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Abstract Background We used transcatheter aortic valve implantation (TAVI) procedure time to investigate the association between surgical team maturity and outcome. Methods Among patients who underwent TAVI between October 2015 and November 2019, those who had Sapien™ implanted with the transfemoral artery approach were included in the analysis. We used TAVI procedure time and surgery number to draw a learning curve. Then, we divided the patients into two groups before and after the number of cases where the sigmoid curve reaches a plateau. We compared the two groups regarding the surveyed factors and investigated the correlation between the TAVI procedure time and survey factors. Results Ninety-nine of 149 patients were analysed. The sigmoid curve had an inflection point in 23.2 cases and reached a plateau in 43.0 cases. Patients in the Late group had a shorter operating time, less contrast media, less radiation exposure, and less myocardial escape enzymes than the Early group. Surgical procedure time showed the strongest correlation with the surgical case number. Conclusion The number of cases required for surgeon proficiency for isolated Sapien™ valve implantation was 43. This number may serve as a guideline for switching the anesthesia management of TAVI from general to local anesthesia.

Abstract Background Malignant hyperthermia (MH) is a rare, life-threatening disorder of calcium homeostasis in skeletal muscle cells that is triggered by volatile anesthetics and succinylcholine, leading to a hypermetabolic reaction. The pathogenic ryanodine receptor 1 (RYR1) gene variant is critical. Patients susceptible to MH should avoid triggering agents, and total intravenous anesthesia (TIVA) is preferred. Remimazolam is safe in patients with suspected MH. Case presentation We present the first case of remimazolam treatment in a genetically confirmed patient with MH without MH development. A 72-year-old man with a family history of MH underwent remimazolam-based TIVA. After informed consent was obtained, a muscle biopsy and genetic testing were performed. Intraoperatively and postoperatively, the patient exhibited no signs of MH. An enhanced function of the RYR1 channel into releasing calcium was indicated, and the genetic testing revealed a pathogenic variant of RYR1. Conclusions Remimazolam-based TIVA is safe in patients confirming the diagnosis of MH.

The Hunga Tonga–Hunga Ha′apai volcano erupted on 15 January 2022, launching Lamb waves and gravity waves into the atmosphere. In this study, we present results using 13 globally distributed meteor radars and identify the volcanogenic gravity waves in the mesospheric/lower thermospheric winds. Leveraging the High-Altitude Mechanistic general Circulation Model (HIAMCM), we compare the global propagation of these gravity waves. We observed an eastward-propagating gravity wave packet with an observed phase speed of 240 ± 5.7 m s−1 and a westward-propagating gravity wave with an observed phase speed of 166.5 ± 6.4 m s−1. We identified these waves in HIAMCM and obtained very good agreement of the observed phase speeds of 239.5 ± 4.3 and 162.2 ± 6.1 m s−1 for the eastward the westward waves, respectively. Considering that HIAMCM perturbations in the mesosphere/lower thermosphere were the result of the secondary waves generated by the dissipation of the primary gravity waves from the volcanic eruption, this affirms the importance of higher-order wave generation. Furthermore, based on meteor radar observations of the gravity wave propagation around the globe, we estimate the eruption time to be within 6 min of the nominal value of 15 January 2022 04:15 UTC, and we localized the volcanic eruption to be within 78 km relative to the World Geodetic System 84 coordinates of the volcano, confirming our estimates to be realistic.

Abstract Stratified turbulence (ST) has been proposed as a model for the dynamics of the mesosphere‐lower thermosphere (MLT) region. This theory postulates that for horizontal mesoscales (∼1–400 km), the kinetic energy of horizontal winds dissipates from large to small scales with an approximately mean constant rate. In this investigation, dissipation rates are quantified using meteor‐radar observations conducted in Northern Norway. The observed seasonal variability of dissipation rates exhibits maxima during the summer and winter, and minima near the equinoxes, between 80 and 95 km altitude. The results are compared with model predictions and earlier medium frequency radar, rocket, lidar, and satellite observations of MLT turbulence. The findings suggest that multi‐static meteor radar measurements of ST can provide a novel way to continuously monitor turbulent dissipation rates in the MLT region.

