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1.
Am J Pathol ; 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38588851

ABSTRACT

The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and shRNA in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mammalian target of rapamycin and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. TFE3 is related to the PI3K/Akt pathway in RCC, and the results of this study suggest that PI3K/Akt inhibitors potentially may aid in treatment of patients with RCC by affecting the tumor microenvironment.

2.
Exp Mol Med ; 56(2): 478-490, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38413821

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling and the excessive accumulation of extracellular matrix (ECM) proteins. In a previous study, we found that the levels of ornithine aminotransferase (OAT), a principal enzyme in the proline metabolism pathway, were increased in the lungs of patients with IPF. However, the precise role played by OAT in the pathogenesis of IPF is not yet clear. The mechanism by which OAT affects fibrogenesis was assessed in vitro using OAT-overexpressing and OAT-knockdown lung fibroblasts. The therapeutic effects of OAT inhibition were assessed in the lungs of bleomycin-treated mice. OAT expression was increased in fibrotic areas, principally in interstitial fibroblasts, of lungs affected by IPF. OAT levels in the bronchoalveolar lavage fluid of IPF patients were inversely correlated with lung function. The survival rate was significantly lower in the group with an OAT level >75.659 ng/mL than in the group with an OAT level ≤75.659 ng/mL (HR, 29.53; p = 0.0008). OAT overexpression and knockdown increased and decreased ECM component production by lung fibroblasts, respectively. OAT knockdown also inhibited transforming growth factor-ß1 (TGF)-ß1 activity and TGF-ß1 pathway signaling. OAT overexpression increased the generation of mitochondrial reactive oxygen species (ROS) by activating proline dehydrogenase. The OAT inhibitor L-canaline significantly attenuated bleomycin-induced lung injury and fibrosis. In conclusion, increased OAT levels in lungs affected by IPF contribute to the progression of fibrosis by promoting excessive mitochondrial ROS production, which in turn activates TGF-ß1 signaling. OAT may be a useful target for treating patients with fibrotic lung diseases, including IPF.


Subject(s)
Idiopathic Pulmonary Fibrosis , Transforming Growth Factor beta1 , Animals , Humans , Mice , Bleomycin , Extracellular Matrix Proteins , Fibrosis , Lung/enzymology , Ornithine-Oxo-Acid Transaminase , Reactive Oxygen Species
3.
World J Mens Health ; 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38164028

ABSTRACT

PURPOSE: This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups. RESULTS: No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups. CONCLUSIONS: ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.

4.
Cancer Res Treat ; 56(2): 634-641, 2024 04.
Article in English | MEDLINE | ID: mdl-38062708

ABSTRACT

PURPOSE: In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC. MATERIALS AND METHODS: Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed. RESULTS: Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002). CONCLUSION: Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Male , Humans , Prostatic Neoplasms, Castration-Resistant/drug therapy , Phenylthiohydantoin/adverse effects , Benzamides/therapeutic use , Nitriles/therapeutic use , Treatment Outcome , Retrospective Studies
5.
J Hosp Palliat Care ; 26(4): 185-189, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38075592

ABSTRACT

Purpose: Limited research has been conducted on the prevalence of non-medical opioid use (NMOU) in Korean cancer patients who have received prescription opioids (PO). This study aimed to identify the potential proportion of NMOU in cancer patients who had been prescribed opioids in Korea. Methods: A retrospective cohort analysis was conducted on 14,728 patients who underwent cancer-related treatment between January 2009 and December 2019, using electronically collected data from a tertiary hospital in Korea. Information regarding the type and duration of opioid use was gathered. A detailed review of medical charts was carried out, focusing on patients who had been prescribed opioids for over 60 days beyond a 12-month period following the completion of their cancer treatment (long-term PO users). Results: Out of the 5,587 patients who were prescribed PO and followed up for at least 12 months, 13 cases of NMOU were identified, representing 0.23% of the patient population. Among the 204 long-term PO users, the rate was 6.37% (13/204). The most commonly misused opioids were oxycodone and fentanyl. For the group confirmed to have NMOU, the median duration of prescription was 1,327 days in total. Of the 13 patients diagnosed with NMOU, 9 reported withdrawal symptoms, 3 exhibited craving behavior for opioids, and 1 experienced both symptoms. Conclusion: This study found that 0.23% of cancer patients who had been prescribed opioids in Korea demonstrated NMOU. Despite this relatively low rate, careful monitoring is necessary to minimize the risk of NMOU in this population, especially among long-term PO users.

