Initiation of belimumab with higher daily prednisolone is effective for rapid glucocorticoid reduction: A 96-week retrospective study.

OBJECTIVES: For appropriate glucocorticoid (GC) reduction, we investigated the optimal strategy including baseline factors that could reduce GC more than 50% with 96 weeks of belimumab. METHODS: This is a retrospective cohort study of Kakogawa Central City hospital from 2019 to 2023. We identified SLE patients who were receiving 200 mg of belimumab weekly by subcutaneous injection for 96 weeks. The background at baseline, trends in clinical indicators, and factors involved in GC reduction were statistically analyzed. Finally, univariate and multivariate logistic analyses were carried out to identify baseline factors associated ≥50% GC reduction at 96 weeks. RESULTS: Forty-seven patients were enrolled, with a median daily prednisolone of 5 mg. Almost 90% of them received concomitant immunosuppressants and/or hydroxychloroquine. Serological indices, daily GC dose, and SLEDAI-2K scores showed significant improvement in 96 weeks. At baseline, a significant negative correlation has been shown between the daily dose of GC and the duration from onset or last flare, as well as C4 levels. At 96 weeks, GC reduction rate and SLEDAI-2K scores were negatively correlated with duration from onset or last flare to initiation of belimumab. Mycophenolate mofetil use was significantly frequent in patients with lupus nephritis (LN), which also correlated with the frequency of past flares. In addition, LN presence was associated with higher SLEDAI-2K scores at 96 weeks, and baseline SLEDAI-2K ≥10 was associated with significantly higher GC dose at 96 weeks. Univariate analysis of the factor contributing to achieving ≥50% GC reduction at 96 weeks has pointed shorter disease duration and higher daily GC dose at baseline as significant variables. Finally, we performed a multivariate analysis by combining above two items with age, which extracted the higher daily GC dose at baseline as a significant variable (OR (95% CI) 1.25 (1.00 to 1.56), p = .047). CONCLUSIONS: Our study showed that a delay in belimumab initiation led to higher SLEDAI-2K score and difficulty in achieving a 50% GC reduction at 96 weeks. Since GC-related adverse events increase with long-term administration of GC though with small daily doses, we proposed here that belimumab should be started in combination with higher daily prednisolone.

[A CASE OF CLINICALLY AMYOPATHIC DERMAMYOSITIS WITH INTERSTITIAL LUNG DISEASE SHOWING TWO DETERIORATIONS IN 4 YEARS].

We report the case of a 45-year-old man who was diagnosed with clinically amyopathic dermamyositis (CADM) and interstitial lung disease (ILD) after presenting with skin lesions typical of CADM and testing positive for anti-Melanoma Diferentiation-Associated gene 5 (anti-MDA5) anti-bodies. He was treated with a regimen including steroid pulse therapy, intravenous cyclophosphamide (IVCY), and calcineurin Inhibitor drug, which initially improved his ILD. However, three months post-treatment, the first deterioration of his conditions occurred, necessitating further administration of steroid pulse therapy and IVCY. After eight cycles of IVCY therapy, the serum levels of KL-6 and anti-MDA5 antibodies decreased, and reaching their lowest values. Nevertheless, two years and six months after the first observed deterioration, the second deterioration of his conditions occurred, leading to acute respiratory failure, treated again with steroid pulse therapy and IVCY. This treatment did not result in improvement of respiratory failure, therefore plasma exchange was attempted, which demonstrated a beneficial effect on the ILD for a short time. This case suggests that IVCY and plasma exchange might be effective therapeutic options for CADM with ILD.

Improvement of hemolysis performance in a hydrodynamically levitated centrifugal blood pump by optimizing a shroud size.