Continuous wind measurements using partial-reflection radars and specular meteor radars have been carried out for nearly 2 decades (2004–2022) at middle and high latitudes over Germany (∼ 54∘ N) and northern Norway (∼ 69∘ N), respectively. They provide crucial data for understanding the long-term behavior of winds in the mesosphere and lower thermosphere. Our investigation focuses on the summer season, characterized by the low energy contribution from tides and relatively stable stratospheric conditions. This work presents the long-term behavior, variability, and trends of the maximum velocity of the summer eastward, westward, and southward winds. In addition, the geomagnetic influence on the summer zonal and meridional wind is explored at middle and high latitudes. The results show a mesospheric westward summer maximum located around 75 km with velocities of 35–54 m s−1, while the lower-thermospheric eastward wind maximum is observed at ∼ 97 km with wind speeds of 25–40 m s−1. A weaker southward wind peak is found around 86 km, ranging from 9 to 16 m s−1. The findings indicate significant trends at middle latitudes in the westward summer maxima with increasing winds over the past decades, while the southward winds show a decreasing trend. On the other hand, only the eastward wind in July has a decreasing trend at high latitudes. Evidence of oscillations around 2–3, 4, and 6 years modulate the maximum velocity of the summer winds. In particular, a periodicity between 10.2 and 11.3 years found in the westward component is more significant at middle latitudes than at high latitudes, possibly due to solar radiation. Furthermore, stronger geomagnetic activity at high latitudes causes an increase in eastward wind velocity, whereas the opposite effect is observed in zonal jets at middle latitudes. The meridional component appears to be disturbed during high geomagnetic activity, with a notable decrease in the northward wind strength below approximately 80 km at both latitudes.

Abstract Necessary and sufficient opioids should be administered for safe and stable anesthesia. However, opioid sensitivity varies among individuals. We previously reported that sympathetic responses to nociceptive stimuli under propofol anesthesia could be predicted by measuring the minimum evoked current of the vascular stiffness value (MECK). However, this result has only been proven under propofol anesthesia. We propose that MECK could be used under anesthesia with a volatile anesthetic. Thirty patients undergoing laparotomy with sevoflurane anesthesia received 0.7 minimum alveolar concentration (MAC) sevoflurane and intravenous remifentanil at a constant concentration of 2 ng/mL, followed by tetanic stimulation, to measure MECK. After tetanic stimulation, the same anesthetic conditions were maintained, and the rate of change in systolic blood pressure (ROCBP) during the skin incision was measured. The correlation coefficient between the MECK and ROCBP during skin incision under sevoflurane anesthesia was R = − 0.735 (P

Abstract Respiratory monitoring is crucial during monitored anaesthesia care (MAC) to ensure patient safety. Patients undergoing procedures like gastrointestinal endoscopy and dental interventions under MAC have a heightened risk of aspiration. Despite the risks, no current system or device can evaluate aspiration risk. This study presents a novel acoustic monitoring system designed to detect fluid retention in the upper airway during MAC. We conducted a prospective observational study with 60 participants undergoing dental treatment under MAC. We utilized a prototype acoustic monitoring system to assess fluid retention in the upper airway by analysing inspiratory sounds. Water was introduced intraorally in participants to simulate fluid retention; artificial intelligence (AI) analysed respiratory sounds pre and post-injection. We also compared respiratory sounds pre-treatment and during coughing events. Coughing was observed in 14 patients during MAC, and 31 instances of apnoea were detected by capnography. However, 27 of these cases had breath sounds. Notably, with intraoral water injection, the Stridor Quantitative Value (STQV) significantly increased; furthermore, the STQV was substantially higher immediately post-coughing in patients who coughed during MAC. In summary, the innovative acoustic monitoring system using AI provides accurate evaluations of fluid retention in the upper airway, offering potential to mitigate aspiration risks during MAC. Clinical trial number: jRCTs 062220054.

Atmospheric gravity waves and traveling ionospheric disturbances can be observed in the neutral atmosphere and the ionosphere at a wide range of spatial and temporal scales. Especially at medium scales, these oscillations are often not resolved in general circulation models and are parameterized. We show that ionospheric disturbances forced by upward-propagating atmospheric gravity waves can be simultaneously observed with the EISCAT very high frequency incoherent scatter radar and the Nordic Meteor Radar Cluster. From combined multi-static measurements, both vertical and horizontal wave parameters can be determined by applying a specially developed Fourier filter analysis method. This method is demonstrated using the example of a strongly pronounced wave mode that occurred during the EISCAT experiment on 7 July 2020. Leveraging the developed technique, we show that the wave characteristics of traveling ionospheric disturbances are notably impacted by the fall transition of the mesosphere and lower thermosphere. We also demonstrate the application of using the determined wave parameters to infer the thermospheric neutral wind velocities. Applying the dissipative anelastic gravity wave dispersion relation, we obtain vertical wind profiles in the lower thermosphere.

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The Hunga Tonga–Hunga Ha′apai volcano eruption was a unique event that caused many atmospheric phenomena around the globe. In this study, we investigate the atmospheric gravity waves in the mesosphere/lower-thermosphere (MLT) launched by the volcanic explosion in the Pacific, leveraging multistatic meteor radar observations from the Chilean Observation Network De Meteor Radars (CONDOR) and the Nordic Meteor Radar Cluster in Fennoscandia. MLT winds are computed using a recently developed 3DVAR+DIV algorithm. We found eastward- and westward-traveling gravity waves in the CONDOR zonal and meridional wind measurements, which arrived 12 and 48 h after the eruption, and we found one in the Nordic Meteor Radar Cluster that arrived 27.5 h after the volcanic detonation. We obtained observed phase speeds for the eastward great circle path at both locations of about 250 m s−1, and they were 170–150 m s−1 for the opposite propagation direction. The intrinsic phase speed was estimated to be 200–212 m s−1. Furthermore, we identified a potential lamb wave signature in the MLT winds using 5 min resolved 3DVAR+DIV retrievals.

