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Recent studies have indicated that the activation of bitter taste receptors (T2R) expressed in gastrointestinal secretory cells has a regulatory effect on the secretion of gastrointestinal hormones. Polyphenols are known to be ingested at a daily intake of 5 g or more and commonly have a bitter taste. Consequently, the interaction between the bitter taste receptor T2R46 and 490 polyphenols was investigated using in silico simulation techniques. It was demonstrated that W88 3.32 and E265 7.39 play a pivotal role in the recognition of polyphenols and known ligands by T2R46, with frequent interactions observed, particularly with flavonoids. The results of the quantitative structure-activity relationship (QSAR) analysis demonstrated a high degree of correlation (R 2  = 0.9359) between polyphenols and T2R46 in a model that incorporated molecular interaction field regions and branching scales. Furthermore, known ligands were also found to fit this model (R 2  = 0.9155). These findings suggest that polyphenols may act as T2R46 ligands., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier B.V.)

Background: This single center prospective observational study was conducted to evaluate the acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery., Methods: This study recruited patients who were scheduled for moderately hypo-fractionated radiotherapy including supraclavicular lymph node area (Cohort M) or ultra-hypo-fractionated radiotherapy for the conserved breast (Cohort U) as postoperative treatment for breast cancer. Radiotherapy plans were generated using automated planning system. Irradiation of 42.5 Gy/16 fractions (Cohort M) or 26 Gy/5 fractions (Cohort U) was delivered, and boost irradiation of 10 Gy/5 fractions was added as needed. The primary endpoint was the proportion of grade ≥ 2 acute adverse events within 90 days. The toxicities were evaluated using CTCAE ver 5.0., Results: Between January 2023 and December 2023, 123 patients (81 in Cohort M and 42 in Cohort U) were enrolled. All the included patients were Japanese and completed their planned radiotherapy and were also able to be evaluated for acute adverse events. Grade 1/2/3-5 acute adverse events were observed in 67/12/0 for Cohort M and 31/4/0 for Cohort U. The proportion of grade ≥ 2 acute adverse events within 90 days was 15% (95% confidence interval 8-24%) for Cohort M and 10% (95% confidence interval 3-23%) for Cohort U., Conclusions: The proportion of acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery was shown to be acceptable in this study., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

A halogen-substituted cyclic disilene compound, bromocyclotrisilene, Si 3 Br(Eind) 3 ( 3a ), bearing fused-ring bulky Eind ( a : R 1 = R 2 = Et) groups, has been synthesized as an extraordinarily air-stable compound by the reduction of 1,2-dibromodisilene, (Eind)BrSi═SiBr(Eind) ( 2a ), or tribromosilane, (Eind)SiBr 3 ( 1a ), with the Mg or Li metal. The X-ray diffraction analysis of 3a showed that the disilene moiety has an almost planar, but slightly trans -bent structure. Even though 3a is quite air-stable both in solutions and in the solid state, its Si-Br bond is reactive under reducing conditions. The further treatment of 3a with the Li metal leads to the formation of room-temperature thermally stable silicon homologues of the cyclopropyl radical, i.e., the cyclotrisilanyl radicals ( 6a ) [ 6a ( syn ) and 6a ( anti )], via intramolecular C-H bond activation in a transient silicon homologue of the cyclopropenyl radical, i.e., the cyclotrisilenyl radical, [Si 3 (Eind) 3 ] • ( 5a ). The formation mechanism of 6a from 5a is discussed based on the theoretical calculations. The unique structural and electronic properties of these Si 3 three-membered ring species incorporating the Eind groups have been experimentally and theoretically investigated.

Fructose occurs in foods and as a metabolite in vivo. It can be degraded, leading to the formation of reactive carbonyl compounds, which may influence food properties and have an impact on health. The present study performed an in-depth qualitative and quantitative profiling of fructose degradation products. Thus, the α-dicarbonyl compounds 3-deoxyglucosone, glucosone, methylglyoxal, glyoxal, hydroxypyruvaldehyde, threosone, 3-deoxythreosone, and 1-desoxypentosone and the monocarbonyl compounds formaldehyde, acetaldehyde, glycolaldehyde, glyceraldehyde, and dihydroxyacetone were detected in fructose solutions incubated at 37 °C. Quantitative profiling after 7 days revealed 4.6-271.6-fold higher yields of all degradation products from fructose compared to glucose. Except for 3-deoxyglucosone, the product formation appeared to be metal dependent, indicating oxidative pathways. CaCl 2 and MgCl 2 partially reduced fructose degradation. Due to its high reactivity compared to glucose, particularly toward metal-catalyzed pathways, fructose may be a strong contributor to sugar degradation and Maillard reaction in foods and in vivo.

