developed for the treatment of inflammation and cancer. DHMEQ IP therapy may also be useful for the treatment of endometriosis.

Maxillary sinus floor elevation combined with a vertical onlay graft.

We performed maxillary sinus floor elevation combined with a vertical onlay graft for a total of 11 sides of nine patients (1 woman and 8 men) in our Hospital. On CT, the preoperative minimum alveolar bone thickness with a mean of 1.8 mm was improved to 15.3 mm within a month after this surgery. A total of 20 dental implants were placed and there was only one failed implant. With the average follow-up of 15.6 months, an average of 3.4 mm of bone absorption was found in the site of the maxillary sinus and 1.1 mm in the site of the onlay graft. The crown-implant ratio in all cases was within the permissible range. Consequently, this bone augmentation surgery was considered to be useful.

Evaluation of perinatal autonomic development in infants using the QT/RR variability ratio.

OBJECTIVES: Development of the autonomic nervous system may play a role in myocardial repolarization lability in infants, but its relationship to repolarization abnormalities remains unclear. Thus, the aim of the present study was to evaluate the relationship between gestational age and ventricular repolarization lability using the variability ratio (VR). METHODS: Infants who underwent electrocardiography at a 1-month check-up were included (n=209; 125 males). Gestational age and the following four VR parameters at 1 month of age were compared: VR-I, SDQT/SDRR; VR-II, SDQT/rMSSD; VR-III, SDQTc/SDRR; and VR-IV, SDQTc/rMSSD; where SD, QTc, and rMSSD are standard deviation, QT interval corrected using Fridericia's formula, and root mean square difference of successive RR intervals, respectively. Twenty-eight preterm infants born at <37 weeks of gestation and 181 full-term infants were included. RESULTS: Significant correlations were observed between gestational age and VR-I, -III, and -IV (all p<0.05). All VR values were significantly higher in preterm infants compared with full-term infants (I: 0.54 vs 0.48, II: 1.15 vs 0.96, III: 0.88 vs 0.68, IV: 1.59 vs 1.39; median, all p<0.05). CONCLUSION: VR assessed at 1 month after birth was impaired in preterm infants, suggesting immaturity of their cardiac autonomic nervous system and ventricular myocardial repolarization.

A synthetic synaptic organizer protein restores glutamatergic neuronal circuits.

Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory-inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer's disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits.

Craniofacial abnormality with skeletal dysplasia in mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase-1.

Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and plays an important part in organogenesis. To elucidate the roles of CS for craniofacial development, we analyzed the craniofacial morphology in CS N-acetylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice. T1KO mice showed the impaired intramembranous ossification in the skull, and the final skull shape of adult mice included a shorter face, higher and broader calvaria. Some of T1KO mice exhibited severe facial developmental defect, such as eye defects and cleft lip and palate, causing embryonic lethality. At the postnatal stages, T1KO mice with severely reduced CS amounts showed malocclusion, general skeletal dysplasia and skin hyperextension, closely resembling Ehlers-Danlos syndrome-like connective tissue disorders. The production of collagen type 1 was significantly downregulated in T1KO mice, and the deposition of CS-binding molecules, Wnt3a, was decreased with CS in extracellular matrices. The collagen fibers were irregular and aggregated, and connective tissues were dysorganized in the skin and calvaria of T1KO mice. These results suggest that CS regulates the shape of the craniofacial skeleton by modulating connective tissue organization and that the remarkable reduction of CS induces hypoplasia of intramembranous ossification and cartilage anomaly, resulting in skeletal dysplasia.

Promoting physical activity in hospitalized patients with mild ischemic stroke: a pilot study.

BACKGROUND: Patients with acute stroke spend most of their hospital day inactive. However, a method to promote physical activity (PA) in stroke has not been established. OBJECTIVE: To evaluate the effectiveness of promoting PA by enhancing self-efficacy in hospitalized patients with mild ischemic stroke. DESIGN: Pre-post interventional study. METHODS: Hospitalized patients with mild ischemic stroke who could walk without assistance were recruited. We measured the daily number of steps taken as the index of daily hospitalized PA using an accelerometer. At the baseline measurement, patients did not receive accelerometer-based feedback. To promote hospitalized PA, a physical therapist provided instruction on the self-monitoring approach and discussed PA targets, encouraged the patients to walk more, and instructed them on the importance of PA after stroke. We also measured self-efficacy for PA using an assessment tool at the baseline and during the intervention. RESULTS: Twenty-two patients (62.5 years old, 68.2% men) were included. PA during the intervention was higher than that at the baseline measurement (5709.4 ± 2236.1 vs. 2813.9 ± 1511.9 steps/day, p < 0.001). Self-efficacy for PA during the intervention was also higher than that at the baseline measurement (76.4 ± 18.8 vs. 58.9 ± 29.0 points, p < 0.001). CONCLUSIONS: Promoting PA by enhancing self-efficacy may increase PA and self-efficacy for PA in hospitalized patients with mild ischemic stroke. The present results might provide new strategies of PA promotion in these hospitalized patients.

Efficacy of neuromuscular electrical stimulation for preventing quadriceps muscle wasting in patients with moderate or severe acute stroke: A pilot study.

BACKGROUND: Stroke-related muscle wasting is one of the factors leading to long-term disability and functional dependency. No study has reported an effective therapeutic intervention for such muscle wasting. OBJECTIVE: The purpose of this study was to investigate the effects of neuromuscular electrical stimulation (NMES) on quadriceps muscle mass preservation in patients with acute moderate or severe stroke by using ultrasonography (US). METHODS: Twenty patients with acute, moderate, or severe stroke (age: 68±11 years) were divided into usual care group (control group) and intervention groups (NMES group), respectively. Patients in the NMES group underwent NMES treatment for bilateral quadriceps muscles for 2 weeks in addition to the usual care. Quadriceps muscle thickness was measured on admission and 2 weeks after the first measurement. RESULTS: The quadriceps muscle thickness on the paretic and non-paretic sides in the NMES group (-12.4% ±12.7%, -5.5% ±15.3%, respectively) significantly decreased to a lesser degree than that in the control group (-29.5% ±12.1%, P = 0.004; and -22.0% ±16.8%, P = 0.04, respectively). CONCLUSIONS: NEMS seemed to have preserved the quadriceps muscle mass in patients with moderate or severe acute stroke.

Magnetic rotations of uric acid crystals and uratic crystals by static magnetic fields of up to 500 mT.

In recent years, the disease concerning ureteral calculus is increasing possibly due to the changing lifestyles. For example, it is well known that the urinary calculi have a large impact to gout. As eating habitual diseases, gout and the hyper-uricemia are related to the formation of urinary calculus. In the previous studies, therapeutic agents were developed to enhance the uric acid excretion. From the viewpoint of side effects induction by the chemical agents, we are motivated to explore an alternative method to control the formation of ureteral crystals stimulator by physical stimulations. Therefore in the present study, we focused on the behaviors of uric acid crystals under magnetic fields of several hundreds of mT (Tesla). The uric acid crystals were re-crystallized from a suspension of uric acid powder, and the micro-crystals were prepared to be floating in the solution. We generated horizontal magnetic fields of maximum 500 mT by an electromagnet which contained a CCD microscope. A permanent magnet with magnetic fields of 200∼400 mT was also utilized. During the magnetic fields were applied to the uric acid crystals, we observed that the uric acid crystals were oriented by the magnetic fields down to 200 mT at the room temperature. It was speculated that the dimagnetic anisotropy in the uric acid crystals exhibited the rotational responses. The results indicate the possible remote control of the uric acid crystals in living body by the magnetic fields of 200 mT to 500 mT.