Patients undergoing gastrectomy for gastric cancer may experience alterations in olfaction, yet the association between olfactory changes and postoperative weight loss remains uncertain. This study aimed to elucidate the relationship between olfactory changes and postoperative weight loss in patients with gastric cancer. Patients who underwent radical gastrectomy for gastric cancer between February 2022 and August 2022 were included in the study. Those experiencing a higher Visual Analog Scale (VAS) score postoperatively compared to preoperatively were deemed to have undergone olfactory changes. Postoperative weight loss was determined using the 75th percentile as a cutoff value, designating patients surpassing this threshold as experiencing significant weight loss. Multivariate logistic regression analysis was employed to identify risk factors for postoperative weight loss, with statistical significance set at p < 0.05. Out of 58 patients, 10 (17.2%) exhibited olfactory changes. The rate of postoperative weight loss at one month was markedly higher in the group with olfactory changes compared to those without (9.6% versus 6.2%, respectively; p = 0.002). In addition, the group experiencing olfactory changes demonstrated significantly lower energy intake compared to the group without such changes (1050 kcal versus 1250 kcal, respectively; p = 0.029). Logistic regression analysis revealed olfactory changes as an independent risk factor for significant weight loss at one month postoperatively (odds ratio: 7.64, 95% confidence interval: 1.09–71.85, p = 0.048). In conclusion, olfactory changes emerged as an independent risk factor for postoperative weight loss at one month in patients with gastric cancer following gastrectomy.

Background and purpose: In this study, we aimed to elucidate the action mechanisms of propofol, particularly those underlying propofol-induced protein kinase C (PKC) translocation.Experimental approach: Various PKCs fused with green fluorescent protein (PKC-GFP) or other GFP-fused proteins were expressed in HeLa cells, and their propofol-induced dynamics were observed using confocal laser scanning microscopy. Propofol-induced PKC activation in cells was estimated using the C kinase activity receptor (CKAR), an indicator of intracellular PKC activation. We also examined PKC translocation using isomers and derivatives of propofol to identify the crucial structural motifs involved in this process.Key results: Propofol persistently translocated PKCα conventional PKCs and PKCδ from novel PKCs (nPKCs) to the plasma membrane (PM). Propofol translocated PKCδ and PKCη of nPKCs to the Golgi apparatus and endoplasmic reticulum, respectively. Propofol also induced the nuclear translocation of PKCζ of atypical PKCs or proteins other than PKCs, such that the protein concentration inside and outside the nucleus became uniform. CKAR analysis revealed that propofol activated PKC in the PM and Golgi apparatus. Moreover, tests using isomers and derivatives of propofol predicted that the structural motifs important for the induction of PKC and nuclear translocation are different.Conclusion and implications: Propofol induced the subtype-specific intracellular translocation of PKCs and activated PKCs. Additionally, propofol induced the nuclear translocation of PKCs and other proteins, probably by altering the permeability of the nuclear envelope. Interestingly, propofol-induced PKC and nuclear translocation may occur via different mechanisms. Our findings provide insights into the action mechanisms of propofol.

Abstract Background We measured catecholamine levels during periodic blood pressure fluctuations in patients with pheochromocytoma. Case presentation A 43-year-old man presented with periodic blood pressure fluctuations during surgery for a renal pelvic tumor. His blood levels of catecholamines (ng/mL) changed dramatically over a short time during blood pressure fluctuations: adrenaline 0.36 to 3.22, noradrenaline 0.47 to 1.98, and dopamine 0.02. After the diagnosis of pheochromocytoma, oral treatment with doxazosin 2 mg/day was administered, and left adrenalectomy was performed 4 months after the initial surgery. Periodic circulation fluctuations occurred after tracheal intubation at the time of anesthesia induction, but the degree of fluctuation was smaller than that of the first surgery. Conclusions The data suggest that the periodic blood pressure fluctuations in pheochromocytoma patients are caused by changes in blood catecholamine levels. Our data suggests that alpha blockers may also be effective against the cyclic fluctuations that occur in patients with pheochromocytoma.