Introduction: Despite advancements in managing autoimmune rheumatic diseases (ARDs) with existing treatments, many patients still encounter challenges such as inadequate responses, difficulty in maintaining remission, and side effects. Chimeric Antigen Receptor (CAR) T-cell therapy, originally developed for cancer, has now emerged as a promising option for cases of refractory ARDs., Methods: A search of the literature was conducted to compose a narrative review exploring the current evidence, potential safety, limitations, potential modifications, and future directions of CAR-T cells in ARDs., Results: CAR-T cell therapy has been administered to patients with refractory ARDs, including systemic lupus erythematosus, antisynthetase syndrome, and systemic sclerosis, demonstrating significant improvement. Notable responses include enhanced clinical symptoms, reduced serum autoantibody titers, and sustained remissions in disease activity. Preclinical and in vitro studies using both animal and human samples also support the efficacy and elaborate on potential mechanisms of CAR-T cells against antineutrophil cytoplasmic antibody-associated vasculitis and rheumatoid arthritis. While cautious monitoring of adverse events, such as cytokine release syndrome, is crucial, the therapy appears to be highly tolerable. Nevertheless, challenges persist, including cost, durability due to potential CAR-T cell exhaustion, and manufacturing complexities, urging the development of innovative solutions to further enhance CAR-T cell therapy accessibility in ARDs., Conclusions: CAR-T cell therapy for refractory ARDs has demonstrated high effectiveness. While no significant warning signs are currently reported, achieving a balance between therapeutic efficacy and safety is vital in adapting CAR-T cell therapy for ARDs. Moreover, there is significant potential for technological advancements to enhance the delivery of this treatment to patients, thereby ensuring safer and more effective disease control for patients., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to examine the potential benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and diabetes mellitus (DM) using a real-world database., Methods: We analyzed individuals with MAFLD and DM newly initiated on SGLT2 or dipeptidyl peptidase 4 (DPP4) inhibitors from a large-scale administrative claims database. The primary outcome was the change in the fatty liver index (FLI) assessed using a linear mixed-effects model from the initiation of SGLT2 or DPP4 inhibitors. A propensity score-matching algorithm was used to compare the change in FLI among SGLT2 and DPP4 inhibitors., Results: After propensity score matching, 6547 well-balanced pairs of SGLT2 and 6547 DPP4 inhibitor users were created. SGLT2 inhibitor use was associated with a greater decline in FLI than DPP4 inhibitor use (difference at 1-year measurement, - 3.8 [95% CI - 4.7 to - 3.0]). The advantage of SGLT2 inhibitor use over DPP4 inhibitor use for improvement in FLI was consistent across subgroups. The relationship between SGLT2 inhibitors and amelioration of FLI was comparable between individual SGLT2 inhibitors., Conclusions: Our analysis using large-scale real-world data demonstrated the potential advantage of SGLT2 inhibitors over DPP4 inhibitors in patients with MAFLD and DM., (© 2023. The Author(s).)

The understanding of the role of LXR in the regulation of macrophages during inflammation is emerging. Here, we show that LXR agonist T09 specifically increases 15-LOX abundance in primary human M2 macrophages. In time- and dose-dependent incubations with T09, an increase of 3-fold for ALOX15 and up to 15-fold for 15-LOX-derived oxylipins was observed. In addition, LXR activation has no or moderate effects on the abundance of macrophage marker proteins such as TLR2, TLR4, PPARγ, and IL-1RII, as well as surface markers (CD14, CD86, and CD163). Stimulation of M2-like macrophages with FXR and RXR agonists leads to moderate ALOX15 induction, probably due to side activity on LXR. Finally, desmosterol, 24( S ),25-Ep cholesterol and 22( R )-OH cholesterol were identified as potent endogenous LXR ligands leading to an ALOX15 induction. LXR-mediated ALOX15 regulation is a new link between the two lipid mediator classes sterols, and oxylipins, possibly being an important tool in inflammatory regulation through anti-inflammatory oxylipins.

A neutral silylyne complex with a Cr≡Si triple bond was prepared by dehydrogenation of a chromium silylene complex with Cr-H and Si-H bonds, and was isolated as monomeric crystals, unlike dimeric forms of its tungsten and molybdenum congeners. The strong Cr(δ-)-Si(δ+) bond polarity was revealed by the reaction with MeOH and DFT calculations. The chromium silylyne complex reacted with H 2 under LED (365 nm) irradiation to reproduce the precursor silylene complex with a (H)Cr=Si(H) moiety, as a result of 1,2-H-H addition across the Cr≡Si triple bond. Similarly, the chromium silylyne complex reacted with benzene under irradiation to afford an 1,2-addition product with a (H)Cr=Si(Ph) moiety, via benzene C-H bond activation accompanied by Si-C bond forming., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Sarcopenia is a prognostic factor for patients with colorectal cancer and is commonly seen in elderly patients. The purpose of the present study was to demonstrate the impact of preoperative sarcopenia on the short- and long-term outcomes of curative surgery for treating colorectal cancer in elderly patients. Between 2016 and 2020, patients aged ≥80 years with colorectal cancer were investigated. The total muscle cross-sectional area was calculated using computed tomography imaging at the mid-3rd lumbar vertebra. Elder sarcopenia was identified using sex-specific cut-offs. Out of 106 elderly colorectal cancer patients, 27 patients were diagnosed with elder sarcopenia. Patients with elder sarcopenia had a reduced body mass index (19.7±2.5 vs. 22.5±2.9 kg/m 2 ; P<0.01), an advanced pN stage (P<0.01) and an advanced stage (stage 3) (P=0.029). Elder sarcopenia had a negative impact on relapse-free survival (3-year, 78.4 vs. 91.1%; P=0.049) and overall survival (3-year, 73.0 vs. 93.9%; P=0.022). Propensity score-matched analysis was performed, matching 27 patients in each group to remove selection bias, which demonstrated elder sarcopenia had a negative impact on overall survival (3-year, 73.0 vs. 100%; P<0.01). Overall, elder sarcopenia was prevalent in 25% of elderly patients with colorectal cancer that received curative surgery, and it was a poor prognostic indicator in this patient population., Competing Interests: All authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

