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1.
Sci Rep ; 14(1): 21894, 2024 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300181

RESUMO

In-home automated scoring systems are in high demand; however, the current systems are not widely adopted in clinical settings. Problems with electrode contact and restriction on measurable signals often result in unstable and inaccurate scoring for clinical use. To address these issues, we propose a method based on ensemble of small sleep stage scoring models with different input signal sets. By excluding models that employ problematic signals from the voting process, our method can mitigate the effects of electrode contact failure. Comparative experiments demonstrated that our method could reduce the impact of contact problems and improve scoring accuracy for epochs with problematic signals by 8.3 points, while also decreasing the deterioration in scoring accuracy from 7.9 to 0.3 points compared to typical methods. Additionally, we confirmed that assigning different input sets to small models did not diminish the advantages of the ensemble but instead increased its efficacy. The proposed model can improve overall scoring accuracy and minimize the effect of problematic signals simultaneously, making in-home sleep stage scoring systems more suitable for clinical practice.


Assuntos
Eletrodos , Eletroencefalografia , Fases do Sono , Humanos , Fases do Sono/fisiologia , Masculino , Eletroencefalografia/métodos , Feminino , Adulto , Polissonografia/métodos , Algoritmos , Pessoa de Meia-Idade , Adulto Jovem
2.
Sci Rep ; 14(1): 17952, 2024 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095608

RESUMO

We present a new approach to classifying the sleep stage that incorporates a computationally inexpensive method based on permutations for channel selection and takes advantage of deep learning power, specifically the gated recurrent unit (GRU) model, along with other deep learning methods. By systematically permuting the electroencephalographic (EEG) channels, different combinations of EEG channels are evaluated to identify the most informative subset for the classification of the 5-class sleep stage. For analysis, we used an EEG dataset that was collected at the International Institute for Integrative Sleep Medicine (WPI-IIIS) at the University of Tsukuba in Japan. The results of these explorations provide many new insights such as the (1) drastic decrease in performance when channels are fewer than 3, (2) 3-random channels selected by permutation provide the same or better prediction than the 3 channels recommended by the American Academy of Sleep Medicine (AASM), (3) N1 class suffers the most in prediction accuracy as the channels drop from 128 to 3 random or 3 AASM, and (4) no single channel provides acceptable levels of accuracy in the prediction of 5 classes. The results obtained show the GRU's ability to retain essential temporal information from EEG data, which allows capturing the underlying patterns associated with each sleep stage effectively. Using permutation-based channel selection, we enhance or at least maintain as high model efficiency as when using high-density EEG, incorporating only the most informative EEG channels.


Assuntos
Eletroencefalografia , Fases do Sono , Humanos , Eletroencefalografia/métodos , Fases do Sono/fisiologia , Aprendizado Profundo , Masculino , Feminino , Adulto , Polissonografia/métodos
3.
Breast Cancer ; 31(5): 969-978, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38980571

RESUMO

BACKGROUND: Although the association between higher physical activity and preventive effect on breast-cancer-related lymphoedema (BCRL) has been reported, it is unclear what intervention is optimal. We aimed to investigate the effect of exercise and educational programs on BCRL development. METHODS: This study was a secondary endpoint analysis from a prospective randomized controlled trial. We enrolled patients with stage 0-III breast cancer from March 2016 to March 2020 and randomly assigned them to the control (n = 111), education (n = 115), or exercise (n = 104) group. As secondary endpoint, we assessed the incidence of and preventive effect on BCRL at 12 months post-intervention. RESULTS: There were no significant differences in the incidence of BCRL at 12 months post-intervention between the exercise and control groups (9.8% and 10.8%, P = 0.83) and the education and control groups (11.6% and 10.8%, P = 1.00). There were no significant differences in time to BCRL onset from the day of surgery between the exercise and control groups (event rate at 12 months: 20.7% and 17.2%, log-rank, P = 0.54) and the education and control groups (18.8% and 17.2%, log-rank, P = 0.57). The multivariable analyses indicated that axillary dissection and obesity significantly increased the risk of BCRL [hazard ratio (HR): 2.36, 95% confidence interval (CI) 1.52-3.67 and HR: 1.68, 95% CI 1.07-2.63, respectively]. CONCLUSIONS: The intervention did not decrease the risk of BCRL, and axillary dissection and obesity were the risk factors of BCRL. TRIAL REGISTRATION NUMBER: UMIN000020595 at UMIN Clinical Trial Registry.


