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1.
Food Chem ; 463(Pt 1): 141052, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39241415

ABSTRACT

Phytic acid (PA) and malic acid (MA), as environmentally friendly, plant-based water-soluble acids, were applied to normal corn starch during dry heating at mildly acidic pH to improve its gelatinization and retrogradation behaviors. A significant increase in peak viscosity (5011-6338 mPa·s) was observed in starch treated with MA compared to native corn starch (1162 mPa·s). The treatment with PA and MA further increased the peak viscosity (8140-8621 mPa·s). The interactions of PA and MA with starch were analyzed using ICP-OES, FTIR, and 13C CP/MAS NMR. Swelling power and solubility increased in MA and PA + MA starches. After storage at 4 °C for 14 d, MA and PA + MA starches produced transparent and fluid gels without forming B-type crystals, which indicated inhibition of starch retrogradation by PA and MA treatments. In conclusion, dry heating with PA and MA produced starch with remarkably superior paste viscosity, swelling, and inhibition of retrogradation.

3.
J Am Coll Cardiol ; 84(12): 1064-1075, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39260927

ABSTRACT

BACKGROUND: Medical therapy for aortic stenosis (AS) remains an elusive goal. OBJECTIVES: This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression. METHODS: A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using 18F-sodium fluoride positron emission tomography (18F-NaF PET). RESULTS: There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (-5.27; 95% CI: -55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (-18.83; 95% CI: -32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm3; 95% CI: 108-163 vs 102 mm3; 95% CI: 75-129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on 18F-NaF PET was significantly lower in both the evogliptin 5 mg (-1,325.6; 95% CI: -2,285.9 to -365.4; P = 0.008) and 10-mg groups (-1,582.2; 95% CI: -2,610.8 to -553.5; P = 0.0038) compared with the placebo group. CONCLUSIONS: This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883).


Subject(s)
Aortic Valve Stenosis , Aortic Valve , Calcinosis , Disease Progression , Humans , Female , Male , Aged , Calcinosis/drug therapy , Calcinosis/diagnostic imaging , Aortic Valve Stenosis/drug therapy , Aortic Valve Stenosis/diagnostic imaging , Middle Aged , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Double-Blind Method , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Positron-Emission Tomography/methods , Treatment Outcome , Tomography, X-Ray Computed , Piperazines
4.
Br Dent J ; 237(5): 379-388, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39271874

ABSTRACT

This article addresses the management of dental implants in joint orthodontic-restorative cases, emphasising the role of temporary skeletal anchorage devices and interdisciplinary treatment. Focused on complex malocclusions that require dental implants, the article navigates through critical aspects such as diagnosis, treatment planning, implant positioning challenges and the strategic role of temporary skeletal anchorage devices in cases with compromised anchorage. Effective communication, collaborative efforts and strategic planning are highlighted in determining optimal implant numbers, locations and timing of placement. A collaborative, strategic approach to managing the complexities of joint orthodontic-restorative cases involving dental implants is recommended.


Subject(s)
Dental Implants , Patient Care Team , Humans , Orthodontic Anchorage Procedures/instrumentation , Orthodontic Anchorage Procedures/methods , Patient Care Planning , Malocclusion/therapy , Orthodontics, Corrective/methods
5.
J Control Release ; 375: 105-115, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39218160

ABSTRACT

For the non-invasive treatment of rheumatoid arthritis (RA), a chondroitin sulfate C (CSC)-based dissolving microneedles (cMN) was prepared to deliver human adipose stem cell-derived extracellular vesicles (hASC-EV) into inflamed joints. Owing to their anti-inflammatory function, the hASC-EV-bearing cMN (EV@cMN) significantly suppressed activated fibroblast-like synoviocytes (aFLS) and M1 macrophages (M1), which are responsible for the progression of RA. In addition, EV@cMN facilitated the chondrogenic differentiation of bone marrow-derived stem cells. In mice with collagen-induced arthritis, EV@cMN efficiently delivered both hASC-EV and CSC to inflamed joints. Interestingly, pro-inflammatory cytokines in the inflamed joints were remarkably downregulated by the synergistic effect of CSC and hASC-EV. Consequently, as judged from the overall clinical score and joint swelling, EV@cMN showed an outstanding therapeutic effect, even comparable to the wild-type mice, without significant adverse effects. Overall, EV@cMN might have therapeutic potential for RA by efficiently delivering CSC and hASC-EV into the inflamed joints in a non-invasive manner.