The AirSeal system (CONMED, NY, USA) can outstandingly keep pneumoperitoneum stable. However, water droplets form on the access port, impairing the performance of comfortable surgical procedures because of the resultant wet surgical field. This study was performed to clarify the mechanism of water droplet formation and to prevent it. Condensation was observed on the AirSeal system. A heater was wrapped around the tri-lumen tube, and the heating effect was assessed. The simulator experiments revealed that condensation formed in the tri-lumen tube and on the wall of the access port. The accumulated weight of the condensation on the wall of the access port was 41.6 g in the Heated group, 138.2 g in the Control group, and 479.4 g in the Cooled group. In the clinical assessment, the accumulated volume of the condensation attached to the inside wall was significantly smaller in the Heated group than in the Unheated group (111.7 g vs. 332.9 g, respectively). We clarified that the volume of condensation attached to the wall of the access port depended on the temperature of the tri-lumen tube. The clinical study revealed that the condensation on the access port was reduced by heating the tri-lumen tube. The development of a novel heating device for the insufflation tube would be effective and useful., (© 2024. The Author(s).)

Background: The Japanese Society for Pharmaceutical Palliative Care and Sciences specializes in pharmacology in the field of palliative medicine. More than 700 board-certified pharmacists in palliative pharmacy (BCPPP) are actively involved in palliative pharmacotherapy at various hospitals and pharmacies. The purpose of this study was to determine the economic effect of pharmaceutical interventions by BCPPPs., Methods: This multicenter retrospective study included 27 medical centers and analyzed the medical economic effect of interventions by BCPPPs (17 pharmacists) and non-BCPPPs (24 pharmacists) on patients using medical narcotics for cancer pain in September 2021., Results: The percentage of patients who received a pharmaceutical intervention and whose drug costs were reduced by pharmacist intervention was significantly higher in the BCPPP group than in the non-BCPPP group. Although there was no significant difference between the two groups in drug cost reduction per patient per month (BCPPP group: $0.89 [-$64.91 to $106.76] vs. non-BCPPP group $0.00 [-$1,828.95 to $25.82]; P = 0.730), the medical economic benefit of pharmacist intervention in avoiding or reducing adverse drug reactions was higher in the BCPPP group ($103.18 [$0.00 to $628.03]) than in the non-BCPPP group ($0.00 [$0.00 to $628.03]) (P = 0.070). The total medical economic benefit-the sum of these-was significantly higher in the BCPPP group ($88.82 [-$14.62 to $705.37]) than in the non-BCPPP group ($0.66 [-$1,200.93 to $269.61]) (P = 0.006)., Conclusion: Pharmacological intervention for patients with cancer using medical narcotics may have a greater medical economic benefit when managed by BCPPPs than by non-certified pharmacists in Japan.

