Impact of frailty on cancer-related fatigue and quality of life in outpatients with prostate cancer: a cross-sectional study of patient-reported outcomes.

OBJECTIVE: To investigate the prevalence of frailty and its effects on cancer-related fatigue and quality of life among patients with prostate cancer. METHODS: In this cross-sectional study, questionnaires were administered to 254 outpatients who visited the Department of Urology at Kagawa University Hospital for prostate cancer; finally, 108 outpatients were analyzed. Frailty, cancer-related fatigue and quality of life were assessed using the G8 screening tool, Japanese version of the Brief Fatigue Inventory and Japanese version of the Short Form 8 Health Survey, respectively. We defined frailty based on a score ≤14 points and divided the patients into frailty and no-frailty groups. We also compared the severity of cancer-related fatigue and quality of life between groups. RESULTS: The prevalence of frailty among 108 outpatients was 63%. Older age correlated with frailty severity (P = 0.0007) but not cancer-related fatigue severity (P = 0.2391). The proportion of patients on treatment or with metastasis was not significantly different between groups. The frailty group had higher cancer-related fatigue severity (P = 0.004) and decreased levels of general activity, mood, walking ability, normal work and enjoyment of life, especially on the Brief Fatigue Inventory subscale. The frailty group had lower physical and mental quality of life than the no-frailty group or general population. CONCLUSIONS: The frailty rate for these patients increased with age, exceeding 60% regardless of the treatment status, and was associated with worsened cancer-related fatigue severity and reduced quality of life. Our study highlights the importance of assessing frailty when selecting treatment, especially in older patients.

Enhancement of visible light response of TiO2 photocatalyst by 3D-deposited Ag nanowires and its charge separation mechanism.

In 3D-deposited AgNW/TiO2, which is prepared by spray-applying titanium dioxide suspension to deposited silver nanowire sheets, the synergistic effects of increased crossing points of AgNWs to enhance localized surface plasmon resonance excitation and longer-lived electrons in the conduction band of TiO2 generated by plasmon-induced charge transfer have successfully resulted in photocatalytic activity in the visible light range. We have developed photocatalytic sheets in which TiO2 particles are uniformly attached to 3D-deposited AgNWs. Regarding the prepared sheet, it was confirmed that TiO2 was indeed well adhered to the AgNWs, and electron transfer was efficient at the interface. This sheet solves the problem that the response wavelength range of the photocatalytic reaction using TiO2 is only in the ultraviolet region and exhibits sufficient photocatalytic effect in the visible light region. Transient absorption spectroscopy measurements in the diffuse reflectance configuration confirmed that the electrons of AgNWs actually move into the conduction band of TiO2 under visible light and that the interaction is independent of the excitation light intensity, thereby extending the lifetime of the electrons.

Disinfection and monitoring of Mycobacterium avium complex in the environment: A novel approach to the management of hot tub lung.

A 45-year-old man visited our hospital with a chronic cough and breathing difficulties. Chest computed tomography revealed diffuse granular shadows. Mycobacterium avium (M. avium) was cultured from bronchoalveolar lavage fluid (BALF). Surgical lung biopsy revealed non-necrotizing granulomas, and M. avium-specific PCR was positive in the tissue. M. avium was also cultured in a sample from the inlet of the patient's bathtub. Mycobacterium avium tandem repeat variable-number tandem-repeat loci (MATR-VNTR) analysis confirmed that the M. avium cultured from BALF and the bathtub inlet had identical allele profiles. The patient's symptoms and oxygenation improved while the patient was in hospital, presumably because of lack of ongoing exposure to M. avium. He was diagnosed with hot tub lung. We advised the patient to avoid bathing to avoid re-exposure. However, the patient was unwilling to follow this advice. Therefore, his bathtub and pipework were disinfected by heating them to over 70 °C. We confirmed that the disinfection has been successful by repeated culture of environmental samples. Three months after resuming bathtub use, the patient's symptoms resolved, and the pulmonary shadows seen on the initial radiography did not recur. For the treatment of hot tub lung, disinfection of M. avium complex in the environment should be considered and the environment should be monitored to confirm eradication.