Assuntos
Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Linfedema Relacionado a Câncer de Mama/etiologia , Linfedema Relacionado a Câncer de Mama/prevenção & controle , Linfedema Relacionado a Câncer de Mama/terapia , Exercício Físico , Educação de Pacientes como Assunto , Idoso , Adulto , Terapia por Exercício/métodos , Incidência , Linfedema/etiologia , Linfedema/prevenção & controle , Linfedema/epidemiologia , Mastectomia/efeitos adversos
4.
Mod Rheumatol ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727535

RESUMO

OBJECTIVES: We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients. METHODS: The ORIGAMI study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once-weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as an historical, weighted control group. The primary endpoint for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years. RESULTS: Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% (95% confidence interval [CI] 34.7%-46.2%) and 28.9% (95% CI 9.9%-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years. CONCLUSIONS: This study confirmed the 3-year effectiveness and safety, and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice.

5.
Intern Med ; 63(5): 687-692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38432894

RESUMO

17q12 deletion syndrome is a rare chromosomal anomaly with variable phenotypes, caused by the heterozygous deletion of chromosome 17q12. We herein report a 35-year-old Japanese patient with chromosomal 17q12 deletion syndrome identified by de novo deletion of the 1.46 Mb segment at the 17q12 band by genetic analyses. He exhibited a wide range of phenotypes, such as maturity-onset diabetes of the young (MODY) type 5, structural or functional abnormalities of the kidney, liver, and pancreas; facial dysmorphic features, electrolyte disorders; keratoconus, and acquired perforating dermatosis. This case report provides valuable resources concerning the clinical spectrum of rare 17q12 deletion syndrome.


Assuntos
Doenças do Sistema Nervoso Central , Esmalte Dentário/anormalidades , Diabetes Mellitus Tipo 2 , Doenças Renais Císticas , Masculino , Humanos , Adulto , Japão , Face , Heterozigoto
6.
Acta Med Okayama ; 78(1): 89-93, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38419320

RESUMO

We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis.


Assuntos
Neoplasias da Mama , Coristoma , Feminino , Humanos , Idoso , Neoplasias da Mama/patologia , Mastectomia , Linfonodos/patologia , Mama , Excisão de Linfonodo , Coristoma/cirurgia , Coristoma/patologia
7.
Case Rep Obstet Gynecol ; 2024: 3938833, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38304761

RESUMO

We present a case of recurrent ovarian cancer at the age of 75, gravida 1 para 0, with 18 years of disease-free survival. Chemotherapy brought a 10-month partial response status; to further improve the overall survival, the patient was evaluated using the AGO score (DESKTOP III trial, 2020), which was originally intended for cases immediately after the diagnosis of recurrence; the score has indicated a significant outcome; the patient went through a hepatosplenic metastatic site resection; and complete resection was achieved. Subsequently, the PARP inhibitor was introduced, which has led to 14 months of disease-free survival. Fifteen cases of late recurrence of epithelial ovarian cancer have been reported and are summarized at the end of this paper.

8.
Int Heart J ; 65(1): 100-108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38296562

RESUMO

The effectiveness of gamification-based feedback systems that utilize non-monetary points to promote exercise among cardiovascular disease (CVD) patients has not been fully evaluated. This study aimed to evaluate the effectiveness of a gamification program using non-monetary points on the daily step counts in CVD patients. We collected 30 patients with a history of heart failure or myocardial infarction at a single tertiary center between January 9, 2023, and April 13, 2023. The primary outcome was the change in daily step counts. The baseline step counts were compared with those during the 4-week gamification and the 1-week follow-up period. A total of 29 participants with a mean age of 64.6 years were finally enrolled, and 8 (27.6%) were female. Among them, 23 (79.3%) had a history of old myocardial infarction, and 9 (31.0%) had a history of chronic heart failure. During the intervention period, the average daily step counts increased significantly from baseline in weeks 1-5 (week 1: 1165 steps; 95% CI, 319-2011; P = 0.009, week 2: 1508; 635-2382; P = 0.001, week 3: 1321; 646-1996; P < 0.001, week 4: 1436; 791-2081; P < 0.001, week 5:1148; 436-1860; P < 0.001). Higher body mass index was statistically associated with the smaller difference in step counts from the baseline, and the lower proportion of achievement of step count goals. Female sex was significantly associated with the higher proportion of achievement of step count goals. In conclusion, this pilot prospective interventional study demonstrated the effectiveness of gamification-based feedback systems that utilize non-monetary points to increase daily step counts in CVD patients.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Retroalimentação , Economia Comportamental , Estudos Prospectivos
9.
Clin Breast Cancer ; 24(1): 27-35.e8, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37852895

