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Photoluminescence (PL) properties of Er2O3 specimens were examined by using visible lasers (532 nm and 635 nm) and a UV LED light source (365 nm) to investigate the applicability for irradiation damage monitoring of materials in fusion reactors. Both in the laser induced and UV light induced PL spectra, green (510–590 nm) and red (630–725 nm) luminescence was observed. In the spectrum measurements on specimens with different crystallinities, it was confirmed that an intensity of the red luminescence weakened significantly compared with that of the green luminescence in an Er2O3 specimen with a lower crystallinity. The results indicate that the PL measurements of Er2O3 materials could be applicable for the irradiation damage monitoring in fusion reactors. The luminescence property of ion beam irradiated Er2O3 showed that information of irradiation damages could be kept up to ∼ 300 ℃ and almost recovered at 700 ℃. Based on the obtained luminescence properties, positions in a fusion reactor where Er2O3 materials could be used as irradiation damage sensors are proposed. Changes in PL spectra at high temperatures up to ∼ 400 ℃ indicate the possibility that the Er2O3 materials might be applicable also for temperature monitoring of in-vessel components during reactor maintenance periods.

Aim: To identify odontogenesis‐promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. Methodology: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'‐geranyl‐naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real‐time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB‐soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant‐bead complexes were implanted into the sub‐renal capsules for 3 weeks. Tooth root formation was analysed using micro‐computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two‐tailed Student's t‐test. The data were considered to have statistical significance when the P‐value was less than 0.05. Results: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen‐activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c‐Jun N‐terminal kinase (JNK), and AKT substantially suppressed the INB‐induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). Conclusions: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries. [ABSTRACT FROM AUTHOR]

The electrical conductivity of the α-Al2O3 layer formed on FeCrAl alloy APMT (Fe-21Cr-5Al-3Mo) in air atmosphere at 1273 K and 1373 K was measured in a temperature range between room temperature and 1073 K. Low electrical conductivity of the α-Al2O3 layer was clarified in the measurement temperature range. Low electrical conductivity of the ZrO2 layer formed on the Zr metal in air atmosphere at 873 K was also measured. Numerical simulation was performed with three-dimensional thermo-fluid code to clarify the reduction of magnetohydrodynamic (MHD) pressure drop with the electrical insulating α-Al2O3 and ZrO2 layers in liquid blankets of magnetic confinement fusion reactors. The MHD pressure drop is significantly reduced when the four inner surfaces of the duct are electrically insulated by the oxide layers. The electrical insulation of the three inner surfaces is also effective to reduce the MHD pressure drop when the magnetic field is parallel to the conductive wall of the flow duct. However, the MHD pressure drop is induced in the three-surface insulation duct when the magnetic field makes an angle with the conductive wall of the duct.

Climate change and increasing food production due to population growth are global challenges that need immediate attention. The introduction of renewable energy to mitigate climate change and the requirement of adequate land to increase food production are generally mutually exclusive. However, an agrivoltaic system generates renewable electricity and produces agricultural products from a common piece of land, thus increasing the land productivity. In addition, this system contributes to local production, thus reducing the CO2 emissions from logistics. Photovoltaic arrays in previous studies were designed by calculating the irradiance in W/m2, even in recent studies. A careful design of the farmland's illumination must be developed for effective agriculture. The simulations must be scaled based on photosynthetic photon flux density rather than irradiance commonly applied in photovoltaic technology simulations.This study focused on the photosynthetic photon flux density and employed an all-climate solar spectrum model to calculate the photosynthetic photon flux density accurately on farmland partially shaded by solar panels and supporting tubes. This study described an algorithm for estimating the photosynthetic photon flux density values under solar panels. The calculated data were validated using the photosynthetic photon flux density sensors. To calculate the photosynthetic photon flux density under the solar panels, it is essential to weigh the direct and diffused components shaded by the solar panels separately because they have different spectrums. A method to quantify the shading was explored here by solar panels and their supporting tubes for the direct and diffused component as the sun moves. The calculation formula was established by defining the sun's moves and the positions of solar panels and their supporting tubes in terms of elevation and azimuth angles from the observation point.It was found that the waveform based on the calculation formula for the photosynthetic photon flux density under the solar panels reproduced the same tendency as the measured photosynthetic photon flux density. To evaluate this trend numerically, the measured and calculated photosynthetic photon flux densities were compared using the standard residuals. Generally, the similarity of the two values is confirmed by a standard residual value between −3 and 3. The result of this study showed that the standard residual values were negative in more frequencies except for the zero photosynthetic photon flux density at night. This indicates that the calculated photosynthetic photon flux density tends to be higher than the measured photosynthetic photon flux density. The peak frequency of the standard residuals was between −6 and −3. This difference probably occurred because the established calculation formula targets the shading provided by the solar panels and supporting tubes but does not cover the shading provided by the other system structures. The calculation formula enables farmers to evaluate the economic efficiency of the system before introducing it using measured solar irradiation data at the target farmlands by introducing published neighborhood solar irradiation data and considering, in advance, measures to avoid the effects of shading on agricultural production. The next study will be to improve the accuracy of the calculation formula by increasing the number of days and develop a method that leads to the best practices of agricultural production and solar power generation by introducing the system.

Climate change and increasing food demand are global issues that require immediate attention. The agrivoltaic system, which involves installing solar panels above farmland, can simultaneously solve climate and food issues. However, current systems tend to reduce agricultural production and delay the harvest period due to shading by the solar panels. A delayed harvest period impacts the income of farmers who wish to sell produce at specific times. Incorporating a model that calculates the amount of electricity generated by solar irradiation, this study establishes a model to estimate the correct start date of cultivation for solar panel covered crops to ensure the correct harvest date and determines the expected income of farmers by calculating agricultural production and power generation. Using taro cultivation in Miyazaki Prefecture as a case study, the model estimated that the start date of cultivation should be brought forward by 23 days to ensure the ideal harvest period and agricultural production. This would prevent an opportunity loss of USD 16,000 per year for a farm area of 10,000 m2. Furthermore, an additional income of USD 142,000 per year can be expected by adjusting shading rates for the cultivation and non-cultivation periods.

Functional ceramic coatings have been investigated for several decades to mitigate tritium permeation through structural materials in a fusion reactor blanket. For the establishment of a liquid blanket system, the coatings require not only tritium permeation reduction but also the tolerance to irradiation damage induced by neutrons and corrosion by liquid tritium breeders. In this study, deuterium permeation measurements under exposure to liquid lithium–lead were performed for a heavy-ion-irradiated zirconium oxide coating sample to elucidate the synergy of irradiation and corrosion on hydrogen isotope permeation. The irradiated coating decreased the deuterium permeation flux under lithium–lead exposure by more than two orders of magnitude in comparison with the unirradiated one. Each activation energy of permeation and diffusion of the coating sample was larger than that of the unirradiated one at around 450 °C and decreased to the level of the unirradiated one at 600 °C. The results indicated that the voids formed by ion irradiation aggregated in grain boundaries of the coating, resulting in an increase in the energy barrier of diffusion at low temperatures and then a decrease due to the defect recovery at high temperatures. Besides, a corrosion product layer formed on the coating during lithium–lead exposure increased the energy barrier of solution. The synergy of irradiation and corrosion on permeation was developed at lower temperatures before the defect recovery.