Peripheral neuropathy and nerve electrophysiological changes with enfortumab vedotin in patients with advanced urothelial carcinoma: a prospective multicenter cohort study.

BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.

Impact of the coronavirus disease pandemic on robot-assisted radical prostatectomy and urologists' treatment behaviors: A single tertiary center retrospective study.

OBJECTIVES: To assess whether the coronavirus disease (COVID-19) pandemic affected the outcomes of robot-assisted radical prostatectomy (RARP) and urologists' treatment behaviors. METHODS: We retrospectively examined the medical records of 208 patients who had undergone RARP between August 2017 and December 2022. We compared the rate of preoperative androgen deprivation therapy (ADT), waiting period for RARP, patients' baseline characteristics and quality of life (QOL), proportion of adverse pathology on the RARP specimen, rate of Gleason grade group upgrading from biopsy to the RARP specimen, and prostate-specific antigen (PSA) recurrence-free survival between the pre-pandemic and pandemic groups. RESULTS: The rate of preoperative ADT was significantly higher during than before the COVID-19 pandemic (13.7% vs. 1.9%; p = 0.002). The baseline physical and mental QOL scores did not differ significantly between the groups. The proportion of D'Amico low-risk patients was significantly lower (13.6% vs. 1.2%, p = 0.005) and waiting period for RARP was significantly shorter (median 3.5 months vs. 4.0 months, p = 0.016) in the pandemic group than in the pre-pandemic group. There was no significant difference in the proportion of adverse pathology between the groups (p = 0.104); however, the upgrading rate was significantly higher in the pre-pandemic group (p = 0.002). There was no significant difference in PSA recurrence-free survival between the groups (log-rank, p = 0.752). CONCLUSIONS: The COVID-19 pandemic did not adversely affect the oncologic outcomes of RARP and QOL before RARP. However, it caused urologists to increase the use of preoperative ADT and to reserve RARP for higher-risk cases.

Ultrastructural changes of vascular smooth muscle cells and resistance to vasospasm treatment in femoral arteries of an arteriosclerotic rat model.

The objective of this study was to establish an animal model of arteriosclerosis for assessing vasospasm and to investigate the relationship between arteriosclerosis and vasospasm. Twelve-week-old male Sprague-Dawley rats were fed a diet supplemented with adenine and vitamin D (adenine/vitD). Body weight, blood, and femoral artery histopathology were assessed at 2, 4, and 6 weeks. Change in the femoral artery was examined by transmission electron microscope (TEM). Vasospasm was induced by administering epinephrine extravascularly into the femoral artery and released by the treatment with lidocaine as a vasodilator. During this period, the extravascular diameter and blood flow were measured. The rats in the adenine/vitD group developed renal dysfunction, uremia, hyperphosphatemia, and elevated serum alkaline phosphatase. Histological and TEM analyses of the femoral arteries in the treated rats revealed the degeneration of elastic fibers and extensive calcification of the tunica media and intima. Vascular smooth muscles were degenerated and osteoblasts were developed, resulting in calcified arteriosclerosis. Vasospasm in arteriosclerotic arteries was detected; however, vasodilation as well as an increase in the blood flow was not observed. This study revealed the development of vasospasm in the femoral arteries of the arteriosclerotic rats and, a conventional vasodilator did not release the vasospasm.

Coronary arterial repair in patients with stable angina pectoris or acute coronary syndrome after ultrathin biodegradable polymer sirolimus-eluting stent implantation at 1-year follow-up by coronary angioscopy.