Background: It has been reported that early detection and treatment of cancer therapy- related cardiac dysfunction (CTRCD) improves its prognosis. The detailed relationships between electrocardiographic repolarization indices and decreased left ventricular function in CTRCD have not been elucidated. We closely assessed such relationships in patients with doxorubicin (DOX)-induced CTRCD., Methods: This retrospective, single-center, cohort study included 471 consecutive patients with malignant lymphoma who received chemotherapy including DOX. Of them, 17 patients with CTRCD and 68 patients without CTRCD who underwent 12‑lead electrocardiogram and an echocardiogram before and after chemotherapy were eventually analyzed. The fluctuations of the following electrocardiographic repolarization indices were evaluated in lead V5: QT, JT, T peak to T end interval (Tp-e), and activation recovery interval (ARI). These indices were corrected by heart rate with the Fridericia formula., Results: The median period from the end of chemotherapy to the diagnosis of the CTRCD group was 346 days (IQR 170-1283 days). After chemotherapy, the QT interval was significantly prolonged in both with and without CTRCD groups compared with that before chemotherapy (pre QTc vs. post QTc in CTRCD group, 386 ± 27 ms vs. 411 ± 37 ms, p = 0.03, pre QTc vs. post QTc in non-CTRCD group, 388 ± 24 ms vs. 395 ± 25 ms, p = 0.04, respectively). ARIc after chemotherapy was characteristically observed only in the CTRCD group (pre ARIc vs. post ARIc in CTRCD group, 258 ± 53 ms vs. 211 ± 28 ms, p = 0.03, pre ARIc vs. post ARIc in non-CTRCD group, 221 ± 19 ms vs. 225 ± 23 ms, NS, respectively) and had negative correlations with left ventricular ejection fraction (r = -0.56, p < 0.001). Using the receiver-operating characteristic curve, the relationship between ARIc and CTRCD morbidity was examined. The optimal cut-off point of ARIc prolongation between before and after chemotherapy was 18 ms (sensitivity 75 %, specificity 79 %, area under the curve 0.76)., Conclusions: ARIc prolongation may be useful in the early detection of developing late-onset chronic DOX-induced CTRCD and lead to early treatment for cardiac protection., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context: There have been insufficient data on the threshold of body mass index (BMI) for developing diabetes mellitus (DM) and the relationship between change in BMI and the subsequent risk of DM., Objective: We sought to clarify the association of BMI and its change with incident DM., Methods: We conducted a retrospective observational cohort study using the JMDC Claims Database between 2005 and 2021. We included 3 400 303 individuals without a prior history of DM or usage of glucose-lowering medications. The median age was 44 years, and 57.5% were men. We categorized the study participants into 4 groups: underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obese (BMI ≥ 30 kg/m2). According to the change in BMI from the initial health check-up to the health check-up 1 year after that, we divided the study participants into 3 groups: ≤-5.0%, -5.0% to +5.0%, and ≥+5.0%., Results: The risk of developing DM increased steeply after BMI exceeded approximately 20 to 21 kg/m2. Compared with participants with stable BMI (-5.0% to +5.0%), the relative risk for DM among those whose BMI had increased by 5.0% or more was 1.33 (95% CI 1.31-1.36). In contrast, the relative risk for DM among those whose BMI decreased by 5.0% or more was 0.82 (95% CI 0.80-0.84). Moreover, people classified as normal weight, overweight, and obese reduced the risk of developing DM when they reduced their BMI, whereas the risk of developing DM for people classified as underweight increased when they reduced their BMI., Conclusion: Our findings offer novel insights into improving an optimal bodyweight management strategy to prevent the development of DM., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel concept of hepatic disease. Although the prevalences of heart failure (HF) and atrial fibrillation (AF) are increasing worldwide, limited data have assessed the extent to which MAFLD is associated with incident HF and AF., Objectives: The authors sought to examine the association of MAFLD with incident HF and AF., Methods: Analyses were conducted using a nationwide epidemiologic database including 3,279,918 individuals (median age 45 years; 57.6% men). Metabolic dysfunction was defined as 1 or more of the following: overweight (body mass index ≥23 kg/m 2 ), metabolic syndrome, or diabetes mellitus. FLD was defined as fatty liver index of >30. MAFLD was defined as the coexistence of metabolic dysfunction and FLD. We categorized study participants into 4 groups: non-FLD/nonmetabolic dysfunction (n = 1,709,116), metabolic dysfunction (n = 584,483), FLD (n = 89,497), and MAFLD (n = 896,822). The primary outcomes were HF and AF., Results: Over a mean follow-up period of 1,160 ± 905 days, 62,746 incident HF events and 15,408 incident AF events were recorded. Compared with the non-FLD/non-metabolic dysfunction group, HRs for HF and AF, respectively, were 1.20 (95% CI: 1.18-1.23) and 1.13 (95% CI: 1.08-1.19) for metabolic dysfunction, 1.24 (95% CI: 1.19-1.30) and 1.13 (95% CI: 1.04-1.23) for FLD, and 1.73 (95% CI: 1.69-1.76) and 1.51 (95% CI: 1.46-1.57) for MAFLD. MAFLD was also associated with a higher risk of developing myocardial infarction, angina pectoris, and stroke. A risk of developing cardiovascular events differed between MAFLD subtypes (Wald test P  < 0.001)., Conclusions: MAFLD was associated with a greater risk of developing HF and AF, suggesting the clinical importance of this novel hepatic disease concept., Competing Interests: This work was supported by grants from the Ministry of Health, Labor, and Welfare, Japan (21AA2007) and the Ministry of Education, Culture, Sports, Science, and Technology, Japan (20H03907, 21H03159, 21K08123, and 22K21133). Drs Kaneko and Fujiu have received research funding and scholarship funds from Medtronic Japan Co, Ltd, Boston Scientific Japan Co, Ltd, Biotronik Japan, Simplex QUANTUM Co, Ltd, and Fukuda Denshi, Central Tokyo Co, Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Aims: HDL cholesterol (HDL-C) has been thought to protect against cardiovascular disease (CVD), whereas a U-shaped association of both low and extremely high HDL-C with a high mortality risk has been increasingly reported in recent years. However, whether this U-shaped association is universal regardless of the individual's clinical background, including lifestyle diseases, remains unclear. We examined whether fasting plasma glucose modifies the U-shaped association between the HDL-C level and clinical outcomes., Methods and Results: This retrospective observational cohort study analysed data from the JMDC Claims Database between 2005 and 2021 for 3 282 389 participants without a history of CVD. The median age was 44 years (IQR, 36-51), and 1 878 164 participants (57.2%) were men. The median HDL-C level was 62 (IQR 52-74) mg/dL. The study participants were categorized according to fasting plasma glucose (FPG) levels (<100 mg/dL, 100-125 mg/dL, and ≥126 mg/dL). The primary endpoint was composite CVD outcome, consisting of myocardial infarction, stroke, and all-cause death. During a mean follow-up period of 1181 ± 932 days, 35 233 composite CVD events were recorded. The association between low HDL-C and CVD risk increased with the FPG level, and the relationship of high HDL-C with CV outcome was prominent only in people with diabetes mellitus. A similar relationship was observed in the individual subgroups and in each CV outcome., Conclusion: The U-shaped association between HDL-C and clinical outcomes was amplified with worsening glucose tolerance, suggesting a potential interaction between HDL-C levels and glycaemic status on clinical outcomes., Competing Interests: Conflict of interest: Research funding and scholarship funds (H.K. and K.F.) were received from Medtronic Japan Co Ltd, Boston Scientific Japan Co Ltd, Biotronik Japan, SIMPLEX QUANTUM Co Ltd, and Fukuda Denshi, Central Tokyo Co Ltd. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Elderly people are thought to be more likely than their non-elderly counterparts to experience a decline in activities of daily living (ADL) and quality of life (QOL) due to the onset and treatment of disease. In this study, we investigated whether there was an age-related difference in changes in health-related QOL indices after surgical resection of colorectal cancer (CRC)., Methods: Patients who underwent elective surgery for primary CRC at our hospital between September 2017 and November 2021 were enrolled. Changes in QOL after surgery were evaluated after dividing the study population into a non-elderly (NE) group (younger than 75 years) and an elderly (E) group. A Short-Form 36-Item Health Survey was used as an index of QOL. The subscale and component summary scores before and 6 months after surgery were compared., Results: Forty-seven patients were included in the E group and 166 patients were the NE group. The E group had significantly worse preoperative performance and physical status than the NE group. However, indices of physical function were not worsened after surgery in either group. In the NE group, there were significant decreases in role physical and role component summary scores and significant increases in general health, mental health, and mental component summary scores. In the E group, there were no significant changes in the subscale or component summary scores after surgery., Conclusion: Our study demonstrated elderly patient did not necessarily show a decline in QOL more than non-elderly patients after CRC surgery. Surgical resection for CRC should be considered even for elderly patients, while considering possible risk factors for worsening ADL and QOL., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study is to investigate the association between the hip abduction angle (HAA) and lower limb alignment as well as the clinical assessments in open-wedge high tibial osteotomy (OWHTO) patients. A total of 90 patients who underwent OWHTO were included. The demographic characteristics and clinical assessments (the Visual Analogue Scale for activities of daily living, the Japanese knee osteoarthritis measure, the Knee injury and Osteoarthritis Outcome Score, the Knee Society score, the Timed Up & Go (TUG) test, the single standing (SLS) test and muscle strength) were recorded. The patients were divided into two groups according to the HAA at 1 month after operation: the HAA (-) group (HAA < 0°) and the HAA (+) group (HAA ≥ 0°). Clinical scores except for the SLS test and radiographic parameters except for the posterior tibia slope (PTS), lateral distal femoral angle (LDFA) and lateral distal tibial angle (LDTA) were significantly improved at 2 years postoperatively. Regarding the two groups, scores on the TUG test in the HAA (-) group were significantly lower than those in the HAA (+) group (p = 0.011). The hip-knee-ankle angle (HKA), weight bearing line (WBLR) and knee joint line obliquity (KJLO) in the HAA (-) group were significantly higher than those in the HAA (+) group (p < 0.001, 0.001 and p = 0.025). In contrast, the LDFA in the HAA (-) group were significantly lower than those in the HAA (+) group (p < 0.001). The TUG test and the LDFA were weakly positively correlated with the HAA (r = 0.34, 0.42, p < 0.001 and 0.001). In contrast, the HKA, WBLR and KJLO had a weak negative correlation with the HAA (r = - 0.43, - 0.38 and - 0.37, p < 0.001, 0.001 and 0.001). This study showed the postoperative HAA was significantly associated with the TUG test and the HKA, WBLR, LDFA, and KJLO. A higher postoperative HAA might induce varus recurrence and poor outcomes of the gait parameter., (© 2023. The Author(s).)