Ceramic coatings have been developed for nearly half a century to mitigate tritium leakage through steels and corrosion of the components in fusion reactor blanket systems. In recent years, irradiation effects of ceramic coatings on their characteristics and functions have been elucidated through heavy-ion irradiation tests. However, most of analytical methods used in these studies were destructive and time-consuming. In this study, yttrium oxide coatings were fabricated by radio-frequency magnetron sputtering, and the electrical impedance measurements were conducted for the coatings to develop a convenient approach for understanding of irradiation effects. The conductivity obtained from Nyquist plots showed lower values for the undamaged sample than for the damaged ones below 350 °C, while the relationship of the conductivity was reversed at 350 °C and higher temperatures. The ac conductivity of the undamaged sample showed a frequency dependence from 200 °C to 550 °C; however, that of the damaged ones did not show at 300 °C and lower temperatures and indicated a tendency similar to undamaged one above 300 °C. These tendencies of the conductivity at low temperatures were attributed to the partial recovery of the irradiation damage, while the remaining irradiation defects and/or irradiation-induced grain growth affected the electrical properties at higher temperatures. The electrical impedance spectroscopy methods have a potential to detect the influence of irradiation on the coating.

Deuterium permeation through a fusion-relevant ferritic steel F82H with and without erbium oxide coatings under γ-ray irradiation has been investigated in a temperature range from 300 to 700 °C. The deuterium permeation flux through F82H sample increased by γ-ray irradiation at lower temperatures below 450 °C. The irradiation effect increased with dose rate, and the percentage of the permeation flux gain might be several percent under the dose rate of a few Gy s‒1. Temperature of the F82H sample surface rose by about 0.5 °C depending on the dose rate, and so the γ-ray irradiation effect is mainly attributed to γ-heating. On the other hand, at higher temperature above 500 °C, no appreciable change of the deuterium permeation was observed. Similarly, the deuterium permeation flux through erbium oxide coated samples increased under γ-ray irradiation at lower temperatures (350‒450 °C), but no appreciable change of permeation flux through coatings was observed at higher temperatures (600‒700 °C). The coating surface temperature increased at lower sample temperatures by γ-heating. Keywords: Tritium, Permeation, γ-ray, Irradiation, F82H, Erbium oxide

Activation analysis of impurities was performed on a test specimen of the reference low-activation vanadium alloy NIFS-HEAT-2 (V-4Cr-4Ti) which has been irradiated in Japan Materials Testing Reactor (JMTR) ~16 years before. Since the radioactive nuclides from V, Cr and Ti are produced with short half-lives, intense peaks of 60Co (T1/2 = 5.27 years) were dominant in the measured gamma-ray energy spectra and peaks of 94Nb (2.03 × 104 years) were also observed. The concentrations were evaluated to be 0.41 wppm and 0.71 wppm respectively from comparison with results of radioactivity calculation using the FISPACT-2005 code. In the analysis, detection of 108mAg (418 years), which would have a considerable influence on the material recycling after the usage in a fusion reactor, was intense motivation. Although the peaks of 108mAg has not been detected, the concentration of Ag was estimated to be

Traumatic visceral arteriovenous fistulae are rare and pose a diagnostic and therapeutic challenge. We present the case of a 20-year-old male who sustained multiple gunshot wounds to the abdomen, injuring the inferior vena cava, duodenum, stomach, and small bowel. The patient was taken emergently to the operating room for repair of his injuries, which required primary small bowel repair, duodenal repair, and inferior vena cava ligation due to exigent hemorrhage. At the initial operation there was a normal pulse in the superior mesenteric artery at the base of the small bowel mesentery, with no evidence of hematoma or thrill in the small bowel mesentery. The patient was subsequently returned to the operating room several times for bowel exploration and abdominal wall closure with mesh. Ten days after his initial injury, the patient was noted to have an abdominal bruit on physical exam. Arteriography demonstrated a fistula between the proximal superior mesenteric artery and vein with significant portal hypertension. The patient underwent surgical repair of the superior mesenteric artery and vein with closure of the fistula. The patient had no further complications and was discharged from the hospital 1 month later, after abdominal wall skin grafting, in good condition. The patient remains in good health 12 months later. Continued vigilance and careful physical examination are important in the identification of delayed vascular injuries and allow timely treatment and avoidance of untoward long-term sequelae. [ABSTRACT FROM AUTHOR]

Yttrium oxide coatings were fabricated on reduced activation ferritic/martensitic steels by metal organic decomposition with a dip-coating technique, and their deuterium permeation behaviors were investigated. The microstructure of the coatings varied with heat-treatment temperature: amorphous at 670ºC (amorphous coating) and crystallized at 700ºC (crystallized coating). Deuterium permeation flux of the amorphous coating was lower than the uncoated steel by a factor of 5 at 500ºC, while that of the crystallized coating was lower by a factor of around 100 at 400‒550ºC. The permeation fluxes of both coatings were drastically decreased during the measurements at higher temperatures by a factor of up to 790 for the amorphous coating and 1000 for the crystallized one, indicating a microstructure modification occurred by an effect of test temperature with hydrogen flux. Temperature dependence of deuterium diffusivity in the coatings suggests that the decrease of the permeation flux has been derived from a decrease of the diffusivity. Characteristic permeation behaviors were observed with different annealing conditions; however, they can be interpreted using the permeation mechanism clarified in the previous erbium oxide coating studies.

Background: Air travel associated with venous thromboembolism has recently achieved public awareness due to intense media coverage. The interest has focused on deep vein thrombosis (DVT) of the lower limbs with pulmonary embolism. The World Health Organization (WHO) is planning several international multicenter trials to study the problem and, if it exists, try to find a means for prevention.Methods: This is a case presentation of acute venous thromboembolism of the upper limbs associated with long-haul flights. Five patients were admitted to Straub Hospital in Honolulu after 5 to 10 hours flight.Results: Patient 1 had a previous shoulder injury with DVT; patient 2 had chronic atrial fibrillation; patients 3 and 5 had clavicular fractures; and patient 4 had a subclavian vein compression.Conclusion: It is not possible to draw any conclusions about the association between air flights and subclavian vein thrombosis from this small retrospective case study. Our objective was to indicate the possibility of such a relationship. [ABSTRACT FROM AUTHOR]

The surface of a Fe-Ni-Cr Alloy (SUS316L) plate was electrochemically nitrided in molten LiF-KF salt including Li3N at 873K. The crystal structure changed from fcc structure to bct structure with nitrogen introduction. The Nitrogen diffusion layers were predominately formed at nitrogen concentration of 23 at%. The nitriding process drastically also changed its magnetic property from non-magnetic to ferromagnetic. The magnetic field of 20 kOe saturated the magnetic moment with its magnetization of 81 emu/g at 10K. The anisotropic magnetization is ascertained. Based on CrN formation and Cr extraction from the original Fe-Ni-Cr system, the induced ferromagnetism was discussed.

Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK)-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P) in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein-protein interactions revealed that CRY-mediated periodic binding of CK2β to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2α. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY-mediated BMAL1-CK2β binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1-P-BMAL1 loop is an integral part of the core clock oscillator.