BACKGROUND: Imaging modality-based evidence is limited that compares the extent of coronary arterial repair after percutaneous coronary intervention between patients with stable angina pectoris (SAP) and those with acute coronary syndrome (ACS). METHODS: Between December 2018 and November 2021, a single-center, nonrandomized, observational study was conducted in 92 patients with SAP (n = 42) or ACS (n = 50), who were implanted with Orsiro sirolimus-eluting stent (O-SES) providing a hybrid (active and passive) coating and underwent 1-year follow-up by coronary angioscopy (CAS) after implantation. CAS assessed neointimal coverage (NIC), maximum yellow plaque (YP), and mural thrombus (MT). RESULTS: Baseline clinical characteristics were comparable between the SAP and ACS groups. The follow-up periods were comparable between the two groups (390.1 ± 69.9 vs. 390.6 ± 65.7 days, p = 0.99). The incidences of MT at 1 year after implantation were comparable between the two groups (11.4% vs. 11.1%, p = 0.92). The proportions of "Grade 1" in dominant NIC grades were highest in both groups, and the proportions of maximum YP grades and MT were comparable between the two groups. CONCLUSION: O-SES-induced coronary arterial repair at the site of stent implantation, irrespective of the types of coronary artery disease.

Direct numerical simulations of a microswimmer in a viscoelastic fluid.

This study presents the application of the smoothed profile (SP) method to perform direct numerical simulations for the motion of both passive and active "squirming" particles in Newtonian and viscoelastic fluids. We found that fluid elasticity has a significant impact on both the transient behavior and the steady-state velocity of the particles. Specifically, we observe that the swirling flow generated by the squirmer's surface velocity significantly enhances their swimming speed as the Weissenberg number increases, regardless of the swimming type. Furthermore, we find that pushers outperform pullers in Oldroyd-B fluids, suggesting that the speed of a squirmer depends on the swimmer type. To understand the physical origin of the phenomenon of swirling flow enhancing the swimming speed, we investigate the velocity field and polymer conformation around non-swirling and swirling neutral squirmers in viscoelastic fluids. Our investigation reveals that the velocity field around the neutral swirling squirmers exhibits pusher-like extensional flow characteristics, as well as an asymmetric polymer conformation distribution, which gives rise to this increased propulsion. This is confirmed by the investigation of the force on a fixed squirmer, which revealed that the polymer stress, particularly its diagonal components, plays a critical role in enhancing the swimming speed of swirling squirmers in viscoelastic fluids. Additionally, our results demonstrate that the maximum swimming speeds of swirling squirmers occur at an intermediate value of the fluid viscosity ratio for all swimmer types. These findings have important implications for understanding the behavior of particles and micro-organisms in complex fluids.

Active surveillance in younger patients with prostate cancer: clinical characteristics including longitudinal patient-reported outcomes.

OBJECTIVE: this study aimed to evaluate the active surveillance continuation period, treatment intervention rate and health-related quality of life in younger patients. METHODS: we prospectively conducted a health-related quality of life survey of patients enrolled in the Prostate Cancer Research International: Active Surveillance-JAPAN study at Kagawa University between January 2010 and December 2020. Health-related quality of life was assessed by mail using a validated Japanese version of the Short-Form 8 Health Survey and Expanded Prostate Cancer Index at active surveillance enrolment and annually thereafter until discontinuation of active surveillance. We divided the patients into two groups, younger (aged <65 years) and older (aged ≥65 years), and compared the two groups. RESULTS: of the 84 patients, 22 were in the younger group. The active surveillance continuation period was shorter in the younger group than in the older group. The 3-year treatment intervention rate was higher in the younger group than in the older group. The majority of the reasons for definitive treatment were related to the protocol, which was similar in both groups (80 versus 76%). The sexual summary scores at active surveillance enrolment were higher in the younger group than in the older group. During active surveillance, the younger group and the older group showed no deterioration in all health-related quality of life scores compared with the scores at the enrolment of active surveillance. CONCLUSIONS: patient-reported health-related quality of life survey indicated that the health-related quality of life of younger Japanese patients was maintained over time during active surveillance, similar to that of older patients.

The efficacy and safety of adaptive servo-ventilation therapy for heart failure with preserved ejection fraction.

