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Abstract Background Elevated creatinine concentrations often indicate acute renal injury and renal biopsies are considered in this situation. However,pseudohypercreatininemia is potential cause of elevated creatinine concentrations, and invasive interventions should be avoided. Case presentation A 54-year-old woman underwent surgery for descending aortic dissection.Nine days postoperatively, her creatinine concentration increased from 1 mg/dl to 5.78 mg/dl (normal range, 0.47–0.7 mg/dl). Azotemia and hyperkalemia were absent and physical examination findings were unremarkable. Cystatin C concentration was 1.56 mg/l (normal range, 0.56–0.8 mg/l) and pseudohypercreatininemia was suspected. Testing with different reagents showed a creatinine concentration of 0.84 mg/dl. Immunoglobulin (Ig)G was markedly elevated, and creatinine and IgG fluctuated in parallel, suggesting the cause of the pseudohypercreatininemia. IgG4 was also elevated at 844 mg/dl. Immunosuppressive steroid therapy effectively decreased the IgG concentration and resolved the pseudohypercreatininemia. Conclusions In cases of elevated creatinine concentration with the presence of abnormal proteins, pseudohypercreatininemia should be considered. We report a rare case of pseudohypercreatininemia caused by polyclonal IgG.

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons — namely, glucose-inhibited (GI) neurons — paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.

Abstract The brain, particularly the ventromedial hypothalamic nucleus (VMH), has been long known for its involvement in glucose sensing and whole-body glucose homeostasis. However, it is still not fully understood how the brain detects and responds to the changes in the circulating glucose levels, as well as brain-body coordinated control of glucose homeostasis. In this review, we address the growing evidence implicating the brain in glucose homeostasis, especially in the contexts of hypoglycemia and diabetes. In addition to neurons, we emphasize the potential roles played by non-neuronal cells, as well as extracellular matrix in the hypothalamus in whole-body glucose homeostasis. Further, we review the ionic mechanisms by which glucose-sensing neurons sense fluctuations of ambient glucose levels. We also introduce the significant implications of heterogeneous neurons in the VMH upon glucose sensing and whole-body glucose homeostasis, in which sex difference is also addressed. Meanwhile, research gaps have also been identified, which necessities further mechanistic studies in future.

The bidirectional reflectance distribution function (BRDF) of recrystallized tungsten mono-blocks exposed to cyclic heat loading for ITER divertor outer vertical target was measured using a goniophotometer at a wavelength of 473 nm. Laser microscope observations revealed that the surface roughness of the mono-block increased by an order of magnitude after cyclic heat loads of approximately 20 MWm−2. Furthermore, the overall values of BRDF decreased with an increase in cyclic heat loading. A comparison between the modeled and measured BRDFs showed that an additional Lambertian component is necessary to a specular function (microfacet model or Gaussian function) to fit the measured BRDFs when the surface of the mono-blocks becomes rough.

Abstract Sufficient feeding is essential for animals’ survival, which requires a cognitive capability to facilitate food seeking, but the neurobiological processes regulating food seeking are not fully understood. Here we show that stimulation of agouti-related peptide-expressing (AgRP) neurons triggers a long-term depression (LTD) of spontaneous excitatory post-synaptic current (sEPSC) in adjacent pro-opiomelanocortin (POMC) neurons and in most of their distant synaptic targets, including neurons in the paraventricular nucleus of the thalamus (PVT). The AgRP-induced sEPCS LTD can be enhanced by fasting but blunted by satiety signals, e.g. leptin and insulin. Mice subjected to food-seeking tasks develop similar neural plasticity in AgRP-innervated PVT neurons. Further, ablation of the majority of AgRP neurons, or only a subset of AgRP neurons that project to the PVT, impairs animals’ ability to associate spatial and contextual cues with food availability during food seeking. A similar impairment can be also induced by optogenetic inhibition of the AgRP→PVT projections. Together, these results indicate that the AgRP→PVT circuit is necessary for food seeking.