RESUMO

BACKGROUND: It is unclear what interventions can sustain long-term higher physical activity (PA) to improve breast cancer outcomes. Thus, this study aimed to evaluate the long-term effects of interventions on PA after breast cancer treatment. METHODS: This was a prospective randomized controlled trial for patients with stage 0 to III breast cancer evaluating the efficacy of exercise and educational programs on long-term PA compared with usual care. The primary endpoint was proportion of patients with recreational PA (RPA) ≥5 metabolic equivalents (METs)/week at 1 year after registration. RESULTS: From March 16, 2016, to March 15, 2020, breast cancer patients were registered in the control (n = 120), education (n = 121), or exercise (n = 115) group. There were no significant differences in proportion of RPA ≥5 METs/week at 1 year between the exercise and control groups (54% and 53%, P = .492) and between the education and control groups (62% and 53%, P = .126). Significant difference in reductions from baseline at 1 year were noted on body weight (P = .0083), BMI (P = .0034), and body fat percentage (P = .0027) between education and control groups. Similarly, the exercise group showed significant difference in reduction in body fat percentage (P = .0038) compared to control group. CONCLUSION: Although there were no significant effects on RPA 1 year after exercise and educational programs for breast cancer survivors, both interventions reduced body composition. Future studies on PA should investigate appropriate interventions to improve overall survival.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Estudos Prospectivos , Exercício Físico , Peso Corporal , Composição Corporal , Qualidade de Vida
10.
Kobe J Med Sci ; 69(3): E96-E105, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37941117

RESUMO

In acute lung injury (ALI), a severe insult induces a hyperinflammatory state in the lungs. The mortality rate of severe ALI remains high, and novel mechanistic insights are required to improve therapeutic strategies. Endothelin-2 (Edn2), the least studied isoform of endothelin, is involved in lung physiology and development and can be affected by various factors. One of them is inflammation, and another isoform of endothelin, endothelin-1 (Edn1), affects lung inflammatory responses. Considering the importance of Edn2 in the lungs and how Edn2 works through the same receptors as Edn1, we postulated that Edn2 may affect inflammatory responses that are central to ALI pathophysiology. In this study, we performed 24 hours intratracheal lipopolysaccharide (LPS) instillation or PBS control as an in vivo ALI model in eight-week-old conditional Edn2 knockout mice (Edn2-iKO), with Edn2-floxed mice as controls. Bronchoalveolar lavage (BAL) fluid and tissue were collected after exsanguination and analyzed for its cellular, molecular, functional, and histological inflammatory phenotypes. We found that Edn2-iKO mice displayed a reduced pro-neutrophilic inflammatory phenotype even after acute LPS treatment, shown by the reduction in the overall protein concentration and neutrophil count in bronchoalveolar lavage fluids. Further investigation revealed a reduction in mRNA interferon gamma (IFNγ) level of Edn2-iKO lungs and suppression of its downstream signaling, including phosphorylated level of STAT1 and IL-1ß secretion, leading to reduced NFĸB activation. To conclude, Edn2 deletion suppressed acute lung inflammation by reducing neutrophil-mediated IFNγ/STAT1/IL-1ß/NFĸB signaling cascade. Targeting Edn2 signaling may be beneficial for the development of novel treatment options for ALI.