We have developed a hydrodynamically levitated centrifugal blood pump. In the blood pump having hydrodynamic bearings, the narrow bearing gap has a potential for high hemolysis. The purpose of the this study is to improve hemolysis performance in a hydrodynamically levitated centrifugal blood pump by optimizing a shroud size. The impeller was levitated passively at the position where the thrust forces acting on the impeller were balanced. We focused on a size of a bottom shroud with a hydrodynamic bearing that could change the bottom hydrodynamic force to balance the thrust force at the wide bearing gap for reducing hemolysis. Five test models with various shroud size were compared: 989 mm2 (HH-10.5), 962 mm2 (HH-12), 932 mm2 (HH-13.5), 874 mm2 (HH-16), and 821 mm2 (HH-18). A numerical analysis was first performed to estimate the bearing gaps in the test model. The bearing gaps were then measured to validate the numerical analysis. Finally, an in vitro hemolysis test was performed. The numerical analysis revealed that the HH-13.5 model had the widest bearing gap of 129 µm. In the measurement test, the estimation error for the bearing gap was less than 10%. In the hemolysis test, the HH-13.5 model achieved the lowest hemolysis level among the five models. The present study demonstrated that the numerical analysis was found to be effective for determining the optimal should size, and the HH-13.5 model had the optimal shroud size in the developed hydrodynamically levitated centrifugal blood pump to reduce hemolysis.

Suitable hemolysis index for low-flow rotary blood pumps.

A suitable index is needed for hemolysis tests that use low-flow pumps, such as pediatric blood pumps or blood purification pumps. To create such an index, the present study investigates the change of plasma-free hemoglobin in the pump circuit with time and the change of the hemolysis rate with flow rate and impeller rotational speed. The results show that the hemolysis rate or the increase rate of the total free hemoglobin are suitable measures for hemolysis evaluation for low-flow pumps.

Clinically remitted childhood asthma is associated with airflow obstruction in middle-aged adults.

BACKGROUND AND OBJECTIVE: While adult asthma has been shown to be a risk factor for COPD, the effect of remitted childhood asthma on adult lung function has not been clarified. The aim of this study was to examine whether remitted childhood asthma is a risk factor for airflow obstruction in a middle-aged general population. METHODS: A total of 9896 participants (range: 35-60 years) from five healthcare centres were included in the study. The participants were classified into four categories based on the presence or absence of physician-diagnosed childhood/adulthood asthma and asthma symptoms as follows: healthy controls (n = 9154), remitted childhood asthma (n = 287), adulthood-onset asthma (n = 354) and childhood-adulthood asthma (n = 101). RESULTS: The prevalence of respiratory symptoms was similar in both the participants with remitted childhood asthma and healthy controls. The prevalence of airflow obstruction (forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) < 0.7) was significantly higher in the participants with remitted childhood asthma, those with adult-onset asthma and those with childhood-adulthood asthma (5.2%, 14.4% and 16.8%, respectively) compared with healthy controls (2.2%). Multivariate logistic regression showed that remitted childhood asthma was independently associated with airflow obstruction. Among the participants with remitted childhood asthma, ever-smokers had significantly lower FEV1 /FVC than never-smokers. CONCLUSION: Clinically remitted childhood asthma is associated with airflow obstruction in middle-aged adults. Smoking and remitted childhood asthma may be additive factors for the development of airflow obstruction.

Long-term durability test of axial-flow ventricular assist device under pulsatile flow.

A long-term durability test was conducted on a newly developed axial-flow ventricular assist device (VAD) with hydrodynamic bearings. The mock circulatory loop consisted of a diaphragm pump with a mechanical heart valve, a reservoir, a compliance tank, a resistance valve, and flow paths made of polymer or titanium. The VAD was installed behind the diaphragm pump. The blood analog fluid was a saline solution with added glycerin at a temperature of 37 °C. A pulsatile flow was introduced into the VAD over a range of flow rates to realize a positive flow rate and a positive pressure head at a given impeller rotational speed, yielding a flow rate of 5 L/min and a pressure of 100 mmHg. Pulsatile flow conditions were achieved with the diastolic and systolic flow rates of ~0 and 9.5 L/min, respectively, and an average flow rate of ~5 L/min at a pulse rate of 72 bpm. The VAD operation was judged by not only the rotational speed of the impeller, but also the diastolic, systolic, and average flow rates and the average pressure head of the VAD. The conditions of the mock circulatory loop, including the pulse rate of the diaphragm pump, the fluid temperature, and the fluid viscosity were maintained. Eight VADs were tested with testing periods of 2 years, during which they were continuously in operation. The VAD performance factors, including the power consumption and the vibration characteristics, were kept almost constant. The long-term durability of the developed VAD was successfully demonstrated.