Meteor radars have become widely used instruments to study atmospheric dynamics, particularly in the 70 to 110 km altitude region. These systems have been proven to provide reliable and continuous measurements of horizontal winds in the mesosphere and lower thermosphere. Recently, there have been many attempts to utilize specular and/or transverse scatter meteor measurements to estimate vertical winds and vertical wind variability. In this study we investigate potential biases in vertical wind estimation that are intrinsic to the meteor radar observation geometry and scattering mechanism, and we introduce a mathematical debiasing process to mitigate them. This process makes use of a spatiotemporal Laplace filter, which is based on a generalized Tikhonov regularization. Vertical winds obtained from this retrieval algorithm are compared to UA-ICON model data. This comparison reveals good agreement in the statistical moments of the vertical velocity distributions. Furthermore, we present the first observational indications of a forward scatter wind bias. It appears to be caused by the scattering center's apparent motion along the meteor trajectory when the meteoric plasma column is drifted by the wind. The hypothesis is tested by a radiant mapping of two meteor showers. Finally, we introduce a new retrieval algorithm providing a physically and mathematically sound solution to derive vertical winds and wind variability from multistatic meteor radar networks such as the Nordic Meteor Radar Cluster (NORDIC) and the Chilean Observation Network De meteOr Radars (CONDOR). The new retrieval is called 3DVAR+DIV and includes additional diagnostics such as the horizontal divergence and relative vorticity to ensure a physically consistent solution for all 3D winds in spatially resolved domains. Based on this new algorithm we obtained vertical velocities in the range of w = ± 1–2 m s−1 for most of the analyzed data during 2 years of collection, which is consistent with the values reported from general circulation models (GCMs) for this timescale and spatial resolution.

Refractory peripheral neuropathy can occur as a side effect in 60–70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Paclitaxel-induced neuropathic pain. All experiments used 6-week-old male Sprague Dawley rats. Mechanical allodynia was evaluated using a dynamic plantar aesthesiometer. A mobile touch-stimulator unit applied progressively increasing force to the mid-plantar region of the hind paw in a vertical direction until the animal withdrew its paw. This was carried out before the Paclitaxel administration and during the first, second, third, and fourth weeks. Using a rat model of PTX-induced neuropathic pain (PTX rat), we injected PTX (intraperitoneally, 2 mg/kg) five times every 2 days. Using the dynamic plantar test, we evaluated the anti-allodynic effect of YKS (orally administered, 1 g/kg). YKS administration on a daily basis significantly enhanced the withdrawal threshold in PTX rats and reduced the expression level of activated microglia immunostaining with Iba1, a specific marker for microglia. The intrathecal administration of WAY-100635 (5-hydroxytryptamine [5-HT]1A receptor antagonist) and Ketanserin (5-HT2A/2C receptor antagonist) inhibited the protective effects of YKS. YKS exhibited an anti-allodynic effect in a rodent model of PTX-induced neuropathic pain by reducing the sensitivity to pain stimuli. These results suggest that Yokukansan may activate 5-HT receptors in the spinal cord, mediating Paclitaxel-induced neuropathic pain.

Abstract Background Myofascial pain syndrome is one of the causes of prolonged postoperative pain after abdominal surgery. However, diagnosis and treatment of myofascial pain syndrome, especially its myofascial trigger point (MTrP), have not been well established. Case presentation A 55-year-old man experienced severe subacute abdominal pain after laparoscopic hepatectomy despite aggressive postoperative pain management. He had a positive Carnett’s sign, indicating abdominal wall pain, 2 weeks after the surgery. Ultrasonography showed a hyperechoic spot surrounded by a hypoechoic area in the inner abdominal oblique muscle under the palpable spot that fulfills the criteria of MTrP. The echogenic MTrP disappeared after repetitive ultrasound-guided trigger point injections (USG TPIs) with pain relief. Conclusions Our present case indicates that diagnosing myofascial pain by visualizing the echogenic MTrPs in the abdominal muscles, and subsequent USG TPIs, might provide an accurate maneuver for diagnosis and treatment of subacute myofascial pain after abdominal surgery.

Abstract Background Intraoperative superior vena cava (SVC) clamping causes hypotension and cerebral congestion. There is no established method for monitoring brain function during cerebral congestion. We encountered a case of cerebral congestion caused by unexpected SVC clamping. Case presentation A 64-year-old man underwent SVC clamping during lung tumor resection. The entropy and electroencephalogram monitoring values decreased with SVC clamping and increased in response to the release of congestion by phlebotomy and SVC declamping. Conclusions Because entropy sharply reflects brain viability during cerebral congestion, it was considered helpful in evaluation of the monitoring of cerebral congestion.

Abstract Background Occlusion or malposition of the venous cannula during cardiopulmonary bypass (CPB) increases central venous pressure (CVP). When high CVP is measured, we need to determine if it is actually high or if it is measured due to catheter occlusion or technical problems with the measurement. Case presentation We experienced a case of excessively high CVP due to malposition of the venous cannula during CPB. A 78-year-old woman underwent an aortic arch replacement for acute aortic dissection. During CPB, CVP increased up to 78 mmHg, and the time above 50 mmHg was 48 min. In this case, ultrasonography of the internal jugular vein (IJV) was useful to confirm high CVP. Conclusions Ultrasonography is now a familiar diagnostic tool and can be used at any time. We should consider ultrasonography as the first choice for diagnosing the cause of high CVP during CPB.

Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber that is effective for defecation control. It influences the gut microbiota, by which it is metabolized to yield short-chain fatty acids (SCFAs), and it was also recently shown to protect against influenza infection in humans. We here investigated the effects of PHGG in a mouse model of influenza H1N1 virus infection. Eight-week-old C57BL/6 mice were fed normal chow with or without PHGG (500 mg/kg per day) for 4 weeks, infected with H1N1 at 10 weeks of age, and analyzed at 12 weeks of age. Administration of PHGG attenuated the decline in body weight induced by H1N1 infection without affecting food intake. It also ameliorated intestinal atrophy and increased the production of SCFAs including acetic acid, propionic acid, and butyric acid in the cecum, thereby preventing the inhibitory effect of H1N1 infection on SCFA production. The H1N1-induced increases in the serum concentrations of inflammatory cytokines including interferon-γ and interleukin-6 and anti-inflammatory cytokine such as interleukin-10 were all inhibited by PHGG intake. In addition, PHGG administration attenuated inflammatory gene expression in the lung and promoted both natural killer cell activity and regulatory T-cell differentiation in the spleen. Our findings suggest that the consumption of PHGG may improve the gut environment and thereby limit the inflammatory response to H1N1 infection. They may thus provide the basis for novel dietary intervention strategies to suppress the excessive inflammation associated with virus infection.

Specular meteor radars (SMRs) and partial reflection radars (PRRs) have been observing mesospheric winds for more than a solar cycle over Germany (∼ 54∘ N) and northern Norway (∼ 69∘ N). This work investigates the mesospheric mean zonal wind and the zonal mean geostrophic zonal wind from the Microwave Limb Sounder (MLS) over these two regions between 2004 and 2020. Our study focuses on the summer when strong planetary waves are absent and the stratospheric and tropospheric conditions are relatively stable. We establish two definitions of the summer length according to the zonal wind reversals: (1) the mesosphere and lower-thermosphere summer length (MLT-SL) using SMR and PRR winds and (2) the mesosphere summer length (M-SL) using the PRR and MLS. Under both definitions, the summer begins around April and ends around middle September. The largest year-to-year variability is found in the summer beginning in both definitions, particularly at high latitudes, possibly due to the influence of the polar vortex. At high latitudes, the year 2004 has a longer summer length compared to the mean value for MLT-SL as well as 2012 for both definitions. The M-SL exhibits an increasing trend over the years, while MLT-SL does not have a well-defined trend. We explore a possible influence of solar activity as well as large-scale atmospheric influences (e.g., quasi-biennial oscillation (QBO), El Niño–Southern Oscillation (ENSO), major sudden stratospheric warming events). We complement our work with an extended time series of 31 years at middle latitudes using only PRR winds. In this case, the summer length shows a breakpoint, suggesting a non-uniform trend, and periods similar to those known for ENSO and QBO.

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint inflammation, abnormal body composition, and an increased risk for sarcopenia. Muscle wasting in turn increases the risk of infection, morbidity, and premature mortality, but little is known of the relation between nutrient intake and sarcopenia in RA. Methods A prospective cohort study with follow‐up for 1 year examined body composition and diet in female outpatients with RA. We performed logistic regression analysis to assess which factors might have contributed to this loss of muscle mass. Multivariate logistic regression analysis with a forward–backward stepwise selection was also analysed. SKG/Jcl mice, which develop RA spontaneously, were fed normal chow or a high‐fat diet (HFD) and evaluated for inflammation and muscle mass. Results A total 53 female patients were included. The median age was 57.0 years, with an interquartile range (IQR) of 49.5 to 62.0 years, and the median disease duration was 4.0 years, with an IQR of 2.0 to 9.0 years. Fourteen patients (26.4%) had skeletal muscle mass index below the cut‐off for sarcopenia (≤5.7 kg/m2) as defined by the Asia Working Group for Sarcopenia. Multiple logistic regression analysis revealed that the intake of saturated fatty acids was associated with a >5% decrease in skeletal muscle index of RA patients over 1 year [odds ratio 95% confidence interval 1.431 (1.082–1.894), P = 0.012]. In 9 weeks old SKG/Jcl mice, HFD feeding precipitated the onset of RA and exacerbated rheumatoid synovitis in association with the induction of T helper 17 cell differentiation. The serum concentrations of inflammatory cytokines including IL‐6 and TNF‐α were significantly higher in HFD‐fed RA mice than in normal chow (NC)‐fed RA mice or in HFD‐fed control mice (IL‐6; 3.8 vs. 32.2 pg/mL, P

Abstract The mesosphere/lower thermosphere (MLT, 80–100 km) region is an important boundary between Earth's atmosphere below and space above and may act as a sensitive indicator for anthropogenic climate change. Existing observational and modeling studies have shown the middle atmosphere and the MLT is cooling and contracting because of increasing greenhouse gas emissions. However, trend analyses are highly sensitive to the time periods covered, their length, and the measurement type and methodology used. We present for the first time the linear and 11‐year solar cycle responses in the meteor ablation altitude distributions observed by 12 meteor radars at different locations. Decreasing altitudes were seen at all latitudes (linear trends varying from −10.97 to −817.95 m dec−1), and a positive correlation with solar activity was seen for most locations. The divergence of responses at high latitudes indicates an important and complex interplay between atmospheric changes and dynamics at varying time scales.