6.
Clin Cancer Res ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39259292

ABSTRACT

PURPOSE: Greater disease burden is a well-established predictor of poorer outcomes following chimeric antigen receptor T-cell therapy (CART). While bridging therapy (BT) is widely used between leukapheresis and CAR T infusion, limited data has evaluated the impact of BT on CART outcomes. In this study, we hypothesized that the quantitative dynamics of radiomic cytoreduction during bridging are prognostic. PATIENTS AND METHODS: Patients with large B-cell lymphoma (LBCL) treated with CD19-CART from 2016-2022 were included. Metabolic tumor volume (MTV) was determined for all patients on pre-leukapheresis PET and on post-BT/pre-infusion PET in those who received BT. Patients were stratified into 'High' and 'Low' disease burden using an MTV cutpoint of 65.4cc established by maximally selected log-rank statistic for progression free survival (PFS). RESULTS: Of 191 patients treated with CART, 144 (75%) received BT. In the BT cohort, 56% had any reduction in MTV post-BT. On multivariate analysis, MTV trajectory across the bridging period remained significantly associated with PFS (p<0.001), however notably patients with improved MTV (High->Low) had equivalent PFS compared to those with initially and persistently low MTV (Low->Low) (HR for High->Low MTV: 2.74, CI: 0.82-9.18). There was a reduction in any Grade ICANS in the High->Low MTV cohort as compared to High->High (13 vs. 41%, p=0.05). CONCLUSIONS: This is the first study to use radiomics to quantify disease burden pre- and post-BT in a large real world LBCL cohort. We demonstrate that effective BT can enable initially high-disease burden patients to achieve post-CART outcomes comparable to low-disease burden patients.

7.
J Am Coll Cardiol ; 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39217573

ABSTRACT

BACKGROUND: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited. OBJECTIVES: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation. METHODS: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery. RESULTS: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027). CONCLUSIONS: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548).

8.
J Invest Dermatol ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39218144

ABSTRACT

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, caused by mutagenesis resulting from excess ultraviolet radiation or other types of oxidative stress. These stressors also upregulate production of a cutaneous innate immune element, cathelicidin antimicrobial peptide (CAMP), via endoplasmic reticulum (ER) stress-initiated, sphingosine-1-phosphate (S1P) signaling pathway. While CAMP has beneficial antimicrobial activities, it also can be pro-inflammatory and pro-carcinogenic. We addressed whether and how S1P-induced CAMP production leads to cSCC development. Our study demonstrated that: 1) CAMP expression is increased in cSCC cells and skin from cSCC patients; 2) S1P levels are elevated in cSCC cells, while inhibition of S1P production attenuates CAMP-stimulated cSCC growth; 3) exogenous CAMP stimulates cSCC, but not normal human keratinocyte growth; 4) blockade of formyl peptide receptor-like (FPRL) 1 protein, a CAMP receptor, attenuates cSCC growth as well as the growth and invasion of cSCC cells mediated by CAMP into an extracellular matrix-containing fibroblast substrate; 5) Foxp3+ regulatory T cell (which decreases anti-tumor immunity) levels increase in cSCC skin; and 6) CAMP induces ER stress in cSCC cells. Together, the ER stress-S1P-CAMP axis forms a vicious circle, creating a favorable environment for cSCC development, i.e., cSCC growth and invasion impedes anti-cancer immunity.

9.
Sci Transl Med ; 16(759): eadi4830, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39110781

ABSTRACT

Effective intracellular delivery of therapeutic proteins can potentially treat a wide array of diseases. However, efficient delivery of functional proteins across the cell membrane remains challenging. Exosomes are nanosized vesicles naturally secreted by various types of cells and may serve as promising nanocarriers for therapeutic biomolecules. Here, we engineered exosomes equipped with a photoinducible cargo protein release system, termed mMaple3-mediated protein loading into and release from exosome (MAPLEX), in which cargo proteins can be loaded into the exosomes by fusing them with photocleavable protein (mMaple3)-conjugated exosomal membrane markers and subsequently released from the exosomal membrane by inducing photocleavage with blue light illumination. Using this system, we first induced transcriptional regulation by delivering octamer-binding transcription factor 4 and SRY-box transcription factor 2 to fibroblasts in vitro. Second, we induced in vivo gene recombination in Cre reporter mice by delivering Cre recombinase. Last, we achieved targeted epigenome editing in the brains of 5xFAD and 3xTg-AD mice, two models of Alzheimer's disease. Administration of MAPLEXs loaded with ß-site amyloid precursor protein cleaving enzyme 1 (Bace1)-targeting single guide RNA-incorporated dCas9 ribonucleoprotein complexes, coupled with the catalytic domain of DNA methyltransferase 3A, resulted in successful methylation of the targeted CpG sites within the Bace1 promoter. This approach led to a significant reduction in Bace1 expression, improved recognition memory impairment, and reduced amyloid pathology in 5xFAD and 3xTg-AD mice. These results suggest that MAPLEX is an efficient intracellular protein delivery system that can deliver diverse therapeutic proteins for multiple diseases.