Dysfunction of circadian clocks exacerbates various diseases, in part likely due to impaired stress resistance. It is unclear how circadian clock system responds toward critical stresses, to evoke life-protective adaptation. We identified a reactive oxygen species (ROS), H2O2 -responsive circadian pathway in mammals. Near-lethal doses of ROS-induced critical oxidative stress (cOS) at the branch point of life and death resets circadian clocks, synergistically evoking protective responses for cell survival. The cOS-triggered clock resetting and pro-survival responses are mediated by transcription factor, central clock-regulatory BMAL1 and heat shock stress-responsive (HSR) HSF1. Casein kinase II (CK2) -mediated phosphorylation regulates dimerization and function of BMAL1 and HSF1 to control the cOS-evoked responses. The core cOS-responsive transcriptome includes CK2-regulated crosstalk between the circadian, HSR, NF-kappa-B-mediated anti-apoptotic, and Nrf2-mediated anti-oxidant pathways. This novel circadian-adaptive signaling system likely plays fundamental protective roles in various ROS-inducible disorders, diseases, and death.

Circadian rhythms are the general physiological processes of adaptation to daily environmental changes, such as the temperature cycle. A change in temperature is a resetting cue for mammalian circadian oscillators, which are possibly regulated by the heat shock (HS) pathway. The HS response (HSR) is a universal process that provides protection against stressful conditions, which promote protein-denaturation. Heat shock factor 1 (HSF1) is essential for HSR. In the study presented here, we investigated whether a short-term HS pulse can reset circadian rhythms. Circadian Per2 rhythm and HSF1-mediated gene expression were monitored by a real-time bioluminescence assay for mPer2 promoter-driven luciferase and HS element (HSE; HSF1-binding site)-driven luciferase activity, respectively. By an optimal duration HS pulse (43°C for approximately 30 minutes), circadian Per2 rhythm was observed in the whole mouse fibroblast culture, probably indicating the synchronization of the phases of each cell. This rhythm was preceded by an acute elevation in mPer2 and HSF1-mediated gene expression. Mutations in the two predicted HSE sites adjacent (one of them proximally) to the E-box in the mPer2 promoter dramatically abolished circadian mPer2 rhythm. Circadian Per2 gene/protein expression was not observed in HSF1-deficient cells. These findings demonstrate that HSF1 is essential to the synchronization of circadian rhythms by the HS pulse. Importantly, the interaction between HSF1 and BMAL1:CLOCK heterodimer, a central circadian transcription factor, was observed after the HS pulse. These findings reveal that even a short-term HS pulse can reset circadian rhythms and cause the HSF1-BMAL1:CLOCK interaction, suggesting the pivotal role of crosstalk between the mammalian circadian and HSR systems.

Substitutional doping, involving the replacement of a host with an aliovalent impurity ion, is widely used to attain ambipolar controllability in semiconductors, which is crucial for device application. However, its effectiveness for p-type doping is limited in monovalent cation compounds due to the lack of suitable aliovalent (i.e., zerovalent) impurities. We propose an alternative approach for p- and n-type doping, mediated by the sizes of isovalent alkali metal impurities in Cu(I)-based semiconductors, such as copper nitride with an electron concentration of ∼10 15 cm -3 . Doping of isovalent Li with a smaller size to interstitial positions improves n-type conductivity, and electron concentration is controllable in the range of 10 15 to 10 18 cm -3 . In contrast, larger isovalent Cs and Rb impurities facilitate p-type conversion, resulting in a hole concentration controllability of 10 14 to 10 17 cm -3 . First-principles calculations indicate that Li is placed as an interstitial impurity acting as a shallow donor in conjunction with the formation of a neutral impurity on Cu defects. As the impurity size increases beyond the capacity of the vacant space, the formation of multiple acceptor-type Cu vacancies is enhanced owing to the repulsion between host Cu + and Cs + /Rb + impurities. Consequently, the Cs or Rb impurity is located at the sites of the N accompanied by six neighboring Cu vacancies, forming acceptor defect complexes. This size-dependent isovalent impurity doping scheme opens up an alternative avenue for advancement in optoelectronic devices using monovalent cation-based semiconductors.

In Japan, the traditional method for measuring plasma aldosterone concentration (PAC) was radioimmunoassay (RIA), which had several challenges, including poor traceability of certified reference materials and reduced detection sensitivity at low concentrations. To overcome these issues, a chemiluminescent enzyme immunoassay (CLEIA) for PAC measurement was introduced in April 2021 and the Japan Endocrine Society published new guidelines for primary aldosteronism (PA). This study aimed to evaluate the impact of the transition from RIA to CLEIA for PAC measurement on PA diagnosis. Data from 190 patients admitted to the Second Department of Internal Medicine, University of the Ryukyus Hospital, between April 2012 and March 2021 were analyzed. Patients who were diagnosed with PA underwent adrenal venous sampling. The PAC measured by RIA (PAC(RIA)) was converted to the estimated PAC measured by CLEIA (ePAC(CLEIA)) using a conversion formula. The present study evaluated the discordance rates in diagnoses based on screening (SC), captopril challenge test (CCT), saline infusion test (SIT), and diagnosis of PA between results judged by PAC(RIA) according to the previous guidelines and those judged by ePAC(CLEIA) according to the new guidelines. The results revealed discordant diagnosis rates of 6.4% for SC and 10.1% for CCT, with no discordance for SIT. The discordant diagnosis rate for PA was 3.7%. Our study reveals the challenges in establishing appropriate diagnostic criteria for PA using PAC(CLEIA) and highlights the demand for further research on provisionally positive categories.

Aims: Paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and protects against atherosclerosis. However, the relationship between functional PON1 Q192R polymorphism, which is associated with the hydrolysis of paraoxon (POXase activity) and atherosclerotic cardiovascular disease (ASCVD), remains controversial. As the effect of PON1 Q192R polymorphism on the HDL function is unclear, we investigated the relationship between this polymorphism and the cholesterol efflux capacity (CEC), one of the biological functions of HDL, in association with the PON1 activity., Methods: The relationship between PON1 Q192R polymorphisms and CEC was investigated retrospectively in 150 subjects without ASCVD (50 with the PON1 Q/Q genotype, 50 with the Q/R genotype, and 50 with the R/R genotype) who participated in a health screening program. The POXase and arylesterase (AREase: hydrolysis of aromatic esters) activities were used as measures of the PON1 activity., Results: The AREase activity was positively correlated with CEC independent of the HDL cholesterol levels. When stratified by the PON1 Q192R genotype, the POXase activity was also positively correlated with CEC independent of HDL cholesterol. PON1 Q192R R/R genotype carriers had a lower CEC than Q/Q or Q/R genotype carriers, despite having a higher POXase activity. Moreover, in a multiple regression analysis, the PON1 Q192R genotype was associated with the degree of CEC, independent of the HDL cholesterol and POXase activity., Conclusions: The PON1 Q192R R allele is associated with reduced CEC in Japanese people without ASCVD. Further studies on the impact of this association on the severity of atherosclerosis and ASCVD development are thus called for.