The hypothalamus is a critical regulator of glucose metabolism and is capable of correcting diabetes conditions independently of an effect on energy balance. The small GTPase Rap1 in the forebrain is implicated in high-fat diet–induced (HFD-induced) obesity and glucose imbalance. Here, we report that increasing Rap1 activity selectively in the medial hypothalamus elevated blood glucose without increasing the body weight of HFD-fed mice. In contrast, decreasing hypothalamic Rap1 activity protected mice from diet-induced hyperglycemia but did not prevent weight gain. The remarkable glycemic effect of Rap1 was reproduced when Rap1 was specifically deleted in steroidogenic factor-1–positive (SF-1–positive) neurons in the ventromedial hypothalamic nucleus (VMH) known to regulate glucose metabolism. While having no effect on body weight regardless of sex, diet, and age, Rap1 deficiency in the VMH SF1 neurons markedly lowered blood glucose and insulin levels, improved glucose and insulin tolerance, and protected mice against HFD-induced neural leptin resistance and peripheral insulin resistance at the cellular and whole-body levels. Last, acute pharmacological inhibition of brain exchange protein directly activated by cAMP 2, a direct activator of Rap1, corrected glucose imbalance in obese mouse models. Our findings uncover the primary role of VMH Rap1 in glycemic control and implicate Rap1 signaling as a potential target for therapeutic intervention in diabetes.

Abstract We experienced a case in which improving the renal damage caused by warfarin‐related nephropathy took a long time. It is important to follow up for a long time after the initiation of dialysis due to warfarin‐related nephropathy.

This study investigated the effects of cooling between exercise bouts and post-exercise with a commercially available fan cooling jacket on thermal and perceptual responses during and following exercise in hot-humid environments. Ten male athletes completed two 30 min cycling bouts at a constant workload (1.4 watts⋅kg–1 of body mass) with a 5 min recovery period in between. Exercise was followed by a 10 min recovery period. In an environmental chamber (33°C, 65% relative humidity), participants performed two trials with (FCJ) or without (CON) the fan cooling jacket on a T-shirt during the 5 min inter-exercise and 10 min post-exercise recovery periods. Mean, chest and upper arm skin temperatures, and thermal sensation and comfort were lower in FCJ than CON trial during and following exercise (P < 0.05). Thigh and calf skin temperatures, infrared tympanic temperature and heart rate were lower in FCJ than CON trial during the experimental trials (P < 0.05). The rates of fall in mean, chest and upper arm skin temperatures, infrared tympanic temperature and thermal sensation and comfort were faster in FCJ than CON trial during both recovery periods (P < 0.05). There were faster rates of fall in thigh and calf skin temperatures and heart rate in FCJ than CON trial during the post-exercise recovery period (P < 0.05). No difference was observed between trials in the rating of perceived exertion (P > 0.05). This study indicates that cooling between exercise bouts and post-exercise with the fan cooling jacket would effectively mitigate thermal strain and perception/discomfort during and following exercise in hot-humid environments. This garment would reduce whole-body skin temperature quickly while promoting falls in lower-body as well as upper-body skin temperatures.

When using the extracorporeal capillary membrane oxygenator (sample A) for ECMO treatments of COVID-19 severely ill patients, which is dominantly used in Japan and worldwide, there is a concern about the risk of SARS-CoV-2 scattering from the gas outlet port of the membrane oxygenator. Terumo has launched two types of membranes (sample A and sample B), both of which are produced by the microphase separation processes using polymethylpentene (PMP) and polypropylene (PP), respectively. However, the pore structures of these membranes and the SARS-CoV-2 permeability through the membrane wall have not been clarified. In this study, we analyzed the pore structures of these gas exchange membranes using our previous approach and verified the SARS-CoV-2 permeation through the membrane wall. Both have the unique gradient and anisotropic pore structure which gradually become denser from the inside to the outside of the membrane wall, and the inner and outer surfaces of the membrane have completely different pore structures. The pore structure of sample A is also completely different from the other membrane made by the melt-extruded stretch process. From this, the pore structure of the ECMO membrane is controlled by designing various membrane-forming processes using the appropriate materials. In sample A, water vapor permeates through the coating layer on the outer surface, but no pores that allow SARS-CoV-2 to penetrate are observed. Therefore, it is unlikely that SARS-CoV-2 permeates through the membrane wall and scatter from sample A, raising the possibility of secondary ECMO infection. These results provide new insights into the evolution of a next-generation ECMO membrane.