7.
Prostate Int ; 11(3): 167-172, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37745905

ABSTRACT

Background: To develop a customized prostate biopsy indication using prostate health index density (PHID) combined with multiparametric magnetic resonance imaging (mpMRI) and assess the reliability of the PHID cutoff value in external populations. Methods: A total of 521 cognitive MRI/ultrasonography fusion prostate biopsies and biomarker tests for prostate-specific antigen (PSA), free PSA, and PHI were performed after mpMRI. The predictive value for clinically significant prostate cancer (csPCa; Gleason score≥7) of PSA derivatives was examined using the ROC curve. We developed a new biopsy indication utilizing a PHID cutoff based on the Prostate Image-Reporting and Data System (PI-RADS) score, which was externally validated. Results: The combination of PHID and mpMRI (AUC = 0.884) demonstrated the highest predictive ability for csPCa, although PHID (AUC = 0.843) and PI-RADS (AUC = 0.806) individually also showed a high diagnostic value. When a PHID cutoff of 0.75 was used in men with PI-RADS 3 lesions, the negative predictive value of csPCa was 100%, and approximately half of the biopsies could be safely avoided. Conclusion: Compared to PHID or PI-RADS scores alone, the combination of PHID and PI-RADS scores increased the accuracy of csPCa detection and the number of cases in which biopsy could be avoided. In men with PI-RADS 3 lesions, the optimal PHID cutoff ≥0.75 can prevent half of the unnecessary biopsies without missing csPCa. In men with PI-RADS 4-5 lesions, biopsies are warranted regardless of PHID values because csPCa could be accompanied by low PHID.

8.
Investig Clin Urol ; 64(5): 466-473, 2023 09.
Article in English | MEDLINE | ID: mdl-37668202

ABSTRACT

PURPOSE: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data. MATERIALS AND METHODS: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded. RESULTS: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups. CONCLUSIONS: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prospective Studies , Treatment Outcome , Republic of Korea
9.
Sci Rep ; 13(1): 9044, 2023 06 03.
Article in English | MEDLINE | ID: mdl-37270622

ABSTRACT

Proper lipid metabolism is crucial to maintain alveolar epithelial cell (AEC) function, and excessive AEC death plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The mRNA expression of fatty acid synthase (FASN), a key enzyme in the production of palmitate and other fatty acids, is downregulated in the lungs of IPF patients. However, the precise role of FASN in IPF and its mechanism of action remain unclear. In this study, we showed that FASN expression is significantly reduced in the lungs of IPF patients and bleomycin (BLM)-treated mice. Overexpression of FASN significantly inhibited BLM-induced AEC death, which was significantly potentiated by FASN knockdown. Moreover, FASN overexpression reduced BLM-induced loss of mitochondrial membrane potential and the production of mitochondrial reactive oxygen species (ROS). Oleic acid, a fatty acid component increased by FASN overexpression, inhibited BLM-induced cell death in primary murine AECs and rescue BLM induced mouse lung injury/fibrosis. FASN transgenic mice exposed to BLM exhibited attenuated lung inflammation and collagen deposition compared to controls. Our findings suggest that defects in FASN production may be associated with the pathogenesis of IPF, especially mitochondrial dysfunction, and augmentation of FASN in the lung may have therapeutic potential in preventing lung fibrosis.


Subject(s)
Bleomycin , Fatty Acid Synthase, Type I , Idiopathic Pulmonary Fibrosis , Animals , Mice , Bleomycin/toxicity , Bleomycin/metabolism , Idiopathic Pulmonary Fibrosis/chemically induced , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/drug therapy , Lung/pathology , Mice, Inbred C57BL , Mice, Transgenic , Mitochondria/metabolism , Humans , Fatty Acid Synthase, Type I/genetics , Fatty Acid Synthase, Type I/metabolism
10.
World J Mens Health ; 41(3): 743-749, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37357753