Phytotoxic compounds isolated and identified from different plants have the ability to use as plant-based herbicides. Phytotoxic chemicals may be essential to weed management and environmental protection in order to reduce the indiscriminate use of synthetic pesticides. It has been reported that Elaeocarpus floribundus plant possesses phytotoxic compounds. The leaf extracts of this species demonstrated significant growth inhibition against the tested plants (dicot plant lettuce and plant monocot timothy) and inhibition was dose- and species-dependent pattern. Two phytotoxic compounds were separated using different purifications methods and identified as compounds 1 and 2 . All phytotoxic compounds displayed potent growth limitation against the tested species (cress). The compound concentrations needed for the inhibition of 50% growth (IC 50 value) of tested species ranged from 1.06 to 8.53  µ M (micromolar). Findings of this research suggest that these compounds might be responsible for the phytotoxicity of Elaeocarpus floribundus plant. The results of this study may be helpful for the development of natural herbicide to control weeds., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Kawsar Hossen et al.)

Post-traumatic pituitary stalk transection syndrome (PSTS) is an extremely rare cause of combined pituitary hormone deficiency (CPHD), affecting approximately 9 per 100,000 cases of traumatic brain injury. In contrast, pituitary stalk interruption syndrome (PSIS) is also a rare cause of CPHD. Importantly, these conditions are often confused due to their similar names and resembling findings on magnetic resonance imaging (MRI). PSIS has been thought to be a prenatal developmental event resulting from a couple of genetic aberrations. In typical PSIS, anterior pituitary hormone deficiencies are restricted to growth hormone (GH) and gonadotropin during the pediatric age, gradually and generally progressing to panhypopituitarism in most cases. In contrast, global deficiencies of the anterior pituitary hormones in PSTS are temporally associated with trauma. To the best of our knowledge, no case reports of PSTS combined with acute traumatic spinal cord injury have been reported. A 34-year-old female was transferred to our hospital after jumping from the fourth building floor. She was diagnosed as an acute traumatic spinal cord injury and underwent the operation of elective posterior spinal fusion. On postoperative day 7, the blood tests revealed considerable hyperkalemia, hyponatremia and eosinophilia. Notably, menstruation stopped after falling from a height. Pituitary function tests revealed GH deficiency, hypogonadism, hypothyroidism and hypoadrenocorticism. MRI revealed loss of the pituitary stalk, whilst the hyperintense signal from distal axon of hypothalamus was still identified. Based on these findings, she was diagnosed as PSTS. Our case highlights endocrinological landscape of transection of the pituitary stalk by acute trauma.

Background: Malignant chest wall tumors need to be excised with wide resection to ensure tumor free margins, and the reconstruction method should be selected according to the depth and dimensions of the tumor. Vascularized tissue is needed to cover the superficial soft tissue defect or bone tissue defect. This study evaluated differences in complications according to reconstruction strategy., Methods: Forty-five patients with 52 operations for resection of malignant tumors in the chest wall were retrospectively reviewed. Patients were categorized as having superficial tumors, comprising Group A with simple closure for small soft tissue defects and Group B with flap coverage for wide soft tissue defects, or deep tumors, comprising Group C with full-thickness resection with or without mesh reconstruction and Group D with full-thickness resection covered by flap with or without polymethyl methacrylate. Complications were evaluated for the 52 operations based on reconstruction strategy then risk factors for surgical and respiratory complications were elucidated., Results: Total local recurrence-free survival rates in 45 patients who received first operation were 83.9% at 5 years and 70.6% at 10 years. The surgical complication rate was 11.5% (6/52), occurring only in cases with deep tumors, predominantly from Group D. Operations needing chest wall reconstruction (p = 0.0016) and flap transfer (p = 0.0112) were significantly associated with the incidence of complications. Operations involving complications showed significantly larger tumors, wider areas of bony chest wall resection and greater volumes of bleeding (p < 0.005). Flap transfer was the only significant predictor identified from multivariate analysis (OR: 10.8, 95%CI: 1.05-111; p = 0.0456). The respiratory complication rate was 13.5% (7/52), occurring with superficial and deep tumors, particularly Groups B and D. Flap transfer was significantly associated with the incidence of respiratory complications (p < 0.0005). Cases in the group with respiratory complications were older, more frequently had a history of smoking, had lower FEV1.0% and had a wider area of skin resected compared to cases in the group without respiratory complications (p < 0.05). Preoperative FEV1.0% was the only significant predictor identified from multivariate analysis (OR: 0.814, 95%CI: 0.693-0.957; p = 0.0126)., Conclusions: Surgical complications were more frequent in Group D and after operations involving flap transfer. Severe preoperative FEV1.0% was associated with respiratory complications even in cases of superficial tumors with flap transfer., (© 2024. The Author(s).)

The plasma protein α 1 -acid glycoprotein (AGP) primarily affects the pharmacokinetics of basic drugs. There are two AGP variants in humans, A and F1*S, exhibiting distinct drug-binding selectivity. Elucidation of the drug-binding selectivity of human AGP variants is essential for drug development and personalized drug therapy. Herein, we aimed to establish the contribution of amino acids 112 and 114 of human AGP to drug-binding selectively. Both amino acids are located in the drug-binding region and differ between the variants. Phe112/Ser114 of the A variant and its equivalent residues in the F1*S variant (Leu112/Phe114) were swapped with each other. Binding experiments were then conducted using the antiarrhythmic drug disopyramide, which selectively binds to the A variant. A significant decrease in the bound fraction was observed in each singly mutated A protein (Phe112Leu or Ser114Phe). Moreover, the bound fraction of the double A mutant (Phe112Leu/Ser114Phe) was decreased to that of wild-type F1*S. Intriguingly, the double F1*S mutant (Leu112Phe/Phe114Ser), in which residues were swapped with those of the A variant, showed only partial restoration in binding. The triple F1*S mutant (Leu112Phe/Phe114Ser/Asp115Tyr), where position 115 is thought to contribute to the difference in pocket size between variants, showed a further recovery in binding to 70% of that of wild-type A. These results were supported by thermodynamic analysis and acridine orange binding, which selectively binds the A variant. Together, these data indicate that, in addition to direct interaction with Phe112 and Ser114, the binding pocket size contributed by Tyr115 is important for the drug-binding selectivity of the A variant.