Abstract Background Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. Methods In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Results Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p

Awake craniotomy with intraoperative open magnetic resonance imaging (MRI) requires special anesthesia management, wherein the use of an anesthesia information management system (AIMS) is important. However, automatic recording using AIMS is generally difficult because of potential noise from electronic devices affecting magnetic resonance images and device malfunction due to magnetic fields emitted during MRI. At our hospital, we have confirmed that wireless local area network (LAN) radio waves do not cause noise during MRI, and have designed a shielded box to house the wireless transmitter and electronic devices that allow a wireless LAN to pass through but shield the electronic devices from noise, thus enabling AIMS recording via a wireless LAN, even during MRI. We demonstrated the usefulness of this system with a wireless LAN connection in three cases of awake craniotomy with open MRI.

Many anesthetics, including Propofol, have been reported to induce elevation of intracellular calcium, and we were interested to investigate the possible contribution of calcium elevation to the mechanism of the newly approved remimazolam actions. Remimazolam is an intravenous anesthetic first approved in Japan in July 2020, and is thought to exert its anesthetic actions via γ-aminobutyric acid A (GABAA) receptors; however, the precise mechanisms of how remimazolam elevates intracellular calcium levels remains unclear. We examined the remimazolam-induced elevation of intracellular calcium using SHSY-5Y neuroblastoma cells, COS-7 cells, HEK293 cells, HeLa cells, and human umbilical vein endothelial cells (HUVECs) loaded with fluorescent dyes for live imaging. We confirmed that high concentrations of remimazolam (greater than 300 μM) elevated intracellular calcium in a dose-dependent manner in these cells tested. This phenomenon was not influenced by elimination of extracellular calcium. The calcium elevation was abolished when intracellular or intraendoplasmic reticulum (ER) calcium was depleted by BAPTA-AM or thapsigargin, respectively, suggesting that calcium was mobilized from the ER. Inhibitors of G-protein coupled receptors (GPCRs)-mediated signals, including U-73122, a phospholipase C (PLC) inhibitor and xestospongin C, an inositol 1,4,5-triphosphate receptors (IP3R) antagonist, significantly suppressed remimazolam-induced calcium elevation, whereas dantrolene, a ryanodine receptor antagonist, did not influence remimazolam-induced calcium elevation. Meanwhile, live imaging of ER during remimazolam stimulation using ER-tracker showed no morphological changes. These results suggest that high doses of remimazolam increased intracellular calcium concentration in a dose-dependent manner in each cell tested, which was predicted to be caused by calcium mobilization from the ER. In addition, our studies using various inhibitors revealed that this calcium elevation might be mediated by the GPCRs-IP3 pathway. However, further studies are required to identify which type of GPCRs is involved.

The goal of this study was to evaluate pediatric patient age with clinical characteristics of malignant hyperthermia (MH). This retrospective cohort study was approved by the Hiroshima University ethics committee, which waived the individual consent requirement. Data was collected from the Hiroshima University MH database using anesthesia record, questionnaires, laboratory data and written case reports from 1960 to 2000. All the patients were Japanese with ages from 0-18 years old. There were three age groups studied: 0-2 years (youngest age), 2-12 years (middle age), and 13-18 years (older age). The Clinical Grading Scale (CGS) was used to calculate scores with all study participants having a score of 35 or higher. Clinical symptoms included muscle breakdown, rigidity, temperature increase, respiratory acidosis, cardiac and other clinical conditions contributing to score points from 0-108 points with 0 point noting a likelihood of MH as 'unlikely' to 108 points noting a likelihood of MH is 'almost certain'. Patient preoperative background included risk factors from history and physical examination, family history, gender, surgery type and anesthetic used, and age at onset and post onset status of survival or death. Anesthesiologists subjectively assessed the initial symptoms of MH based on the first suspicious symptom. Physical findings supportive of initial MHsymptoms were a body tempature increasing by = 40° or = 0.05°C in 15 minutes, end tidal carbon dioxide (EtCO2) = 55 mm Hg, myoglobin urine, and masseter muscle spasms. There were 609 patients included in the study, 285 were under 18 years old and 187 (65.6%) were eligible for the study with CGS scores = 35. Most common case types by are groups were youngest and middle age groups -otolarungology and oldest age group-orthopedics. The second most common case types were youngest age group -urology and cardiovascular, middle age group -orthopedics, and oldest age group -dentistry. The most common initial MH symptom in the oldest age group was elevated EtCO2, in the middle age group was masseter muscle spasm, and in the youngest age group was elevated temperature. The most common physical examination characteristics were sinus tachycardia (98.1%), elevated temperature (91.4%), and rapid temperature increase (88.4%) no matter the age. Clinical characteristics of and the differences in initial physical symptoms of malignant hyperthermia varied by patient age. Comment: Knowing the association of age and the initial characteristics of malignant hyperthermia (MH) in pediatric patients, the appropiate medical treatment can be initiated faster to save more lives of children with MH. [ABSTRACT FROM AUTHOR]