ABSTRACT

PURPOSE: To evaluate the impact of paired transrectal ultrasonography (TRUS) findings of index lesions identified by multiparametric magnetic resonance imaging (mpMRI) on the detection rate of clinically significant prostate cancer (csPCa, Gleason score ≥7) during MRI/US fusion-targeted biopsies. MATERIALS AND METHODS: From 2019 to 2021, TRUS findings of paired index lesions were prospectively collected from MRI/US cognitive (cTB, n=299) or program-assisted (pTB, n=294) fusion-targeted biopsies. csPCa detection rates according to the presence of a paired hypoechoic lesion (HoEL) and predictive factors for csPCa detection by targeted biopsy were evaluated. RESULTS: Among 593 patients with visible lesions on upfront mpMRI (Prostate Imaging-Reporting and Data System score ≥3), 288 (48.6%) had paired HoELs on TRUS. The csPCa detection rates in targeted biopsy patients with and without paired HoELs were 56.3% and 10.5% (p<0.001), respectively. Detection rates in patients with and without paired HoELs in the peripheral zone were 65.0% and 14.5%, respectively, and in the transition zone, 37.4% and 8.2%, respectively. In the cTB cohort, a paired HoEL (OR=6.25; p<0.001) was an independent predictive factor for the detection of csPCa in the target core, but not in the pTB cohort (OR=1.92; p=0.107). CONCLUSIONS: During MRI/US fusion-targeted biopsy, csPCa detection rate was higher in patients with paired HoELs on TRUS than in those without it. After adjustment of the zonal location and mpMRI findings, the presence of paired HoELs is an independent predictive factor for csPCa detection in cTB, but not in pTB. Therefore, paired HoELs improve only the targeting of visually estimated biopsies.

11.
Foods ; 12(9)2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37174339

ABSTRACT

This study aims to develop a freshness indicator for fish products that changes color to indicate ammonia among volatile base compounds (TVB-N) generated during storage. Through an optimization experiment, we observed the indicator's color change relative to the ammonia concentration standard, finally selecting cresol red and bromocresol purple for the indicator mixture. In addition, eco-DEHCH and Breathron film were applied to the freshness indicator, considering environmental and economic values. For the storage experiment, Chub mackerel (Scomber japonicus), Spanish mackerel (Scomberomorus niphonius), and Largehead hairtail (Trichiurus lepturus) samples were stored at three different temperatures (4, 10, and 20 °C) for seven days, and we measured pH, TVB-N, total bacterial count, and ammonia content every 24 h. The pH-sensitive sensors' color changes monitor amine release, especially ammonia, from decomposing fish. The chromatic parameter ∆E value increased significantly with fish product storage periods. We confirmed that when the freshness limit and bacterial spoilage level were reached, the color of the indicator changed from yellow to black and sequentially changed to purple as the storage period increased. Therefore, a developed freshness indicator can be used for determining the quality of fish products quickly and non-destructively by reflecting the freshness and spoilage degree of fish products during storage.

12.
J Anim Sci Technol ; 65(2): 401-411, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37093902

ABSTRACT

Many studies have been conducted to improve technology for semen cryopreservation in pigs. However, computer-assisted analysis of sperm motility and morphology is insufficient to predict the molecular function of frozen-thawed semen. More accurate expression patterns of boar sperm proteins may be derived using the isobaric tags for relative and absolute quantification (iTRAQ) technique. In this study, the iTRAQ-labeling system was coupled with liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis to identify differentially expressed CM10-fractionated proteins between fresh and frozen-thawed boar semen. A total of 76 protein types were identified to be differentially expressed, among which 9 and 67 proteins showed higher and lower expression in frozen-thawed than in fresh sperm samples, respectively. The classified functions of these proteins included oxidative phosphorylation, mitochondrial inner membrane and matrix, and pyruvate metabolic processes, which are involved in adenosine triphosphate (ATP) synthesis; and sperm flagellum and motile cilium, which are involved in sperm tail structure. These results suggest a possible network of biomarkers associated with survival after the cryopreservation of Duroc boar semen.

13.
J Korean Med Sci ; 38(14): e106, 2023 Apr 10.
Article in English | MEDLINE | ID: mdl-37038643

ABSTRACT

BACKGROUND: Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. METHODS: In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. RESULTS: From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. CONCLUSION: These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.


Subject(s)
COVID-19 Vaccines , COVID-19 , Pneumonia , Aged , Female , Humans , Male , Ad26COVS1 , BNT162 Vaccine , ChAdOx1 nCoV-19 , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Republic of Korea/epidemiology , SARS-CoV-2 , Vaccination
14.
Int J Rheum Dis ; 26(5): 850-861, 2023 May.
Article in English | MEDLINE | ID: mdl-36967612