Subject(s)
Alzheimer Disease , CRISPR-Cas Systems , Exosomes , Gene Editing , Exosomes/metabolism , Animals , Alzheimer Disease/genetics , Alzheimer Disease/therapy , Alzheimer Disease/pathology , Alzheimer Disease/metabolism , CRISPR-Cas Systems/genetics , Gene Editing/methods , Humans , Mice , Epigenesis, Genetic , Drug Delivery Systems , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Peptides/metabolism , Disease Models, Animal , Integrases/metabolism
10.
Article in English | MEDLINE | ID: mdl-39115514

ABSTRACT

The American Board of Orthodontics (ABO) has updated its clinical examination process to remove barriers to the case-based examination and to distinguish board-certified orthodontists from uncertified dental practitioners who provide orthodontic care. In 2017, the ABO took the bold step of adopting a new clinical examination format (a scenario-based examination), thereby, addressing the challenges that were inherent in the former case-based examination format. The coronavirus disease 2019 pandemic forced the scenario-based clinical examination scheduled for July 2020 to be canceled. This caused the ABO to regroup and adapt the scenario-based clinical examination to a format that could be administered worldwide in a testing center environment, eliminating the need to travel to St Louis, Missouri. The ABO-written examination remained unaltered. Since the scenario-based format was adopted, 63% of the AAO members are now board-certified, and the trend is upward. In support of our mission to elevate the quality of orthodontics through certification, education, and professional collaboration, the ABO is responsible for certifying orthodontists in a fair, reliable, and valid manner. This requires continuous evaluation and review of our certification process to ensure that our examination reliably evaluates the ability of orthodontists to provide the highest level of patient care.

11.
Aust J Gen Pract ; 53(8): 567-570, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39099124

ABSTRACT

BACKGROUND: Globus pharyngeus, or globus, is characterised by the sensation of a lump or tightness in the throat. Symptoms can be persistent, difficult to treat and often reoccur. Globus is a common issue in the community, with lifetime prevalence occurring in up to 45% of the population. OBJECTIVE: This article aims to provide a narrative review of potential causes of globus, as well as a suggested guideline for work-up and management in the primary care setting. DISCUSSION: Causes for globus remain uncertain; however, current opinion focuses on a mixture of muscle tension and mucosal irritation. It is estimated that globus makes up 4% of all primary care referrals to otolaryngologists. There are a handful of proposed causes, with treatments often able to be initiated in the primary care setting. Although most causes are benign, it is important for clinicians to maintain suspicion for malignancy, because this is often the patient's main concern.


Subject(s)
Globus Sensation , Humans , Globus Sensation/physiopathology , Globus Sensation/therapy , Globus Sensation/complications , Pharyngeal Diseases/physiopathology , Pharyngeal Diseases/diagnosis , Pharyngeal Diseases/therapy , Primary Health Care
13.
Article in English | MEDLINE | ID: mdl-39160451

ABSTRACT

Backgrounds/Aims: Systematic investigations into the prognostic impact of the longitudinal tumor location in gallbladder cancer (GBC) remain insufficient. To address the limitations of our pilot study, we conducted a multicenter investigation to clarify the impact of the longitudinal tumor location on the oncological outcomes of GBC. Methods: A retrospective multicenter study was conducted on 372 patients undergoing radical resections for GBC from January 2010 to December 2019 across seven hospitals that belong to the Daejeon-Chungcheong branch of the Korean Association of Hepato-Biliary-Pancreatic Surgery. Patients were divided into GBC in the fundus/body (FB-GBC) and GBC in the neck/cystic duct (NC-GBC) groups, based on the longitudinal tumor location. Results: Of 372 patients, 282 had FB-GBC, while 90 had NC-GBC. NC-GBC was associated with more frequent elevation of preoperative carbohydrate antigen (CA) 19-9 levels, requirement for more extensive surgery, more advanced histologic grade and tumor stages, more frequent lymphovascular and perineural invasion, lower R0 resection rates, higher recurrence rates, and worse 5-year overall and disease-free survival rates. Propensity score matching analysis confirmed these findings, showing lower R0 resection rates, higher recurrence rates, and worse survival rates in the NC-GBC group. Multivariate analysis identified elevated preoperative CA 19-9 levels, lymph node metastasis, and non-R0 resection as independent prognostic factors, but not longitudinal tumor location. Conclusions: NC-GBC exhibits more frequent elevation of preoperative CA 19-9 levels, more advanced histologic grade and tumor stages, lower R0 resection rates, and poorer overall and disease-free survival rates, compared to FB-GBC. However, the longitudinal tumor location was not analyzed as an independent prognostic factor.