It is unclear whether adaptive servo-ventilation (ASV) therapy for heart failure with preserved ejection fraction (HFpEF) is effective. The aim of this study was to investigate the details of ASV use, and to evaluate the effectiveness and safety of ASV in real-world HFpEF patients. We retrospectively enrolled 36 HFpEF patients at nine cardiovascular centers who initiated ASV therapy during hospitalization or on outpatient basis and were able to continue using it at home from 2012 to 2017 and survived for at least one year thereafter. The number of hospitalizations for heart failure (HF) during the 12 months before and 12 months after introduction of ASV at home was compared. The median number of HF hospitalizations for each patient was significantly reduced from 1 [interquartile range: 1-2] in the 12 months before introduction of ASV to 0 [0-0] in the 12 months after introduction of ASV (p < 0.001). In subgroup analysis, reduction in heart failure hospitalization was significantly greater in female patients, patients with a body mass index < 25, and those with moderate or severe tricuspid valve regurgitation. In patients with HFpEF, the number of HF hospitalizations was significantly decreased after the introduction of ASV. HFpEF patients with female sex, BMI < 25, or moderate to severe tricuspid valve regurgitation are potential candidates who might benefit from ASV therapy.

A national questionnaire survey of Japanese urologists on active surveillance for low- and intermediate-risk prostate cancer.

OBJECTIVE: To conduct a national questionnaire survey of Japanese urologists on active surveillance (AS) for low- and intermediate-risk prostate cancer (PCa). METHODS: A questionnaire was sent to 922 Japanese Urological Association Teaching Base Hospitals. The items included were years of experience as a urologist, sex, workplace, treatment equipment owned, specialty area of daily practice, specialty area of urological cancer, and six hypothetical cases of AS. The cases were categorized by the following Gleason scores: 3 + 3 low risk of PCa, 3 + 4 intermediate risk, and 4 + 3 intermediate risk, with or without comorbidities for each case. Comorbidities were defined as cardiovascular diseases or illnesses warranting anticoagulant therapy. RESULTS: Altogether, 1962 questionnaires were analyzed. Responses were almost equally distributed among all age groups. Workplaces included general hospitals (49.4%), university hospitals (40.3%), and cancer centers (4.2%). Percentages of proposed AS for low risk/no comorbidity, low risk/with comorbidity, intermediate-risk 3 + 4/no comorbidity, intermediate risk 3 + 4/with comorbidity, intermediate risk 4 + 3/no comorbidity, and intermediate risk 4 + 3/with comorbidity were 90.5%, 90%, 39.5%, 48.7%, 15%, and 22%, respectively. Analysis of the correspondents' backgrounds showed that the more the urologists' years of experience, the less they were to advise AS of low-risk patients. In the presence of comorbidities, urologists across all age groups tended to propose AS, even in the same Gleason grade group. Cancer center urologists recommended AS more often than their counterparts at general and university hospitals. CONCLUSIONS: Approximately 40% of urologists proposed AS for intermediate-risk cases, confirming that AS for intermediate-risk patients is being considered in Japan.

A national questionnaire survey of Japanese urologists on treatment perspectives for elderly prostate cancer patients.

OBJECTIVE: This study conducted a national questionnaire survey of Japanese urologists from a treatment perspective for older patients with prostate cancer. METHODS: A questionnaire was distributed to 922 teaching hospitals of the Japanese Urological Association. Questionnaire items included years of urologist experience, gender, workplace, treatment equipment owned, daily specialty practice area, urological cancer specialty, treatment reference items for older adults, upper age limit for radical treatment, medication, and two hypothetical cases of Gleason grade group 2 prostate cancer with or without oligometastasis. RESULTS: In total, 1732 questionnaires were analyzed, with responses evenly distributed across all age groups. Workplaces included general hospitals (49.4%), university hospitals (40.3%), and cancer centers (4.2%). Performance status was the most frequently mentioned treatment-related item, followed by comorbidities and cognitive function. In addition, geriatric assessment was used by only 13.3% of respondents. No upper age limit was found for total prostatectomy, brachytherapy, and external beam radiation. Anti-androgens, androgen receptor-axis-targeted agents, chemotherapy, poly ADP ribose polymerase inhibitors, and immune-checkpoint inhibitors were selected by 6.8%, 35.6%, 47.3%, 89%, 62.8%, 24.7%, 41.9%, and 41.7% of the respondents, respectively. Response rates for administration of hormone therapy for hypothetical cases of Gleason grade group 2 prostate cancer with or without oligometastases were 96.8% and 61.2%, respectively. CONCLUSIONS: Less than 15% of urologists used geriatric assessments. Several responded that they would set age limits for highly invasive radical and systemic therapies.