Mammary glands with mastitis are usually treated with antibiotics in combination with anti-inflammatory drug application on the udder skin. Menthol is an anti-inflammatory drug. The aim of the present study was to investigate the effect of surface application of menthol on goat udders on the production of antimicrobial components in milk. Goats (5 Shiba and 11 Tokara goats) were subjected to menthol application to the udder under both healthy and inflammatory conditions. An intramammary infusion of lipopolysaccharides was carried out to induce inflammatory conditions in the udder. Milk samples were collected to determine somatic cell count (SCC) and sodium ion (Na + ), antimicrobial component and cytokine concentrations. In healthy udders, menthol application increased the concentration of antimicrobial components (S100A7 and S100A8), but not in the control. In the inflamed udder, antimicrobial component (lactoferrin, S100A7, and S100A8) and inflammatory cytokine (IL-1β) concentrations were higher in the menthol group than in the control group. These results suggest that menthol application on udders augments the antimicrobial component concentration in the mammary gland under both healthy and inflammatory conditions., (© 2023 Japanese Society of Animal Science.)

Despite having a higher risk of cardiovascular disease (CVD), there are currently limited data for stratifying CVD risk among cancer survivors. The purpose of this study was to uncover the relationship of subjective gait speed with incident CVD among cancer survivors.This retrospective observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2021 including 56,589 patients with a prior history of breast, colorectal, or stomach cancer but no history of CVD. Gait speed was evaluated using information from self-reported questionnaires collected during health checkups. The primary endpoint was composite CVD outcome, which included heart failure, myocardial infarction, angina pectoris, and stroke.The median (interquartile range) age was 54 (48-61) years, and 20,981 (37.1%) were male. Among them, 25,933 patients (45.8%) reported fast gait speed. During a mean follow-up period of 1002 ± 803 days, 3,221 composite CVD outcomes were recorded. In multivariate Cox regression analysis, slow gait speed was associated with a higher risk of developing CVD compared with fast gait speed (hazard ratio, 1.14, 95% confidence interval, 1.06-1.22). This association was consistent across a variety of sensitivity analyses.We demonstrated that subjective slow gait speed was associated with a greater risk of CVD development among cancer survivors. This suggests the potential value of gait speed assessment for the CVD risk stratification of cancer patients as well as the clinical importance of maintaining exercise capacity among patients living with cancer.