Background: Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan., Methods: A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients)., Results: The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis., Conclusions: The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Aims: This cohort study investigated the association between treatment cessation and incidence/progression of diabetic retinopathy (DR) in Japanese patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: Data were extracted from electronic medical records at the University of the Ryukyu Hospital and the Tomishiro Central Hospital of Okinawa, Japan. We enrolled 417 diabetic patients without DR ( N  = 281) and with nonproliferative DR ( N  = 136) at the baseline. Treatment cessation was defined as failing to attend outpatient clinics for at least twelve months prior to the baseline. After a median follow-up of 7 years, we compared the incidence/progression rate of DR including nonproliferative and proliferative DR between patients with and without treatment cessation and calculated the odds ratio (OR) in the treatment cessation group using a logistic regression model., Results: The overall prevalence of treatment cessation was 13% in patients with T2DM. Characteristics of treatment cessation included relative youth (57 ± 11 years vs. 63 ± 12 years, P  < 0.01). Treatment cessation was tightly associated with the incidence of DR (OR 4.20 [95% confidence interval [CI] 1.46-12.04, P  < 0.01) and also incidence/progression of DR (OR 2.70 [1.28-5.69], P  < 0.01), even after adjusting for age, sex, BMI, duration of T2DM, and HbA1c level., Conclusions: By considering major confounding factors, the present study demonstrates an independent association between treatment cessation and incidence of DR in patients with T2DM, highlighting treatment cessation as an independent risk for DR in T2DM., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00724-7., Competing Interests: Conflict of interestNone of the authors have any conflicts of interest to disclose., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound healing, the molecular mechanism and timing of action of the healing process are unknown. This study, using human epidermal-derived HaCaT cells and human normal epidermal keratinocyte cells, was performed to investigate the mechanism involved in the effect of magnesium on wound healing. The expression levels of epidermal differentiation-promoting factors were reduced by MgCl 2 , suggesting an inhibitory effect on epidermal differentiation in the remodeling stage of the late wound healing process. On the other hand, MgCl 2 treatment increased the expression of matrix metalloproteinase-7 (MMP7), a cell migration-promoting factor, and enhanced cell migration via the MEK/ERK pathway activation. The enhancement of cell migration by MgCl 2 was inhibited by MMP7 knockdown, suggesting that MgCl 2 enhances cell migration which is mediated by increased MMP7 expression. Our results revealed that MgCl 2 inhibits epidermal differentiation but promotes cell migration, suggesting that applying magnesium to the early wound healing process could be beneficial.

Objectives: The efficacy of endovascular aneurysm repair (EVAR) against abdominal aortic aneurysm (AAA) in younger patients remains unknown. Hence, the current study aimed to investigate whether the aneurysm-related mortality rate of EVAR is acceptable among patients aged ≤70 years. Methods: Among 644 patients, 148 underwent EVAR (EVAR group), and 496 received open surgical repair (OSR group). The cumulative incidence rates of aneurysm-related death, any intervention, and serious aneurysm-related events after AAA repair were evaluated using the cumulative incidence function in the presence of competing risks. Results: The EVAR group had higher prevalences of several comorbidities, and overall survival for the EVAR group was significantly inferior to that of the OSR group. The cumulative incidence rates of aneurysm-related death, any intervention, and serious aneurysm-related events at 5 years were 1.5%, 11.7%, and 6.4% in the EVAR group and 1.3%, 5.3%, and 5.9% in the OSR group, respectively. EVAR was not a significant prognostic factor of aneurysm-related mortality and serious aneurysm-related events. However, it was an independent poor prognostic factor of any intervention. Conclusion: EVAR was not a significant prognostic factor of aneurysm-related mortality and serious aneurysm-related events. Therefore, it demonstrated acceptable procedure-related long-term outcomes, at least in high-risk young patients., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

Nuclear factor κB (NF-κB) is activated by various inflammatory and infectious molecules and is involved in immune responses. It has been elucidated that ADP-β-D-manno-heptose (ADP-Hep), a metabolite in gram-negative bacteria, activates NF-κB through alpha-kinase 1 (ALPK1)-TIFA-TRAF6 signaling. ADP-Hep stimulates the kinase activity of ALPK1 for TIFA phosphorylation. Complex formation between phosphorylation-dependent TIFA oligomer and TRAF6 promotes the polyubiquitination of TRAF6 for NF-κB activation. TIFAB, a TIFA homolog lacking a phosphorylation site and a TRAF6 binding motif, is a negative regulator of TIFA-TRAF6 signaling and is implicated in myeloid diseases. TIFAB is indicated to regulate TIFA-TRAF6 signaling through interactions with TIFA and TRAF6; however, little is known about its biological function. We demonstrated that TIFAB forms a complex not with the TIFA dimer, an intrinsic form of TIFA involved in NF-κB activation, but with monomeric TIFA. The structural analysis of the TIFA/TIFAB complex and the biochemical and cell-based analyses showed that TIFAB forms a stable heterodimer with TIFA, inhibits TIFA dimer formation, and suppresses TIFA-TRAF6 signaling. The resultant TIFA/TIFAB complex is a "pseudo-TIFA dimer" lacking the phosphorylation site and TRAF6 binding motif in TIFAB and cannot form the orderly structure as proposed for the phosphorylated TIFA oligomer involved in NF-κB activation. This study elucidated the molecular and structural basis for the regulation of TIFA-TRAF6 signaling by TIFAB., Competing Interests: Competing interests statement:The authors declare no competing interest.

Introduction: Musculoskeletal transfer for chest wall tissue defects is a crucial method, and pedicled flaps around the chest wall are preferred in terms of location and simplicity of transfer. These require special care because of complications such as partial necrosis, fistula, wound dehiscence, infection, hematoma and restricted function of the arm or shoulder. However, studies of respiratory function are rare. In the present study, we investigated the complications including respiratory problems after wide resection for malignant chest wall tumors with musculoskeletal pedicle transfer., Methods: A total of 13 patients (15 operations) who underwent wide resection of primary, recurrent, or metastatic malignant chest wall tumors and musculoskeletal pedicle transfer for coverage of tissue defects were enrolled in the present study. A retrospective review of all patients was performed using data collected from hospital records and follow-up information. The complications of musculoskeletal transfer after chest wall wide resection, including respiratory problems, are evaluated., Results: Rib or sternal resection was performed in 12 operations, and only soft tissue resection was performed in 3 operations. Latissimus dorsi (LD) pedicle transfer was performed in 13 operations, and pectoralis major (PM) pedicle transfer was performed in 2 operations; basically, wounds were closed primarily. Surgical complications were observed following 5 of the 15 operations (33.3%). Respiratory complications were seen in 7 of the 15 operations (46.7%). Patients with respiratory complications showed significantly lower preoperative FEV1.0% values than those without respiratory complications ( p  = 0.0196). Skin resection area tended to be higher in the complication group than in the no complication group ( p  = 0.104)., Discussion: Pedicled myocutaneous flap transfers such as LD, PM, and rectus abdominus can be used following multiple resections. After harvesting LD or PM, the wound can be closed primarily for an 8-10-cm skin defect in patients with normal respiratory function. However, for patients with low FEV1.0%, after primary closure of LD or PM transfer for wide soft tissue defects, attention should be paid to postoperative respiratory complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Asanuma, Tsujii, Hagi, Nakamura, Uchiyama, Adachi, Nakata, Kataoka and Sudo.)