ABSTRACT

AIM: Coronavirus disease 2019 (COVID-19) has been proposed as triggering autoimmunity. The aim of this study was to evaluate the presence and clinical significance of autoantibodies in patients with COVID-19. METHODS: We retrospectively collected data from 245 patients who were hospitalized for COVID-19. All patients were tested for the presence of antinuclear antibody (ANA), rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), and anti-cytoplasmic neutrophil antibody (ANCA). Risk factors for death and critical COVID-19, defined as the need for invasive mechanical ventilation or extracorporeal membrane oxygenation, were analyzed. RESULTS: Ninety (36.7%) patients tested positive for ANA, and 51 (20.8%) patients tested positive for RF. Three patients each (1.2%) tested positive for ACPA and ANCA. RF-positive patients had higher rates of invasive mechanical ventilation and death than RF-negative patients (70.6% vs 28.4%, P < 0.001 and 45.1% vs 18.6%, P < 0.001, respectively). Underlying lung disease, kidney disease, heart disease, quick COVID severity index (qCSI), and lactate dehydrogenase (LDH) were associated with in-hospital death. RF (odds ratio [OR] 7.31, 95% CI 2.50-21.37, P < 0.001), qCSI (OR 1.42, 95% CI 1.19-1.69, P < 0.001), and LDH (OR 1.004, 95% CI 1.002-1.005, P < 0.001) were associated with critical COVID-19. Combination of RF, qCSI, and LDH showed good prognostic value (area under the curve = 0.903, P < 0.001) for critical COVID-19. CONCLUSIONS: ANA and RF were frequently detected in COVID-19 patients. RF could be a risk factor for critical COVID-19. The results of this study suggest immune dysfunction contributes to the complications of COVID-19.


Subject(s)
Arthritis, Rheumatoid , COVID-19 , Humans , Rheumatoid Factor , Retrospective Studies , Antibodies, Antineutrophil Cytoplasmic , Hospital Mortality , Autoantibodies , Antibodies, Antinuclear
15.
Front Med (Lausanne) ; 10: 1052129, 2023.
Article in English | MEDLINE | ID: mdl-36760404

ABSTRACT

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry. Materials and methods: This is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model. Results: Among 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38-3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60-4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p < 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality. Conclusion: The GAP6 model adding nadir SpO2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system.

16.
J Affect Disord ; 324: 8-15, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36566932

ABSTRACT

BACKGROUND: We investigated the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, on a depression-like phenotype in mice exposed to chronic unpredictable stress (CUS). Learning and memory were also assessed using the Morris water maze (MWM) test. METHODS: Liraglutide (0.3 mg/kg/day for 21 days) was administered to mice with or without exposure to CUS. After 21 days of CUS, the forced swim test (FST) was performed to assess its antidepressant effect. To evaluate cognitive function, liraglutide was administered to mice under stress-free conditions for 21 days, and then the MWM test was performed on 6 consecutive days. RESULTS: Chronic liraglutide treatment reduced FST immobility in mice with and without CUS. In the probe trial of the Morris water maze test, the search error rate was reduced and the time spent and path length in the target quadrant and the number of platform crossings were increased. LIMITATION: Additional animal model experiments and molecular level studies are needed to support the results obtained in this study. CONCLUSIONS: Liraglutide appears to exert antidepressant effects and could improve cognitive function. Based on these results, GLP-1 agonists could have potential as novel antidepressants.


Subject(s)
Liraglutide , Morris Water Maze Test , Mice , Animals , Liraglutide/pharmacology , Liraglutide/therapeutic use , Depression/drug therapy , Maze Learning , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Cognition , Glucagon-Like Peptide 1 , Disease Models, Animal , Behavior, Animal , Stress, Psychological
17.
Adv Sci (Weinh) ; 10(6): e2205424, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36575365

ABSTRACT

Lithium-sulfur batteries (LSBs) can replace lithium-ion batteries by delivering a higher specific capacity. However, the areal capacity of current LSBs is low because the intrinsic limitations of sulfur make achieving a high sulfur loading difficult. Herein, the authors report vertically aligned reduced graphene oxide (rGO) with sulfur and poly(ethylene oxide)-based polymer electrolyte double-shell layers (VRG@S@PPE) as a high-loading sulfur cathode. The addition of vapor-grown carbon fiber (VGCF) into rGO is the key to success, as it allows for gas evacuation from internal nano/micropores without structural collapse, enabling perfect double-shell layer contact. Owing to the anisotropic rGO lamellar structure that enables straightforward ion/electron transport and provides numerous active sites, sulfur-infiltrated rGO reinforced via VGCF (VRG@S) exhibits a high capacity of 998 mAh g-1 after 100 cycles at 0.1 C under high sulfur loading (6 mg cm-2 ). Interestingly, an additional polymer electrolyte layer further increases the cycle retention (1005 and 718 mAh g-1 after 100 cycles at 0.1 and 1 C, respectively), because intimate contact between the solid polymer electrolyte and sulfur could suppress the loss of sulfur due to lithium polysulfide (LPS) shuttling or volume change during lithiation/delithiation. Therefore, it is possible to realize safe and stable quasi-solid-state LSBs with high sulfur loading.