In Japan, a low-dose transdermal fentanyl (TDF; 0.5 mg) has been approved to address pain in opioid-naïve patients with cancer; however, efficacy and safety data are lacking. To determine the efficacy and safety of TDF, patients with opioid-naïve cancer pain prescribed TDF (0.5 mg/d) and oral oxycodone sustained-release formulation (OXY) 10 mg/d were extracted from electronic medical and nursing records. Overall, 40 and 101 subjects were analyzed in the TDF and OXY groups, respectively. Compared with baseline (median [minimum, maximum]) values, changes in the Numerical Rating Scale (NRS) score on days 1, 3, and 7 post-administration were as follows: TDF (0 [-5, 4]) and OXY (-1.0 [-8, 3]); TDF (-1.5 [-6, 3]) and OXY (-2.0 [-8, 4]); and TDF (-2.0[-6, 3]) and OXY (-3.0[-8, 5]), respectively. No significant difference was observed between the groups on days 1 and 3; however, the change in the NRS on day 7 was significantly higher in the OXY group than that in the TDF group. Regarding adverse events, nausea occurred in 12.5 and 13.9% of patients in the TDF and OXY groups, respectively, while 12.5% of TDF- and 10.9% of OXY-treated patients experienced somnolence, revealing similar occurrence in both groups. However, constipation was more common in the OXY group (TDF: 50.0%, OXY: 71.3%). No serious adverse events (e.g., respiratory depression) were observed in either group. Low-dose TDF (0.5 mg), available only in Japan, showed comparable efficacy and safety to OXY (10 mg/d) and can be a first choice for opioid-naïve patients with cancer pain.

Background: It remains controversial whether the abdominoperineal resection (APR) procedure itself has a negative impact on prognosis compared with sphincter-saving surgery (SSS). The purpose of this study was to investigate whether the operation type affects the prognostic outcome in rectal cancer using a multicenter database in Japan., Methods: The study involved 2533 patients who underwent APR or SSS and were registered in the Japanese Society for Cancer of the Colon and Rectum database, which includes data from 74 centers, between 2003 and 2007. The primary endpoints were overall survival (OS) and relapse-free survival (RFS). The secondary endpoints were local recurrence rate (LRR) and pathological radial margin (pRM) status., Results: Multivariate analysis identified pathological tumor depth, lymph node status, and pRM status to be associated with oncological outcomes (OS, RFS, LRR). Although the oncological outcomes were worse after APR than after SSS in univariate analysis, there was no significant difference in OS (hazard ratio 1.08; 95% confidence interval [CI] 0.85-1.37) or RFS (hazard ratio 1.06; 95% CI 0.87-1.30) between APR and SSS. There was also no significant difference in LRR (odds ratio 1.11, 95% CI 0.70-1.77). Multivariate analysis showed that operation type was associated with positive pRM (odds ratio 3.13, 95% CI 0.18-0.56)., Conclusions: There was no significant difference in oncological outcomes between APR and SSS for rectal cancer. The risk of positive pRM was higher for APR and performing radial margin-negative surgery is an important factor in improving the oncological outcomes of APR., 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 © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The transanal/perineal (ta/tp) endoscopic approach has been widely used for anorectal surgery in recent years, but carbon dioxide embolism is a possible lethal complication. The frequency of this complication in this approach is not known. In this study, we investigated the frequency of intraoperative (including occult) carbon dioxide embolism using transesophageal echocardiography. Patients who underwent surgery via the ta/tp approach and consented to participate were included. Intraoperative transesophageal echocardiography was used to observe the right ventricular system in a four-chamber view. Changes in end-tidal carbon dioxide (EtCO 2 ), oxygen saturation (SpO 2 ), and blood pressure were taken from anesthesia records. Median maximum insufflation pressure during the ta/tp approach was 13.5 (12-18) mmHg. One patient (4.8%) was observed to have a bubble in the right atrium on intraoperative transesophageal echocardiography, with a decrease in EtCO 2 from 39 to 35 mmHg but no obvious change in SpO 2 or blood pressure. By lowering the insufflation pressure from 15 to 10 mmHg and controlling bleeding from the veins around the prostate, the gas rapidly disappeared and the operation could be continued. Among all patients, the range of variation in intraoperative EtCO 2 was 5-22 mmHg, and an intraoperative decrease in EtCO 2 of > 3 mmHg within 5 min was observed in 19 patients (median 5 mmHg in 1-10 times).Clinicians should be aware of carbon dioxide embolism as a rare but potentially lethal complication of anorectal surgery, especially when using the ta/tp approach., (© 2022. The Author(s).)

Hypertension increases arterial stiffness, leading to dysfunction and structural changes in the left atrium (LA) and left ventricle (LV). However, the effects of hypertension on the right atrium (RA) and the right ventricle are still not fully understood. The purpose of this study was to clarify whether there is an interaction not only in the left ventricular system but also in the right ventricular system in hypertensive patients with preserved LV ejection fraction. The current retrospective observational study included patients ( n = 858) with some risk of metabolic abnormalities (hypertension, diabetes, and dyslipidemia) who had visited our hospital and undergone echocardiography between 2015 and 2018. Among them, we retrospectively studied 165 consecutive hypertensive patients with preserved LV ejection fraction who had echocardiography performed on the same day as a cardio-ankle vascular index (CAVI) in our hospital. The phasic function of both atria was evaluated by two-dimensional speckle-tracking echocardiography. CAVI was measured using Vasela 1500 (Fukuda Denshi ® ). In the univariate analysis, CAVI was significantly correlated with LA and RA conduit function (LA conduit function, r = -0.448, p = 0.0001; RA conduit function, r = -0.231, p = 0.003). A multivariate regression analysis revealed that LA and RA conduit function was independently associated with CAVI (LA, t = -5.418, p = 0.0001; RA, t = -2.113, p = 0.036). CAVI showed a possibility that the association between heart and vessels are contained from not only LA phasic function but also RA phasic function in hypertensive patients.