Introduction: In the context of double-valve surgery for elderly high-risk patients involving both the aortic and mitral valves, a clinically significant problem has been that no clear criteria or surgical strategies have been reported for the selection of mitral valve plasty (MVP) or mitral valve replacement (MVR) for mitral valve disease management during surgical aortic valve replacement (SAVR) to achieve better clinical outcomes. This study investigated valve durability and survival using our surgical strategy for mitral valve disease with concomitant SAVR in elderly patients., Methods: Eighty-six patients aged > 65 years (mean 75 years) who underwent a double-valve procedure for mitral valve surgery with concomitant SAVR from 2010 to 2022 were reviewed. Our surgical strategy for mitral valve disease with concomitant SAVR for the elderly patients was as follows: MVP was selected for patients in whom mitral valve disease was expected to be controlled with simple surgical procedures ( n  = 47), otherwise MVR was selected ( n  = 39)., Results: The hospital mortality rate was 8% ( n  = 7). The mean follow-up was 4.9 (0-12.3) years. And the 10-year survival rate was 62%. The 10-year freedom from aortic valve reoperation rate was 95%. No mitral valve reintervention was performed during follow-up. Echocardiographic follow-up demonstrated freedom from at least moderate mitral regurgitation in 86% of cases at 10 years., Conclusion: In double-valve surgery for elderly high-risk patients, appropriate selection of the mitral valve procedure with concomitant SAVR provided better early and long-term survival and valve durability. This surgical strategy may be beneficial in elderly patients with combined aortic and mitral valve disease., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest., (© Indian Association of Cardiovascular-Thoracic Surgeons 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background/aim: 5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of protoporphyrin IX (PpIX). Following light irradiation, the PpIX generates reactive oxygen species (ROS) in the presence of oxygen. Increased ROS levels can cause apoptotic cell death and necrosis of targeted cancer cells. This study examined whether photodynamic therapy using 5ALA (5-ALA PDT) could be used as a potential adjuvant therapy for bone and soft tissue sarcomas., Materials and Methods: The human osteosarcoma (143B), mouse osteosarcoma (LM8), human fibrosarcoma cell (HT1080) cell lines were used. In vitro, cultured cells were exposed to 5-ALA at various concentrations followed by strobe scope light irradiation for 10 min as 5-ALA PDT. Cell viability was then measured. In vivo, each tumor cell line was inoculated subcutaneously into the backs of mice. In the 5-ALA PDT group, 5-ALA (250 mg/kg) was administered intraperitoneally followed by light irradiation. Change in tumor volume by 5-ALA PDT were primarily evaluated., Results: In vitro, treatment of sarcoma cells with 100 and 200 μg/ml 5-ALA PDT significantly inhibited cell proliferation at 24 and 48 h compared with the group treated with 0 and 10 μg/ml 5-ALA PDT. In vivo, in all cell lines, a significant inhibition of the tumor volume was observed in the 5-ALA-PDT group as compared to that in control, strobe scope light, and 5-ALA groups., Conclusion: 5-ALA PDT effectively inhibited proliferation of bone and soft tissue sarcoma cell lines. Further in vivo research using other subtypes of bone and soft tissue sarcoma is warranted to confirm the applicability in the clinical setting., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: Long-term outcomes of gastric subepithelial lesions have not been elucidated. To reveal the natural history, we initiated a prospective, 10-year follow-up of patients with small (≤20 mm) gastric subepithelial lesions in September 2014. Here, we report the results of an interim analysis of a prospective observational study., Methods: In total, 567 patients with 610 lesions were prospectively registered between September 2014 and August 2016. The location, size, morphology, and number of subepithelial lesions were recorded on a web-based case report form. This study has been conducted as an Academic Committee Working Group of the Japan Gastroenterological Endoscopy Society., Results: The endoscopic follow-up period was 4.60 ± 1.73 years (mean ± standard deviation), and survival data were investigated for 5.28 ± 1.68 years. This interim analysis revealed that the estimated cumulative incidence of a size increase ≥5 mm, after accounting for patients' death and resection of the tumor as competing risk events, was 4.5% at 5 years. In addition, the estimated cumulative incidence of lesion size increase ≥5 mm or resection of lesions was 7.9% at 5 years, and that of size increase ≥10 mm or resection of lesions was 4.5% at 5 years., Conclusion: These results indicate that approximately one in 13 patients with small (≤20 mm) gastric subepithelial lesions may require resection or further investigation for increased tumor size (≥5 mm) within 5 years., (© 2023 Japan Gastroenterological Endoscopy Society.)

In the past few decades, especially since the outbreak of the coronavirus disease (COVID-19), the effects of atmospheric bioaerosols on human health, the environment, and climate have received great attention. To evaluate the impacts of bioaerosols quantitatively, it is crucial to determine the types of bioaerosols in the atmosphere and their spatial-temporal distribution. We provide a concise summary of the online and offline observation strategies employed by the global research community to sample and analyze atmospheric bioaerosols. In addition, the quantitative distribution of bioaerosols is described by considering the atmospheric bioaerosols concentrations at various time scales (daily and seasonal changes, for example), under various weather, and different underlying surfaces. Finally, a comprehensive summary of the reasons for the spatiotemporal distribution of bioaerosols is discussed, including differences in emission sources, the impact process of meteorological factors and environmental factors. This review of information on the latest research progress contributes to the emergence of further observation strategies that determine the quantitative dynamics of public health and ecological effects of bioaerosols., 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 © 2023 Elsevier B.V. All rights reserved.)

The fruit of Forsythia suspensa (Thunb.) Vahl has been used in traditional Chinese medicine as " Forsythiae fructus ". The species is also grown in parks and gardens, and on streets and building lots, as an ornamental plant, but it requires pruning. In this study, the allelopathic activity and allelopathic substances in the leaves of pruned branches of F. suspensa were investigated to determine any potential application. The leaf extracts of F. suspensa showed growth inhibitory activity against three weed species; Echinochloa crus-galli , Lolium multiflorum, and Vulpia myuros. Two allelopathic substances in the extracts were isolated through the bioassay-guided purification process, and identified as (-)-matairesinol and (-)-arctigenin. (-)-Matairesinol and (-)-arctigenin, which showed significant growth inhibitory activity at concentrations greater than 0.3 mM in vitro. The inhibitory activity of (-)-arctigenin was greater than that of (-)-matairesinol. However, both compounds were more active than (+)-pinolesinol which is their precursor in the biosynthetic pathway. The investigation suggests that F. suspensa leaves are allelopathic, and (-)-matairesinol and (-)-arctigenin may contribute to the growth inhibitory activities. Therefore, the leaves of the pruned branches can be applied as a weed management strategy in some agricultural practices such as using the leaf extracts in a foliar spray and the leaves in a soil mixture, thereby reducing the dependency on synthetic herbicides in the crop cultivation and contributing to developing eco-friendly agriculture.

Aegle marmelos (L.) Correa is an economically and therapeutically valuable tree. It is cultivated as a fruit plant in southeast Asian countries. In this research, we investigated the allelopathy and possible allelochemicals in the leaves of A. marmelos . Aqueous methanol extracts of A. marmelos exhibited significant inhibitory effects against the growth of Lepidium sativum , Lactuca sativa , Medicago sativa , Echinochloa crusgalli , Lolium multiflorum , and Phleum pratense . Bioassay-directed chromatographic purification of the A. marmelos extracts resulted in identifying five active compounds: umbelliferone ( 1 ), trans -ferulic acid ( 2 ), ( E )-4-hydroxycinnamic acid methyl ester ( 3 ), trans -cinnamic acid ( 4 ), and methyl ( E )-3'-hydroxyl-4'-methoxycinnamate ( 5 ). The hypocotyl and root growth of L. sativum were considerably suppressed by these compounds. Methyl ( E )-3'-hydroxyl-4'-methoxycinnamate also suppressed the coleoptile and root growth of E. crusgalli . The concentrations of these compounds, causing 50% growth reduction ( I 50 ) of L. sativum , were in the range of 74.19-785.4 μM. The findings suggest that these isolated compounds might function in the allelopathy of A. marmelos .