18.
World J Mens Health ; 41(1): 110-118, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35118841

ABSTRACT

PURPOSE: To establish a prospective registry for the active surveillance (AS) of prostate cancer (PC) using the Korean Urological Oncology Society (KUOS) database and to present interim analysis. MATERIALS AND METHODS: The KUOS registry of AS for PC (KUOS-AS-PC) was organized in May 2019 and comprises multiple institutions nationwide. The eligibility criteria were as follows: patients with (1) pathologically proven PC; (2) pre-biopsy prostate-specific antigen (PSA) ≤20 ng/mL; (3) International Society of Urological Pathology (ISUP) grade 1 or 2 (no cribriform pattern 4); (4) clinical T stage ≤T2c; (5) positive core ratio ≤50%; and (6) maximal cancer involvement in the core ≤50%. Detailed longitudinal clinical information, including multi-parametric magnetic resonance imaging and disease-specific outcomes, was recorded. RESULTS: From May 2019 to June 2021, 296 patients were enrolled, and 284 were analyzed. The mean±standard deviation (SD) age at enrollment was 68.7±8.2 years. The median follow-up period was 11.2 months (5.9-16.8 mo). Majority of patients had pre-biopsy PSA ≤10 ng/mL (91.2%), PSA density <0.2 ng/mL² (79.7%), ISUP grade group 1 (94.4%), single positive core (65.7%), maximal cancer involvement in the core ≤20% (78.1%), and clinical T stage of T1c or lower (72.9%). Fifty-two (18.3%) discontinued AS for various reasons. Interventions included radical prostatectomy (80.8%), transurethral prostatectomy (5.8%), primary androgen deprivation therapy (5.8%), radiation (5.8%), and focal therapy (1.9%). The mean±SD time to intervention was 8.9±5.2 months. The reasons for discontinuation included pathologic reclassification (59.6%), patient preference (25.0%), and radiologic reclassification (9.6%). Two (4.8%) patients with pathologic Gleason score upgraded to ISUP grade group 4, no biochemical recurrence. CONCLUSIONS: The KUOS established a successful prospective database of PC patients undergoing AS in Korea, named the KUOS-AS-PC registry.

19.
World J Mens Health ; 41(1): 227-235, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36047076

ABSTRACT

PURPOSE: Persistent levels of prostate-specific antigen (PSA) is a poor prognostic factor for recurrence after radical prostatectomy (RP). We investigated the impact of the percentage of residual PSA (%rPSA) [(post-/preoperative PSA)×100], representing a biochemical residual tumor, and the first postoperative PSA (fPSA) level on metastasis-free survival (MFS) in men with persistent levels of PSA after RP. MATERIALS AND METHODS: We retrospectively identified male patients within a single tertiary referral hospital database who harbored persistent (≥0.1 ng/mL) vs. undetectable (<0.1 ng/mL) PSA levels 4 to 8 weeks after RP. Kaplan-Meier analyses and Cox regression models were used to test the effect of persistent PSA levels, the fPSA level, and %rPSA on MFS. RESULTS: Of 1,205 patients, 178 patients with persistent PSA levels were enrolled. Seven-year MFS rates were 60.5% vs. 84.3% (p<0.001) for patients with a %rPSA ≥6% and <6%, respectively. Multivariable Cox regression models of the overall cohort revealed that persistent PSA levels (hazard ratio [HR], 3.94; p=0.010), extracapsular extension (HR, 4.17; 95% confidence interval [CI], 1.06-16.41; p=0.041), and pathological Gleason grade group (pGGG) (HR, 3.69; 95% CI, 1.32-10.27; p=0.013) were independent predictors of metastasis. Multivariable Cox regression models in men with persistent PSA levels revealed that the %rPSA (HR, 8.92; 95% CI, 1.74-45.71; p=0.009) and pGGG 4-5 (HR, 4.13; 95% CI, 1.22-13.96; p=0.022) were independent predictors of distant metastasis, but not the fPSA level after surgery. CONCLUSIONS: Persistent levels of PSA were associated with worse MFS after RP. In men with persistent PSA levels after RP, the %rPSA is a valuable predictor of MFS unlike the fPSA level.