It is common for visitors to have rich and varied experiences in the limited space of a classical Chinese garden. This leads to the sense that the garden's scale is much larger than it really is. A main reason for this perceptual bias is the gardener's manipulation of visual information. Most studies have discussed this phenomenon in terms of qualitative description with fragmented perspectives taken from static points, without considering ambient visual information or continuously changing observation points. A general question arises, then, on why depth perception can vary from one observation point to another along a garden path. To better understand the spatial experience in classical Chinese gardens, this study focused on variations in perceived depth among different observation points and aimed to identify influential visual information through psychophysical experimentation. As stimuli for the experiment, panoramic photos of Liu garden were taken from three positions at Lvyin Pavilion. Considering the effects of pictorial visual cues on depth perception, the photos were processed to create 18 kinds of stimuli (six image treatments * three positions). Two tasks were presented to the participants. In Task 1, 71 participants were asked to rate the depth value of the garden using the magnitude estimation method in a cave automatic virtual environment (CAVE). Statistical analysis of Task 1 revealed that depth values differed significantly among different viewpoints. In Task 2, participants were asked to compare 18 stimuli and 3D images presented on three connected monitors and to judge the depth of the garden using the adjustment method. The results of Task 2 again showed that depth values differed significantly among different viewpoints. In both tasks, ambient information (i.e., the perspective of interior space) significantly influenced depth perception., 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 © 2022 Zhu, Gu, Ohno and Kong.)

Phosphine-stabilized Pb(II) cations, generated by chloride abstraction from chloroplumbylene 1 , readily react with Lewis bases (L) such as phosphines and amines to give the corresponding donor-acceptor complexes 3 . These complexes 3 react with phenylacetlylene via alkyne insertion into the Pb-L bond to afford the corresponding vinylplumbylenes 4 . Of particular interest, the stable complex 4-HNiPr 2 (with a secondary amine) can be used as a hydroamination catalyst of phenylacetylene.

Background: Several serious complications are associated with the lithotomy position, including well-leg compartment syndrome and peroneal nerve paralysis. The aims of this study were to identify risk factors for the intraoperative elevation of lower leg pressure and to evaluate the effectiveness of monitoring external pressure during surgery for preventing these complications., Methods: The study included 106 patients with a diagnosis of sigmoid colon or rectal cancer who underwent elective laparoscopic surgery between June 2019 and December 2020. We divided the posterior side of the lower leg into four parts (upper outside, upper inside, lower outside, lower inside) and recorded the peak pressure applied to each area at hourly intervals during surgery (called "regular points") and when the operating position was changed (e.g., by head-tilt or leg elevation; called "points after change in position"). When the pressure was observed to be higher than 50 mmHg, we adjusted the position of the leg and re-recorded the data. Data on postoperative leg-associated complications were also collected., Results: The pressure was measured at a total of 1125 points (regular, n = 620; after change of position, n = 505). The external pressure on the upper outer side of the right leg (median, 36 mmHg) was higher than that on any other area of the lower leg. The pressure increase to more than 50 mmHg was observed not only during the change of position (27.5%) but also during regular points (22.4%). Bodyweight, strong leg elevation, and low head position were identified as factors associated with increased external pressure. There have been no compression-related complications in 534 cases at our institution since the introduction of intraoperative pressure monitoring., Conclusions: Several risk factors associated with increased external pressure on the lower leg were identified. Intraoperative pressure monitoring might help reduction of pressure-related complications, needing further and larger prospective data collections., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Bone bruises with anterior cruciate ligament (ACL) injury are well studied, but the association between bone bruises and multiple factors is unclear. The main objective of this study was to investigate the association between bone bruising and ACL injury and concomitant injury as well as clinical and functional scores. The second objective was to investigate the presence and distribution patterns of bone bruises., Method: A total of 176 patients who underwent ACL reconstruction for primary ACL injury were included. The demographic characteristics and responses to clinical and functional assessments (the Visual Analog Scale for activities of daily living and sports, the Cincinnati Knee Rating System, the Lysholm score, the Knee Osteoarthritis Outcome Score and side-to-side difference in anterior laxity) were recorded at the initial visit. Concomitant injuries were evaluated by intraoperative assessment., Results: Bone bruises were detected in 141 patients (80.1%). The lateral femoral condyle (LFC) was the most common site in 116 patients (65.9%), followed by the lateral tibial plateau (LTP) in 82 patients (46.6%), medial tibial plateau (MTP) in 47 patients (26.7%) and medial femoral condyle (MFC) in 29 patients (16.5%). Regarding the distribution patterns, bone bruising at only the LFC, which was the most common pattern, was detected in 38 patients (27.0%). Bone bruising at the LTP or MTP was significantly associated with lateral (LM) and medial meniscus (MM) tears (odds ratios 4.0, 3.0, 4.3 and 40.5, 95% confidence intervals 1.5-11.6, 1.2-15.1, 1.2-17.3 and 8.6-283.0, respectively). No marked differences in the functional or clinical scores were noted. The severity of bone bruising at the MTP was significantly associated with MM tears and that at the LTP was significantly associated with LM tears. (p < 0.01)., Conclusion: This study showed association between bone bruising at LTP and LM tears or at MTP and MM tears. Additionally, it provided detailed information on the presence and distribution patterns of bone bruises at each anatomic site. These findings are clinically relevant and will aid in preoperatively diagnosing meniscus tears in cases of ACL injury., Level of Evidence: Level III., (© 2021. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background: Paraganglioma of the urinary bladder (Pub) is rare and presents with clinical symptoms caused by catecholamine production and release. The typical symptoms of Pub are hypertension, macroscopic hematuria, and a hypertensive crisis during micturition. The average size of detected Pubs is approximately 3 cm. Herein, we report a case of a large Pub in which the symptoms were masked by oral medication, precise preoperative diagnosis was difficult, and intraoperative confirmation of tumoral adhesion to the rectum resulted in hypertensive attacks during surgery., Case Presentation: A 64-year-old Japanese male with a history of hypertension and arrhythmia controlled with oral medication presented with a large tumor in the pelvic region, detected on examination for weight loss, with no clinical symptoms. Computed tomography and magnetic resonance imaging revealed a tumor measuring 77 mm in diameter in the posterior wall of the urinary bladder. The border with the rectum was unclear, and the tumor showed heterogeneous enhancement in the solid part with an enhancing hypodense lesion. Cystoscopy revealed compression of the bladder trigone by external masses; however, no tumor was visible in the lumen. Endoscopic ultrasonography-guided fine-needle aspiration revealed CD34-positive spindle-shaped cells in the fibrous tissue, suggestive of a mesenchymal neoplasm. The tumor was suspected to be a gastrointestinal stromal tumor, and surgery was performed. After laparotomy, we suspected that the tumor had invaded the rectum, and total cystectomy and anterior resection of the rectum were performed. Histologically, the tumor cells had granular or clear amphophilic cytoplasm with an oval nucleus and nests of cells delimited by connective tissue and vascular septations. Immunohistochemically, the tumor was positive for chromogranin A, CD56, and synaptophysin, and a diagnosis of paraganglioma of the urinary bladder was confirmed. There was no tumor recurrence at the 7-month follow-up., Conclusion: This case highlights the importance of careful examination of pelvic tumors, including endocrine testing, for detecting paraganglioma of the urinary bladder in patients with a history of hypertension or arrhythmia., (© 2022. The Author(s).)