Wheat α-gliadin and high-molecular-weight glutenin subunit accumulate in different storage compartments of transgenic soybean seed.

Wheat seed storage proteins (prolamins) are important for the grain quality because they provide a characteristic texture to wheat flour products. In wheat endosperm cells, prolamins are transported from the Endoplasmic reticulum to Protein storage vacuoles through two distinct pathways-a conventional pathway passing through the Golgi apparatus and an unconventional Golgi-bypassing pathway during which prolamins accumulate in the ER lumen, forming Protein bodies. Unfortunately, transport studies conducted previously achieved limited success because of the seed-specificity of the latter pathway and the multigene architecture of prolamins. To overcome this difficulty, we expressed either of the two families of wheat prolamins, namely α-gliadin or High-molecular-weight subunit of glutenin, in soybean seed, which naturally lacks prolamin-like proteins. SDS-PAGE analysis indicated the successful expression of recombinant wheat prolamins in transgenic soybean seeds. Their accumulation states were quite different-α-gliadin accumulated with partial fragmentation whereas the HMW-glutenin subunit formed disulfide-crosslinked polymers without fragmentation. Immunoelectron microscopy of seed sections revealed that α-gliadin was transported to PSVs whereas HMW-glutenin was deposited in novel ER-derived compartments distinct from PSVs. Observation of a developmental stage of seed cells showed the involvement of post-Golgi Prevacuolar compartments in the transport of α-gliadin. In a similar stage of cells, deposits of HMW-glutenin surrounded by membranes studded with ribosomes were observed confirming the accumulation of this prolamin as ER-derived PBs. Subcellular fractionation analysis supported the electron microscopy observations. Our results should help in better understanding of molecular events during the transport of prolamins in wheat.

The Paris System for reporting urinary cytology improves the negative predictive value of high-grade urothelial carcinoma.

BACKGROUND: The Paris System (TPS) for reporting urinary cytology differs from conventional systems (CS) in that it focuses on the diagnosis of high-grade urothelial carcinoma (HGUC). This study investigated the impact of TPS implementation on the diagnostic accuracy of HGUC by comparing it with our institutional CS. METHODS: A total of 649 patients who underwent transurethral resection of bladder tumor (TURBT) between January 2009 and December 2020 were included in this study. Our institution adopted TPS to report urinary cytology in February 2020. The diagnostic accuracy of HGUC in preoperative urinary cytology was compared with the presence or absence of HGUC in resected specimens of TURBT before and after TPS implementation. RESULTS: After implementing TPS in urinary cytology, 89 patients were reviewed and compared with 560 patients whose urinary cytology was diagnosed by CS. TPS and CS for detecting HGUC had 56.0% and 58.2% sensitivity, 97.8% and 91.2% specificity, and 93.3% and 87.9% positive predictive values, respectively. There were no significant differences between TPS and CS in terms of sensitivity, specificity, and positive predictive value for HGUC (P = 0.83, 0.21, 1.00). On the other hand, the negative predictive value for HGUC using TPS was 80.0%, which was significantly higher than that of CS (66.4%, P = 0.04) The multivariate logistic regression analysis indicated that not using TPS was one of the independent predictive factors associated with false-negative results for HGUC (odds ratio, 2.26; 95% confidence interval, 1.08-4.77; P = 0.03). CONCLUSION: In instances where urinary cytology is reported as negative for HGUC by TPS, there is a low probability of HGUC, indicating that TPS has a potential diagnostic benefit.

Incidental Bladder Cancer Found on Cystoscopy during Prostate Biopsy: Prevalence, Pathological Findings, and Oncological Outcome.