Assuntos
Lesão Pulmonar Aguda , Endotelina-2 , Animais , Camundongos , Endotelina-2/metabolismo , Lipopolissacarídeos , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Pulmão/patologia , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/uso terapêutico
11.
Reprod Med Biol ; 22(1): e12543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745035

RESUMO

Purpose: Tamoxifen is used for the suppression of estrogen-sensitive tumor recurrence in oocyte retrieval cycles. This meta-analysis aimed to evaluate the quality of controlled ovarian stimulation (COS) with co-administration of gonadotropins and tamoxifen (COS with tamoxifen). Methods: PubMed, Embase, and Cochrane Library were searched for articles on October 30, 2022. The authors included studies comparing COS with tamoxifen and COS with gonadotropins and letrozole (COS with letrozole) or gonadotropin only (COS with gonadotropin only) for fertility preservation in patients with breast cancer. The main outcome measures were the COS quality, total number of retrieved oocytes (TOR), total number of mature oocytes (TMO), and peak estradiol levels (PEL). Results: Four studies (348 patients, two randomized controlled trials, and two cohort studies) were included in our meta-analysis. There was no significant difference in TOR (95% CI, [-3.84, 2.90]) and TMO (95% CI, [-2.20, 2.64]) between COS with tamoxifen and COS with letrozole. There was also no difference in TOR (95% CI, [-6.14, 1.86]) between COS with tamoxifen and COS with gonadotropin only. Statistically significant decrease was observed in PEL during COS with letrozole compared with tamoxifen (95% CI, [1414.4, 4953.7]). Conclusions: The quality did not differ between COS with tamoxifen and COS with letrozole or gonadotropin only.

12.
Breast Cancer ; 30(5): 856-868, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37422608

RESUMO

PURPOSE: Emojis are commonly used for daily communication and may be useful in assessing patient-reported outcomes (PROs) in breast cancer. The purpose of this study is to develop and validate a Symptom Illustration Scale (SIS) as a new PRO measurement. METHODS: Eighteen original SIS items were developed from the PRO-CTCAE. In cohort one, the SIS validity and reliability were examined in patients with breast cancer, using a semi-structured five-question survey to investigate content validity. PROs with PRO-CTCAE and SIS were examined twice to determine criteria validity and test-retest reliability. In cohort two, the responsiveness of the scales were examined in patients treated with anthracycline, docetaxel, paclitaxel, and endocrine therapy. PROs with PRO-CTCAE and SIS were investigated two or three times, depending on the therapy. RESULTS: Patients were enrolled from August 2019 to October 2020. In cohort one (n = 70), most patients had no difficulties with the SIS, but 16 patients indicated that it was difficult to understand severities in the SIS. For criterion validity, Spearman rank correlation coefficients (rs) between PRO-CTCAE and SIS items were ≥ 0.41, except for "Decreased appetite." For test-retest reliability, κ coefficients of the SIS were ≥ 0.41 for 16/18 items (88.9%). Response time was significantly shorter for the SIS than for PRO-CTCAE (p < 0.001). In cohort two (n = 106), score changes between PRO-CTCAE and SIS for relevant symptoms all had correlations with rs ≥ 0.41. CONCLUSION: An original SIS from the PRO-CTCAE for patients with breast cancer were verified the validity, reliability, and responsiveness. Further studies to improve and validate the SIS are needed.


Assuntos
Neoplasias da Mama , Neoplasias , Estados Unidos , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Reprodutibilidade dos Testes , National Cancer Institute (U.S.) , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários
13.
iScience ; 26(5): 106662, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37192975

RESUMO

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a progressive increase in pulmonary artery pressure caused by pathological pulmonary artery remodeling. Here, we demonstrate that endothelial cell (EC) senescence plays a negative role in pulmonary hypertension via juxtacrine interaction with smooth muscle cells (SMCs). By using EC-specific progeroid mice, we discovered that EC progeria deteriorated vascular remodeling in the lungs, and exacerbated pulmonary hypertension in mice. Mechanistically, senescent ECs overexpressed Notch ligands, which resulted in increased Notch signaling and activated proliferation and migration capacities in neighboring SMCs. Pharmacological inhibition of Notch signaling reduced the effects of senescent ECs on SMCs functions in vitro, and improved the worsened pulmonary hypertension in EC-specific progeroid mice in vivo. Our findings show that EC senescence is a critical disease-modifying factor in PAH and that EC-mediated Notch signaling is a pharmacotherapeutic target for the treatment of PAH, particularly in the elderly.