Plasma Skimming in a Spiral Groove Bearing of a Centrifugal Blood Pump.

Plasma skimming is a phenomenon in which discharge hematocrit is lower than feed hematocrit in microvessels. Plasma skimming has been investigated at a bearing gap in a spiral groove bearing (SGB), as this has the potential to prevent hemolysis in the SGB of a blood pump. However, it is not clear whether plasma skimming occurs in a blood pump with the SGB, because the hematocrit has not been obtained. The purpose of this study is to verify plasma skimming in an SGB of a centrifugal blood pump by developing a hematocrit measurement method in an SGB. Erythrocyte observation using a high-speed microscope and a bearing gap measurement using a laser confocal displacement meter was performed five times. In these tests, bovine blood as a working fluid was diluted with autologous plasma to adjust the hematocrit to 1.0%. A resistor was adjusted to achieve a pressure head of 100 mm Hg and a flow rate of 5.0 L/min at a rotational speed of 2800 rpm. Hematocrit on the ridge region in the SGB was measured using an image analysis based on motion image of erythrocytes, mean corpuscular volume, the measured bearing gap, and a cross-sectional area of erythrocyte. Mean hematocrit on the ridge region in the SGB was linearly reduced from 0.97 to 0.07% with the decreasing mean bearing gap from 38 to 21 µm when the rotational speed was changed from 2250 to 3000 rpm. A maximum plasma skimming efficiency of 93% was obtained with a gap of 21 µm. In conclusion, we succeeded in measuring the hematocrit on the ridge region in the SGB of the blood pump. Hematocrit decreased on the ridge region in the SGB and plasma skimming occurred with a bearing gap of less than 30 µm in the hydrodynamically levitated centrifugal blood pump.

Effect of Impeller Geometry on Lift-Off Characteristics and Rotational Attitude in a Monopivot Centrifugal Blood Pump.

The effect of the flow path geometry of the impeller on the lift-off and tilt of the rotational axis of the impeller against the hydrodynamic force was investigated in a centrifugal blood pump with an impeller supported by a single-contact pivot bearing. Four types of impeller were compared: the FR model with the flow path having both front and rear cutouts on the tip, the F model with the flow path having only a front cutout, the R model with only a rear cutout, and the N model with a straight flow path. First, the axial thrust and the movement about the pivot point, which was loaded on the surface of the impeller, were calculated using computational fluid dynamics (CFD) analysis. Next, the lift-off point and the tilt of the rotational axis of the impeller were measured experimentally. The CFD analysis showed that the axial thrust increased gently in the FR and R models as the flow rate increased, whereas it increased drastically in the F and N models. This difference in axial thrust was likely from the higher pressure caused by the smaller circumferential velocity in the gap between the top surface of the impeller and the casing in the FR and R models than in the F and N models, which was caused by the rear cutout. These results corresponded with the experimental results showing that the impellers lifted off in the F and N models as the flow rate increased, whereas it did not in the FR and R models. Conversely, the movement about the pivot point increased in the direction opposite the side with the pump outlet as the flow rate increased. However, the tilt of the rotational axis of the impeller, which oriented away from the pump outlet, was less than 0.8° in any model under any conditions, and was considered to negligibly affect the rotational attitude of the impeller. These results confirm that a rear cutout prevents lift-off of the impeller caused by a decrease in the axial thrust.

Properties of a monopivot centrifugal blood pump manufactured by 3D printing.