The effects of helium (He) on mechanical properties of hot-rolled pure W were investigated using a high-energy He-implantation technique and post-implantation tensile tests. After the He implantation, the tensile specimens were heat treated at 1100 °C for 100 h in order to recrystallize the pure W. The post-implantation tensile tests were conducted in vacuum at 400 and 700 °C. The post-implantation annealed specimens showed almost the same hardness as-received unimplanted specimens. Tensile properties of He-implanted specimens after the post-implantation annealing indicated almost the same trend as those of as-received specimens under these experimental conditions. Dimples were formed and ductile fracture was observed on the ruptured surface of all specimens. No grain-boundary fracture surface was observed under these experimental conditions. The results showed that He clusters would suppress the recrystallization of hot-rolled pure W because the He clusters might form on dislocations in low angle grain boundaries or in cell walls in the matrix. Because of the suppression of recrystallization by the He clusters, the tensile properties of He-implanted specimens after post-implantation annealing show almost the same trend as those of as-received specimens under the experimental conditions. The results indicate that 20 appm of He implantation is level enough to suppress the recrystallization of pure W. Keywords: Tungsten, Helium implantation, Tensile properties, Recrystallization

We aimed to clarify the behavior of change in the grain structure and hardness of hot-rolled pure W and its alloys plates developed for various properties by holding at high temperature for long and short durations in the absence of irradiation. The isothermal annealing was performed at 1100 °C for 10–3115 h. The isochronous annealing was performed for 1 h in a temperature range of 1100 to 2300 °C. After heat treatment, the grain structure was observed using electron backscatter diffraction (EBSD) and the Vickers hardness was measured in the observed plane. Pure W did not recrystallize by the heat treatment for a short duration of 1 h at 1100 °C, while the recrystallization of pure W progressed during the heat treatment for long duration of 3115 h at 1100 °C. The temperature and duration at which the recrystallization occurs increase because of the dispersion of K bubbles and solid solution of Re. Considering the actual operation period of fusion reactors, a temperature of 1100 °C can result in recrystallization. It is necessary to decrease the maximum operating temperature or to use materials having a high recrystallization temperature by alloying. Keywords: Tungsten, Thermal history, Recrystallization, Grain structure, Recovery

Abstract Background The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab is a low-density lipoprotein (LDL)-lowering drug with a new mechanism, which is currently available in Japan. Here, for the first time, we report the successful use of the PCSK9 inhibitor in a patient with refractory nephrotic syndrome. Case presentation A 61-year-old woman was diagnosed with minimal change-type nephrotic syndrome in October 2012. She received prednisolone (PSL) and cyclosporin A (CyA), but she experienced several cycles of relapse and remission and was hospitalized in May 2016 due to relapse. However, in spite of steroid pulse therapy and adrenocorticotropic hormone (ACTH) administration, her urinary protein level did not improve. We started her on evolocumab with the expectation of equivalent LDL-lowering effects as seen with LDL apheresis. After that, the LDL cholesterol level and UP/UC were concomitantly decreased, and the serum albumin was increased. This was maintained even when we reduced the PSL dose. This suggests that evolocumab clinically improves the nephrotic condition. Conclusion No other report has described the use of evolocumab for nephrotic syndrome (NS) or its effect on similar nephrotic conditions. We believe that the findings presented here are unique and may be beneficial when treating similar cases.

Abstract Background Goodpasture’s syndrome is a rare disease that is characterized by rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. Case presentation A 71-year-old Japanese man who had chronic interstitial pneumonia was diagnosed as having Goodpasture’s syndrome. Both anti-glomerular basement membrane antibody and myeloperoxidase anti-neutrophil cytoplasmic antibody were increased. Despite intensive treatments, including mechanical ventilation, he died from respiratory failure. Pathological findings at autopsy showed rapidly progressive glomerulonephritis in his kidneys, diffuse alveolar hemorrhage, hyaline membranes, and fibroblastic foci in his lungs. The cause of death was diagnosed as respiratory failure as a result of diffuse alveolar damage induced by a combination of diffuse alveolar hemorrhage and exacerbation of interstitial pneumonia. Conclusions We report a case of Goodpasture’s syndrome complicated with pre-existing chronic interstitial pneumonia and positive myeloperoxidase anti-neutrophil cytoplasmic antibody. We reviewed six similar cases reported in the literature and concluded that Goodpasture’s syndrome with pre-existing interstitial pneumonia and myeloperoxidase anti-neutrophil cytoplasmic antibody is related to a poor prognosis.