14.
Rev Sci Instrum ; 94(5)2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37125859

RESUMO

We report an experimental setup for simultaneously measuring specific heat and thermal conductivity in feedback-controlled pulsed magnetic fields of 50 ms duration at cryogenic temperatures. A stabilized magnetic field pulse obtained by the feedback control, which dramatically improves the thermal stability of the setup and sample, is used in combination with the flash method to obtain absolute values of thermal properties up to 37.2 T in the 22-16 K temperature range. We describe the experimental setup and demonstrate the performance of the present method with measurements on single-crystal samples of the geometrically frustrated quantum spin-dimer system SrCu2(BO3)2. Our proof-of-principle results show excellent agreement with data taken using a standard steady-state method, confirming the validity and convenience of the present approach.

15.
Fukushima J Med Sci ; 69(1): 11-20, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36990790

RESUMO

OBJECTIVES: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. METHODS: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. RESULTS: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). CONCLUSIONS: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Metotrexato/efeitos adversos , Antirreumáticos/efeitos adversos , Estudos de Coortes , Estudos de Viabilidade , Quimioterapia Combinada , Artrite Reumatoide/tratamento farmacológico , Resultado do Tratamento
16.
Front Physiol ; 14: 1040425, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36776965

RESUMO

Pulse rate variability (PRV), derived from Laser Doppler flowmetry (LDF) or photoplethysmography, has recently become widely used for sleep state assessment, although it cannot identify all the sleep stages. Peripheral blood flow (BF), also estimated by LDF, may be modulated by sleep stages; however, few studies have explored its potential for assessing sleep state. Thus, we aimed to investigate whether peripheral BF could provide information about sleep stages, and thus improve sleep state assessment. We performed electrocardiography and simultaneously recorded BF signals by LDF from the right-index finger and ear concha of 45 healthy participants (13 women; mean age, 22.5 ± 3.4 years) during one night of polysomnographic recording. Time- and frequency-domain parameters of peripheral BF, and time-domain, frequency-domain, and non-linear indices of PRV and heart rate variability (HRV) were calculated. Finger-BF parameters in the time and frequency domains provided information about different sleep stages, some of which (such as the difference between N1 and rapid eye movement sleep) were not revealed by finger-PRV. In addition, finger-PRV patterns and HRV patterns were similar for most parameters. Further, both finger- and ear-BF results showed 0.2-0.3 Hz oscillations that varied with sleep stages, with a significant increase in N3, suggesting a modulation of respiration within this frequency band. These results showed that peripheral BF could provide information for different sleep stages, some of which was complementary to the information provided by PRV. Furthermore, the combination of peripheral BF and PRV may be more advantageous than HRV alone in assessing sleep states and related autonomic nervous activity.

17.
Prostate Cancer Prostatic Dis ; 26(1): 59-66, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-34593983

RESUMO

BACKGROUND: The taxane cabazitaxel (CBZ) is a promising treatment for docetaxel-resistant castration-resistant prostate cancer (CRPC). However, the survival benefit with CBZ for patients with CRPC is limited. This study used screening tests for candidate drugs targeting CBZ-resistant-related gene expression and identified pimozide as a potential candidate for overcoming CBZ resistance in CRPC. METHODS: We established CBZ-resistant cell lines, DU145CR and PC3CR by incubating DU145 cells and PC3 cells with gradually increasing concentrations of CBZ. We performed in silico drug screening for candidate drugs that could reprogram the gene expression signature of a CBZ-resistant prostate cancer cells using a Connectivity Map. The in vivo effect of the drug combination was tested in xenograft mice models. RESULTS: We identified pimozide as a promising candidate drug for CBZ-resistant CRPC. Pimozide had a significant antitumor effect on DU145CR cells. Moreover, combination treatment with pimozide and CBZ had a synergic effect for DU145CR cells in vitro and in vivo. Microarray analysis identified AURKB and KIF20A as potential targets of pimozide in CBZ-resistant CRPC. DU145CR had significantly higher AURKB and KIF20A expression compared with a non-CBZ-resistant cell line. Inhibition of AURKB and KIF20A had an antitumor effect in DU145CR xenograft tumors. Higher expression of AURKB and KIF20A was a poor prognostic factor of TGCA prostate cancer cohort. CBZ-resistant prostate cancer tissues in our institution had higher AURKB and KIF20A expression. CONCLUSIONS: Pimozide appears to be a promising drug to overcome CBZ resistance in CRPC by targeting AURKB and KIF20A.