An impeller the same geometry as the impeller of a commercial monopivot cardiopulmonary bypass pump was manufactured using 3D printing. The 3D-printed impeller was integrated into the pump casing of the commercially available pump to form a 3D-printed pump model. The surface roughness of the impeller, the hydraulic performance, the axial displacement of the rotating impeller, and the hemolytic properties of the 3D-printed model were measured and compared with those of the commercially available model. Although the surface roughness of the 3D-printed model was significantly larger than that of the commercially available model, the hydraulic performance of the two models almost coincided. The hemolysis level of the 3D-printed model roughly coincided with that of the commercially available model under low-pressure head conditions, but increased greatly under high-pressure head conditions, as a result of the narrow gap between the rotating impeller and the pump casing. The gap became narrow under high-pressure head conditions, because the axial thrust applied to the impeller increased with increasing impeller rotational speed. Moreover, the axial displacement of the rotating impeller was twice that of the commercially available model, confirming that the elastic deformation of the 3D-printed impeller was larger than that of the commercially available impeller. These results suggest that trial models manufactured by 3D printing can reproduce the hydraulic performance of the commercial product. However, both the surface roughness and the deformation of the trial models must be considered to precisely evaluate the hemolytic properties of the model.

Within-species divergence in the seminal fluid proteome and its effect on male and female reproduction in a beetle.

BACKGROUND: Male seminal fluid proteins (SFPs), transferred to females during mating, are important reproductive proteins that have multifarious effects on female reproductive physiology and that often show remarkably rapid and divergent evolution. Inferences regarding natural selection on SFPs are based primarily on interspecific comparative studies, and our understanding of natural within-species variation in SFPs and whether this relates to reproductive phenotypes is very limited. Here, we introduce an empirical strategy to study intraspecific variation in and selection upon the seminal fluid proteome. We then apply this in a study of 15 distinct populations of the seed beetle Callosobruchus maculatus. RESULTS: Phenotypic assays of these populations showed significant differences in reproductive phenotypes (male success in sperm competition and male ability to stimulate female fecundity). A quantitative proteomic study of replicated samples of male accessory glands revealed a large number of potential SFPs, of which ≥127 were found to be transferred to females at mating. Moreover, population divergence in relative SFP abundance across populations was large and remarkably multidimensional. Most importantly, variation in male SFP abundance across populations was associated with male sperm competition success and male ability to stimulate female egg production. CONCLUSIONS: Our study provides the first direct evidence for postmating sexual selection on standing intraspecific variation in SFP abundance and the pattern of divergence across populations in the seminal fluid proteome match the pattern predicted by the postmating sexual selection paradigm for SFP evolution. Our findings provide novel support for the hypothesis that sexual selection on SFPs is an important engine of incipient speciation.

Evaluation of a Spiral Groove Geometry for Improvement of Hemolysis Level in a Hydrodynamically Levitated Centrifugal Blood Pump.

The purpose of this study is to evaluate a spiral groove geometry for a thrust bearing to improve the hemolysis level in a hydrodynamically levitated centrifugal blood pump. We compared three geometric models: (i) the groove width is the same as the ridge width at any given polar coordinate (conventional model); (ii) the groove width contracts inward from 9.7 to 0.5 mm (contraction model); and (iii) the groove width expands inward from 0.5 to 4.2 mm (expansion model). To evaluate the hemolysis level, an impeller levitation performance test and in vitro hemolysis test were conducted using a mock circulation loop. In these tests, the driving conditions were set at a pressure head of 200 mm Hg and a flow rate of 4.0 L/min. As a result of the impeller levitation performance test, the bottom bearing gaps of the contraction and conventional models were 88 and 25 µm, respectively. The impeller of the expansion model touched the bottom housing. In the hemolysis test, the relative normalized index of hemolysis (NIH) ratios of the contraction model in comparison with BPX-80 and HPM-15 were 0.6 and 0.9, respectively. In contrast, the relative NIH ratios of the conventional model in comparison with BPX-80 and HPM-15 were 9.6 and 13.7, respectively. We confirmed that the contraction model achieved a large bearing gap and improved the hemolysis level in a hydrodynamically levitated centrifugal blood pump.