We report the case of a 69-year-old male patient with extensor pollicis longus (EPL) tendon rupture associated with a scaphoid nonunion advanced collapse (SNAC) wrist. He could not actively extend the left thumb interphalangeal joint and visited our institution for an examination. Plain X-rays revealed advanced stage SNAC and an enlarged soft tissue shadow owing to dorsal ridge growth. The patient was diagnosed with EPL tendon subcutaneous rupture due to SNAC. During surgery, the EPL tendon was found to be absent, a proximal-type scaphoid nonunion was detected, and bone growth to the dorsal part of the dorsal ridge was observed. Considering that the EPL tendon rupture was associated with the bone growth, we performed scaphoid lunate advanced collapse (SLAC) reconstruction and extensor indicis proprius tendon transfer which needed a revision tendon surgery afterward. To the best of our knowledge, EPL tendon ruptures caused by SLAC or SNAC are considered rare and have not yet been reported.

The objective of this study is to clarify the pore structure of ECMO membranes by using our approach and theoretically validate the risk of SARS-CoV-2 permeation. There has not been any direct evidence for SARS-CoV-2 leakage through the membrane in ECMO support for critically ill COVID-19 patients. The precise pore structure of recent membranes was elucidated by direct microscopic observation for the first time. The three types of membranes, polypropylene, polypropylene coated with thin silicone layer, and polymethylpentene (PMP), have unique pore structures, and the pore structures on the inner and outer surfaces of the membranes are completely different anisotropic structures. From these data, the partition coefficients and intramembrane diffusion coefficients of SARS-CoV-2 were quantified using the membrane transport model. Therefore, SARS-CoV-2 may permeate the membrane wall with the plasma filtration flow or wet lung. The risk of SARS-CoV-2 permeation is completely different due to each anisotropic pore structure. We theoretically demonstrate that SARS-CoV-2 is highly likely to permeate the membrane transporting from the patient’s blood to the gas side, and may diffuse from the gas side outlet port of ECMO leading to the extra-circulatory spread of the SARS-CoV-2 (ECMO infection). Development of a new generation of nanoscale membrane confirmation is proposed for next-generation extracorporeal membrane oxygenator and system with long-term durability is envisaged.

The CNS contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (HFD)-induced obesity. Genetic ablation of CNS Rap1 protects mice from dietary obesity, glucose imbalance, and insulin resistance in the periphery and from HFD-induced neuropathological changes in the hypothalamus, including diminished cellular leptin sensitivity and increased endoplasmic reticulum (ER) stress and inflammation. Furthermore, pharmacological inhibition of CNS Rap1 signaling normalizes hypothalamic ER stress and inflammation, improves cellular leptin sensitivity, and reduces body weight in mice with dietary obesity. We also demonstrate that Rap1 mediates leptin resistance via interplay with ER stress. Thus, neuronal Rap1 critically regulates leptin sensitivity and mediates HFD-induced obesity and hypothalamic pathology and may represent a potential therapeutic target for obesity treatment.

This article developes a pediatric membrane oxygenator that is compact, high performance, and highly safe. This novel experimental approach, which imaging the inside of a membrane oxygenator during fluid perfusion using high-power X-ray CT, identifies air and blood retention in the local part of a membrane oxygenator. The cause of excessive pressure drop in a membrane oxygenator, which has been the most serious dysfunction in cardiovascular surgery and extracorporeal membrane oxygenation (ECMO), is the local retention of blood and air inside the oxygenator. Our designed blood flow channel for a membrane oxygenator has a circular channel and minimizes the boundary between laminated parts. The pressure drop in the blood flow channel is reduced, and the maximum gas transfer rates are increased by using this pediatric membrane oxygenator, as compared with the conventional oxygenator. Furthermore, it would be possible to reduce the incidents, which have occurred clinically, due to excessive pressure drop in the blood flow channel of the membrane oxygenator. The membrane oxygenator is said to be the “last stronghold” for patients with COVID-19 receiving ECMO treatment. Accordingly, the specification of our prototype is promising for low weight and pediatric patients.