This study analyzed 31 patients with symptomatic osteoarthritic knees scheduled to undergo knee arthroplasty or high tibial osteotomy and demonstrated shape variations in their proximal tibia using an average three-dimensional (3D) bone model. Preoperative computed tomography of the affected knees was reconstructed as 3D bone models using a triangle mesh of surface layers. The initial case was defined as the template, and the other models were reconstructed into homologous models with the same number of mesh vertices as that in the template. The corresponding mesh vertices of the other models were averaged to evaluate the spatial position on the particular mesh vertex of the template. This was applied to all the mesh vertices of the template to generate the average 3D model. To quantify the variation in surface geometry, average minimum distance from the average bone model to 31 models was recorded. The medial proximal tibial cortex (1.63 mm) revealed lesser variation compared to the tibial tuberosity (2.50 mm) and lateral cortex (2.38 mm), (p = 0.004 and p = 0.020, respectively). The medial tibial plateau (1.46 mm) revealed larger variation compared to the lateral tibial plateau (1.16 mm) (p = 0.044). Understanding 3D geometry could help in development of implants for arthroplasty and knee osteotomy., (© 2024. The Author(s).)

Six aromatic secondary metabolites, pestalone (1), emodin (2), phomopsilactone (3), pestalachlorides B (4), C (5), and D (6), were isolated from Pestalotiopsis sp. FKR-0115, a filamentous fungus collected from white moulds growing on dead branches in Minami Daito Island. The efficacy of these secondary metabolites against methicillin-resistant Staphylococcus aureus (MRSA) with and without meropenem (β-lactam antibiotic) was evaluated using the paper disc method and broth microdilution method. The chemical structures of the isolated compounds (1-6) were characterised using spectroscopic methods, including nuclear magnetic resonance and mass spectrometry. All six isolated compounds exhibited synergistic activity with meropenem against MRSA. Among the six secondary metabolites, pestalone (1) overcame bacterial resistance in MRSA to the greatest extent.

Background: The single-radius design is one of the major total knee arthroplasty (TKA) designs and widely used all over the world. The objective of this study was to compare in vivo kinematics between the anteroposterior (AP) single-radius design with mediolateral (ML) single-radius (Non Restricted Geometry; NRG) and ML dual-radius (Triathlon) during stair activities., Methods: A total of 21 knees in 18 patients (NRG group: 10 knees in 7 patients, Triathlon group: 11 knees in 11 patients) with a clinically successful posterior stabilized TKA were examined. Under fluoroscopic surveillance, each patient performed stair ascending and descending motions. In vivo kinematics were analyzed using 2D/3D registration technique. The knee flexion angle, rotation angle, varus-valgus angle, AP translation of the femorotibial contact point for both the medial and lateral sides of the knee, and post-cam engagement were evaluated., Results: There were no significant differences between the two groups in rotation angle and AP translation at each flexion angle. Examining the varus-valgus angle, the NRG group showed varus position at an early flexion angle during both stair activities.Post-cam engagement was observed in both groups during both stair activities. The mean flexion angle of engagement in the NRG group, the post of which was located anterior to the Triathlon, was larger than that in the Triathlon group during both stair activities., Conclusion: Despite the same AP single-radius TKA, ML single-radius might affect varus motion at an early flexion angle., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Non-curative endoscopic resection of T1 colorectal cancer (CRC) carries a substantial risk of recurrence. However, previous studies have reported a significant proportion of cases in which the deep margin of endoscopic resection was positive for cancer due to the technical difficulties of colorectal endoscopic submucosal dissection (ESD). With the advancement of endoscopic technology and techniques resulting in the reduction of positive resection margins, it is important to reassess the long-term prognosis and major risk factors for recurrence in cases of negative deep margins., Methods: We conducted a retrospective cohort study of consecutive patients with T1 CRC who underwent endoscopic resection between January 2006 and December 2021 with negative deep margins. The histological findings of the resected specimens were analyzed to determine the risk factors associated with the primary outcomes of this study, including recurrence and cancer-related deaths., Results: The median age of the 190 patients was 70 years, of which 63% were male, and endoscopic treatment was performed in 64% by endoscopic mucosal resection and 36% by ESD. Eighty-two patients were in the curative resection (CR) group and 108 were in the non-curative resection (NCR) group, wherein the latter comprised 79 patients who underwent additional surgery (AS) and 29 patients who did not receive AS. Five-year recurrence-free survival rates were 98.4% (95% CI: 89.3-99.8) for CR, 98.3% (95% CI: 88.8-99.8) for NCR with AS, and 73.7% (95% CI: 46.5-88.5) for NCR without AS. Lymphatic invasion and budding grade 2/3 were the major risk factors for recurrence, with hazard ratios of 40.7 (p &lt; 0.001) and 23.1 (p = 0.007), respectively. Of the patients in the NCR group without AS, the 5-year recurrence-free rate was 85.6% (95% CI: 52.5-96.3) if there were no major risk factors (i.e., no lymphatic invasion or budding grade 2/3) (n = 21), whereas the prognosis was poor in the presence of one or more of the major risk factors, with a median recurrence-free survival and disease-specific survival of 2.5 and 3.1 years, respectively (n = 8)., Discussion: In endoscopically resected T1 CRC with negative deep margins, lymphatic invasion or budding grade 2/3 may indicate a higher risk of recurrence when followed up without AS., (© 2024 S. Karger AG, Basel.)

Three-dimensional preoperative surgical simulation of the medial open-wedge high tibial osteotomy (OWHTO), simplified as the rigid rotation around the hinge axis, has been performed to predict postoperative realignment. However, the practicality of this highly simplified simulation method has not been verified. This study aimed to investigate the validity of realignment simulation simplified as a rotation around a hinge axis compared with a postoperative CT model. A three-dimensional surface model of the tibia and femur was created from preoperative computed tomography (CT) images (preoperative model) of three patients. The simulation of medial OWHTO created sixty computer simulation models in each patient simplified as the rigid rotation of the proximal part of the tibia relative to the distal part from 1° to 20° around three types of hinge axes. The simulation models were compared with the actual postoperative model created from postoperative CT images to assess the reality of the simulation model. The average surface distance between the two models was calculated as an index representing the similarity of the simulation model to the postoperative model. The minimum value of average surface distances between the simulation and postoperative CT models was almost 1 mm in each patient. The rotation angles at which the minimum value of average surface distances was represented were almost identical to the actual correction angles. We found that the posterior tibial tilt and the axial rotation of the proximal tibia of the simulation model well represented those of the postoperative CT model, as well as the valgus correction. Therefore, the realignment simulation of medial OWHTO can generate realistic candidates for postoperative realignment that includes the actual postoperative realignment, suggesting the efficacy of the preoperative simulation method., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Konda, Ishibashi, Tamaki and Tomita.)