INTRODUCTION: We examined the prevalence, pathological findings, and oncological outcomes of incidental bladder cancer found on cystoscopy among patients eligible for prostate biopsy (PB). METHODS: We retrospectively reviewed 803 patients who underwent cystoscopy prior to PB between January 2010 and September 2020. In cases of bladder tumor-like findings on cystoscopy, biopsy or transurethral resection of the bladder tumor was performed. The primary and secondary outcomes were the prevalence of incidental bladder cancer and pathological and oncological outcomes of incidental bladder cancer, respectively. RESULTS: Incidental findings were observed in 31/803 patients (3.9%). Bladder tumor-like findings were found in 24/803 patients (3%), while 9/803 patients (1.1%) were pathologically diagnosed with urothelial carcinoma. The stage and grade of incidental bladder cancer were pTa in 8/9 patients and pT1 in 1/9 and low grade in 8/9 and high in 1/9, respectively. The median tumor size of the papillary pedunculated type was 0.5 cm. At 26-month median follow-up, no recurrence was observed. CONCLUSION: Cystoscopy during PB may yield incidental bladder cancer findings, although the prevalence is very low. Incidental bladder cancer was of low stage and grade, which seemed unrelated to survival. Moreover, performing routine cystoscopy in conjunction with PB is not recommended as it may lead to overdiagnosis of low-risk bladder cancer.

Accelerated Angiogenesis of Human Umbilical Vein Endothelial Cells Under Negative Pressure Was Associated With the Regulation of Gene Expression Involved in the Proliferation and Migration.

ABSTRACT: Negative pressure has been used as a preferred therapy for wound healing; however, the mechanisms by which negative pressure promotes tissue restoration remain unclear. In the present study, RNA-sequencing analysis was performed to identify differentially expressed genes in human umbilical vein endothelial cells (HUVECs) exposed to negative pressure. Cell viability and DNA synthesis were examined using the cell counting kit-8 assay and bromodeoxyuridine incorporation, respectively. Cell migration was assessed using tube formation, Transwell, and wound healing assays. Activity of the serine/threonine kinase (AKT) signaling pathway was also examined by measuring the levels of phospho-paxicillin, phospho-focal adhesion kinase (p-FAK), and p-AKT1. The exposure of HUVECs to negative pressure enhanced cell proliferation and DNA synthesis. Negative pressure enhanced the migration and invasion of HUVECs, which was accompanied by upregulation of genes involved in angiogenesis, extracellular matrix organization, and cytoskeletal organization. The mRNA levels of growth factors, including placental growth factor and platelet-derived growth factor B, also increased. In addition, phosphorylation of paxicillin, focal adhesion kinase, and AKT increased under negative pressure. Collectively, the findings of this study demonstrated that negative pressure stimulates the angiogenic activity of HUVECs by increasing their proliferation and migration via activation of the AKT signaling pathway.

Antitumor Effects of Orally Administered Rare Sugar D-Allose in Bladder Cancer.

D-allose is a rare sugar that has been reported to up-regulate thioredoxin-interacting protein (TXNIP) expression and affect the production of intracellular reactive oxygen species (ROS). However, the antitumor effect of D-allose is unknown. This study aimed to determine whether orally administered D-allose could be a candidate drug against bladder cancer (BC). To this end, BC cell lines were treated with varying concentrations of D-allose (10, 25, and 50 mM). Cell viability and intracellular ROS levels were assessed using cell viability assay and flow cytometry. TXNIP expression was evaluated using Western blotting. The antitumor effect of orally administered D-allose was assessed using a xenograft mouse model. D-allose reduced cell viability and induced intracellular ROS production in BC cells. Moreover, D-allose stimulated TXNIP expression in a dose-dependent manner. Co-treatment of D-allose and the antioxidant L-glutathione canceled the D-allose-induced reduction in cell viability and intracellular ROS elevation. Furthermore, oral administration of D-allose inhibited tumor growth without adverse effects (p < 0.05). Histopathological findings in tumor tissues showed that D-allose decreased the nuclear fission rate from 4.1 to 1.1% (p = 0.004). Oral administration of D-allose suppressed BC growth in a preclinical mouse model, possibly through up-regulation of TXNIP expression followed by an increase in intracellular ROS. Therefore, D-allose is a potential therapeutic compound for the treatment of BC.