Assuntos
Antineoplásicos , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Animais , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Pimozida/farmacologia , Pimozida/uso terapêutico , Detecção Precoce de Câncer , Taxoides/farmacologia , Taxoides/uso terapêutico , Linhagem Celular Tumoral
18.
Mod Rheumatol ; 33(2): 271-278, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35389481

RESUMO

OBJECTIVES: We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Humanos , Metotrexato/efeitos adversos , Abatacepte/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Resultado do Tratamento , Quimioterapia Combinada , Produtos Biológicos/uso terapêutico
19.
Front Aging Neurosci ; 14: 1050648, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561133

RESUMO

Study objective: Traditionally, age-related deterioration of sleep architecture in older individuals has been evaluated by visual scoring of polysomnographic (PSG) recordings with regard to total sleep time and latencies. In the present study, we additionally compared the non-REM sleep (NREM) stage and delta, theta, alpha, and sigma wave stability between young and older subjects to extract features that may explain age-related changes in sleep. Methods: Polysomnographic recordings were performed in 11 healthy older (72.6 ± 2.4 years) and 9 healthy young (23.3 ± 1.1 years) females. In addition to total sleep time, the sleep stage, delta power amplitude, and delta, theta, alpha, and sigma wave stability were evaluated by sleep stage transition analysis and a novel computational method based on a coefficient of variation of the envelope (CVE) analysis, respectively. Results: In older subjects, total sleep time and slow-wave sleep (SWS) time were shorter whereas wake after sleep onset was longer. The number of SWS episodes was similar between age groups, however, sleep stage transition analysis revealed that SWS was less stable in older individuals. NREM sleep stages in descending order of delta power were: SWS, N2, and N1, and delta power during NREM sleep in older subjects was lower than in young subjects. The CVE of the delta-band is an index of delta wave stability and showed significant differences between age groups. When separately analyzed for each NREM stage, different CVE clusters in NREM were clearly observed between young and older subjects. A lower delta CVE and amplitude were also observed in older subjects compared with young subjects in N2 and SWS. Additionally, lower CVE values in the theta, alpha and sigma bands were also characteristic of older participants. Conclusion: The present study shows a decrease of SWS stability in older subjects together with a decrease in delta wave amplitude. Interestingly, the decrease in SWS stability coincided with an increase in short-term delta, theta, sigma, and alpha power stability revealed by lower CVE. Loss of electroencephalograms (EEG) variability might be a useful marker of brain age.

20.
Plants (Basel) ; 11(19)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36235346

RESUMO

Pharmaceutical plants contain several phytochemicals that are sources of myriad biological activities. These biological activities can be explored in multiple fields for the benefit of mankind. Pharmaceutical plants with high ethnobotanical indices (i.e., use value and relative frequency of citation) were reported with the potential to inhibit lettuce elongation through leachates and volatiles. The focus of the study was to assess Chinese pharmaceutical plants for both antioxidants, as well as allelopathic potentials to explore any underlying relationship. The estimation of antioxidative capacity and content of total phenolics (TPC) for the 55 Chinese pharmaceutical plants was conducted by the assays of DPPH radical scavenging activity (DPPH-RSA), oxygen radical absorbance capacity (ORAC) and the means of Folin−Ciocalteu. The estimation of the activity of allelopathy for collected medicinal plants was done by adopting the sandwich method for plant leachates and the dishpack method for volatile constituents, respectively. The fruits of sea buckthorn (Hippophae rhamnoides) had the most remarkable ORAC value (168 ± 7.04 µmol TE/g) and DPPH radical scavenging activity (440 ± 7.32 µmol TE/g) and contained the highest contents of total phenolic compounds (236 ± 7.62 mg GAE/g) in the 55 pharmaceutical plant species according to the results. In addition, sea buckthorn showed dominant allelopathic potential through plant leachates evaluated by using the sandwich method. Star anise (Illicium verum Hook. f.) showed conspicuous allelopathic activity through plant volatiles assessed by the dishpack bioassay method. Among the same plant species, antioxidative ability and total phenolics, in comparison with potential allelopathy of medicinal herbs indicated that volatile allelochemical had a weak active effect (r = 0.407 to 0.472, p < 0.01), with antioxidant capacity by the dishpack method. However, the evaluation by the sandwich method showed a significant positive correlation (r = 0.718 to 0.809, p < 0.001) with antioxidant capacity. Based on these results, a new hypothesis is that the antioxidant activity of plants may have an involvement with the potential allelopathic activity.

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