The filamentous fungus Synnemellisia sp. strain FKR-0921 was obtained from soil collected on Kume Island, Okinawa. The MeOH extract of FKR-0921 cultured on a solid rice medium yielded a new aromatic compound, synnemellisitriol A (1). The structure, including the absolute configuration, was elucidated by spectroscopic analysis (FT-IR, NMR, and HR-ESI-MS), and the absolute configuration at C-9 of 1 was determined using the modified Mosher's method. Additionally, 1 was evaluated for its biological activities, including metallo-β-lactamase inhibitory activity, type III secretion system inhibitory activity, antimicrobial activity, antimalarial activity, and cytotoxicity., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Objective: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms., Methods: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 10 6 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (-) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery., Results: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors., Conclusion: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation., Competing Interests: Declaration of Competing Interest No conflicts of interest were declared., (Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objectives: The concept of locomotive syndrome (LS) and its evaluation method, the LS risk test, have been applied in an integrated manner to capture the decline in mobility resulting from musculoskeletal disorders. The purpose of this study was to evaluate the impact of total knee arthroplasty (TKA) in the elderly with knee osteoarthritis, a common disorder found in LS., Methods: A total of 111 patients were registered prior to TKA and postoperatively followed up for 1 year. Three components of the LS risk test (the two-step test, stand-up test, and Geriatric Locomotive Function Scale-25) were assessed pre- and postoperatively., Results: After surgery, all three components of the test showed significant improvements from the baseline. The ratio of Stage 3 LS patients (progressed stage of decrease in mobility) reduced from 82.3% to 33.9% postoperatively. There was no significant difference in the degree of change in the scores between the younger (60-74 years) and older (≥75 years) age groups., Conclusions: We found that TKA has a major impact in preventing the progression of LS in patients with knee osteoarthritis. The LS risk test is a feasible tool for the longitudinal evaluation of patients with musculoskeletal diseases of varying severity and with multiple symptoms., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Background: Tumor-devitalized autografts treated with deep freezing, pasteurization, and irradiation are biological reconstruction methods after tumor excision for aggressive or malignant bone or soft tissue tumors that involve a major long bone. Tumor-devitalized autografts do not require a bone bank, they carry no risk of viral or bacterial disease transmission, they are associated with a smaller immunologic response, and they have a better shape and size match to the site in which they are implanted. However, they are associated with disadvantages as well; it is not possible to assess margins and tumor necrosis, the devitalized bone is not normal and has limited healing potential, and the biomechanical strength is decreased owing to processing and tumor-related bone loss. Because this technique is not used in many countries, there are few reports on the results of this procedure such as complications, graft survival, and limb function., Questions/purposes: (1) What was the rate of complications such as fracture, nonunion, infection, or recurrence in a tumor-devitalized autograft treated with deep freezing, pasteurization, and irradiation, and what factors were associated with the complication? (2) What were the 5-year and 10-year grafted bone survival (free from graft bone removal) of the three methods used to devitalize a tumor-containing autograft, and what factors were associated with grafted bone survival? (3) What was the proportion of patients with union of the tumor-devitalized autograft and what factors were associated with union of the graft-host bone junction? (4) What was the limb function after the tumor-devitalized autograft, and what factors were related to favorable limb function?, Methods: This was a retrospective, multicenter, observational study that included data from 26 tertiary sarcoma centers affiliated with the Japanese Musculoskeletal Oncology Group. From January 1993 to December 2018, 494 patients with benign or malignant tumors of the long bones were treated with tumor-devitalized autografts (using deep freezing, pasteurization, or irradiation techniques). Patients who were treated with intercalary or composite (an osteoarticular autograft with a total joint arthroplasty) tumor-devitalized autografts and followed for at least 2 years were considered eligible for inclusion. Accordingly, 7% (37 of 494) of the patients were excluded because they died within 2 years; in 19% (96), an osteoarticular graft was used, and another 10% (51) were lost to follow-up or had incomplete datasets. We did not collect information on those who died or were lost to follow-up. Considering this, 63% of the patients (310 of 494) were included in the analysis. The median follow-up was 92 months (range 24 to 348 months), the median age was 27 years (range 4 to 84), and 48% (148 of 310) were female; freezing was performed for 47% (147) of patients, pasteurization for 29% (89), and irradiation for 24% (74). The primary endpoints of this study were the cumulative incidence rate of complications and the cumulative survival of grafted bone, assessed by the Kaplan-Meier method. We used the classification of complications and graft failures proposed by the International Society of Limb Salvage. Factors relating to complications and grafted autograft removal were analyzed. The secondary endpoints were the proportion of bony union and better limb function, evaluated by the Musculoskeletal Tumor Society score. Factors relating to bony union and limb function were also analyzed. Data were investigated in each center by a record review and transferred to Kanazawa University., Results: The cumulative incidence rate of any complication was 42% at 5 years and 51% at 10 years. The most frequent complications were nonunion in 36 patients and infection in 34 patients. Long resection (≥ 15 cm) was associated with an increased risk of any complication based on the multivariate analyses (RR 1.8 [95% CI 1.3 to 2.5]; p < 0.01). There was no difference in the rate of complications among the three devitalizing methods. The cumulative graft survival rates were 87% at 5 years and 81% at 10 years. After controlling for potential confounding variables including sex, resection length, reconstruction type, procedure type, and chemotherapy, we found that long resection (≥ 15 cm) and composite reconstruction were associated with an increased risk of grafted autograft removal (RR 2.5 [95% CI 1.4 to 4.5]; p < 0.01 and RR 2.3 [95% CI 1.3 to 4.1]; p < 0.01). The pedicle freezing procedure showed better graft survival than the extracorporeal devitalizing procedures (94% versus 85% in 5 years; RR 3.1 [95% CI 1.1 to 9.0]; p = 0.03). No difference was observed in graft survival among the three devitalizing methods. Further, 78% (156 of 200 patients) of patients in the intercalary group and 87% (39 of 45 patients) of those in the composite group achieved primary union within 2 years. Male sex and the use of nonvascularized grafts were associated with an increased risk of nonunion (RR 2.8 [95% CI 1.3 to 6.1]; p < 0.01 and 0.28 [95% CI 0.1 to 1.0]; p = 0.04, respectively) in the intercalary group after controlling for confounding variables, including sex, site, chemotherapy, resection length, graft type, operation time, and fixation type. The median Musculoskeletal Tumor Society score was 83% (range 12% to 100%). After controlling for confounding variables including age, site, resection length, event occurrence, and graft removal, age younger than 40 years (RR 2.0 [95% CI 1.1 to 3.7]; p = 0.03), tibia (RR 6.9 [95% CI 2.7 to 17.5]; p < 0.01), femur (RR 4.8 [95% CI 1.9 to 11.7]; p < 0.01), no event (RR 2.2 [95% CI 1.1 to 4.5]; p = 0.03), and no graft removal (RR 2.9 [95% CI 1.2 to 7.3]; p = 0.03) were associated with an increased limb function. The composite graft was associated with decreased limb function (RR 0.4 [95% CI 0.2 to 0.7]; p < 0.01)., Conclusion: This multicenter study revealed that frozen, irradiated, and pasteurized tumor-bearing autografts had similar rates of complications and graft survival and all resulted in similar limb function. The recurrence rate was 10%; however, no tumor recurred with the devitalized autograft. The pedicle freezing procedure reduces the osteotomy site, which may contribute to better graft survival. Furthermore, tumor-devitalized autografts had reasonable survival and favorable limb function, which are comparable to findings reported for bone allografts. Overall, tumor-devitalized autografts are a useful option for biological reconstruction and are suitable for osteoblastic tumors or osteolytic tumors without severe loss of mechanical bone strength. Tumor-devitalized autografts could be considered when obtaining allografts is difficult and when a patient is unwilling to have a tumor prosthesis and allograft for various reasons such as cost or socioreligious reasons., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)