15.
J Neurochem ; 2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39183510

ABSTRACT

Epidermal growth factor (EGF) is known to be a critical stimulant for inducing the proliferation of glioma cancer cells. In our study, we observed that GST-RhoA binds to pyruvate kinase M2 (PKM2) in vitro. While EGF reduced the levels of RhoA protein, it significantly increased p-Y42 RhoA, as well as PKM1 and PKM2 in LN18 glioma cell line. We determined that RhoA undergoes degradation through ubiquitination involving SCF1 and Smurf1. Interestingly, we observed that p-Y42 RhoA binds to PKM2, while the dephosphomimetic form, RhoA Y42F, did not. Additionally, our observation revealed that PKM2 stabilized both RhoA and p-Y42 RhoA. Importantly, RhoA, p-Y42 RhoA, and PKM2, but not RhoA-GTP, were localized in the nucleus upon EGF stimulation. Knockdown of RhoA with siRNA resulted in the reduced levels of phosphoglycerate kinase1 (PGK1) and microtubule affinity-regulating kinase 4 (MARK). Furthermore, we found that the promoter of PGK1 was associated with ß-catenin and YAP. Notably, p-Y42 RhoA and PKM2 co-immunoprecipitated with ß-catenin and YAP. Based on these findings, we proposed a novel mechanism by which p-Y42 RhoA and PKM2, in conjunction with ß-catenin and YAP, regulate PGK1 expression, contributing to the progression of glioma upon EGF.

16.
J Obstet Gynaecol Can ; : 102644, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39179155

ABSTRACT

OBJECTIVE: This study investigated the potential of the slow-developing blastocysts using preimplantation genetic testing-aneuploidy (PGT-A) in patients undergoing frozen-thawed embryo transfer, stratified by age. STUDY DESIGN: A retrospective analysis was performed including a total of 743, the first frozen embryo transfer (FET) cycle with single embryo transfer (SET), who underwent treatment between January 2020 and July 2023 in a single fertility center, XXXX Fertility Center. A total of 743 cycles, in which we performed intracellular sperm injection and freeze all strategy, from 743 patients were included. The patient group was divided into 4 groups as follows: Group 1 (G1), 208 FET on day 5; Group 2 (G2), 177 FET with PGT-A on day 5; Group 3 (G3), 220 FET on day 6; Group 4 (G4), 138 FET with PGT-A on day 6. We also divided into two groups-under 35 years of age and over 35 years of age-and performed the analysis separately for each group. RESULTS: In under 35 years of age groups, there were no significant differences in clinical pregnancy and miscarriage rates in G1 and G2 (67.2% vs 63.8%, NS). Also, G4 had a higher clinical pregnancy rate than G3, but it was not significant (51.8% vs 54.7%, NS). In 35 years or older group, G2 had higher pregnancy rates than G1 and lower miscarriage rates (CPR: 43.3% vs 67.7%, P = 0.001, MR: 22.5% vs 3.4%, P = 0.001). In addition, G4 had a higher pregnancy rate than G3 and lower miscarriage rate (CPR: 31.8% vs. 46.9%, P = 0.003, MR: 22.9% vs 2.2%, P = 0.023). CONCLUSIONS: In ≥35 years group, PGT-A on day 5 and day 6 showed a high pregnancy rate and a low miscarriage rate. Therefore, using PGT-A seems advantageous for patients of an advanced maternal age.

17.
Asian J Urol ; 11(3): 450-459, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39139527

ABSTRACT

Objective: The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor (TKI) as the first-line therapy for patients with metastatic renal cell carcinoma (mRCC) in terms of overall survival (OS), progression-free survival (PFS), and rates of discontinuation and adverse effects during the treatment period. Methods: This is a retrospective, nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017. We focused on patients at either "favorable" or "intermediate" risk according to the International mRCC Database Consortium criteria, and they were followed up (median 335 days). Finally, a total of 1409 patients were selected as the study population. We generated a Cox proportional hazard model adjusted for covariates, and the different therapy schemes were statistically tested in terms of OS as well as PFS. In addition, frequencies of discontinuation and adverse events were compared among the therapy schemes. Results: Of the primary patterns of treatment sequences (24 sequences), "sunitinib-pazopanib" and "sunitinib-everolimus-immunotherapy" showed the most beneficial results in both OS and PFS with significantly lower hazards than "sunitinib", which is the most commonly treated agent in Korea. Considering that the "TKI-TKI" structure showed relatively higher discontinuation rates with higher adverse effects, the overall beneficial sequence would be "sunitinib-everolimus-immunotherapy". Conclusion: Among several sequential therapy starting with TKIs, "sunitinib-everolimus- immunotherapy" was found to be the best scheme for mRCC patients with "favorable" or "intermediate" risks.