We have successfully improved the fluorescence quantum yield of isoindolo[2,1-a]quinoline derivatives by suppressing the rotation of the phenyl groups at positions 5 and 11 (or 13). Additionally, we found that the planarity of these phenyl groups at positions 5 and 13 of isoindolo[2,1-a]quinoline derivatives is crucial for two-photon absorption properties., (© 2024 Wiley‐VCH GmbH.)

Background: Warfarin interacts with antibacterials to prolong the prothrombin time international normalized ratio (PT-INR) and increase the risk of bleeding. Patients initiating warfarin therapy often undergo precise dosage adjustments; however, the clinical implications of these interactions with antibacterials remain unclear. This study aimed to clarify the effect of antibacterials on PT-INR during the warfarin induction phase., Methods: This was a retrospective, observational study. Patients who were newly treated with warfarin after cardiovascular surgery were included. The primary endpoint was the comparison of the maximum PT-INR and time in therapeutic range (TTR) after warfarin initiation between the antibacterial-treated (ABx) and non-treated (non-ABx) groups., Results: The maximum PT-INR was significantly higher in the ABx group (which included β-lactams, glycopeptides, quinolones, tetracyclines, and aminoglycosides) than in the non-ABx group (median [interquartile range] 2.37 [2.03-2.71] vs. 2.08 [1.93-2.33]; P = 0.005); however, the TTR did not differ significantly (65% [44-76] vs. 71% [43-85]; P = 0.150). The odds ratio for maximum PT-INR > 2.6 with antimicrobial therapy was 2.51 (95% confidence interval 1.21-5.21)., Discussion: Antibacterial therapy was a risk factor for a maximum PT-INR >2.6. However, there was no association with the TTR, which is a marker of good outcomes. This was due to the strict warfarin dosing regimen according to the algorithm, which immediately and appropriately adjusted for PT-INR overexpansion., Conclusions: Antibacterials have been suggested to increase PT-INR during the induction phase of warfarin. However, with strict dose adjustments, the clinical impact on the PT-INR and TTR is likely limited., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Membranes undergo various patterns of deformation during vesicle fusion, but how this membrane deformation is regulated and contributes to fusion remains unknown. In this study, we developed a new method of observing the fusion of individual late endosomes and lysosomes by using mouse yolk sac visceral endoderm cells that have huge endocytic vesicles. We found that there were two distinct fusion modes that were differently regulated. In homotypic fusion, two late endosomes fused quickly, whereas in heterotypic fusion they fused to lysosomes slowly. Mathematical modeling showed that vesicle size is a critical determinant of these fusion types and that membrane fluctuation forces can overcome the vesicle size effects. We found that actin filaments were bound to late endosomes and forces derived from dynamic actin remodeling were necessary for quick fusion during homotypic fusion. Furthermore, cofilin played a role in endocytic fusion by regulating actin turnover. These data suggest that actin promotes vesicle fusion for efficient membrane trafficking in visceral endoderm cells., Competing Interests: SK, MT, MT, TO, TN, KK, MM No competing interests declared, (© 2024, Koike et al.)

Objective: To elucidate the local microcirculation of the infrapatellar fat pad (IFP) in patients with knee osteoarthritis (KOA) by determining the changes in IFP hardness and hemoglobin concentration during isometric quadriceps exercise (IQE)., Design: In this observational cross-sectional study, patients diagnosed with bilateral KOA were included in the KOA group (30 knees), healthy older adults in the control group (20 knees), and younger adults in the young group (20 knees). Ultrasonography was performed at rest and during IQE to measure IFP hardness based on shear wave velocity. Near-infrared spectroscopy was performed to measure oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), and total hemoglobin (cHb) in the IFP before (Baseline), during (IQE task), and after IQE (Post). IFP hardness and O2Hb, HHb, and cHb concentration were analyzed using a linear mixed model for the groups and measurement points., Results: During IQE, IFP hardness changes were significantly less in the KOA group than in the other groups (KOA: 95 % confidence intervals (CIs) [-0.854, 0.028]; control: 95 % CI [-0.941, -0.341]; and young: 95 % CI [-2.305, -1.706]). In the KOA group, O2Hb concentration exhibited no significant changes at Post compared with Baseline; however, significant changes were observed in the other groups (KOA: 95 % CI [-1.176, 0.423]; control: 95 % CI [-1.452, -0.276]; and young: 95 % CI [-4.062, -2.102])., Conclusions: During IQE, changes in hardness and hemoglobin concentration in the IFP were not significant in the KOA group, suggesting impaired local microcirculation of the IFP., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare for the authors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies., Methods: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS)., Results: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone., Conclusions: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