Hemoconcentration membranes used in cardiopulmonary bypass require a pore structure design with high pure water permeability, which does not allow excessive protein adsorption and useful protein loss. However, studies on hemoconcentration membranes have not been conducted yet. The purpose of this study was to analyze three-dimensional pore structures and protein fouling before and after blood contact with capillary membranes using the tortuous pore diffusion model and a scanning probe microscope system. We examined two commercially available capillary membranes of similar polymer composition that are successfully used in hemoconcentration clinically. Assuming the conditions of actual use in cardiopulmonary bypass, bovine blood was perfused inside the lumens of these membranes. Pure water permeability before and after bovine blood perfusion was measured using dead-end filtration. The scanning probe microscopy system was used for analysis. High-resolution three-dimensional pore structures on the inner surface of the membranes were observed before blood contact. On the other hand, many pore structures after blood contact could not be observed due to protein fouling. The pore diameters calculated by the tortuous pore diffusion model and scanning probe microscopy were mostly similar and could be validated reciprocally. Achievable pure water permeabilities showed no difference, despite protein fouling on the pore inlets (membrane surface). In addition, low values of albumin sieving coefficient are attributable to protein fouling that occurs on the membrane surface. Therefore, it is essential to design the membrane structure that provides the appropriate control of fouling. The characteristics of the hemoconcentration membranes examined in this study are suitable for clinical use.

Various factors are considered to be mechanisms of the increase in the sizes of cysts in patients with polycystic kidney disease. Vasopressin is one of the causes, and drinking large volumes of water shows an effect of suppressing an increase in cysts. On the other hand, it is known that hydrogen-rich water reduces oxidative stress and has a good effect on kidney injury. We examined whether drinking large volumes of hydrogen-rich water affected the increase in the sizes of cysts. Forty 5-week-old PCK rats were randomly assigned to four groups: C(Control), purified water; W(Water), water with sugar; H(Hydrogen), hydrogen-rich water; WH(Water+Hydrogen), hydrogen-rich water with sugar. They consumed water from 5 to 15 weeks of age. The intake of water in the groups in which sugar was added to the water (W, WH) significantly increased in comparison to C, but there was no significant change in the serum Creatinine concentration. The kidney weight per body weight in W was significantly decreased in comparison to C. The kidney weights in H and WH were significantly increased in comparison to W. There were no significant differences in the ratio of the cross-sectional area of the cysts to the whole area among the groups. This experiment showed that the effect of drinking large volumes of hydrogen-rich water was not significantly different from that of normal water, in terms of preventing an increase in the size of cysts in PCK rats. However, some papers acknowledge the influence of hydrogen water. Significant differences might become obvious if we change aspects such as the administration method or administration period.

Calcaneal osteomyelitis (CO) is considered to be difficult to cure when it turned into a chronic phase. We report one case of calcaneal osteomyelitis which arises after the operation of calcaneal fracture. Remission was obtained by performing curettage of the infected cancellous bone of the calcaneal body and filling antibiotic-containing calcium phosphate cements (CPC) within its bone defect. This one-stage surgery is useful to treat calcaneal osteomyelitis.

The soundness of the edge of the round hole made in the aluminum flat plate is confirmed by using the second harmonic of Lamb wave. To efficiently generate Lamb waves in S0 mode and detect second harmonic Lamb waves, from the velocity dispersion curve of Lamb waves, we created a probe using a wedge that has an appropriate critical angle. As a result of the experiment, the second harmonic increases because the peripheral part of the hole is plastically deformed by making a round hole. On the other hand, in the case of the peripheral part of the hole is scratched, the second harmonic is scattered. The amount of second harmonic components detection would decrease was discussed. [ABSTRACT FROM AUTHOR]