Relative permittivity measurement during the thrombus formation process using the dielectric relaxation method for various hematocrit values.

The relative permittivity ε' and the dielectric loss ε″ for various hematocrit values H for static bovine blood condition have been measured using the dielectric relaxation method to detect thrombosis in real time. The suitable measurement frequency f m ranged within 60 kHz to 1 MHz, and the relaxation frequency of red blood cells (RBCs) f rc was observed to be 2 MHz. In the f m, the temporal change of normalized ε' exhibited a minimum (called as bottom point). The bottom point was observed to be exponentially shortened as H increased. This characteristic of the ε'* minimum is discussed from three viewpoints: during fibrin formation, direct thrombus formation, and rouleaux formation processes. ε'* during the fibrin formation process decreased over time, irrespective of f. However, ε'* in f m during the direct thrombus formation process and during the aggregation formation process increased immediately and rapidly over time. Therefore, the ε'* bottom point in f m might be the indication of micrometer-scale thrombus formation by RBC aggregation due to fibrin formation.

Genetic variation in the effect of monoamines on female mating receptivity and oviposition in the adzuki bean beetle, Callosobruchus chinensis (Coleoptera: Bruchidae).

BACKGROUND: Female mate choice after mating is a strong force in sexual selection and could lead to coevolution of mating traits between the sexes. How females of different genotypes respond to substances in the male ejaculate should be mediated by females' mate choices. Monoamines regulate animal physiology and behavior, including the post-mating behavior of females of the adzuki bean beetle, Callosobruchus chinensis (Coleoptera: Bruchidae). This study examined differences in females' response to four monoamines (dopamine, octopamine, tyramine, serotonin) between strains from different populations of C. chinensis. RESULTS: Injection with either octopamine or tyramine, two kinds of monoamines significantly reduced female receptivity in two strains with low remating frequencies. None of the four monoamines reduced female receptivity in one strain with high remating frequencies. However, all monoamines reduced it in another strain with high remating frequencies. Oviposition was activated by tyramine on days 1-5 or by serotonin on days 4 and 5 in the two strains with low remating frequencies, but only on day 1 or day 4 in the strains with high remating frequencies. CONCLUSION: These differences in female response to monoamines, especially tyramine and serotonin, correspond with results of previous studies. They indicate differences in female response to male substances that reduce receptivity and activate oviposition. These findings suggest relationships between the differences in female response to male substances among populations and mutations in the pathways of monoamine biosynthesis or transmission, which in turn determine female mate choice in response to male substances.

Pba3-Pba4 heterodimer acts as a molecular matchmaker in proteasome α-ring formation.

Eukaryotic proteasome assembly is assisted by multiple dedicated chaperones. In yeast, formation of the heteroheptameric ring composed of α1-α7 subunits is promoted by the heterodimeric chaperone Pba3-Pba4. Here we reveal that in the absence of this dimeric chaperone, α2 replaces α4 during α-ring assembly, thereby giving rise to a non-productive complex that lacks α4, ß1, ß5, ß6, and ß7 subunits and aggregates of α4. Furthermore, our structure-guided mutational data demonstrate that the Pba3-Pba4 heterodimer acts as molecular matchmaker reinforcing the interaction between α4 and α5, which is the crucial step in the α-ring formation.

The effects of mating status and time since mating on female sex pheromone levels in the rice leaf bug, Trigonotylus caelestialium.