In drug-coated balloon (DCB) angioplasty for femoropopliteal lesions, there are adverse effects of drug embolization on downstream non-target organs following the slow-flow phenomenon. We devised a novel method, known as VaSodilator injection via the Over-the-wire lumen during DCB dilatation to Prevent the slow-flow phenomenon in treatment of femoropopliteal lesions (V.S.O.P.), and evaluated its efficacy and safety. This single-center, retrospective, observational study analyzed 196 femoropopliteal lesions treated with IN.PACT Admiral between April 2018 and July 2023. The IN.PACT Admiral is a DCB consisting of a 0.035-inch over-the-wire (OTW) lumen balloon coated with high-dose paclitaxel. Regarding the V.S.O.P. method, we injected vasodilators through the OTW lumen during DCB dilation of the lesions. The cohort was classified into two groups according to the use of the V.S.O.P. method (V.S.O.P. group: n = 53; non-V.S.O.P. group: n = 143). The V.S.O.P. group had lower rates of hemodialysis (21% vs. 43%, p = 0.01) and higher rates of critical limb-threatening ischemia (56% vs. 23%, p < 0.01) and severe calcification lesions (Peripheral Arterial Calcium Scoring Systems score 3/4) (53% vs. 34%, p = 0.01) than the non-V.S.O.P. group. The occurrence of the slow-flow phenomenon was significantly lower in the V.S.O.P. group than in the non-V.S.O.P. group. The V.S.O.P. method could be an effective method for preventing the slow-flow phenomenon after DCB angioplasty for femoropopliteal lesions., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Ischemia-reperfusion (IR) or reoxygenation injury is the paradoxical exacerbation of cellular impairment following restoration of blood flow after a period of ischemia during surgical procedures or other conditions. Acute interruption of blood supply to the liver and subsequent reperfusion can result in hepatocyte injury, apoptosis, and necrosis. Since the liver requires a continuous supply of oxygen for many biochemical reactions, any obstruction of blood flow can rapidly lead to hepatic hypoxia, which could quickly progress to absolute anoxia. Reoxygenation results in the increased generation of reactive oxygen species and oxidative stress, which lead to the enhanced production of proinflammatory cytokines, chemokines, and other signaling molecules. Consequent acute inflammatory cascades lead to significant impairment of hepatocytes and nonparenchymal cells. Furthermore, the expression of several vascular growth factors results in the heterogeneous closure of numerous hepatic sinusoids, which leads to reduced oxygen supply in certain areas of the liver even after reperfusion. Therefore, it is vital to identify appropriate therapeutic modalities to mitigate hepatic IR injury and subsequent tissue damage. This review covers all the major aspects of cellular and molecular mechanisms underlying the pathogenesis of hepatic ischemia-reperfusion injury, with special emphasis on oxidative stress, associated inflammation and complications, and prospective therapeutic approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Femoroacetabular impingement (FAI), characterized by a pathological contact between the proximal femur and acetabulum, is a common precursor of hip osteoarthritis. Cam morphology is a bony prominence that causes FAI and frequently forms on the anterosuperior femoral head-neck junction. Despite anatomical consensus regarding the femoral head-neck junction as a boundary area covered by the articular cartilage and joint capsule, it remains unclear whether the joint capsule is continuous with the anterosuperior articular cartilage. For the anatomical consideration of cam morphology formation, this study aimed to investigate the histological characteristics of the capsular attachment on the anterosuperior femoral head-neck junction, particularly focusing on the presence or absence of continuity of the joint capsule to the articular cartilage. A total of 21 anterosuperior regions (seven hips each for the 12:00, 1:30, and 3:00 positions) from seven hips (three males and four females; mean age at death, 68.7 years) were histologically analyzed in this study for quantitative evaluation of the capsular thickness using histological sections stained with Masson's trichrome, as well as qualitative evaluation of the capsular attachment. The present study showed that the joint capsule, which folded proximally to the femoral head-neck junction from the recess, exhibited a blend of the fibrous and synovial regions. Notably, it not only continued with the superficial layer of the articular cartilage, but also attached to the articular cartilage via the fibrocartilage. This continuous region was relatively fibrous with dense connective tissue running in the longitudinal direction. The capsular thickness at the recess point (mean, 1.7 ± 0.9 mm) and those at the distal end of the articular cartilage (0.35 ± 0.16 mm) were significantly greater than the control value for the most superficial layer thickness of the articular cartilage (0.019 ± 0.003 mm) (Dunnett's T3, both p-value <0.001). Based on the fibrous continuity between the joint capsule and articular cartilage and its thickness, this study suggests the anatomical possibility that some mechanical stress can be transmitted from the joint capsule to the articular cartilage at the frequent sites of cam morphology., (© 2024 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)