20.
Arq Neuropsiquiatr ; 80(10): 1017-1025, 2022 10.
Article in English | MEDLINE | ID: mdl-36535286

ABSTRACT

BACKGROUND: Individuals with spinocerebellar ataxia type 3 (SCA3) present communication and swallowing disorders, and consequent deterioration in quality of life (QOL). OBJECTIVE: To evaluate the impact of a speech therapy rehabilitation program on the QOL of patients with SCA3. METHODS: All participants were randomly assigned to two groups, an intervention group receiving speech therapy (STG) and a control group (CG). The International Cooperative Ataxia Rating Scale scores were 32.4 ± 20.2, and the Scale for the Assessment and Rating of Ataxia scores were 11.8 ± 8.0. The intervention consisted of a 12-session speech therapy rehabilitation program with oral, pharyngeal, and laryngeal strengthening exercises-the so-called ATAXIA-Myofunctional Orofacial and Vocal Therapy (A-MOVT). They all were submitted to pre- and postintervention evaluations using the World Health Organization's Quality of Life (WHOQOL-BREF) assessment, as well as the Living with Dysarthria (LwD), Quality of Life in Swallowing Disorders (SWAL-QOL), and Food Assessment Tool (EAT-10). RESULTS: The study sample consisted of 48 patients with SCA3 (STG = 25; CG = 23), mean age was 47.1 ± 11.4 years; mean age at symptom onset was 36.9 ± 11.3 years; disease duration was 11.9 ± 13.3 years. After the 3-month intervention, there were significant changes in the QOL in the STG compared with the CG, when assessed by the LwD (179.12 ± 62.55 vs. 129.88 ± 51.42, p < 0.001), SWAL-QOL (869.43 ± 153.63 vs. 911.60 ± 130.90, p = 0.010), and EAT-10 (5.16 ± 7.55 vs. 2.08 ± 3.85, p = 0.018). CONCLUSIONS: Patients with SCA3 should receive continuous speech therapy as part of the A-MOVT program, because therapy helps to improve difficulty swallowing and dysarthria.


ANTECEDENTES: Indivíduos com ataxia espinocerebelar tipo 3 (AEC3) apresentam distúrbios da comunicação e deterioração da deglutição e, consequentemente, na qualidade de vida (QV). OBJETIVO: Avaliar o impacto de um programa de reabilitação fonoaudiológica na QV em pacientes com AEC3. MéTODOS: Todos os participantes foram alocados aleatoriamente em dois grupos, um grupo intervenção que recebeu terapia fonoaudiológica (GTF) e um grupo controle (GC). As pontuações das escalas: International Cooperative Ataxia Rating Scale (ICARS) foram 32,4 ± 20,2 e da Scale for the Assessment and Rating of Ataxia (SARA) foram 11,8 ± 8,0. A intervenção consistiu em um programa de reabilitação fonoaudiológica de 12 sessões composto por exercícios de fortalecimento oral, faríngeo e laríngeo - denominados ATAXIA - Terapia Miofuncional Orofacial e Vocal (A-TMOV). Todos foram submetidos a avaliações pré e pós-intervenção por meio dos protocolos World Health Organization's Quality of Life (WHOQOL-BREF), Vivendo com Disartria (VcD), Quality of Life in Swallowing Disorders (SWAL-QOL) e Food Assessment Tool (EAT-10). RESULTADOS: A amostra foi composta por 48 pacientes com AEC3 (25 no GTF e 23 no GC), média de idade 47,1 ± 11,4anos; média de idade de início dos sintomas 36,9 ± 11,3anos; duração da doença 11,9 ± 13,3anos. Após intervenção de três meses, houve mudanças significativas na QV no GTF em comparação com o GC quando avaliado pelo VcD (179,12 ± 62,55 versus129,88 ± 51,42, p < 0,001), SWAL-QOL (869,43 ± 153,63 versus 911,60 ± 130,90, p = 0,010), EAT-10 (5,16 ± 7,55 versus 2,08 ± 3,85, p = 0,018). CONCLUSõES: Pacientes com AEC3 devem receber terapia fonoaudiológica contínua como parte do programa A-TMOV, pois a terapia ajuda a melhorar a dificuldade de deglutição e a disartria.


Subject(s)
Cerebellar Ataxia , Deglutition Disorders , Machado-Joseph Disease , Humans , Adult , Middle Aged , Deglutition Disorders/etiology , Quality of Life , Dysarthria , Speech Therapy , Ataxia
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