Although mating status affects future mating opportunities, the biochemical changes that occur in response to mating are not well understood. This study investigated the effects of mating status on the quantities of sex pheromone components found in whole-body extracts and volatile emissions of females of the rice leaf bug, Trigonotylus caelestialium. When sampled at one of four time points within a 4-day postmating period, females that had copulated with a male had greater whole-body quantities of sex pheromone components than those of virgin females sampled at the same times. The quantities of sex pheromone components emitted by virgin females over a 24-h period were initially high but then steadily decreased, whereas 24-h emissions were persistently low among mated females when measured at three time points within the 4 days after mating. As a result, soon after mating, the mated females emitted less sex pheromones than virgin females, but there were no significant differences between mated and virgin females at the end of the experiment. Thus, postmating reduction in the rate of emission of sex pheromones could explain previously observed changes in female attractiveness to male T. caelestialium.

Optimal bearing gap of a multiarc radial bearing in a hydrodynamically levitated centrifugal blood pump for the reduction of hemolysis.

We have developed a hydrodynamically levitated centrifugal pump as a bridge-to-decision device. The purpose of the present study is to determine the optimal bearing gap of a multiarc radial bearing in the developed blood pump for the reduction of hemolysis. We prepared eight pump models having bearing gaps of 20, 30, 40, 80, 90, 100, 180, and 250 µm. The driving conditions were set to a pressure head of 200 mm Hg and a flow rate of 4 L/min. First, the orbital radius of the impeller was measured for the evaluation of the impeller stability. Second, the hemolytic property was evaluated in an in vitro hemolysis test. As a result, the orbital radius was not greater than 15 µm when the bearing gap was between 20 and 100 µm. The relative normalized index of hemolysis (NIH) ratios in comparison with BPX-80 were 37.67 (gap: 20 µm), 0.95 (gap: 30 µm), 0.96 (gap: 40 µm), 0.82 (gap: 80 µm), 0.77 (gap: 90 µm), 0.92 (gap: 100 µm), 2.76 (gap: 180 µm), and 2.78 (gap: 250 µm). The hemolysis tended to increase at bearing gaps of greater than 100 µm due to impeller instability. When the bearing gap decreased from 30 to 20 µm, the relative NIH ratios increased significantly from 0.95 to 37.67 times (P < 0.01) due to high shear stress. We confirmed that the optimal bearing gap was determined between 30 and 100 µm in the developed blood pump for the reduction of hemolysis.

Selective ophthalmic arterial injection using a balloon catheter for retinoblastoma: a seven-year clinical evaluation.

PURPOSE: To evaluate the effectiveness and safety of selective ophthalmic arterial injection (SOAI) for retinoblastoma utilizing a microballoon catheter system with an M chamber. STUDY DESIGN: Retrospective analysis. METHODS AND PATIENTS: This study was sanctioned by theNational Cancer Center Hospital' Independent Ethics Committee. The surgeon was a general interventional radiologist. After confirming that the distal internal carotid artery was not delineated by balloon occlusion and the ophthalmic artery was visualized using digital subtraction angiography, melphalan was manually administered. Notably, in cases presenting bilateral retinoblastoma, both eyes received treatment in a singular, low-dose procedure. Between July 2015 and December 2021, 125 patients with retinoblastoma (68 boys and 57 girls) underwent SOAI at our facility. The average age at initial treatment was 19.3 months. The study covered 250 procedures, with patients undergoing an average of 3.7 procedures. RESULTS: The success rate of the procedure was 99.2%, with a mean procedure duration of 18.3 min. Two distinct technical failures were recorded: one attributed to an internal carotid artery having a wide lumen and the other due to the ophthalmic artery remaining undetected on angiography post-balloon occlusion of the internal carotid artery. Adverse events were minimal but included bronchospasm post-procedure and severe orbital inflammation in 0.8% and 0.4% of cases, respectively. CONCLUSION: SOAI using the microballoon catheter with the M chamber is a feasible and safe procedure for the treatment of retinoblastoma. The success rate was 99.2%. This system can be recommended as intra-arterial chemotherapy for retinoblastoma.

Diffraction structural biology - a new horizon.

An introductory overview to the special issue papers on diffraction structural biology in this issue of the journal.