A New Indicator to Differentiate Thyroid Follicular Inclusions in Cervical Lymph Nodes from Patients with Thyroid Cancer.

Nodal metastasis is crucial for determining the stage of well-differentiated thyroid cancer (WTC) in patients older than 55. Well-formed thyroid follicular inclusions (TFIs) are occasionally encountered in the cervical lymph nodes (LNs) of patients with papillary thyroid carcinoma (PTC), and it is difficult to determine whether they are true nodal metastases or ectopic thyroid tissues (ETT). This study aimed to elucidate the impact of the expression of the DNA damage response molecule TP53-binding protein 1 (53BP1) using immunofluorescence (IF) as a biomarker to differentiate TFIs in cervical LN by comparing the mutation analyses of primary thyroid cancers. The data demonstrated the necessity for the differential diagnosis of true metastases from ETT among TFIs in cervical LNs. PTC-like nuclear features using hematoxylin-eosin staining combined with immunohistochemistry for conventional biomarkers of PTC, including BRAFV600E protein, were most helpful in identifying metastatic follicular-patterned carcinomas. In conclusion, IF analysis of 53BP1 expression could be an excellent ancillary technique to distinguish metastatic carcinoma or ETT from TFIs in LNs, particularly in cases other than BRAFV600E-mutated PTC.

Protection of rat artery grafts from tissue damage by voltage-applied supercooling.

Supercooling preservation below 0 °C allows the storage of the transplantable sources in an unfrozen state. This can improve the safety and efficacy of storage by improving the inhibition of metabolism and organ preservation in comparison with conventional preservation at 4 °C. We have developed a supercooling technique using a voltage-applied apparatus without perfusion. We examined the preservation effects of our supercooling preservation technique in a rat model of artery transplantation. Our technique produces a supercooled state at - 2 °C with application of 1000 V. The viability of tissue cells from rat arteries was found to be higher with storage using the proposed method than that under ordinary conditions. Damage to the vascular endothelium of the femoral artery preserved by voltage-applied supercooling at - 2 °C was reduced compared to storage under ordinary conditions. Artery graft revival was successfully achieved with graft patency after supercooling preservation, and 1 week outcomes for post-transplanted grafts, including thrombosis, were better with supercooling preservation than with conventional 4 °C preservation. Supercooling artery preservation at - 2 °C with 1000 V promises to greatly prolong preservation time and improve post-transplant outcomes.

Metformin repositioning in rheumatoid arthritis.

OBJECTIVES: Metformin is a known therapeutic agent for diabetes. Recently, several reports suggested the possibility of improvement in autoimmune disease and malignancy conditions through the effect of metformin on the immune system. Although there have been reports on the therapeutic effects of metformin on mouse models of collagen-induced arthritis, simulating human rheumatoid arthritis (RA), the effect of metformin on human RA remains unknown. Therefore, we investigated the inhibitory effect of metformin on the pathogenesis of human RA in vitro. METHODS: Osteoclastogenesis was evaluated with or without metformin. through tartrate-resistant acid phosphatase staining, osteoclast-specific enzyme expression analysis, and a bone resorption assay. Human fibroblast-like synoviocyte MH7A cells were stimulated with TNF-α, and the expression of proinflammatory cytokines and protease and growth factor genes was evaluated with or without metformin. Metformin has been used to evaluate their potential modulatory effects on cells treated with TNF-α. Moreover, we examined angiogenesis by performing a tube formation assay using human umbilical vein endothelial cells (HUVECs) with or without metformin. RESULTS: Osteoclastogenesis was suppressed in the presence of metformin, and the expression of osteoclast-specific genes was reduced. The TNF-α-induced expression of inflammatory cytokines and protease and growth factor genes in MH7A cells was downregulated by metformin. Additionally, the induced formation of tubular networks in HUVECs was also disrupted following treatment with metformin. CONCLUSIONS: These results suggest that metformin might improve the pathogenesis of RA, including joint inflammation and destruction. Thus, metformin might be utilised as a potential therapeutic agent in the treatment of RA.