18.
Ann Surg Treat Res ; 107(2): 81-90, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39139834

ABSTRACT

Purpose: This study aims to analyze the learning curve of hand-assisted laparoscopic living donor nephrectomy (HLDN) conducted by a trained gastrointestinal surgeon. Methods: A retrospective analysis was performed on the perioperative clinical data of 96 consecutive patients who underwent HLDN from May 2013 to March 2023. The learning curve was evaluated using the cumulative sum (CUSUM) test based on operation time and risk-adjusted CUSUM for postoperative complications. Patients were divided into three groups (novice, development, and competency phases) based on changes in operation time. Patient demographics and perioperative outcomes were compared between each group. Results: Among the patients, 35 were male, with a mean age of 48.9 ± 11.3 years and a mean body mass index (BMI) of 24.5 ± 3.2 kg/m2. The novice phase (phase 1) included the first 30 cases, with the development phase (phase 2) up to the 65th case. Operation times were significantly different across phases, averaging 263.2 ± 33.4, 211.1 ± 34.4, and 161.1 ± 31.3 minutes for phases 1, 2, and 3, respectively (P < 0.001). Blood loss decreased gradually across phases (phase 1, 264.7 ± 144.4 mL; phase 2, 239.7 ± 166.3 mL; phase 3, 198.8 ± 103.5 mL), though not statistically significant. BMI impacted operation time only in phase 1. Overall postoperative complications occurred in 13 cases (Clavien-Dindo grade I, 4 cases; grade II, 9 cases), with no significant differences across phases. Conclusion: HLDN can be safely performed by a trained gastrointestinal surgeon, with approximately 30 cases needed to achieve proficiency.

19.
BMC Med ; 22(1): 335, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39148087

ABSTRACT

BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.


Subject(s)
Clopidogrel , Cytochrome P-450 CYP2C19 , Drug-Eluting Stents , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Proton Pump Inhibitors , Humans , Clopidogrel/therapeutic use , Clopidogrel/adverse effects , Clopidogrel/administration & dosage , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Male , Female , Drug-Eluting Stents/adverse effects , Aged , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Percutaneous Coronary Intervention/adverse effects , Cytochrome P-450 CYP2C19/genetics , Treatment Outcome , Registries , East Asian People
20.
Rice (N Y) ; 17(1): 48, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39115620

ABSTRACT

BACKGROUND: Photoperiod sensitivity is among the most important agronomic traits of rice, as it determines local and seasonal adaptability and plays pivotal roles in determining yield and other key agronomic characteristics. By controlling the photoperiod, early-maturing rice can be cultivated to shorten the breeding cycle, thereby reducing the risk of yield losses due to unpredictable climate change. Furthermore, early-maturing and high-yielding rice needs to be developed to ensure food security for a rapidly growing population. Early-maturing and high-yielding rice should be developed to fulfill these requirements. OsCKq1 encodes the casein kinase1 protein in rice. OsCKq1 is a gene that is activated by photophosphorylation when Ghd7, which suppresses flowering under long-day conditions, is activated. RESULTS: This study investigates how OsCKq1 affects heading in rice. OsCKq1-GE rice was analyzed the function of OsCKq1 was investigated by comparing the expression levels of genes related to flowering regulation. The heading date of OsCKq1-GE lines was earlier (by about 3 to 5 days) than that of Ilmi (a rice cultivar, Oryza sativa spp. japonica), and the grain length, grain width, 1,000-grain weight, and yield increased compared to Ilmi. Furthermore, the culm and panicle lengths of OsCKq1-GE lines were either equal to or longer than those of Ilmi. CONCLUSIONS: Our research demonstrates that OsCKq1 plays a pivotal role in regulating rice yield and photoperiod sensitivity. Specifically, under long-day conditions, OsCKq1-GE rice exhibited reduced OsCKq1 mRNA levels alongside increased mRNA levels of Hd3a, Ehd1, and RFT1, genes known for promoting flowering, leading to earlier heading compared to Ilmi. Moreover, we observed an increase in seed size. These findings underscore OsCKq1 as a promising target for developing early-maturing and high-yielding rice cultivars, highlighting the potential of CRISPR/Cas9 technology in enhancing crop traits.

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