Background: It has been recognized that psychological factors influence the return to sports after anterior cruciate ligament reconstruction (ACLR). The ACL-return to sports after injury (RSI) scale was developed based on subcategories of emotions, confidence in physical performance and risk appraisal. However, it has not been clarified describing which is the most influential psychological factor of the ACL-RSI scale., Hypothesis: Risk appraisal is the most influent for return to sports in the subcategories of the ACL-RSI scale., Patients and Methods: A total of 85 competitive patients who had undergone ACLR were evaluated at 6, 12 and 24 months after surgery. They were classified the return to sports (RTS) group and non-return to sports (NRTS) group. Evaluations were several clinical and functional scores including Cincinnati knee rating system, Knee Osteoarthritis Outcome Score (KOOS), Lysholm score, limitation in activities of daily living (ADL) and sports which estimated by Visual Analog Scale (VAS) score, Isokinetic Muscle Strength (quadriceps and hamstrings), single hop test and anterior laxity. They were investigated their relationship with the ACL-RSI scale including each subcategory., Results: The total ACL-RSI scale significantly improved at each point. Of the subcategories, only risk appraisal was not significantly different at each point (p=0.21 and p=0.13). There was a significant difference at 24 months after ACLR between the RTS group and NRTS group. In terms of risk appraisal, compared with emotion and performance confidence, the difference in the mean value was the most divergent (RTS group: 55.9±22.7 and NRTS group: 23.8±19.3) and took time to improve through 24 months. Among various clinical and functional scores, there were significant differences in the VAS score for sports, KOOS-symptoms, sports and QOL, Cincinnati Knee Rating System-cut, and single hop test values between two groups. Of these, the KOOS-QOL and VAS score for sports showed particularly strong correlations with ACL-RSI risk appraisal (r=0.75 and -0.68, respectively)., Conclusion: Of the ACL-RSI scale, risk appraisal took the longest time to improve and strongly affected the return to sports. The KOOS-QOL and VAS score for sports were most strongly correlated with the ACL-RSI risk appraisal. It seems that it is important to reduce the psychological risk as soon as possible after ACL injury in ACLR patients., Level of Evidence: II., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

A multicenter phase II study was conducted in 44 elderly (≥ 65 years) Japanese patients with newly diagnosed acute myeloid leukemia (AML) to evaluate whether azacitidine is also effective and feasible in Japanese AML patients. The 28 patients with AML with poor-risk cytogenetics and/or myelodysplasia-related changes (unfavorable AML) were randomly assigned to receive either azacitidine or conventional care regimens (CCR), and the other 16 patients without unfavorable AML received azacitidine alone. The primary endpoint was overall survival. At the median follow-up of 29 months, among the 26 evaluable patients with unfavorable AML, the median survival time (MST) of patients who received azacitidine (N = 14) was 9.6 months and that of patients who received CCR (N = 12) was 5.3 months (HR 0.73; 95% CI 0.31-1.69; log-rank P = 0.459). The MST of all 29 patients who received azacytidine, including the 15 evaluable patients without unfavorable AML, was 12.4 months. Adverse events of azacitidine were manageable and consistent with its established safety profile. Azacitidine tended to prolong survival in newly diagnosed elderly Japanese patients with AML, and was feasible as a front-line therapy for elderly AML patients., (© 2022. Japanese Society of Hematology.)